Research over the past 2 decades has demonstrated that ADHD occurs frequently and causes considerable suffering in patients and their families. ADHD begins in early childhood and persists through adolescence and into adulthood in 70% of those affected. Two large epidemiological studies in the US have placed its prevalence at 8.7% in children and 4.4% in adults.1
In addition to the well-known, emotionally costly symptomatology at the individual level, a review paper just presented at the 2012 American Psychiatric Association (APA) meeting found that ADHD was also associated with a substantial impact on education costs among children and adolescents and on income and productivity losses among adults, ranging from approximately $86 billion to $138 billion dollars.2 Therefore, not surprisingly, there is an increased interest in all aspects of the illness, and the number of papers being published has grown every year for the past decade (Figure 1).
Such a large body of literature makes it challenging for busy clinicians to discern which of the hundreds of articles they should read to keep current with relevant, clinically applicable findings. In that spirit, this article reviews the most recently published ADHD literature as well as some of the presentations from the May 2012 APA meeting in Philadelphia and provides a clinical perspective on how findings may apply to everyday practice.
ADHD and cardiovascular risk of medication
The effects of stimulants on the cardiovascular system of healthy individuals are established. In therapeutic dosages, these agents increase blood pressure and heart rate, but such changes are not clinically meaningful.1 The rise in stimulant prescriptions and a renewed examination of sudden death case reports provided the stimulus for the FDA and its Canadian counterpart and the American Heart Association to review concerns about potential stimulant cardiotoxicity. In response to concerns, these agencies issued clinical guidance recommendations that were not universally accepted and became controversial. Following discussions with professional associations of physicians, these guidelines were ultimately reversed.
A 2009 large case-control study by Gould and colleagues3 found an association between the use of stimulants and sudden unexplained death among children and adolescents. Given the level of uncertainty in the field, several investigators launched a number of studies with varied methodological approaches geared toward generating additional data to clarify the issue.4-9 The resulting reports were published in 2011 and 2012 and are outlined in the Table.
Gould and colleagues reported a significant association, or “signal,” between sudden unexplained death and the use of stimulant medication, specifically methylphenidate. They acknowledged that the data had limitations that precluded a definitive conclusion, but their findings drew attention to the potential risks of stimulant medications. Since the publication of this study, other researchers have pointed to additional methodological issues that may have biased results away from the null.5 Furthermore, a number of well-designed large studies have not replicated this signal.
Practical tip: Psychotropics in general should not be prescribed for patients with current or past cardiac illness without obtaining medical clearance and coordinating follow-up care with a specialist. In such patients, a benefit-risk assessment determines whether medications should be recommended. Is there, however, a risk of significant cardiotoxicity when stimulants are prescribed in usual therapeutic doses for otherwise normal individuals?
1. Kaplan G, Newcorn JH. Pharmacotherapy for child and adolescent attention-deficit hyperactivity disorder. Pediatr Clin North Am. 2011;58:99-120, xi.
2. Hodgkins P, Kahle J, Sikirica V, et al. The hidden costs of attention-deficit/hyperactivity disorder (ADHD): a focus on school and work in the United States. Presented at: 165th Annual Meeting of the American Psychiatric Association; May 5-9, 2012; Philadelphia. Abstract NR4-19.
3. Gould MS, Walsh BT, Munfakh JL, et al. Sudden death and use of stimulant medications in youths. Am J Psychiatry. 2009;166:992-1001.
4. Hammerness PG, Perrin JM, Shelley-Abrahamson R, Wilens TE. Cardiovascular risk of stimulant treatment in pediatric attention-deficit/hyperactivity disorder: update and clinical recommendations. J Am Acad Child Adolesc Psychiatry. 2011;50:978-990.
5. Schelleman H, Bilker WB, Strom BL, et al. Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics. 2011;127:1102-1110.
6. Habel LA, Cooper WO, Sox CM, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA. 2011;306:2673-2683.
7. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med. 2011;365:1896-1904.
8. Olfson M, Huang C, Gerhard T, et al. Stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2012;51:147-156.
9. Vitiello B, Elliott GR, Swanson JM, et al. Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD. Am J Psychiatry. 2012;169:167-177.
10. Comer JS, Olfson M, Mojtabai R. National trends in child and adolescent psychotropic polypharmacy in office-based practice, 1996-2007. J Am Acad Child Adolesc Psychiatry. 2010;49:1001-1010.
11. Stocks JD, K Taneja B, Baroldi P, L Findling R. A phase 2a randomized, parallel group, dose-ranging study of molindone in children with attention-deficit/hyperactivity disorder and persistent, serious conduct problems. J Child Adolesc Psychopharmacol. 2012;22:102-111.
12. Pliszka SR, Sikirica V, Dammerman R, et al. A comparison of rates and reasons for urgent care utilization among children with ADHD treated with atypical antipsychotics vs non-antipsychotics. Presented at: 165th Annual Meeting of the American Psychiatric Association; May 5-9, 2012; Philadelphia. Abstract NR4-12.
13. Ben Amor L. Antipsychotics in pediatric and adolescent patients: a review of comparative safety data. J Affect Disord. 2012;138(suppl):S22-S30.
14. Pappadopulos E, Rosato NS, Correll CU, et al. Experts’ recommendations for treating maladaptive aggression in youth. J Child Adolesc Psychopharmacol. 2011;21:505-515.
15. Kupfer DJ, Regier DA. The future of psychiat-ric diagnosis: updates on proposed diagnostic criteria. Presented at: 165th Annual Meeting of the American Psychiatric Association; May 5-9, 2012; Philadelphia.
16. American Psychiatric Association. DSM-5 Development: A 06 Attention Deficit/Hyperactivity Disorder. http://www.dsm5.org/ProposedRevision/Pages/proposedrevision.aspx?rid=383#. Accessed September 26, 2012.
17. Bloch MH, Qawasmi A. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2011;50:991-1000.
18. Nigg JT, Lewis K, Edinger T, Falk M. Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives. J Am Acad Child Adolesc Psychiatry. 2012;51:86-97.e8.
19. Biederman J, Fried R, Hammerness P, et al. The effects of lisdexamfetamine dimesylate on the driving performance of young adults with ADHD: a randomized, double-blind, placebo-controlled study using a validated driving simulator paradigm. J Psychiatr Res. 2012;46:484-491.
20. Cox DJ, Davis M, Mikami AY, et al. Long-acting methylphenidate reduces collision rates of young adult drivers with attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2012;32:225-230.