The Use of Psychotropics in the Pediatric Population · Pulse, BP, prolactin, fasting BG, HbA1c,...
Transcript of The Use of Psychotropics in the Pediatric Population · Pulse, BP, prolactin, fasting BG, HbA1c,...
12/21/2015
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The Use of Psychotropics in the Pediatric
Population
Noor Daghistani
PGY2 Psychiatric Pharmacy Resident
Nova Southeastern University
Objectives
� Define psychotropics and discuss the different classes used in pediatrics
� Discuss barriers for the effective use of psychotropics in the pediatric population
� Understand the role that psychotropics play in the treatment of varying mental disorders
in the pediatric population
� Review the most commonly used psychotropics in pediatrics
� Describe important side effects and monitoring parameters for psychotropics used in the pediatric population
Introduction
� Psychotropic: a chemical substance that changes brain function and results in alteration of perception, mood, or consciousness
� Psychotropic Classes Utilized:� Antipsychotics
� Antidepressants
� Benzodiazepines
� Anticonvulsants
� Hypnotics
� Stimulants
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Barriers in Pediatric Psychopharmacology
� Limited research on existing medications for new indications
� Lack of adequately trained work force
�Consent
� Sets of knowledge and attitudes about
medications
� Competent to make the decision?
� Understanding changes with age
Barriers in Pediatric Psychopharmacology
�Compliance
� Network
� Attitude
� Ability to swallow
� Taste of the medication
� Adverse effects
Place of Medication in Therapeutic Planning
� Targets of Medication need to be:
� Clear enough to allow monitoring
� Practical enough to change
� Simple enough for explanation
� Targets:
� Symptoms
� Course of a condition
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Place of Medication in Therapeutic Planning
� Pharmacological versus Psychological interventions
� Advise patients on the best treatment for them
� Medication is not always a last resort
� Initial treatment based on each case
� Choice of intervention is not due to cause
Mental Illnesses in Pediatrics
� Attention Deficit Hyperactivity Disorder (ADHD): 8.4%
� Anxiety: 4.7%� Behavioral or conduct problems: 4.6%� Depression: 3.9%� Bipolar Disorder: 1.8%� Autism Spectrum Disorder: 1.1%
� Tourette's Syndrome: 0.3%� Schizophrenia: 0.23%� Substance Use Disorder
� Alcohol: 4.2%
� Illicit drug: 4.7%
� Cigarette 2.8%
SCHIZOPHRENIA
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Schizophrenia
�General principles:
• Antipsychotic drug regimens are the
cornerstone
• Require pharmacotherapy, family and
individual counseling
� Antipsychotics
• Safety and efficacy based on adult trials
• Young show greater sensitivity to adverse
events
Antipsychotics
�Recent randomized control trials on:
� Risperidone, olanzapine, aripiprazole,
paliperidone
�Choice of antipsychotic determined
primarily by side effect profile
� Atypicals preferred in young and
treatment naïve
� Start below the usual range for adults
and titrate slowly upwards to minimum effective dose
� First-Generation (aka typical):
� Haloperiodol (haldol): ≥3 years
� Trifluoperazine (Stelazine): ≥6 years
� Thiothixene (Navane): ≥12 years
� Second-Generation (aka atypical):
� Risperidone (Risperdal): ≥13 years
� Olanzapine (Zyprexa): ≥13 years
� Quetiapine (Seroquel):≥13 years
� Aripiprazole (Abilify): ≥13 years
� Paliperidone (Invega): ≥12 years
Antipsychotics
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Schizophrenia: Recommended order of treatment
AtypicalAtypical
No response/ intolerable
No response/ intolerable
Different atypical or typical
Different atypical or typical
No Response/ intolerable
No Response/ intolerable
ClozapineClozapine
ResponseResponse
ResponseResponse
Continue for 2 yearsContinue
for 2 years
� First-Generation
� Extrapyramidal
motor symptoms (EPS)
•Dystonia
• Parkinsonism
•Akathesia
• Tardive Dyskinesia
� Second-Generation
� Obesity
� � triglycerides
� � Nonhigh-density
lipoprotiens
� � Cholesterol
� � Glucose
� Diabetes II
� Hyperprolactinemia
Antipsychotics: Adverse Events
�Weight gain� Greatest with Olanzapine
� Least with aripiprazole
�EPS� Greater with typicals (eg: haloperidol) and higher doses of risperidone
� Aripiprazole: akathisia
Antipsychotics: Adverse Events
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�Sedation� Greater with olanzapine, clozapine, quetiapine and haloperidol than with risperidone and aripiprazole
�Hyperprolactinaemia� Greatest with risperidone and haloperidol
� Least with quetiapine and aripiprazole
