MedicationManagementinTicDisorders
EricaGreenberg,MDPediatricPsychiatryOCDandTicDisordersProgram
7/29/18
Norelevantdisclosures(ClinicalresearchstudyfundedinpartbytheAmericanAcademyofChildandAdolescent
Psychiatry(AACAP)’sPilotResearchAwardforAttentionDisorders,supportedbyAACAP’sElaineSchlosserLewisFund)
Discussionofoff-label&investigationaluse:Yes X No__
SpeakerDisclosures:
Outline
•BriefreviewofticsandTourettesyndrome(TS)•Pharmacologyfortics•PharmacologyforOCDandADHDwhenticsarealsopresent
Whataretics?
• Sudden,recurrent,non-rhythmic,movementsorsounds• Unvoluntary
•Waxandwaneovertime• Treatmentimplications
•Oftenprecededbyapremonitoryurge/itch/tension• Somatic,sensory,orideationalsymptomsthatprecedetics• Feelingof“notjustright”or“incompleteness”• Temporarilyrelievedbyperformingthetic
• They“jump”• Changelocation,number,frequency,type,complexityseverity
Millsetal.,2014Hallett 2015
WhatisTouretteSyndrome?
• Childhood-onsetneuropsychiatricdisordercharacterizedbytics• Estimatedtobebetween0.3%and0.9%(Scharfetal2015)
• Criteria:• AtleastTwomotorandOnevocalticoverthecourseoftheillness• Atleastoneyearduration,thoughtheticscanwaxandwaneinfrequency• Onsetbeforeage18• Notsecondarytoasubstanceoranothermedicalcondition
OtherTicDisorders
• Persistent(Chronic)MotororVocalTicDisorder:• SamecriteriaasTS,butonlymotorORvocaltics• Additional1-2%ofchildren
• ProvisionalTicDisorder• Partofnormaldevelopment?(~20-25%ofkids)
TSPathophysiology
• Dysfunctionoffronto-striatal-thalamo-corticalcircuits• Leadstodisinhibitionofthemotorandlimbicsystem
• Neurotransmittersinthiscircuit:• Glutamate• Serotonin• Dopamine• GABA
Beddows 2015 - http://scitechconnect.elsevier.com/neurobiology-basis-of-ocd/. Modified from original image, credits: Patrick J. Lynch and C. Carl Jaffe.
TreatmentconsiderationsinTourettesyndrome:• Improvement with age• Rule of Thirds: 1/3 resolve, 1/3 improve, 1/3 stay the same•~10% of patients have persistent, severe symptoms as adults
•Modifying factors (internal vs. external)
WhentoTreatTics?
• Whentics/urgesarecausingphysicalpain/impairment• Whenticsarecausingseveresocial/functionalproblems• Whenticsleadtopsychologicaldistress,suchasdepressiveandanxioussymptoms,lowself-esteemand/orsocialwithdrawal
ChildhoodPsychosocialMorbidity
•Over 2/3 children with TS reported impaired peer relations, difficulties with friendships• Rated as less popular/more withdrawn by peers and
teachers vs. healthy controls• Higher rates of peer victimization when compared to
children with a “medical” illness (Type I diabetes) and healthy controls
•Quality of life in children with TS significantly worse than normative sample
(Eapen,Cavanna,Robertson2016)
Treatments
•Behavioral•Pharmacologic
healthncare.info
OverallTreatmentGuidelines
• NostudiescomparingtheeffectivenessofbehavioralandpharmacologicaltreatmentsinpatientswithTS• Treatmentaimstoreduceticseverityandfrequency• Oftenmoreimportanttomanagethecomorbidconditionsinordertoimprovepsychosocialfunctioningand(child)development• Intensityofticsdoesnothavetoequatewithimpairment
EuropeanSocietyfortheStudyofTouretteSyndrome,2011
Pharmacotherapy
• Only FDA approved treatments: Pimozide, Haloperidol and Aripiprazole• Broadrangeofclinicalexperiences,butactualevidence(basedonRCTs)islimited
TSPharmacologyOverview
•Three“tiers”ofticmedications•Tier1:Alpha-2agonists:
• Clonidine,guanfacine, extended-releaseguanfacine
•Tier2:Atypicalneuroleptics(antipsychotics)• Risperidone, aripiprazole,etc.
•Tier3:Typicalneuroleptics(antipsychotics)• Haloperidol,pimozide,etc.
DosesofMedication
The image part with relationship ID rId3 was not found in the file.
