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Psychopharmacology for Kids: an Overview

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Psychopharmacology for Kids: an Overview Psychopharmacology for Kids: An Overview Robert Hilt, MD, FAAP Professor of Child Psychiatry University of Washington Director Partnership Access Line Disclosure Statement • I have been a facility site reviewer for Optum/WYHealth • I have received a book royalty from the American Psychiatric Association • I will be specifying all non-FDA approved uses of medications which appear in this presentation • I am participating in a HRSA grant funded “PAL-PAK” consultation service with AK Department of Health Partnership Access Line for Alaska (PAL-PAK) For PAL-PAK Call 855-599-7257 PAL PAK Resources • Follow-up consult notes faxed the following business day • Televideo consults available for Medicaid patients • Additional education, webinars • Help Me Grow will provide you with support in identifying care resources • Care Guide is free, on the web, and we can mail you a hard copy PAL-PAK number is 855-599-7257 Objectives • Discuss effective use and monitoring for: • Stimulants • Alpha 2 agonists • SSRIs • Antipsychotics Common Categories used • Stimulants • For ADHD • Selective Serotonin Reuptake Inhibitors (SSRI) • For anxiety, depression • Alpha2-agonists • For ADHD, some disruptive behaviors • Antipsychotics • For psychosis, bipolar, severe aggression Stimulants • Methylphenidate • Ritalin, Methylin, Concerta, Metadate, Focalin • Dextroamphetamine • Dexedrine, Dextrostat, Adderall, Vyvanse • About 5% of school age children use stimulants Stimulants—why so popular? • Most effective medication treatment in child psychiatry • Immediately effective, no build-up required • 85% of children with ADHD will respond to a stimulant treatment • Degree of benefit typically greater than other medications • Stimulants effect size ~ 0.95 • Alpha2 agonists and atomoxetine ~ 0.65 • Generally more clinically effective for ADHD than non- medication treatments Stimulants for ADHD • Valid to start with either a methylphenidate or an amphetamine product • Amphetamines FDA approved > or = age 3 • Methylphenidates FDA approved > or = age 6 • Similar efficacy • Side effects may be more pronounced with amphetamine products • If first stimulant family doesn’t help/isn’t tolerated, about ½ of non-responders get benefit from the other stimulant family Stimulant Starting Doses • Pre-pubertal equivalency of ~5mg TID methylphenidate • Post-pubertal equivalency of ~10mg TID methylphenidate • Increase a well tolerated stimulant before switching • Usually effective before reaching 0.5 mg/kg amphetamine, or 1 mg/kg methylphenidate • note 1mg/kg/day was the mean final dose of the MTA study of 7-9 year olds • Absolute max dosages typically considered to be 2x that amount Immediate Release Stimulants Name Duration of Action Methylphenidate (Ritalin, Methylin) 4-6 h Dexmethylphenidate (Focalin) 4-6 h *2x potency of methylphenidate Mixed amphetamine salts (Adderall) 4-6 h Dextroamphetamine (Dextrostat, Dexedrine) 4-6 h Micromedex Long Acting Stimulants Name Mode of Delivery Duration of Action Ritalin SR, Metadate ER, Gradual release wax matrix 4-8 h Methylin ER Metadate CD 30% IR, 70% 3 h later 7-9 h Ritalin LA 50% IR, 50% 4 h later 7-9 h Focalin XR 50% IR, 50% 4 h later Up to 12 h Concerta 22% IR, pump Up to 12 h Quillivant XR Liquid suspension Up to 12 h Daytrana patch Gradual release patch 3-5 h after removal Adderall XR 50% IR, 50% 4 h later 8-12 h Dexedrine spansule 50% IR, 50% gradual 10 h Vyvanse Activated in GI tract 10 h Common pitfall: Increasing dose does NOT increase duration of action Converting Doses Between Stimulants • 2mg methylphenidate = 1mg dextroamphetamine (ex. Adderall) • 2mg methylphenidate = 1mg dexmethylphenidate (ex. Focalin) • 70mg Vyvanse roughly bio equivalent to 35mg Adderall XR • When switching I start at a lower than direct mg:mg conversion, then increase if needed • Example Metadate CD 40mg, switch to either Adderall XR 10 or 15mg, then adjust 2007 Biederman et al Biological Psychiatry Common Stimulant Side Effects • Decreased appetite, weight loss • Nausea • Insomnia • Headaches • Stomach aches • Dry mouth • Dizziness Dealing With Common Side Effects • If good response, could work around common side effects • Rebound • longer acting doses, or a small PM short acting? • Appetite suppression • Lower the dose, take after a big breakfast, evening snacks, weekends off? • Insomnia • Change doses to wear off earlier, or give α2-agonist? • Dysphoria, Irritability • change preparation? Unique Stimulant Concerns • Tics • Historical “contraindication,” still in PDR • Some tics ↑, some tics , usually no change • No longer a contraindication per experts • Height loss • Data is mixed on if this happens • If it occurs, may be up to about one inch in adult height • Greater