Antipsychotics: Adverse Events
Antipsychotics: Monitoring
�Baseline Monitoring
� Physical examination
•Height & weight (BMI)
•CV exam: pulse & BP
•Neurological exam: evidence of
abnormal movement
� Labs:
•CBC, LFTs, BMP, prolactin, fasting BG, HbA1c, plasma lipids
�Monitoring while on treatment
� Weight:
•Weekly 1st 6 wks
•At 12 wks
•Every 6 months thereafter
� Pulse, BP, prolactin, fasting BG, HbA1c,
lipids
•At 12 wks
•Every 6 months thereafter
Antipsychotics: Monitoring
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BIPOLAR DISORDER
Bipolar Disorder
�General Approaches
• Focus treatment on most disabling
aspects
• Later treatment can address other issues
• Must consider common issues affecting children and adolescents, such as
substance abuse and pregnancy
• Comprehensive treatment requires both psychotherapy and psychopharmacology
• Treatment must address the phase of the illness
Step 1: Initiate antimanic agent
1st-line: lithium, valproate, carbamazepine, risperidone, olanzapine, quetiapine
Step 1: Initiate antimanic agent
1st-line: lithium, valproate, carbamazepine, risperidone, olanzapine, quetiapine
Full Response: - Continue maintenance treatment (with side effect monitoring)- Proceed to Step 2
Full Response: - Continue maintenance treatment (with side effect monitoring)- Proceed to Step 2
Step 2: Assess and treat associated conditions- ADHD: consider stimulants- Depression/anxiety: consider SSRIs, lithium, lamotrigine, or atypical antipsychotic medication
Step 2: Assess and treat associated conditions- ADHD: consider stimulants- Depression/anxiety: consider SSRIs, lithium, lamotrigine, or atypical antipsychotic medication
Partial Response:- Consider augmentation with second antimanicagent- Consider how associated/comorbid conditions are affecting response
Partial Response:- Consider augmentation with second antimanicagent- Consider how associated/comorbid conditions are affecting response
Re-evaluate responseRe-evaluate response
Non Response or not tolerated:- Switch to other antimanicagent
Non Response or not tolerated:- Switch to other antimanicagent
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Bipolar Disorder: Mania
� Current available antimanic medications:
� Second-generation antipsychotics (SGA)
� Lithium
� Antiepileptic drugs (AED)
� Recent RCT support the following:
� SGA are effective and potentially superior
� Lithium’s role in pediatric BD is less clear
� AED may be less efficacious
� SGA
� Strongest efficacy data
� FDA-indications to treat mania or mixed states in 10-17 years:
• Risperidone, aripiprazole, quetiapine,
asenapine
� Lithium
� Mixed support for efficacy
� FDA-indicated to treat mania in 12 years and older
Bipolar Disorder: Mania
� Adverse Events:
� Early: fine tremor, polydipsia, polyuria,
nausea, malaise, weight gain, headache, diarrhea
� Late: continued hand tremor that may
worsen, polydipsia, polyuria, weight gain and edema, thyroid and renal
abnormalities, dermatologic abnormalities, fatigue, leukocytosis
Lithium: Adverse Events
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� Toxicity:
� Diarrhea, vomiting, mild ataxia, coarse
hand tremor, muscular weakness and fasciculations, drowsiness, sedation, slurred speech, and impaired
coordination
� Life-threatening toxic effects: cardiac
arrhythmias and severe central nervous system difficulties
Lithium: Adverse Events
� Serum Lithium Concentrations:
� Every 3-4 days during initiation
� 1-2 months once stabilized
� Obtain 8-12 hours post-dose
� Reference Range:
• Acute mania: 0.6-1.2 mEq/L
•Maintenance: 0.8-1 mEq/L
• Toxic: > 1.5 mEq/L
Lithium: Monitoring
� Baseline:
� CBC, urine analysis, pregnancy test,
thyroid function tests, ECG
� Serum Na, calcium, crieatinine, BUN
� EEG in children with seizures or known abnormalities in EEG
� Periodic Monitoring: thyroid, kidney,
and cardiac function
Lithium: Monitoring
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� AED:
� Weak evidence of efficacy
•Benefits seen in small open-label trials with carbamazepine, valproate, and
lamotrigine
� No placebo control group
� Safety data is stronger
Bipolar Disorder: Mania
Antiepileptics
� Valproic acid� Boxed Warnings:
•Hepatotoxicity and pancreatitis� More common in < 2 years old
•Mitochondrial disease
• Teratogenic
� Adverse effects:• Transient: nausea, vomiting, indigestion
• Psychiatric effects: emotional upset, depression, psychosis, aggression, hyperactivity, behavioral deterioration
• Thrombocytopenia
• Polycystic ovary syndrome
� Valproic acid
� Monitoring:
•Liver enzymes
� Especially during 1st 6 months
•CBC with platelets
� Prior to initiation and periodically
