1. Pharmacotherapy of ADHD Side Effects of Stimulants
Flavio Guzman, MD

2. Overview Cardiovascular risks Effects on growth Risk of tics
Potential for abuse / diversion
Sleep disturbances

3. FDA warning on sudden cardiac death
Based on rare reports
Warning (as appears in PI):
Sudden death has been reported with usual doses of CNS stimulants in children and adolescents with structural cardiac abnormalities or other serious heart problems.
Sudden death, stroke , and myocardial infarction have been reported in adults taking CNS stimulants at usual doses.
U.S. Food and Drug Administration, Drug Safety and Risk Management Advisory Committee Meeting. February 9-10, 2006

4. ADHD, stimulants and sudden cardiac death
What is the relationship between ADHD, stimulants and sudden cardiac death?
No evidence that shows that SCD is more common in:
Children with ADHD
Children with ADHD receiving stimulants
Berger, S. Cardiac evaluation of children receiving pharmacotherapy for attention deficit hyperactivity disorder. In: UpToDate, Triedman, J (Ed), UpToDate, Waltham, MA. (Accessed February, 2015.)

5. Stimulants, heart rate and blood pressure
Stimulants cause slight but clinically insignificant increases in
heart rate
blood pressure
Awudu, G. A., & Besag, F. M. (2014). Cardiovascular Effects of Methylphenidate, Amphetamines and Atomoxetine in the Treatment of Attention-Deficit Hyperactivity Disorder: An Update. Drug Safety, 37(9),

6. Not suggestive of cardiac disease
Pharmacotherapy can be initiated or continued without additional evaluation
History and examination
Not suggestive of cardiac disease
Perrin JM, Friedman RA, Knilans TK, et al. Cardiovascular monitoring and stimulant drugs for attention deficit/hyperactivity disorder. Pediatrics 2008; 122:451.

7. History
Special attention to symptoms such as palpitations, syncope or near syncope
Family history of sudden death
History of loss of consciousness particularly with exercise
History of marked exercise intolerance
Pharmacological Management of ADHD, in: Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Third Edition, Toronto ON; CADDRA. Version: November 2014

8. Physical examination Measurement of: Cardiac auscultation
Blood pressure
Heart rate
Cardiac auscultation
Presence of a cardiac murmur
Irregular or rapid cardiac rhythm
Wilens TE, Prince JB, Spencer TJ, Biederman J. Stimulants and sudden death: what is a physician to do? Pediatrics 2006; 18:1215.

9. The role of ECG Should we order a screening ECG? Not recommended
No data of ECG findings associated with serious cardiac events
It may delay treatment
Perrin JM, Friedman RA, Knilans TK, et al. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics 2008; 122:451.
American Academy of Pediatrics/American Heart Association clarification of statement on cardiovascular evaluation and monitoring of children and adolescents with heart disease receiving medications for ADHD.

10. ECG Cardiac disease Further evaluation (including ECG)
History or physical examination suggestive of cardiac disease
Further evaluation (including ECG)
Consultation with pediatric cardiologist
Perrin JM, Friedman RA, Knilans TK, et al. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics 2008; 122:451.
American Academy of Pediatrics/American Heart Association clarification of statement on cardiovascular evaluation and monitoring of children and adolescents with heart disease receiving medications for ADHD.

11. Effects of stimulants on growth
Appetite suppression
Growth retardation
Purushothaman, Priti. "What's New with Stimulants?." Child and Adolescent Psychopharmacology News 18.4 (2013): 1-8.

12. Effects of stimulants on growth
Prolonged treatment (more than 3 years)
Slower rate of physical development during puberty
Poulton, A. S et al (2013). Growth and pubertal development of adolescent boys on stimulant medication for attention deficit hyperactivity disorder. Med J Aust,198(1),

13. “ADHD, Stimulant Treatment, and Growth: A Longitudinal Study”
Medications did not affect children’s final height as adults
Growth spurt at a later age than boys not treated with stimulants
Mean age of peak height velocity delayed about 7 months
Magnitude not affected
Harstad EB et al. ADHD, stimulant treatment, and growth: A longitudinal study. Pediatrics 2014 Sep; 134:1

14. Effects on growth - Management
Monitor:
Appetite
Weight
Height
BMI
Baseline and every 6 months
Purushothaman, Priti. "What's New with Stimulants?." Child and Adolescent Psychopharmacology News 18.4 (2013): 1-8.

