Are The American Academy of Pediatrics New ADHD Guidelines Justified by the Evidence?
November 17, 2011
The American Academy of Pediatrics (AAP) recently updated their guidelines for the diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) to include preschool children and adolescents (www.pediatrics.org/cgi/doi/10.1542/peds.2011-2654). Previously AAP published clinical guidelines addressed the diagnosis and treatment of ADHD for school-age children ages 6-12. The AAP states that emerging evidence now supports expansion of the age range to preschool children.
The lowered age limit for treatment in the new AAP guidelines inevitably will increase the use of stimulant medications for this vulnerable age group. In the first three years of the last decade, spending for ADHD drugs increased 183% for children overall (Medco Health Solutions, Inc., 2004), and the prescribed use of these drugs and diagnoses of ADHD continue to rise (http://psychiatryonline.org/cgi/content/abstract/appi.ajp.2011.1103038). In 2007, 9.5% of children between the ages of 4 and 17 were diagnosed with ADHD, with 60% taking prescribed stimulants. These numbers are sure to swell as pediatricians are given the green light to prescribe psychostimulants for very young patients. Is the AAP’s expansion of its ADHD guidelines warranted, particularly given the likely consequence that many more children under the age of 6 will take these drugs for at least a portion of their earliest years?
Prescriber and parents/caregiver decisions to treat very young children with ADHD drugs must be based on a rigorous risk/benefit analysis. Treatment related evidence for the AAP clinical ADHD practice guidelines relied on a recent review prepared by the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services (Charach, 2011). This review examined 15 reports representing 11 investigations of the use of psychostimulants by preschoolers and claimed that studies found the drugs to be safe and efficacious. However, the review acknowledges that “the evidence comes primarily from short-term trials lasting days to weeks with small samples” (p. Es-8). When comparing methylphenidate with parent behavior training (PBT), the review concludes:
The SOE [strength of evidence] for use of PBT was judged high due to number of studies and consistency of results. The SOE for methylphenidate [MPH] was judged low because there is only one good-quality study [The Preschool ADHD Treatment Study (PATS)] . . . Both interventions are effective, with no adverse events reported for PBT, while there are adverse effects with MPH. This favors the use of PBT for preschoolers at risk for ADHD due to disruptive behavior.” (p. ES-8)
The assessment of efficacy for PATS in this review is optimistic. While PATS found modest significant differences on endpoint measures between the drug and placebo, only 21% of best-dose MPH achieved defined criterion for remission set for school-age children diagnosed with ADHD. Moreover, 30% of parents spontaneously reported moderate to severe adverse events in all phases of the study, and 11% discontinued due to intolerability (Wigal et al., 2006). Adverse events included irritability, repetitive behaviors, tics, and emotional outbursts. For those children who remained on medication, annual growth rates were 20.3% less than expected for height and 55.2% for weight (Swanson et al., 2006). NIMH director Insel issued an unenthusiastic endorsement based on PATS: “preschoolers may benefit from low doses of medication when it is closely monitored, but the positive effects are less evident and side-effects are somewhat greater than previous reports in older children" (http://www.nimh.nih.gov/press/preschooladhd.cfm).
Other noteworthy studies challenge the wisdom of giving our youngest children these drugs. The American Psychological Association (APA) Report of the Working Group on Psychoactive Medications for Children and Adolescents (APA Working Group, 2006), analyzing forty years of trials, found overall effect sizes for ADHD drugs in the moderate range, with low to moderate ranges for academic productivity and in the zero range for academic achievement (Conners, 2002). The Working Group noted the lack of data supporting long term efficacy or safety and highlighted that stimulants, while reducing symptoms, show minimal efficacy in general life domains of the child, including social and academic success. The Multimodal Treatment Study of Children with ADHD (MTA) (MTA Cooperative Group, 1999), the largest, most complexly designed trial of interventions for ADHD, found equivalent outcomes for medicated and non-medicated groups at 36 months (Jensen et al., 2007), with non-rebounded decreases in growth for children on Ritalin (Swanson et al., 2007).
