Post on 30-Jan-2020
7262019
1
Update on
Tourette
DisorderREBECCA K LEHMAN MD FAAN
ASSOCIATE PROFESSOR OF CLINICAL PEDIATRICS (CHILD NEUROLOGY)
PALMETTO HEALTH-UNIVERSITY OF SOUTH CAROLINA MEDICAL GROUP
PRISMA HEALTH CHILDRENrsquoS HOSPITAL-MIDLANDS
AUGUST 9 2019
Disclosures
Financial disclosures
Reimbursement from TAA for travel to MAB meeting and lectures
Participating (Sub-IPIRater) in clinical trials for Neurocrine Teva and Emalex Reimbursed for travel to investigator meetings No other financial conflicts
All of the treatments for Tourette Disorder are off-label with the following exceptions
Haloperidol (3 years and older)
Pimozide (12 years and older)
Aripiprazole (6-18 years)
Tetrabenazine (orphan drug designation for children 5-16 years)
1
2
7262019
2
Objectives
By the end of the lecture attendees should be able to
Describe the clinical characteristics of tics
Define Tourette Disorder (Syndrome)
Review the symptom criteria for the diagnosis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections)
Examine the controversies surrounding the diagnosis and treatment of PANDAS
List the neuropsychiatric conditions that commonly co-occur with TD
Outline the range of management strategies for TD
Identify resources that are available for patient education and support
What are tics
Movements or vocalizations that are
Sudden
Abrupt
Transient
Repetitive
Coordinated (stereotyped)
3
4
7262019
3
Premonitory Urge
Leckman JF Walker DE Cohen DJ 1993
Other Characteristics of Tics
bull Variable in appearance and frequency over time
bull Briefly suppressible
bull Worsened by stress and excitement
bull Often reduced by focused concentration
bull May persist in sleep but often abate
5
6
7262019
4
Classification of Tics
Tic Symptom Dimensions Examples
Simple motor tics Sudden brief
meaningless movementsEye blinking nose twitching grimacing grinning pouting
mouth opening head jerking shoulder shrugging abdominal
or buttock tensing kicking finger movements rapid jerking of
any part of the body
Complex motor tics Slower longer more
ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching
objectsself thrusting arms throwing banging gestures with
hands gyrating and bending dystonic postures copropraxia
(obscene gestures)
Simple phonic tics Sudden meaningless
sounds or noises
Throat clearing coughing sniffing spitting screeching
barking grunting gurgling clacking hissing sucking animal
noises and innumerable other sounds
Complex phonic tics Sudden more
ldquomeaningfulrdquo utterances
Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)
speech atypicalities (variations in pitch volume etc)
palilalia (repetition of onersquos own words) or echolalia
(repetition of anotherrsquos words or phrases) coprolalia
(obscene or inappropriate words or phrases)
I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me
7
8
7262019
5
Tourette Disorder
(Syndrome)
A Both multiple motor and gt= 1 vocal tics have been present at some time during the illness although not necessarily concurrently
B The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of gt1 year and during this period there was never a tic-free period of gt3 consecutive months
C Onset before age 18 years
D The disturbance is not due to the direct physiological effects of a substance (eg stimulants) or a general medical condition (eg HD or post-viral encephalitis)
9
10
7262019
6
Other Tic Disorders
bull Persistent (Chronic) Motor Tic Disorder
bull Multiple motor tics
bull Duration gt1 year
bull Persistent (Chronic) Vocal Tic Disorder
bull Multiple vocal tics
bull Duration gt1 year
Other Tic Disorders
Provisional Tic Disorder
Single or multiple motor andor vocal tics
Duration gt4 weeks but lt12 consecutive months
Other Specified Tic Disorder Unspecified Tic
Disorder
Any tic disorder that does not meet criteria for a
specific tic disorder (eg tics lasting lt4 weeks onset
after age 18)
11
12
7262019
7
Epidemiology
bull Boys girls = 3-4 1
bull Affects all ethnic groups
bull Prevalence among school-age children
