1. Pediatric Psychopharm Charts July 2011 Meg Cary, MD, MPh Mick Storck, MD Summary of … FDA APPROVED MEDICATIONS – in child psychiatry – (little specific data for FASD) Attention-deficit Hyperactivity Disorder – All amphetamine and methylphenidate formulations (≥6yo) Dexedrine IR (≥3yo) – Atomoxetine – Guanfacine ER – Clonidine ER Aggression – Risperidone & Aripiprazole for aggression associated with autism Major Depression – Fluoxetine (≥8yo) – Escitalopram (≥12yo) Obsessive-Compulsive Disorder – Sertraline (≥6yo) – Fluoxetine (≥7yo) – Fluvoxamine (≥8yo) – Clomipramine (≥10yo) Bipolar Disorder – Risperidone (≥10yo) – Aripiprazole (≥10yo) – Quetiapine (≥10yo) – Lithium (≥12yo) – Olanzapine (≥13yo) – acute treatment only Schizophrenia – Risperidone (≥13yo) – Aripiprazole (≥13yo) – Quetiapine (≥13yo) – Olanzapine (≥13yo)

2. STIMULANTS Stimulants: GENERIC TRADE NAMEADVERSE EFFECTSCOSTNOTES MIXED AMPHETAMINE SALTS Adderall Dexedrine Decreased appetite, Weight & height loss, Headache, Insomnia, Tics, Irritability No increased risk of sudden death in youth without cardiac dz. $100 Short-acting FDA Max dose: 40mg/d Off-label Max dose: 60mg/d (if >50kg) Immediate-release Dexedrine FDA approval for ADHD ≥ 3yo Dexedrine Spansules$85 Long-acting FDA Max dose: 40mg/d Off-label Max dose: 60mg/d (if >50kg) First long-acting formulation, not significantly more effective than immediate release Dexedrine ER$220 Long-acting FDA Max dose: 40mg/d Off-label Max dose: 60mg/d (if >50kg) Adderall XR$165 Long-acting FDA Max dose: 30mg/d Off-label Max dose: 60mg/d (if >50kg) No demonstrated increased effect >20mg/d Capsule can be opened and sprinkled on food LISDEXAMPHETAMINEVyvanse$120 Long-acting (12-14hr duration of action) Pro-drug FDA Max dose: 70mg/d No comparison trials (2009) Least preferred amphetamine formulation METHYLPHENIDATE Ritalin, Methylin, Focalin $20 Short-acting More effective than amphetamine among youth with autism spectrum disorders Ritalin & Methylin: Generic FDA Max dose: 60mg/d Off-label Max dose: 100mg/d if >50kg Focalin: FDA Max dose: 20mg/d Off-label Max dose: 50mg/d Ritalin SR$60 Intermediate-acting First long-acting formulation, not significantly more effective than immediate release Generic Ritalin LA Metadate CD $90 Intermediate-acting FDA Max dose: 60mg/d Off-label Max dose: 100mg/d if >50kg Capsule can be opened and sprinkled on food Concerta$100 Long-acting FDA Max dose: 72mg/d Off-label Max dose: 108mg/d Cannot crush capsule Daytrana$175 Long-acting (9hr duration of action) FDA Max dose: 30mg/d Patch D-THREO METHYLPHENIDATEFocalin XR$105 Long-acting FDA Max dose: 30mg/d Off-label Max dose: 50mg/d No consistent evidence more effective, better tolerated, faster onset, shorter duration of action than mixed isomers ATOMOXETINEStrattera Nausea, Dyspepsia, Decreased appetite, Sedation, Headache, Suicidal ideation (4/1000 increased risk), maybe Hepatitis (2 cases) $190 FDA Max dose: 1.4mg/kg/d or 100mg/d Off-label Max dose: 1.8mg/kg/d or 100mg/d – single or divided dose Lower effect size Cannot open capsule

3. Alpha Adrenergic Agents (for autonomic hyperarousal GENERICTRADE NAMECLINICAL USE EVIDENCE (separation from placebo in randomized trials) FDA-APPROVED USE in YOUTHADVERSE EFFECTS COST (US$, average dose, 1mo supply) ClonidineCatapres Tics, Autonomic reactivity, Aggression, Stimulant adjunct, Hypnotic ADHD: small effect size NONE Sedation, Hypotension, Bradycardia $20 CLONIDINE ERKapvay ADHDADHD monotherapy and stimulant adjunct ? GuanfacineTenex ADHD w/ tics: 1 small RCT NONE $20 GUANFACINE ERIntuniv Industry- sponsored RCT ADHD (≥6yo) $155 Prazosin PTSD nightmares NONE Hypotension, Bradycardia, Pancreatitis $18