risk in presence of weight loss Stimulants and Drug Abuse • ADHD itself creates higher risk of substance use disorder (SUD) • No clear association between stimulant treatment and risk of initiating a SUD • Stimulant diversion is commonplace • ~20% of high school kids divert their doses • Avoid prescribing to known substance abusers • Consider instead atomoxetine, alpha-2 agonists, bupropion • Set up a medication administer/monitoring plan with family Stimulants and the Heart • Stimulants cause small increases in BP (2-4 mm Hg) and pulse (3-6 BPM) • Theoretically makes cardiac event during exercise more likely • Atomoxetine does the same thing • Because of “outlier” responses, check BP/pulse after initiation • AAP does not recommend routine ECG. • Consider ECG for high dose, combined medications, significant BP/pulse change, or cardiac symptoms. If stimulant treatment fails Comorbidity not impacted by the stimulant? Re-evaluate the ADHD diagnosis Inattention from Anxiety, Depression, Substance abuse, Learning disability, Hearing impairment, Poor parenting practices, Psychosocial stressors, PTSD, Poor motivation Consider increased role for behavior therapy and/or alternative medications Atomoxetine (Strattera) • Noradrenergic reuptake inhibitor • A failed antidepressant, works in ADHD care, FDA approved • Start at 0.5 mg/kg/day for 2 weeks. Increase to 1.2 mg/kg/day. • Maximum 100 mg or 1.4 mg/kg (whichever is less). Atomoxetine • Consider if • Family opposed to stimulants • Substance abuse history • Late evening behavior problems (has better 24 hour a day coverage) • Stimulants ineffective • Effect size 0.6 (similar to guanfacine) • For comparison, effect size of stimulants ≈ 0.9-1.0 • Mental health effect size 0.2 is mild, 0.6 is moderate, and >0.8 is high. Bimodal Atomoxetine Response 30 25 20 Mild/Non- responders 15 (N=318) Much improved 10 responders (N=279) Decrease in ADHDRS score in ADHDRS Decrease 5 0 2 4 6 8 Time (weeks) Newcorn et al. 2009 Atomoxetine Side Effects headache (about 1 in 5) abdominal pain/nausea (about 1 in 7) decreased appetite, weight loss (in 7-30%) somnolence (about 1 in 10) Blood pressure & Pulse elevation (in 4-5%) Liver injury (rare, but severe) – discontinue if signs of hepatic injury and do not restart Risk of sudden cardiac death (rare) Micromedex Alpha2 agonists • May be more effective for hyperactivity than inattention • Clonidine more soporific; guanfacine sometimes better for inattention • Soporific effect may wane after 2-3 weeks • May not see full benefit for 4-6 weeks • Sedation, dizziness, hypotension, bradycardia • Review personal and family cardiac history • Review risk of rebound hypertension • XR formulations are “reduced peak,” not necessarily extended duration Guanfacine Starting dose Maximum dose Half life FDA Guanfacine <45kg, 0.5 mg 2 mg (27-40 kg); 14 h Not 3 mg (40-45 kg); approved >45 kg, 1 mg 4 mg (>45 kg) Guanfacine XR 1 mg daily 7 mg 16 h Approved (Intuniv) 6-17yo Wait one week between dose increases. Pliszka S et al, 2007 Clonidine Starting dose Maximum dose Half FDA life Clonidine <45kg, 0.05 0.2 mg (27-40 kg); 12 h Not mg 0.3 mg (40-45 kg); approved 0.4 mg (>45 kg). >45 kg, 0.1 mg Clonidine –XR 0.1 mg qhs; 0.4 mg 12-16 h Approved (Kapvay) doses greater 6-17yo than 0.1 mg should be bid Wait one week between dose increases. Pliszka S et al, 2007 When I Consider α2-Agonists for ADHD • Stimulants don’t work/not tolerated • Want to generate a sedative effect • Want to treat co-morbid tics • Want to try reducing co-morbid PTSD nightmares • Cardiac concerns or substance abuse that contraindicate stimulants • Add on to stimulants that aren’t working well enough on their own • FDA approved combination Bupropion • Brand name: Wellbutrin • Not FDA approved for pediatric use • Combined dopaminergic/noradrenergic mechanism of action • Some reported ADHD benefits • Consider when primary treatments have failed or in adolescents with co-occurring mood disorders, substance abuse Bupropion • Side effects: • irritability, insomnia, appetite decrease, less commonly tics, seizures • Often not well tolerated • Risk of drug induced seizures increases 10x at doses > 450 mg/day Kratochvil CJ et al, 2009 Omega 3 and 6 fatty acids • Not FDA approved • Mixed results in controlled research, at best • Could augment other ADHD interventions • Could be option for families that decline other medications • Far less effective than stimulants Bloch M et al, 2011 Antidepressants Selective Serotonin Reuptake Inhibitors (SSRI) Less commonly used: SNRI TCA MAOI buproprion Positive Adolescent Depression Randomized Controlled Trials Response rates (CGI much/very much improved) 3 fluoxetine 52-61% vs. placebo 33-37% 1 sertraline 63% vs. placebo 53% 1 citalopram* 47% vs. placebo 45% 1 escitalopram 64% vs. placebo 53% *Note the CGI was not the primary outcome
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