Provisional (transient) tic disorders ndash 20-25
Chronic tic disorders ndash ~1
Tourette syndrome ndash 03-08
Prevalence of TD
Community studies 06
Diagnosed + Not Diagnosed
Ages 0-19 years
National survey data 03
Diagnosed only
Ages 6-17 years
Suggests that ~50 of
children with TS are
undiagnosed
Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)
13
14
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
2
Objectives
By the end of the lecture attendees should be able to
Describe the clinical characteristics of tics
Define Tourette Disorder (Syndrome)
Review the symptom criteria for the diagnosis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections)
Examine the controversies surrounding the diagnosis and treatment of PANDAS
List the neuropsychiatric conditions that commonly co-occur with TD
Outline the range of management strategies for TD
Identify resources that are available for patient education and support
What are tics
Movements or vocalizations that are
Sudden
Abrupt
Transient
Repetitive
Coordinated (stereotyped)
3
4
7262019
3
Premonitory Urge
Leckman JF Walker DE Cohen DJ 1993
Other Characteristics of Tics
bull Variable in appearance and frequency over time
bull Briefly suppressible
bull Worsened by stress and excitement
bull Often reduced by focused concentration
bull May persist in sleep but often abate
5
6
7262019
4
Classification of Tics
Tic Symptom Dimensions Examples
Simple motor tics Sudden brief
meaningless movementsEye blinking nose twitching grimacing grinning pouting
mouth opening head jerking shoulder shrugging abdominal
or buttock tensing kicking finger movements rapid jerking of
any part of the body
Complex motor tics Slower longer more
ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching
objectsself thrusting arms throwing banging gestures with
hands gyrating and bending dystonic postures copropraxia
(obscene gestures)
Simple phonic tics Sudden meaningless
sounds or noises
Throat clearing coughing sniffing spitting screeching
barking grunting gurgling clacking hissing sucking animal
noises and innumerable other sounds
Complex phonic tics Sudden more
ldquomeaningfulrdquo utterances
Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)
speech atypicalities (variations in pitch volume etc)
palilalia (repetition of onersquos own words) or echolalia
(repetition of anotherrsquos words or phrases) coprolalia
(obscene or inappropriate words or phrases)
I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me
7
8
7262019
5
Tourette Disorder
(Syndrome)
A Both multiple motor and gt= 1 vocal tics have been present at some time during the illness although not necessarily concurrently
B The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of gt1 year and during this period there was never a tic-free period of gt3 consecutive months
C Onset before age 18 years
D The disturbance is not due to the direct physiological effects of a substance (eg stimulants) or a general medical condition (eg HD or post-viral encephalitis)
9
10
7262019
6
Other Tic Disorders
bull Persistent (Chronic) Motor Tic Disorder
bull Multiple motor tics
bull Duration gt1 year
bull Persistent (Chronic) Vocal Tic Disorder
bull Multiple vocal tics
bull Duration gt1 year
Other Tic Disorders
Provisional Tic Disorder
Single or multiple motor andor vocal tics
Duration gt4 weeks but lt12 consecutive months
Other Specified Tic Disorder Unspecified Tic
Disorder
Any tic disorder that does not meet criteria for a
specific tic disorder (eg tics lasting lt4 weeks onset
after age 18)
11
12
7262019
7
Epidemiology
bull Boys girls = 3-4 1
bull Affects all ethnic groups
bull Prevalence among school-age children
Provisional (transient) tic disorders ndash 20-25
Chronic tic disorders ndash ~1
Tourette syndrome ndash 03-08
Prevalence of TD
Community studies 06
Diagnosed + Not Diagnosed
Ages 0-19 years
National survey data 03
Diagnosed only
Ages 6-17 years
Suggests that ~50 of
children with TS are
undiagnosed
Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)
13
14
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