4. Antidepressants ; GENERICTRADE NAMECLINICAL USE EVIDENCE (separation from placebo in randomized trials) FDA-APPROVED USE in YOUTHADVERSE EFFECTS COST (US$, average dose, 1mo supply)NOTES FLUOXETINEProzac Anxiety disorders, MDD (Response rates 40-70%, placebo rates 30-60%) OCD, MDD AvD, GAD, Mut, SAD, SP, (2 positive RCTs, 1 neutral RCT) MDD (≥8yo) OCD (≥7yo) Increased suicidality, Precipitation of mania, Akathisia, Agitation, Anxiety, Irritability Headache, Nausea, Diarrhea, Dyspepsia, Insomnia, Hypersomnia, Vivid dreams, Weight & height loss, Decreased libido, Anorgasmia $25  t 1/2 : 4-6days  Max dose: 80mg/d  Liquid formulation SERTRALINEZoloft OCD GAD, SAD, SP (1 RCT) OCD (≥6yo) $15  t 1/2 : ~25hrs  Max dose: 300mg/d  Liquid Formulation ESCITALOPRAMLexapro MDD (1 RCT)MDD (≥12yo) GAD (≥18yo) $110  Max dose: 30mg/d FLUVOXAMINELuvox GAD, OCDOCD (≥8yo) $110  t 1/2 :~15hrs  Max dose: 300mg/d  High incidence of nausea, dyspepsia CitalopramCelexa MDD (1 RCT)NONE $40  t 1/2 : ~35hrs  Max dose: 60mg/d  Liquid Formulation ParoxetinePaxil OCD SP (1 RCT) NONE $15  t 1/2 :~20hrs  Max dose: 80mg/d TRICYCLIC ANTIDEPRESSANTS Anafranil (clomipramine) Tofranil (imipramine) ADHD, Anxiety disorders, Enuresis, MDD Depression: Meta-analysis: No evidence of efficacy for depression in pre-pubertal youth, moderate reduction in symptoms, but no association with recovery in adolescents, questionable clinical utility Anxiety: Imipramine: 1 positive, 2 neutral RCTs for SP Clomipramine: OCD ADHD: Multiple TCAs Enuresis: Imipramine OCD: Clomipramine (≥10yo, max dose: 5mg/kg/d or 250mg/d) Enuresis: Imipramine (≥6yo; dose range: 10- 100mg/d) Hypotension, Tachycardia, Tremor, Dry mouth, Vertigo, Constipation, Vision changes $40  High risk of death with overdose limits use

5. Antidepressants – cont.TRADE NAMECLINICAL USE EVIDENCE (separation from placebo in randomized trials) FDA- APPROVED USE in YOUTHADVERSE EFFECTSCOSTNOTES Bupropion Wellbutrin Wellbutrin SR, Wellbutrin XL MDD, adjunct for treatment resistant MDD, ADHD ADHD (1 RCT)NONE Insomnia, Decreased appetite, Tremor, Headache, Constipation $70  Max dose: 450mg/d  Contraindicated if w/ epilepsy MirtazapineRemeron MDD, particularly with insomnia No evidenceNONE Weight gain, Hypotension, Dry mouth, Constipation, Fatigue, Dizziness $85  Max dose: 45mg/d Venlafaxine (Desvenlafaxine) Effexor (Pristiq) MDD, particularly with chronic pain, SP Venlafaxine: GAD, SP (1 RCT each) Worsening of suicidal ideation Desvenlafaxine: No evidence NONE Insomnia, Anxiety, Nausea, Sedation, Sweating, Dizziness, Headache, Constipation, Dry mouth, Decreased appetite, Withdrawal symptoms $60  Max dose: 375mg/d DuloxetineCymbalta MDD, particularly with chronic pain No RCTsNONE $155  Max dose: 120mg/d  Among adults, less anxiety than with venlafaxine Anxiolytics BuspironeBusparAnxiety disorders No evidenceNONE Headache, Lightheadedness, Dyspepsia, Bruxism $20 LorazepamAtivanPanic attacks No evidenceNONE Sedation, Disinhibition, Impaired cognitive restructuring or exposure/response prevention therapy, Dependence $20 ClonazepamKlonopinAnxiety disorders NONE $10 HydroxyzineVistaril Anxiety disorders, Insomnia No evidenceNONE Anticholinergic$15

