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Safety Considerations in the use of Psychotropic Medication in Children and Teens


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This presentation for the medical staff of Child and Adolescent Behavioral Health in Canton, OH is an introduction to basic safety concerns and monitoring associated with the use of psychotropics in children and teens. The presentation was tailored to newly graduated advanced practice nurses.

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Safety Considerations in the use of Psychotropic Medication in Children and Teens

  1. 1. Safety Considerations in the use of Psychotropic Medication in Children and Teens Stephen Grcevich, MD President, Family Center by the Falls, Chagrin Falls OH Clinical Associate Professor of Psychiatry, NEOMED Transitional Medical Director Child and Adolescent Behavioral Health September 5, 2018
  2. 2. Learning objectives: • Review the comparative safety and adverse effect profiles of the following classes of medication indicated for use in commonly seen mental health conditions in children and teens… • Antipsychotics • Antidepressants • Stimulants • Mood stabilizers • Discuss current standards for monitoring for potential adverse events during pharmacologic treatment of children and teens.
  3. 3. True or false… • Aripiprazole is not associated with significantweight gainwhen used asmonotherapy in youth with bipolar disorder (and other conditions) who are naïve to pharmacotherapy.
  4. 4. The answer is…FALSE
  5. 5. Metabolic effects of second-generation antipsychotics in pediatric patients: Agent: Metabolic Effects: Olanzapine fasting glucose triglycerides insulin insulin resistance Quetiapine total cholesterol triglycerides HDL cholesterol triglyceride:HDL ratio Risperidone triglycerides Aripiprazole No significant metabolic effects Correll,CU etal., JAMA.2009;302:1765–1773.
  6. 6. Metabolic Monitoring with SGAs
  7. 7. Tardive Dyskinesia • Annualized incidence rate – 4% per year • Higher rates in females, African-Americans, patients with intellectual disabilities • AIMS test recommended by APA at baseline prior to initiating antipsychotics, q6 months with FGAs, q12 months with SGAs.
  8. 8. TADS: Suicidal ideation in acute treatment
  9. 9. Do risks and benefits vary by the condition being treated? (Number Needed to Harm) 0 50 100 150 200 250 Depression Anxiety OCD Risks and benefits of antidepressant therapy Harm=New onset suicidal thinking, behavior NNH
  10. 10. Risk/Benefit Ratio of SSRIs by condition treated 0 5 10 15 20 25 30 35 40 Depression Anxiety OCD Risks and benefits of antidepressant therapy Harm=New onset suicidal thinking, behavior NNT Risk/Benefit
  11. 11. Predictors of Suicidal Events Grcevich SJ et al. Presented at American Academy of Child and Adolescent Psychiatry, October 2009
  12. 12. SSRI side effects: • Nausea • Weight gain • Behavioral activation/disinhibition • Restlessness • Vivid dreams • Increased clotting time • Fatigue • Sexual side effects
  13. 13. SSRI Withdrawal
  14. 14. Mood Stabilizer Side Effects • Lithium: toxicity, potential lethality in overdose, gastroenteritis (compounded by NSAIDs), renal, thyroid toxicity, acne, weight gain, tremor, polyuria • Divalproex: PCOS, weight gain, hair loss, tremor • Lamotrigine: rare cases of Stevens-Johnson (need slow titration) David Axelson, MD, AACAPBoard ReviewCourse, 2012
  15. 15. Side effect, safety issues with stimulants: • Cardiovascular safety: sudden death, heart rate, BP • Effects upon growth • Relationship to substance abuse risk • Other long-term consequences? • Management of effects upon appetite, sleep
  16. 16. Sudden Death Overview in Children and Adolescents on Stimulants: • Rate in children, adolescents: AMP: 0.36/1,000,000 RX MPH: 0.16/1,000,000 RX (difference is non- significant) • Background rate in pediatric population: 1.3- 8.5/100,000 patient years (more common in males than females) • FDA Pediatric Advisory Committee recommended against boxed warnings for stimulants Liberthson RR. New England Journal of Medicine 1996:(334) 1039-1044 Meeting of the FDA Pediatric Advisory Committee, Washington DC, March 22, 2006
  17. 17. Sudden death overview in adults on stimulants: • Rate in adults: AMP: 0.53/1,000,000 RX MPH: 0.07/1,000,000 RX (difference is non-significant) • Background rate in adult population: 1-2/1000 patient years • 3 of 5 deaths in adult patients occurred in individuals over 40 with preexisting HTN (coronary artery disease and dysrhythmia was a pre-existing condition in one case) • More data needed to evaluate risk in patients over 40 with HTN, preexisting cardiovascular disease, obesity Janse MJ. Pharmacol and Therapeutics 2003(100) 89-99 Cardiovascular Safety Review, Office of Drug Safety , February 9, 2006 (
  18. 18. Screening for Cardiac Risk: American Heart Association Guidelines • Medical history • History of congenital or acquired cardiac disease • Family history of or premature cardiac disease (<30 years of age) • Palpitations, chest pain, syncope, seizures, post-exercise symptoms • Ask about other medications (including OTC) • Routine medical exam • Monitor blood pressure & pulse at baseline and follow-up • No need for baseline ECG, Holter, ECHO in children • Adults: Work-up as medically indicated • Suspicion of CV defect (e.g., idiopathic hypertrophic sub-aortic stenosis): work-up as indicated Gutgesell H et al. Circulation. 1999:99:979-982.