3
Premonitory Urge
Leckman JF Walker DE Cohen DJ 1993
Other Characteristics of Tics
bull Variable in appearance and frequency over time
bull Briefly suppressible
bull Worsened by stress and excitement
bull Often reduced by focused concentration
bull May persist in sleep but often abate
5
6
7262019
4
Classification of Tics
Tic Symptom Dimensions Examples
Simple motor tics Sudden brief
meaningless movementsEye blinking nose twitching grimacing grinning pouting
mouth opening head jerking shoulder shrugging abdominal
or buttock tensing kicking finger movements rapid jerking of
any part of the body
Complex motor tics Slower longer more
ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching
objectsself thrusting arms throwing banging gestures with
hands gyrating and bending dystonic postures copropraxia
(obscene gestures)
Simple phonic tics Sudden meaningless
sounds or noises
Throat clearing coughing sniffing spitting screeching
barking grunting gurgling clacking hissing sucking animal
noises and innumerable other sounds
Complex phonic tics Sudden more
ldquomeaningfulrdquo utterances
Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)
speech atypicalities (variations in pitch volume etc)
palilalia (repetition of onersquos own words) or echolalia
(repetition of anotherrsquos words or phrases) coprolalia
(obscene or inappropriate words or phrases)
I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me
7
8
7262019
5
Tourette Disorder
(Syndrome)
A Both multiple motor and gt= 1 vocal tics have been present at some time during the illness although not necessarily concurrently
B The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of gt1 year and during this period there was never a tic-free period of gt3 consecutive months
C Onset before age 18 years
D The disturbance is not due to the direct physiological effects of a substance (eg stimulants) or a general medical condition (eg HD or post-viral encephalitis)
9
10
7262019
6
Other Tic Disorders
bull Persistent (Chronic) Motor Tic Disorder
bull Multiple motor tics
bull Duration gt1 year
bull Persistent (Chronic) Vocal Tic Disorder
bull Multiple vocal tics
bull Duration gt1 year
Other Tic Disorders
Provisional Tic Disorder
Single or multiple motor andor vocal tics
Duration gt4 weeks but lt12 consecutive months
Other Specified Tic Disorder Unspecified Tic
Disorder
Any tic disorder that does not meet criteria for a
specific tic disorder (eg tics lasting lt4 weeks onset
after age 18)
11
12
7262019
7
Epidemiology
bull Boys girls = 3-4 1
bull Affects all ethnic groups
bull Prevalence among school-age children
Provisional (transient) tic disorders ndash 20-25
Chronic tic disorders ndash ~1
Tourette syndrome ndash 03-08
Prevalence of TD
Community studies 06
Diagnosed + Not Diagnosed
Ages 0-19 years
National survey data 03
Diagnosed only
Ages 6-17 years
Suggests that ~50 of
children with TS are
undiagnosed
Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)
13
14
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
4
Classification of Tics
Tic Symptom Dimensions Examples
Simple motor tics Sudden brief
meaningless movementsEye blinking nose twitching grimacing grinning pouting
mouth opening head jerking shoulder shrugging abdominal
or buttock tensing kicking finger movements rapid jerking of
any part of the body
Complex motor tics Slower longer more
ldquopurposefulrdquo movementsSustained ldquolooksrdquo facial gestures biting touching
objectsself thrusting arms throwing banging gestures with
hands gyrating and bending dystonic postures copropraxia
(obscene gestures)
Simple phonic tics Sudden meaningless
sounds or noises
Throat clearing coughing sniffing spitting screeching
barking grunting gurgling clacking hissing sucking animal
noises and innumerable other sounds
Complex phonic tics Sudden more
ldquomeaningfulrdquo utterances
Syllables words or phrases (eg ldquoShut uprdquo ldquoOh okayrdquo)
speech atypicalities (variations in pitch volume etc)
palilalia (repetition of onersquos own words) or echolalia