6. Mood Stabilizers: GENERICTRADE NAMECLINICAL USE EVIDENCE (separation from placebo in randomized trials) FDA- APPROVED USE in YOUTHADVERSE EFFECTS COST (US$, average dose, 1mo supply)NOTES LITHIUM Lithobid Eskalith Bipolar disorder, Aggression associated with RCT underwayBipolar disorder (≥12yo) Diarrhea, Headache, Tremor, Weight gain, Acne/Psoriasis, Alopecia, Hypothyroidism, Renal failure, Diabetes insipidus $25 Target Serum Level:  Acute 0.8- 1.2mEq/L,  Maintenance: 0.5- 0.8mEq/L Divalproex Sodium Depakote, Depakote ER Contradictory results NONE Pancreatitis, Hepatitis, Ototoxicity, Alopecia, Weight gain, Nausea, Diarrhea, Headache, Tremor $30 – IR $140 - ER Lamotrigine Lamictal, Lamictal XR Bipolar disorder, MDD adjunctive No evidenceNONE Rash, Stevens Johnson, Erythema multiforme, Nausea, Headache, Hepatitis, Blood dyscrasias $30  Max dose: 400mg/d Carbamazepi ne Tegretol, Tegretol XR Bipolar disorder No evidenceNONE Stevens Johnson, Blood dyscrasias, Nausea, Blurry vision, Hypotension $15 Target Serum Level:  8-12µg/mL  Self-induced metabolism Oxcarbazepi ne Trileptal No evidenceNONE Stevens Johnson, Hyponatremia, Nausea, Dizziness, Headache $300  Max dose: 2400mg/d TopiramateTopamax Preliminary results of some symptom reduction NONE Stevens Johnson, Hepatitis, Loss of appetite, Cognitive blunting, Nystagmus $40  Max dose: 400mg/d

7. Antipsychotics : GENERICTRADE NAMECLINICAL USE EVIDENCE (separation from placebo in randomized trials) FDA-APPROVED USE in YOUTHADVERSE EFFECTS COST (US$, average dose, 1mo supply)NOTES RISPERIDONERisperdal Psychosis, Aggression associated with DBD Mania, Psychosis, Aggression Schizophrenia (≥13yo) Bipolar (≥10yo) Irritability associated with autism (≥5yo) NMS, Acute Dystonia, Extrapyramidal Symptoms, Tardive Dyskinesia, Hyperglycemia, Hypotension, Leukocytosis, Seizures, Insomnia, Hypersomnia, Increased appetite, Weight gain, Headache, Nausea, Priapism, Salivation $?30-40 Now available in generic…  Max dose: 6mg/d, but no increased efficacy with ≥3mg/d for psychosis and ≥2.5mg/d mania  Most evidence among antipsychotics for aggression.  Injection and disintegrating tablet formulations.  Additional Adverse Effect: Hyperprolactinemia ARIPIPRAZOLEAbilify Mania, Psychosis, Aggression Schizophrenia (≥13yo) Bipolar (≥10yo, primary and adjunct), Irritability associated with autism (≥6yo) $500  Max dose: 30mg/d, but no increased efficacy with ≥10mg/d for psychosis and mania  Disintegrating tablet formulation QUETIAPINESeroquel Mania, AggressionSchizophrenia (≥13yo) Bipolar (≥10yo) $500  Max dose: 800mg/d OLANZAPINEZyprexa Mania, Psychosis, Aggression Schizophrenia (≥13yo), Mania, Mixed Episode (≥13yo) $475  Max dose: 40mg/d  Adolescents more likely than adults to experience long term adverse effects ZiprasidoneGeodonPsychosis ManiaNONE $550  Max dose: 240mg/d ClozapineClozaril Treatment refractory psychosis Case reports of efficacy with youth ≥10yo NONE ?  Max dose: 900mg/d  Additional Adverse Effect: Myocarditis, Agranulocytosis New Antipsychotics: Paliperidone Lurasidone Invega Latuda Psychosis No evidenceNONE $1375  Max dose: 12mg/d

8. Hypnotics GENERICTRADE NAMECLINICAL USE EVIDENCE (separation from placebo in randomized trials) FDA- APPROVED USE in YOUTHADVERSE EFFECTS COST (US$, average dose, 1mo supply) DiphenhydramineBenadryl Insomnia No evidenceNONE $10 TrazodoneDesyrel No evidenceNONE Priapism, Anticholinergic $10 Melatonin No evidenceNONE Dysphoria, Gynecomastia, Elevated liver enzymes, Pruritus, Tachycardia, Insulin resistance, Increased seizures, Withdrawal dyskinesia $5 ZolpidemAmbien No evidenceNONE Headache, Dizziness, Abnormal Dreams, Amnesia, Palpitations, Nausea, Diarrhea, Constipation $20 ZaleplonSonata No evidenceNONE $40

9. Selected REFERENCES AACAP Practice Parameters. FDA.gov. Calles JL Jr. Use of psychotropic medications in children with developmental disabilities. Pediatr Clin North Am. 2008 Oct;55(5):1227-40 Calles JL Jr McClellan JM, Werry JS. Evidence-based treatments in child and adolescent Psychiatry: an inventory. J Am Acad Child Adolesc Psychiatry 2003;42(12): 1388–400. McVoy M, Findling R. Child and adolescent psychopharmacology update. Psychiatr Clin North Am 2009;32(1):111–33. Treatment for Adolescents With Depression Study (TADS) Team: March J, Silva S, Curry J, et alThe Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow-up. Am J Psychiatry. 2009 Oct;166(10):1141-9. Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. 2008 Dec 25;359(26):2753-66.