THOMSONREUTERS– DrugsofToday2014,50(2)
Alpha-agonists
•Clonidine,guanfacine• “Bloodpressure”medications
• IndicationintreatingADHD• Off-label,usedforsleep,impulsivity,?anxiety• Short-acting,extended-release,transdermal
• Leastsideeffects• Sedation,dizziness,headache,lowbloodpressure
•Goodforticsoflimitedseverity**• Improvementabout30%
•**Caveat:Mayonlybehelpfulifco-occurringADHD• Recentnegativestudyusingextended-releaseguanfacineinchildrenwithchronictics (Murphyetal.,2017)
AtypicalAntipsychotics
• Risperidone,Aripiprazole(Dopaminergic/serotonergic)• (ClassB:Ziprasidone,Olanzapine,Quetiapine)
• Otherindications:Mooddisorders(bipolardisorder,severeaggressivebehavior/mooddysregulationinASD,psychosis)
•Moderatesideeffects:•Metabolicsymptoms(cholesterol,weightgain,glucose)• Akathisia,lowbloodpressure,GI,sedation• Lowriskoftardivedyskinesia• Requiresmonitoring(blood)
•Moderatebenefit:• 35-60%ticreduction
TypicalAntipsychotics
•Haloperidol,Pimozide(Dopaminergic)• (ClassB:Fluphenazine)
•Otherindications:Psychoticdisorders,severebipolardisorder/mooddysregulation
•Potentialforseveresideeffects:•Tardivedyskinesia,dystonia,•Sedation,weightgain,fogginess•Requiresmonitoring(EKG)
•Oftennottolerated2otosideeffects
•Largestbenefit:•Haloperidol upto80%;fluphenazine/pimozideupto60%
OtherMedications
• Benzodiazepines (clonazepam)
• Topiramate (anticonvulsant): Meta-analysis negative, but positive RCT in kids
• Baclofen (GABA modulator): Some positive effect
• Atomoxetine: Some benefit, at times exacerbates tics
• Nicotine: Some benefit• Tetrabenazine: some positive effect, increased risk of
depression• Trialing new VMAT-2 inhibitors
• Metoclopramide(mixeddopamine/serotoninantagonist)• Botox:Onlyforsimplemotortic• Cannabinoids**
Thomasetal2013EgolfandCoffey2014
Cannabanoids(Delta-9-THC)
• Anecdotalreportsthatmarijuana maybehelpfulwithticsand behavioralproblems• WhitingetalinJAMA(2015)suggestedthat“suggestedthatTHCcapsulesmaybeassociatedwithasignificantimprovementinticseverityinpatientswithTourettesyndrome”• Tworecentcontrolledtrialswithselfandexaminerscales
• Statisticallysignificantticreductionwithoutsignificantadverseeffects(someshort-termmemoryloss,reboundanxiety)
• RecentCochranestudy,however,statesinabilitytodrawdefinitiveconclusionsatthistime• NOTforchildren<21
• Concernforassociationwithpsychosis
Curtisetal2009Mueller-Vahl2012
OCDinTS
• 30-60% of TS pts meet DSM-IV criteria for OCD• Compared to 0.5-3.6% in general population
• Distinct symptoms:• Obsessions: symmetry, aggression, sexuality, religiosity• Compulsions: checking, touching, re-writing, evening
• Anxietyanddepressionmorelikely• PatientswithOCD+ticsshowlessrobustresponsetoSSRIscomparedtothosewithouttics• Augmentation:
• Haloperidol,risperidone,aripiprazole– positivetrials
GomesdeAlvarenga etal2012Høolgaard Detal.2012Mansueto andKeuler 2005
ADHDinTouretteSyndrome
• 60-90%ofTSpatientshaveADHD• Vs.5.8-13.6%inmales;1.9-4.5%infemales
• TicdisordersaremorefrequentinchildrenwithADHD
• TSandADHDisassociatedwith:• Decreasedqualityoflife(secondarytoADHDandOCD)• Worsesocialdifficulties
• Additionalco-occurringdisorders:• Oppositionaldefiantdisorder,Intermittentexplosivedisorder
TheTSStudyGroup(2002).NeurologyPeasgood etal(2016).Eur ChildAdol PsychEddyetal(2012).MovementDis.Pringsheim etal(2017).ChildPsychandHumanDev.
TreatmentofADHDandTics(TACT):TargetedCombinedPharmacotherapyStudy
•Multi-centertreatmentstudyinchildrenwithADHDandTourette/chronicticdisorder• Clonidine(alpha-agonist)•Methylphenidate(stimulant)• Combined(clonidineandmethylphenidate)• Placebo
•Design:136children(ages7-14);16weeks•Summarizedresults:• TicsandADHDsymptomsbothdidbestwithCombinedalpha-agonist/stimulant
TouretteSyndromeStudyGroup(2002).Neurology.
TSandADHDPharmacotherapy
• IfADHDismildandticsareproblematic,cantryalpha-agonist• Goodforhyperactivity/impulsivity
•Solostimulantuseinpatientswithticshastraditionallybeenavoided,but•Meta-analysisbyCohenetal(2015)• Nodifferenceinticworseninginstimulantvs.placebogroup• Noassociationbetweennewonsetorworseningofticsandstimulantuse
Cohenetal.(2015)JAACAP
Summary
• Formildticsthatneedpharmacologictreatment,firsttryclonidineorguanfacine,especiallyifADHD• Atypicalortypicalneurolepticsshouldbereservedforseverecases,usedcautiously&monitoredclosely.
• New medications using different proposed mechanisms in the pipeline• It is okay to use stimulants (case by case)• SSRIs do not worsen tics• Ultimate goal is to help patient develop and maintain
appropriate self-esteem and coping skills
Questions?
SpecialthankstoDrs.JeremiahScharf,SabineWilhelm,CathyBudman
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