(repetition of anotherrsquos words or phrases) coprolalia
(obscene or inappropriate words or phrases)
I Have Tourettersquos But Tourettersquos Doesnrsquot Have Me
7
8
7262019
5
Tourette Disorder
(Syndrome)
A Both multiple motor and gt= 1 vocal tics have been present at some time during the illness although not necessarily concurrently
B The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of gt1 year and during this period there was never a tic-free period of gt3 consecutive months
C Onset before age 18 years
D The disturbance is not due to the direct physiological effects of a substance (eg stimulants) or a general medical condition (eg HD or post-viral encephalitis)
9
10
7262019
6
Other Tic Disorders
bull Persistent (Chronic) Motor Tic Disorder
bull Multiple motor tics
bull Duration gt1 year
bull Persistent (Chronic) Vocal Tic Disorder
bull Multiple vocal tics
bull Duration gt1 year
Other Tic Disorders
Provisional Tic Disorder
Single or multiple motor andor vocal tics
Duration gt4 weeks but lt12 consecutive months
Other Specified Tic Disorder Unspecified Tic
Disorder
Any tic disorder that does not meet criteria for a
specific tic disorder (eg tics lasting lt4 weeks onset
after age 18)
11
12
7262019
7
Epidemiology
bull Boys girls = 3-4 1
bull Affects all ethnic groups
bull Prevalence among school-age children
Provisional (transient) tic disorders ndash 20-25
Chronic tic disorders ndash ~1
Tourette syndrome ndash 03-08
Prevalence of TD
Community studies 06
Diagnosed + Not Diagnosed
Ages 0-19 years
National survey data 03
Diagnosed only
Ages 6-17 years
Suggests that ~50 of
children with TS are
undiagnosed
Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)
13
14
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
5
Tourette Disorder
(Syndrome)
A Both multiple motor and gt= 1 vocal tics have been present at some time during the illness although not necessarily concurrently
B The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of gt1 year and during this period there was never a tic-free period of gt3 consecutive months
C Onset before age 18 years
D The disturbance is not due to the direct physiological effects of a substance (eg stimulants) or a general medical condition (eg HD or post-viral encephalitis)
9
10
7262019
6
Other Tic Disorders
bull Persistent (Chronic) Motor Tic Disorder
bull Multiple motor tics
bull Duration gt1 year
bull Persistent (Chronic) Vocal Tic Disorder
bull Multiple vocal tics
bull Duration gt1 year
Other Tic Disorders
Provisional Tic Disorder
Single or multiple motor andor vocal tics
Duration gt4 weeks but lt12 consecutive months
Other Specified Tic Disorder Unspecified Tic
Disorder
Any tic disorder that does not meet criteria for a
specific tic disorder (eg tics lasting lt4 weeks onset
after age 18)
11
12
7262019
7
Epidemiology
bull Boys girls = 3-4 1
bull Affects all ethnic groups
bull Prevalence among school-age children
Provisional (transient) tic disorders ndash 20-25
Chronic tic disorders ndash ~1
Tourette syndrome ndash 03-08
Prevalence of TD
Community studies 06
Diagnosed + Not Diagnosed
Ages 0-19 years
National survey data 03
Diagnosed only
Ages 6-17 years
Suggests that ~50 of
children with TS are
undiagnosed
Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)
13
14
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
6
Other Tic Disorders
bull Persistent (Chronic) Motor Tic Disorder
bull Multiple motor tics
bull Duration gt1 year
bull Persistent (Chronic) Vocal Tic Disorder
bull Multiple vocal tics
bull Duration gt1 year
Other Tic Disorders
Provisional Tic Disorder
Single or multiple motor andor vocal tics
Duration gt4 weeks but lt12 consecutive months
Other Specified Tic Disorder Unspecified Tic
Disorder
Any tic disorder that does not meet criteria for a
specific tic disorder (eg tics lasting lt4 weeks onset
after age 18)
11
12
7262019
7
Epidemiology
bull Boys girls = 3-4 1
bull Affects all ethnic groups
bull Prevalence among school-age children
Provisional (transient) tic disorders ndash 20-25