•Serum concentrations
� Trough: 50-125 mcg/mL
Antiepileptics
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�Carbamazepine
� Boxed Warnings
• Aplastic anemia/agranulocytosis
� Very rare
• Serious dermatologic reactions
� SJS/TEN
� HLA-B*1502 allele
� Adverse Effects: dizziness, drowsiness, unsteadiness, nausea, vomiting
� Monitoring:
• CBC with diff, LDL, LFTs, TSH, BUN, serum Na
• Serum levels: 4-12 mcg/mL
Antiepileptics
� Lamotrigine
� Boxed Warning: Serious skin rashes
• SJS/TEN
• Increased risk with age <12 or co-
administration of valproic acid
� Monitor:
• CBC with diff, kidney and liver function,
hypersensitivity reactions
Antiepileptics
� Lack of RCT to guide medication treatment of depression and anxiety in
BD
�Data suggests that:
� Youth spend considerable time struggling
with depression
� Youth often receive SSRIs with no induction to mania
� Risk of antidepressant-induced mania higher in prepubertal children
Bipolar Disorder: Depression
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DEPRESSION
Depression
� Type and intensity of treatment depends on severity
• Mild: assessment and education
• Moderate:
• NICE guidelines: CBT, IPT, or family therapy
first; then add medication if no response
• Never use antidepressants without psychotherapy
• AACAP guidelines:
• Combination therapy preferable
• Monotherapy acceptable in certain cases
• Persistent or Severe:
• SSRIs, CBT, IPT, or combination
� Progress should be reassessed in 4-6 weeks
� Tricyclic antidepressants:
� Not efficacious
� Selective Serotonin Reuptake Inhibitors:
� Fluoxetine (Prozac): first-line
•Only agent recommended for use in
adolescents by NICE guidelines
• FDA-approved for both preadolescent and
adolescent depression (≥ 8 years)
Depression
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� Selective Serotonin Reuptake Inhibitors:
� Escitalopram (Lexapro):
• FDA-approved for depression in 12-17 years
� Sertraline (Zoloft):
•Has been reported superior to placebo
•Not FDA approved for pediatric depression
� Citlaopram (Celexa):
• Found to be as efficacious as fluoxetine
• Not FDA approved for pediatric depression
� Paroxetine (Paxil):
• Not recommended
Depression
SSRIs: Adverse Effects & Monitoring
�Headache, N/V, diarrhea, sleep disturbance, weight gain/loss,
anxiety, SIADH
� Behavioral disinhibition
� Sexual dysfunction
� Serotonin Syndrome
�Discontinuation syndrome
SSRIs: Adverse Effects & Monitoring
� Suicidal ideation
� Incidence is rare
• Studies have shown attempts more
common prior to initiation of SSRI
� Occurs within first 3-5 wks
� Combination of meds and therapy
needed
�Monitoring: weight, CBC, LFTs,
Electrolytes, suicidality
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�Only two non-SSRIs with some support for efficacy in adolescents:
� Nefazodone (Serzone)
• Increased risk of hepatotoxicity
� Venlafaxine (Effexor)
• Post-hoc analysis of two clinical trials:
� Showed efficacy in adolescent, but not
preadolescent, depression
� As efficacious as fluoxetine in treatment resistant
depression
� Bupropion (Wellbutrin):
� Only open-label studies
Depression
Depression
� Treatment-resistant depression
� Non-response to SSRI: switch to
another SSRI and add CBT
� Non-response with two consecutive
trials of SSRIs: consider other classes
• Ex: Venlafaxine, bupropion
� If partial response: augment with an antipsychotic, bupropion, or lithium
• No empirical studies in the youth
ANXIETY
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Anxiety
� Several effective approaches, both psychotherapeutic and psychopharmacological, have been documented• Studies show additive effects of using combination over either alone
�SSRIs are highly effective• Sertraline, fluoxetine, paroxetine, fluvoxamine
• Efficacious for anxiety experienced while in the feared situation• Not as good for anticipatory anxiety
OBSESSIVE COMPULSIVE
DISORDER
Obsessive Compulsive Disorder
�Relative abundance of RCT demonstrating efficacy with:
� SSRIs: Sertraline, fluoxetine, paroxetine, fluvoxamine
• Fluvoxamine FDA-approved for ≥ 8 years
• Fluoxetine FDA-approved for ≥ 7 years
• Sertraline FDA-approved for ≥ 6 years
� Clomipramine
• FDA-approved for ≥ 10 years
•Meta-analysis showed superiority to SSRIs
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Clomipramine: Adverse Events
�Class: Tricyclic antidepressant
� Adverse Events:
� Anticholinergic effects
� CND depression
� Hematologic effects
� Orthostatic hypotension
� Seizures
� Sexual dysfunction
� Weight gain
� Conduction abnormalities
�Weight
� Pulse rate and BP
� Prior to and during therapy
� EEG and cardiac status
� LFTs
�CBC with diff
