Management of Adverse Effects in ADHD Treatment
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Management of Adverse Effects in ADHD Treatment Katherine Wang, Pharm.D., AE-C Clinical Pharmacist The Center for Children and Women - Greenspoint Conflict of Interest Disclosure The presenters, planners, reviewers (including CME administrator) of today’s CME activity do not have any financial relationships or commercial interests to disclose Objectives By the end of this presentation, participants should be able to… ■ Distinguish the role of medications in Attention Deficit/Hyperactivity Disorder (ADHD) management ■ Identify common adverse effects of ADHD treatment ■ Design an appropriate plan to address adverse effects Epidemiology ■ National ADHD estimates fall between 5-9% of all US children ■ 5.2% of children in the U.S. are taking ADHD medication % of Youth Aged 4-17 Receiving ADHD Medication Treatment by State Treatment of Children with ADHD Neither Medication 23% Alone 30% Medication and Behavioral Behavioral Treatment Treatment Alone 32% 15% National Survey of Children's Health 2011 Health Children's of Survey National CDC Website - Data and Statistics about ADHD. (2018); CDC Website - State-based Prevalence Data of Parent Reported ADHD Medication Treatment. (2018) Forming a Treatment Plan Adjunctive Recognition that books, videos, ADHD is a and chronic disorder noncommercial Web sites if ■ Plans should be necessary comprehensive Community supports and Pharmacological and/or behavior ■ Treatment plans school resources therapy should be reviewed as necessary regularly and modified Advice to if the patient’s improve Family academic and preferences and symptoms do not behavioral concerns functioning respond Education about ADHD, treatment, and developmental challenges Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007) The Debate between Treatment Modalities AACAP Practice Parameter AAP Guidelines Pharmacological Behavioral Pharmacological Behavioral Treatment Treatment Treatment Treatment versus versus Depends on their age! Preschoolers (Aged 4-5) Pharmacological intervention should be a part of – behavioral therapy first treatment. line, then methylphenidate if needed Aged 6-11 – ADHD medications AND/OR behavioral Medication treatment is more effective than a therapy (preferably both) behavioral treatment alone. Aged 12-18 – ADHD medications and maybe behavioral therapy Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); Subcommittee on Attention-Deficit/Hyperactivity Disorder. et al. Pediatrics. (2011) Medication Treatment Algorithm ■ Initial pharmacological therapy should be trialed with an FDA Approved stimulant First (No preference between the approved stimulant Line stimulants) o Two main groups of stimulants • Amphetamine preparations • Methyphenidate preparations o Evidence suggests stimulant classes are Second Alternate approved stimulant equally efficacious Line o Consider extended release (ER) formulations vs immediate release (IR) formulations ■ Consider non-stimulant Third Other FDA approved agent (atomoxetine, clonidine ER, or medications after both stimulant Line groups have been tried guanfacine ER) Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); Subcommittee on Attention-Deficit/Hyperactivity Disorder. et al. Pediatrics. (2011) ADHD Medication Primer – Amphetamines FDA Off-label Brand Names Generic? Starting Doses Comments ■ Stimulants ■ NonMax/Day-stimulantsMax/Day Short Acting Mixed amphetamine Adderall® 3-5 YO: 2.5 mg IR formulations can be used in salts daily > 50 kg: 60 younger/smaller children Yes 40 mg Dexedrine®, ≥6 YO: 5 mg mg Have to be dosed 2-3 times Dextroamphetamine Zenzedi®, ProCentra® daily or BID per day Long Acting ≥6 YO: 5-10 mg > 50 kg: 60 Adderall XR® and Mydayis® Adderall XR® Yes 30 mg Mixed amphetamine daily or BID mg contains different salts extended concentration mixes of 13-17 YO: 12.5 release Mydayis® No 25 mg N/A amphetamine salts, so not mg daily exchangeable. Dextroamphetamine ≥6 YO: 5 mg > 50 kg: 60 Dexedrine Spansule® Yes 40 mg extended release daily or BID mg ≥6 YO: 20-30 Lisdexamfetamine Vyvanse® No 70 mg N/A mg daily Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); CMS. Pediatric Stimulants Dosing Chart. (2015); Lexi-Drugs Online (2019) ADHD Medication Primer – Methyphenidate FDA Off-label Brand Names Generic? Starting Doses Comments Max/Day Max/Day Short Acting Methylphenidate Ritalin®, Methylin® Yes 5 mg BID 60 mg > 50 kg: 100 mg IR formulations can be used in Dexmethylphenidate Focalin® 2.5 mg BID 20 mg 50 mg younger/ smaller children Intermediate and Long Acting Methylin ER® Yes 10 mg qAM 60 mg > 50 kg: 100 mg “Intermediate acting” Metadate CD®, Ritalin LA® Yes 20 mg qAM Concerta®, Relexxii® Yes 18 mg qAM 72 mg 108 mg These formulations Methylphenidate Aptensio XR® Yes 10 mg qAM 60 mg Unknown may differ in extended release delivery systems or Quillivant XR®, QuilliChew XR® No 20 mg qAM 60 mg Unknown long/short acting Cotempla XR-ODT® No 17.3 mg qAM 51.8 mg Unknown mixes. May affect bioavailability and ® Daytrana patch No 10 mg patch daily 30 mg