Chronic tic disorders ndash ~1
Tourette syndrome ndash 03-08
Prevalence of TD
Community studies 06
Diagnosed + Not Diagnosed
Ages 0-19 years
National survey data 03
Diagnosed only
Ages 6-17 years
Suggests that ~50 of
children with TS are
undiagnosed
Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)
13
14
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
7
Epidemiology
bull Boys girls = 3-4 1
bull Affects all ethnic groups
bull Prevalence among school-age children
Provisional (transient) tic disorders ndash 20-25
Chronic tic disorders ndash ~1
Tourette syndrome ndash 03-08
Prevalence of TD
Community studies 06
Diagnosed + Not Diagnosed
Ages 0-19 years
National survey data 03
Diagnosed only
Ages 6-17 years
Suggests that ~50 of
children with TS are
undiagnosed
Knight et al (2012) Scharf et al 2014Bitsko et al (2014) CDC (2009)
13
14
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
8
Copyright copy1998 American Academy of Pediatrics
Leckman J F et al Pediatrics 199810214-19
Take Home Point 1
15
16
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
9
Differential Diagnosis
Eye rolling -gt Absence seizures
Blinking -gt Allergy poor vision blepharospasm
Facial grimacing -gt Dystonia
Sniffing -gt Allergy
Scratching -gt Scabies lice skin disorders
Tics during sleep -gt Hypnic myoclonus PLMS epilepsy parasomnias
Extremely exaggerated tics -gt Functional movement disorder
Other movement disorders (myoclonus tremor chorea dystonia)
Compulsions
PANDAS
Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcal Infections (Swedo
et al 1998)
OCD and or tics
Prepubertal onset
Episodic (saw-tooth) course
Associated with Group A beta-hemolytic Strep
infections
Association with neurological signs
17
18
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
10
PANS
Pediatric Acute-Onset Neuropsychiatric Syndrome (Swedo et al 2012)
Abrupt dramatic onset
OCD or severely restricted food intake
Two or more of
Anxiety
Emotional lability or depression
Irritability aggression andor severely oppositional behavior
Behavioral regression
Deterioration in school
Sensory or motor abnormalities
Somatic symptoms including sleep disturbances enuresis and urinary frequency
Symptoms not better explained by another neurological or medical disorder
Cunningham Panel
Antibody Moleculara Upper
Limit of Normal
Hesselmark Upper
Limit of Normal
Calcium
Calmodulin Kinase II
130 197
Anti-Dopamine
Receptor 1
8000 15200
Anti-Dopamine
Receptor 2
16000 18400
Lysoganglioside
GM01 Antibody
640 1280
Beta-Tubulin
Antibody
1000 8000
19
20
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
11
Current State of Evidence
Guidelines are based on expert consensus
Insufficient high-quality data to support the use of
long-term antibiotics immunomodulation andor
tonsillectomy
Treatment studies have small numbers of subjects
Controlled studies have been negative
No studies of more specific immunomodulators
21
22
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
12
EMTICSEuropean Multicentre Tics in Children Studies
Longitudinal observational prospective study
involving 16 sites in Europe
Goal
To investigate the association of environmental factors (GAS infection psychosocial stress) with the onset and course of tics andor OCD
To characterize the immune response to microbial
antigens and the hosts immune response regulation in association with onset and exacerbations of tics
To increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders
To develop prediction models for the risk of onset and exacerbations of tic disorders
httpscordiseuropaeuprojectrcn102102reportingen
EMTICS Design
ONSET cohort
At-risk individuals
N = 260 children aged 3-10 years who are tic-free at
study entry and have a first-degree relative with a
chronic tic disorder
COURSE cohort
Affected individuals
N = 715 youth aged 3-16 years with a tic disorder
23
24
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
13
EMTICS Conclusions
No indication for a role of new GAS exposures in
relation to exacerbations of tic disorders