In March of 2006, the Drug Safety and Risk Management Advisory Committee of the FDA urged stronger warnings on ADHD drugs, citing reports of serious cardiac risks, psychosis or mania, and suicidality for children taking them. The drugs reviewed by the committee were primarily amphetamines (Adderall and other brands) and methylphenidate (Ritalin, Concerta, and others). Adverse effects included increases in heart rate and blood pressure which are associated with a number of events such as stroke or heart failure. According to a report in the Wall Street Journal (Dooren, March 15, 2006), a memo from the FDA review team stated that they were particularly struck by the fact that signs of psychosis and mania occurred in children who had never been at risk for these before and at standard ADHD medication doses. The review found 1,000 reports of psychosis or mania possibly linked to the drugs from January 1, 2000 through June 30, 2005. While it was not definite what caused the hallucinations, the events resolved when the children stopped their ADHD medications. Additionally, many of the children hallucinating were under the age of 10, an age group where such experiences are extremely rare. Despite the advisory committee’s black box recommendation, the FDA decided to forgo a black box for all ADHD drugs (Aderall has a black box for cardiac risk and Strattera for suicidality) and, instead, to highlight risks on the label and include an information guide for parents with each prescription.
Stimulant medications have been associated with increased emergency room visits. A recent study found that thousands of children go to the ER with chest pain, stroke, high blood pressure, fast heart rate, and overdose on these drugs. While many of these young people may have had legitimate prescriptions, others likely take the drugs for recreational or performance reasons. Prescription drug abuse has become the new drug habit for youth, with nearly one in five teens reporting abuse of prescription medications to get high (Partnership for a Drug Free American, 2006). Is this a path we want to set for our youngest?
A review of past studies on the effect of ADHD drugs on children’s growth found that the drugs suppress both height and weight for the duration of the trials that were studied (Drappatz et al., 2006). The effect persisted after adjustment for age, study quality, treatment duration, and stimulant type. Height and weight effects were noted by the AHRQ review. In the PATS, for those who remained on MPH, the annual growth rate was 22 percent (1.4cm/yr.) less than expected for height and 55 percent (1.3kg/yr) less than expected for weight.
No long-term trials examining the use of ADHD drugs begun in preschool years are discussed in the AHRQ review. The authors state: “Evidence that psychostimulant use in childhood improves long-term outcomes was inconclusive” (p. vii). The review refers to the natural course of maturation of young children as confounding results from longer term studies—essentially, children often mature out of their troubling behavior patterns. Moreover, the AHRQ review notes that the majority of studies examining the long-term safety and efficacy of ADHD drugs are industry-funded and may result in “enhanced representations of efficacy and safety” (p. ES-9). The authors issue the following summary of their risk/benefit analysis: “The increasing use of off-label prescriptions for very young children is concerning, especially as PBT is effective for the disruptive behavior which is often the primary impairment when ADHD occurs in preschoolers” (p. 171). In closing, they conclude: “There is one primary implication from the review of interventions for preschoolers at risk of ADHD: the first line intervention for young children is evidence-based PBT. Other interventions may also be effective, but further research is required before definitive recommendations can be made” (p. 171).
It is clear that the very review relied upon by the AAP to support its expansion of ADHD guidelines was non-committal, at best, regarding the use of ADHD drugs for preschooler behavior problems. Based on their own investigation, opening the floodgates for ADHD medications for children under the age of 6 is not justified. When it comes to the very youngest in our society, we must err on the side of extreme caution and utilize known interventions that do not entail the significant risks of powerful psychostimulant drugs.
In light of current evidence, the International Society for Ethical Psychology and Psychiatry (ISEPP) strongly opposes the new AAP Guidelines and urges the AAP to reconsider the implications for lowering the age for which ADHD drugs may be recommended. The ISEPP further urges the AAP to retract their new guidelines until such evidence surfaces that ADHD drugs provide an acceptable risk relative to their benefit for children under the age of 6.