Unknown interchangeability. Dexmethylphenidate Focalin XR® 5 mg qAM 30 mg 50 mg extended release Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); CMS. Pediatric Stimulants Dosing Chart. (2015); Lexi-Drugs Online (2019) ADHD Medication Primer – Non-stimulants Brand Usual Daily Generic? Starting Doses Comments Names Doses Selective norepinephrine reuptake inhibitor Good option if patient has active suBstance 6-17 YO (≤70 kg): 6-17 YO (≤70 kg): aBuse or severe side effects of stimulants 0.5 mg/kg/day 1.2 mg/kg (mood laBility, tics) Atomoxetine Strattera® Yes 6-17 YO (>70 kg): 6-17 YO (>70 kg): Monitor closely for suicidal thinking and 40 mg /day 100 mg Behavior, clinical worsening, or unusual changes in Behavior Alpha-adrenergic agonist Clonidine Can Be used as adjunctive medication with Kapvay® Yes 0.1 mg 0.1-0.4 mg extended release stimulants or as monotherapy Only ER formulations are FDA approved for Guanfacine ADHD Intuniv® Yes 1 mg 1-4 mg extended release Needs to Be gradually tapered off to avoid reBound hypertension Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); SuBcommittee on Attention-Deficit/Hyperactivity Disorder. et al. Pediatrics. (2011); CMS. Pediatric Stimulants Dosing Chart. (2015); Lexi-Drugs Online (2019) What to do with Adverse Effects STEP 1 • However, if side Monitor effects persist… ■ For all adverse effects, it is STEP 2 important to assess the • If reduced dose results in Reduce loss of ADHD control… severity and burden it imposes Dose on the patient • If after trying other STEP 3 medications, ■ Most adverse effects are Try different patient’s ADHD still responds best to a managed with the same basic medication medication that causes side strategy STEP 4 effects… Add adjunctive medication Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007) What to do with Adverse Effects STEP 1 Step 1: Monitor Monitor ■ Many side effects are transient and will generally subside STEP 2 ■ Monitoring parameters for each Reduce Dose side effect may differ STEP 3 Try different medication STEP 4 Add adjunctive medication Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); National Institute for Health and Care Excellence. NICE Guideline 87. (2018) What to do with Adverse Effects STEP 1 Monitor Step 2: Reduce Dose STEP 2 ■ Most medications will be started Reduce at low doses and gradually Dose titrated upward ■ If a patient experiences an STEP 3 Try different adverse effect after a dose medication increase, then titrate back down to the most recent effective dose STEP 4 Add adjunctive at which the side effect did not medication occur Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); Greenhill LL et al. J Am Acad Child Adolesc Psychiatry. (2002) What to do with Adverse Effects STEP 1 Monitor Step 3: Try different medication STEP 2 ■ Can refer to… Reduce Dose o Changing from short-acting to long-acting or vice-versa STEP 3 o Changing to a new medication in the other Try stimulant class different medication ■ When changing medications always using clinical judgment when coming STEP 4 Add adjunctive up with “dose equivalents” medication Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007); Greenhill LL et al. J Am Acad Child Adolesc Psychiatry. (2002) What to do with Adverse Effects Step 3: Try different medication (cont’d) ■ If switching from short-acting to long-acting (or vice versa) of the same medication, then generally give same total daily dose o Example: amphetamine salts 5 mg BID à amphetamine salts XR 10 mg once daily ■ If switching to a different medication… Switching to… Mixed Methylphenidate Dexmethylphenidate amphetamine Dextroamphetamine salts Methylphenidate Half the total daily dose Half the total daily dose Same daily Dexmethylphenidate Double the daily dose Same daily dose dose Mixed amphetamine 1) Same total daily dose Same daily dose Same daily dose salts then titrate up, OR 2) Start with Dextroamphetamine recommended initial Same daily Initial Medication Same daily dose dose and titrate up dose Greenhill LL et al. J Am Acad Child Adolesc Psychiatry. (2002); Pharmacist’s Letter / Prescriber’s Letter: Comparison of Drugs for ADHD. Edition 271202; ); CMS. Pediatric Stimulants Dosing Chart. (2015) What to do with Adverse Effects STEP 1 Monitor Step 4: Add adjunctive medication STEP 2 Reduce Dose ■ Typically considered a last resort STEP 3 ■ May not be an option for all Try different adverse effects medication STEP 4 Add adjunctive medication Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007) Common Adverse Effects Common Less Common Appetite Suppression/ Weight Loss Tics Growth Slowing Emotional lability Insomnia Pliszka S et al. J Am Acad Child Adolesc Psychiatry. (2007) Appetite Suppression/Weight Loss Monitor ■ Higher risk with longer acting formulations Lifestyle Monitor strategies ■ Monitor weight o ≤10 years old: every 3 months Reduce o >10 years old: every 6 months Dose • At 3 and 6 months after starting treatment • More often if concerns arise Try different o Adults: every 6 months medication ■ Plot height and weight on a growth chart Add adjunctive medication Pliszka S et al.