GAS infections are frequent and exposure at some
point in childhood is nearly universal
Co-occurrence of tic exacerbations and recent
new GAS exposures is most likely due to chance
Anti-GAS responses in patients with tics did not
increase after tic exacerbations
Assessing GAS exposure in children with tic disorders
is not clinically meaningful
Possible altered post-infectious immune response
in patients with TD OCD
25
26
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
14
Take Home Point 2
Co-morbid Conditions
bull ADHD
bull Anxiety OCD
bull Learning difficulties
bull Mood disorders
bull Impulse control
disorders
bull Dysgraphia fine
motor impairment
27
28
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
15
Treatment of Tics
Take Home Point 3 Not all patients require treatment
Current treatments do not ldquocurerdquo tics
Think about treating patients whose tics are causing
Paininjury
Social distress
Significant disturbance to others in classroom environment
No scientific evidence to support the use of dietary interventions
Take Home Point 4 Comorbid disorders are often more impairing than the tics themselves and are associated with poorer long-term outcomes Assess for comorbid disorders and treat most impairing condition first
Take Home Point 5
29
30
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
16
Figure 2 Mean change from Questionnaire-Teacher baseline on the ConnersAbbreviated Symptom (ASQ-Teacher) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
Figure 3 Mean change from baseline on the Yale Global Tic Severity Scale (Y-GTSS) at each evaluation visit for the four treatment groups Error bars represent 1 SEM CLON = clonidine MPH = methylphenidate
(Tourette Syndrome Study Group 2002)
31
32
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
17
Take Home Point 6
Patients with TD CTD are
at increased risk of
suicide
Clinicians must inquire
about suicidal thoughts
and suicide attempts in
people with TS and refer
to appropriate resources
if present
Fernandez del la Cruz L Rydell M Runeson B et al Suicide in Tourettersquos and chronic tic disorders BiolPsychiatry 201782111-118
Treatment Options
33
34
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
18
Comprehensive
Behavioral Intervention in
Tics (CBIT)
Components of CBIT
Habit Reversal Training
Tic-awareness
Self-monitoring of current tics
Focus on premonitory urge or other early sign that tic is going to occur
Competing response training
Engagement in a voluntary behavior that is physically incompatible with the tic
Goal is to disrupt the negative reinforcement cycle rather than to simply suppress the tic
PlushellipRelaxation training and a functional intervention to address situations that sustain or worsen tics
35
36
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
19
Piacentini et al JAMA 2010303(19)1929-1937
CBIT Study Design
Baseline Week 5 and
Week 10 Scores
37
38
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
20
bull Durable response at 3 and 6 months
bull Clinical Global Impressions Improvement Scale was significantly higher for the behavioral vs control (525 3261 vs 185 1265 plt0001)
NNT=3
ARR=34
Alpha-2 Agonists
Act presynaptically to inhibit NE release
Examples
Clonidine (Catapres)
Clonidine ER (Kapvay)
Guanfacine (Tenex)
Guanfacine XR (Intuniv)
Side effects
Sedation
Drowsiness
Hypotension
Bradycardia
QTc prolongation (guanfacine XR)
39
40
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
21
Alpha-2 Agonist Safety
Issues
1) Counsel about side effects
2) Monitor pulse and blood pressure
3) Monitor QTc interval if patient is taking guanfacine
XR and has a history of cardiac conditions are on
other QTc prolonging agents andor have a family
history of long QTc syndrome
4) Taper alpha-2 agonists gradually to avoid rebound
hypertension
D2 AntagonistsAtypical and Typical Antipsychotics
41
42
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
22
D2 Antagonists
Medication Initial dose Dose range
Typical
Haloperidol 025-05 mgd 025-6 mgd
Pimozide 1 mgd 1-10 mgd