APA Working Group on Psychoactive Medications for Children and Adolescents. (2006). Report
of the Working Group on Psychoactive Medications for Children and Adolescents. Psychopharmacological, psychosocial, and combined interventions for childhood disorders: Evidence base, contextual factors, and future directions. Washington, DC: American Psychological Association.
Charach, A., Dashti, B., Carson, P., Booker, L., Lim, C. G., Lillie E., Yeung, E., Ma, J., Raina, P., Schachar, R. (October, 2011). Attention Deficit Hyperactivity Disorder: Effectiveness of Treatment in At-Risk Preschoolers; Long-Term Effectiveness in All Ages; and Variability in Prevalence, Diagnosis, and Treatment. Comparative Effectiveness Review No. 44. (Prepared by the McMaster University Evidence-based Practice Center under Contract No. MME2202 290-02- 0020.) AHRQ Publication No. 12-EHC003-EF. Rockville, MD: Agency for Healthcare Research and Quality. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Conners, C. K. (2002). Forty years of methylphenidate treatment in attention-deficit/hyperactivity disorder. Journal of Attention Disorders, 6(Suppl. 1), S17-S30.
Dooren, J. C. (2006, March 15). FDA urges stronger warnings on ADHD drugs. Wall Street Journal, p. D6.
Drappatz, J., Khwaja, O. S., Neovius, M., & Sarco, D. P. (2006). Growth in children with ADHD treated with stimulant medications: A meta-analysis. Poster Session presented May 1, 2006 at the Pediatric Academic Societies annual meeting, San Francisco, available at http://www.abstracts2view.com/pas/search.php?search=do&intMaxHits=10&where=&andornot=&query=Khwaja
Jensen, P. S., Arnold, L. E., Swanson, J. M., Vitiello, B., Abikoff, H. B., et al. (2007). 3-year follow-up of the NIMH MTA study. Journal of the American Academy of Child & Adolescent Psychiatry, 46(8), 989-1002.
Medco Health Solutions, Inc. (May 18, 2004). Medco study reveals pediatric spending spike on drugs to treat behavioral problems. Retrieved May 24, 2004, from http://www.drugtrend.com/medco/consumer/drugtrend/trends.
MTA Cooperative Group (1999). A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Archives of General Psychiatry, 56 (12), 1073-1086.
Partnership for a Drug Free America (2006). Generation Rx: National study confirms abuse of prescription and over-the-counter drugs. Retrieved July 11, 2006 from http://www.drugfree.org/Portal/DrugIssue/Research/Teens_2005/Generation_Rx_Study_Confirms_Abuse_of_Prescription#
Swanson, J. M., Elliott, G. R., Greenhill, L. L., Wigal, T., Arnold, L. E., et al. (2007). Effects of stimulant medication on growth rates across 3 years in the MTA follow-up. Journal of the American Academy of Child and Adolescent Psychiatry, 46(8), 1015-1027.
Swanson, J., Greenhill, L., Wigal, T., Kollins, S., Stehli, A., Davies, M. et al. (2006). Stimulant-related reductions of growth rates in the PATS. Journal of the American Academy of Child & Adolescent Psychiatry, 45(11), 1304-1313.
Wigal, T., Greenhill, L., Chuang, S., et al. (2006). Safety and tolerability of methylphenidate in preschool children with ADHD. Journal of the American Academy of Child & Adolescent Psychiatry, 45(11), 1294-303.
The current prescribing label instructions emphasize that children should receive a physical examination and a review of personal and family history for relevant cardiac events prior to starting stimulant treatment. Pretreatment ECG screening is recommended when abnormalities are suspected and some advocate across-the-board ECG screening. It is unknown the extent to which these guidelines are followed in practice.