15. Effects on growth - Management
Appetite suppression
Give medication after meals rather than before
If growth concerns occur:
Consider drug holidays on weekends or school holidays
Consider reducing the dose
Consider switching to an alternative class or formulation
Purushothaman, Priti. "What's New with Stimulants?." Child and Adolescent Psychopharmacology News 18.4 (2013): 1-8.

16. Stimulants and tics
Do stimulants cause tics? No evidence that stimulants cause tics in children who do not already have them
Law SF et al., J Am Acad Child Adolesc Psychiatry 1999;38 (8):944–951; Varley CK et al., Compr Psychiatry2001;42(3):527–536; Tourette’s Syndrome Study Group, Neurology2002;58 (4):527 –53

17. Pathogenesis: increased DA in the basal ganglia
Stimulants and tics
Pathogenesis: increased DA in the basal ganglia
Theoretically, stimulants could:
Increase the risk of tics
Worsen the severity of existing tics
Purushothaman, Priti. "What's New with Stimulants?." Child and Adolescent Psychopharmacology News 18.4 (2013): 1-8.

18. Stimulants and tics In children with ADHD + tic disorders:
MPH did not seem to worsen tics
Supratherapeutic doses of D-AMP were shown to worsen tics
Bloch, M. H., et al (2009). Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. Journal of the American Academy of Child & Adolescent Psychiatry, 48(9),

19. Stimulants and tics Cochrane review: Stimulants are effective
Will likely continue to be a first-line treatment for children with comorbid ADHD and tic disorders
Pringsheim, T., & Steeves, T. (2011). Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders.The Cochrane Library

20. Potential for abuse / diversion
Stimulants are associated with significant misuse potential
Drug diversion is a concern in college and university settings
Pharmacological Management of ADHD, in: Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Third Edition, Toronto ON; CADDRA. Version: November 2014

21. Potential for abuse / diversion
Non-medical use of stimulants improves academic performance
Stimulants are more effective at correcting deficits
False
True
Lakhan, S. E., & Kirchgessner, A. (2012). Prescription stimulants in individuals with and without attention deficit hyperactivity disorder: misuse, cognitive impact, and adverse effects. Brain and behavior, 2(5),

22. Potential for abuse / diversion
Students are the main source of diversion to other students
Bolea-Alamañac, B., Nutt, D. , et al(2014). Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: Update on recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology, 28(3),

23. Potential for abuse /diversion
Avoiding risks of abuse
Use long-acting formulations
Prodrug lisdexamfetamine
Bolea-Alamañac, B., Nutt, D. , et al(2014). Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: Update on recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology, 28(3),

24. Sleep disturbances May be associated with
ADHD
ADHD medication
Stimulant effects vary considerably
Graham, J., Banaschewski, T., Buitelaar, J., Coghill, D., Danckaerts, M., Dittmann, R. W., ... & Taylor, E. (2011). European guidelines on managing adverse effects of medication for ADHD. European child & adolescent psychiatry, 20(1),

25. Sleep disturbances Management Sleep hygiene Dose adjustment
Dose scheduling
Medication switch
Atomoxetine
Graham, J., Banaschewski, T., Buitelaar, J., Coghill, D., Danckaerts, M., Dittmann, R. W., ... & Taylor, E. (2011). European guidelines on managing adverse effects of medication for ADHD. European child & adolescent psychiatry, 20(1),

26. Other side effects Headache Dizziness GI symptoms
Precipitation of mania or psychosis
Irritability, dysphoric mood

27. End of presentation