� In patients who develop fever and sore throat during treatment
Clomipramine: Monitoring
�Combination Treatment
� Studies show superiority of CBT with
medication than to medication or CBT alone
� While medications alone help, CBT is first-line
� Augmentation strategies
� In adults: SGA, clonazepam, morphine
• No controlled studies to guide clinicians for
child and adolescent treatment-resistance
Obsessive Compulsive Disorder
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AUTISM SPECTRUM DISORDER
Autism Spectrum Disorder
� Nonpharmacological interventions are first-line� Psychotropics for more severe cases
� Systematic reviews have demonstrated some evidence for use of antipsychotics� Disagreement in the field exists
• NICE guidelines do not recommend antipsychotics for core treatment of ASD
• AACAP guidelines recommend the use of pharmacotherapy when there is a specific target symptom or comorbid condition
� Pharmacotherapy used to allow child to better engage in treatment plans
ASD: Antipsychotics
�Management of maladaptive behaviors
�Haloperidol (Haldol)
� Not FDA approved, but most commonly studied prior the SGA
�Risperidone (Risperdal)
� FDA-approved for treatment of irritability associated with ASD in 5-15 years
� Aripiprazole (Abilify)
� FDA-approved for treatment of irritability
associated with ASD in 6-17 years
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ASD: Antipsychotics
�Other SGA researched in ASD:
� Olanzapine (Zyprexa)
• Placebo-controlled, double blind study
• Positive efficacy for aggression and irritability
� Agents with modest efficacy in reducing irritability
• Clozapine (Clozaril)
• Ziprasidone (Geodon)
•Quetiapine (Seroquel)
ASD: Antidepressants
� SSRIs studied and used in clinical practice for the repetitive behaviors in
ASD
� Overall efficacy appears inconsistent
• A systematic review in 2010 showed no data
supporting their use in ASD and strong data
recording incidence of ADE
� Antidepressants evaluated:
� Clomipramine
� Fluoxetine, sertraline, escitalopram, fluvoxamine
� Psychostimulants for the treatment of ADHD-like symptoms have been used
with mixed results
� Amphetamines have limited efficacy data, with no controlled studies since 1970s
� Results indicate minimal benefit and potential ADE, including worsening of ASD symptoms
� Clonidine and guanfacine: moderate
efficacy in reducing stereotypy, hyperactivity, and irritability
ASD: Psychostimulants
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OPPOSITIONAL DEFIANT
& CONDUCT DISORDERS
Oppositional and Conduct Disorders
� Differing views as to the usefulness of medications
� Prescribing medications is increasing� Modest evidence for effectiveness
� Antipsychotics: risperidone, aripiprazole• Clinical experience suggests they can reduce
aggression in some cases
� Mood stabilizers: lithium, carbamezapine
� Buspirone, clonidine
� Best studied pharmacological interventions in youth with ODD/CD and ADHD: psychostimulants
TIC DISORDERS
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Tic Disorders
�Decision on use of medications depends on clinical presentation and
level of symptoms
� Best to withhold medication use until tic become a significant source of impairment
� Many cases can be managed without medications
� Treat co-morbid conditions first
�Goal of pharmacotherapy: use as little medication as possible to render tics
more tolerable
� Typical antipsychotics remain most predictably effective tic-suppressing agents� Haloperidol, pimozide, fluphenazine
•Haloperidole FDA-approved for ≥3 years
• Pimozide FDA-approved for ≥ 2 years
� To avoid EPS, atypicals have been used to treat tic symptoms� Risperidone, olanzapine, ziprasidone, aripiprazole•Only aripiprazole FDA-approved for 6-18 years
� Botulinum toxin injections
Tic Disorders
Summary
�Greater barriers to the effective use of psychotropic medications exist in pediatric population
� Psychotropics are not always a last resort treatment
�Use of specific psychotropic agents should be guided by the best available evidence
�Monitoring patients for improvement and ADE should be part of the treatment plan
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True or False?
�One barrier to the effective use of psychotropic medications in pediatrics may be inadequate adult supervision.
� Psychotropics are a last resort treatment, only to be used after all other methods have failed.
� The second generation antipsychotics are the standard for treating the first episode of psychosis in pediatric patients with risperidone being the most widely used atypical.
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