Atypical
Risperidone 025-05 mgd 025-6 mgd
Ziprasidone 5-20 mgd 5-100 mgd
Aripiprazole 25-5 mgd 5-30 mgd
General Principles of
Prescribing D2 Antagonists
Insufficient evidence to determine the relative
efficacy of the antipsychotic drugs
Atypical antipsychotics are not inherently safer
than typical antipsychotics
Use the lowest effective dose
Reevaluate need for treatment on an ongoing
basis
43
44
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
23
D2 Antagonist Safety
Issues Side Effects
Drug-induced movement disorders
Weight gain
Somnolence
Adverse metabolic side effects
Increased prolactin
QTc prolongation
Monitor for side effects using evidenced-based protocols (wwwcamesaguidelineorg)
Obtain an EKG before and after starting pimozide and ziprasidone or if antipsychotics are being co-administered with medications that prolong the QTc interval
Taper antipsychotics gradually to avoid withdrawal dyskinesias
Pringsheim T Panagiotopoulos C Davidson J Ho J Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group Evidence-based recommendations for monitoring safety of second-generation antipsychotics in children and youth Paediatr Child Health 201116(9)581ndash589
45
46
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
24
The Other Playershellip
Benzodiazepines
Clonazepam
Substituted benzamides
Sulpiride
Tiapride
Metoclopromide
Monoamine-depleting
Tetrabenazine
Botulinum toxin
Limited Evidence
Baclofen
Anticonvulsants
Topiramate (Topamax)
Levetiracetam (Keppra)
Dopamine agonists
Pergolide (Permax) (Cianchetti et al 2005 Gilbert et al 2005)
Ropinirole (Requip) (Anca et al 2004)
Levodopa
Apomorphine (Feinberg and Carroll 1979)
Cannabinoids
Nicotine
47
48
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
25
Experimental Therapies
Ineffective
Discontinued
N-Acetylcysteine
Fatty acid amide
hydrolase
Pramipexole
Valbenazine (T-Force
Gold Platinum
Neurocrine)
Under Investigation
D1 dopamine receptor antagonist
Ecopipam (D1amond Emalex)
VMAT inhibitors
Deutetrabenazine(Artists2 Teva)
Cannabis-related cannabinoid compounds
D-cycloserine (Abide)
Oral appliance
Deep brain stimulation
Augustine F Singer HS Merging the Pathophysiology and Pharmacotherapy of Tics Tremor Other Hyperkinet Mov (N Y) 20198595 Published 2019 Jan 9 doi107916D89C8F3C
49
50
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
26
Oral Orthotic
Proof of Concept Study of an Oral Orthotic
to Reduce Tic Severity in Chronic Tic
Disorder and Tourette Syndrome
51
52
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
27
Schrock LE et al and Tourette Syndrome Association International Deep Brain Stimulation (DBS) Database and Registry Study Group (2015) Tourette syndrome deep brain stimulation A review and updated recommendations Mov Disord 30 448ndash471 doi 101002mds26094
DBS Targets for TS
(Hariz MI and Robertson MM EJNR 2010)
53
54
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
28
Additional ResourcesEDUCATIONAL MATERIALS amp PATIENT FAMILY
SUPPORT
55
56
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
29
Tourette Association of
America (wwwtouretteorg)
Family Guide Care Providers Guide
Tourette Association
YouTube
57
58
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
30
Helpful Books amp ResourcesFamily Information for Tourette
A Families Guide to TS
10 Secrets to a Happier Life with TS
TS- What Families Should Know
The Keeper (Tim Howardrsquos Book for Adults and Children)
Natural Remedies for Tics and Tourettersquos Syndrome
Tourette Education for Children
Quit It
A Test of Will
Matthew Sally and Simon Story Series
Twitch and Shout
Front of The Class (Movie)
I Have Tourettersquos but It Doesnrsquot Have Me
OCD
Anxiety Workbook for Teens
Up and Down the Worry Hill
Freeing Your Child from OCD
Talking Back to OCD
Taming the Tiger
Executive Functioning
See It Say It Do It
Smart but Scattered
Smart but Scattered Planner
CPRI Brake Shop
Brake Shop ClinicLeaky Brake Toolkit
httpwwwcpricacontentpageaspxsection=26
59
60
7262019
31
Tic Helper
61
7262019
31
Tic Helper
61