  19. 19. Hypertension and ADHD medication in adults • Cardiovascular data from five controlled studies (MPH, MAS-XR, pemoline, buproprion, desipramine) • Stimulants and non-stimulants associated with increases in heart rate, blood pressure • Also common on placebo • New-onset systolic or diastolic hypertension (BP>140/90) • 10% of patients on active drug • 8% on placebo • Baseline HR and BP measurement, along with periodic monitoring is recommended in adults Wilens TE, Hammerness PG, Biederman J et al. J Clin Psychiatry 2005:66(2) 253-259
  20. 20. Cardiovascular effects of stimulants in kids • Amphetamine, atomoxetine associated with, small, statistically significant changes in heart rate, systolic, diastolic BP • Methylphenidate associated with significant increase in systolic BP • No difference in severity of effects between treatments • Long term significance unclear Hennissen, L., Bakker, M.J., Banaschewski, T. et al. CNS Drugs (2017) 31: 199. doi:10.1007/s40263-017-0410-7
  21. 21. Effects on Stature: MTA • Statistically, but not clinically significant differences in height, weight • Effects appear primarily in first 12-18 months • Kids with ADHD experience growth spurts later than peers • Group averages at 14 months (end of MTA study): • Gain in height: • Medical management only: 4.75 cm • Behavioral therapy only: 6.19 cm • Variance: –1.44 cm/14 months (= –1.23 cm/year) • Gain in weight: • Medical management only: 1.64 kg • Behavioral therapy only: 4.53 kg • Variance: –2.89 kg/14 months (= –2.48 kg/year) MTA Cooperative Group. Pediatrics. 2004;113:762-769.
  22. 22. ADHD and Substance Abuse • ADHD is a significant risk factor for substance abuse disorders in teens, adults • Medication during adolescence may reduce risk, but protective effects disappear by age 25 • Smoking • Adults with ADHD smoke more, experience more difficulty quitting • Children with ADHD start younger, smoke more Biederman et al. Pediatrics. 1999;104:e20. Pomerleau et al. J Subst Abuse. 1995;7:373-378. Milberger et al. J Am Acad Child Adolesc Psychiatry. 1997;36:37-44.
  23. 23. Trends in stimulant misuse, abuse • Rate of stimulant misuse, diversion calculated at 2.0% • Statistically significant reduction in misuse, diversion of stimulants (p<0.01) between 2002 and 2004 • Reduction in abuse rates corresponds to time period during which use of extended release products was rapidly expanding • Misuse rates at college proportional to mean SAT scores of incoming freshman class 2004 National Survey on Drug Use and Health, DHHS Publication #SMA 05-4062 McCabe SE et al. Addiction, 99, 96–106
  24. 24. Stimulants and rebound effects: • Rate: 8.6% vs 1.9% on placebo (Adderall XR) • Possible causes • Fatigue factor • Hypoglycemia • Comorbid anxiety • Patients with anxiety/OCD often experience more irritability on stimulants-decreased distractibility may intensify anxiety awareness Biederman J et al. Pediatrics (2002) 110:258-266 Swanson JM et al. J Am Acad Child Adolesc Psychiatry (1998) 37:519-526 Grcevich S. Future Neurology. 2006; 1(5) 525-534
  25. 25. Do stimulants cause long term changes in brain function? Wang G-J, Volkow ND, Wigal T, Kollins SH, Newcorn JH, et al. (2013) PLoS ONE 8(5): e63023. doi:10.1371/journal.pone.0063023 • Study examined long-term changes in DA transporter in never-treated adults with ADHD after 12 months on Concerta vs. controls • 24% increase in DA transporter in caudate and putamen after 12 months (significant) • Does long term use of ADHD medication make ADHD symptoms worse when medication is stopped? • More studies needed of other medications, impact upon functional impairment
  26. 26. Do stimulants cause long term changes in brain function? Wang G-J, Volkow ND, Wigal T, Kollins SH, Newcorn JH, et al. (2013) PLoS ONE 8(5): e63023. doi:10.1371/journal.pone.0063023
  27. 27. Drug Holidays • Recommended by many pediatricians, especially during summer months • Driven by concerns that kids aren’t eating enough, achieving expected growth • Often driven by difficulty tolerating stimulant- related side effects • Does ADHD significantly impact functioning in one or more major life domains (school/work, family, friends, community) during weekends, vacation?
  28. 28. Managing stimulant-related side effects: • Appetite/weight: • Eat Breakfast • Encourage small snacks throughout day • Bedtime snacks replace missing lunchtime calories • Sleep: • Limit access to electronics before bed • Melatonin (3-6 mg, two hours before bedtime) • Consider adjusting duration of medication coverage • Adjunctive clonidine • Irritability: • Evaluate for comorbid conditions • Consider “dose-sculpting” in late afternoon • Consider alternative medication • Most stimulant related side effects resolve within three months of treatment initiation McGough JJ et al. J Am Acad Child Adolesc Psychiatry (2005) 44:530-538
  29. 29. Components of a Clinical Case Presentation Stephen Grcevich, MD Child and Adolescent Behavioral Health September 26, 2018
  30. 30. The purpose