OBJECTIVE: Little is known about the effect of stimulant treatment in youth with attention-deficit/hyperactivity disorder (ADHD) on the subsequent development of comorbid psychiatric disorders. We tested the association between stimulant treatment and the subsequent development of psychiatric comorbidity in a longitudinal sample of patients with ADHD.
METHODS: We conducted a case-control, 10-year prospective follow-up study into young-adult years of youth with ADHD. At baseline, we assessed consecutively referred white male children with (n = 140) and without (n = 120) ADHD, aged 6 to 18 years. At the 10-year follow-up, 112 (80%) and 105 (88%) of the children in the ADHD and control groups, respectively, were reassessed (mean age: 22 years). We examined the association between stimulant treatment in childhood and adolescence and subsequent comorbid disorders and grade retention by using proportional hazards survival models.
RESULTS: Of the 112 participants with ADHD, 82 (73%) were previously treated with stimulants. Participants with ADHD who were treated with stimulants were significantly less likely to subsequently develop depressive and anxiety disorders and disruptive behavior and less likely to repeat a grade compared with participants with ADHD who were not treated.
CONCLUSIONS: We found evidence that stimulant treatment decreases the risk for subsequent comorbid psychiatric disorders and academic failure in youth with ADHD.
Comments
Re: Case series does not provide insight into effects of stimulant treatment for ADHD
The following statement was inadvertently omitted from the above letter:
The views expressed in this letter do not necessarily represent the views of the National Institute of Mental Health, the National Institutes of Health, the Department of Health and Human Services, or the United States Government.
Conflict of Interest:
None declared
Case series does not provide insight into effects of stimulant treatment for ADHD
To the editors:
In the July 2009 issue of Pediatrics, Biederman et al[1] report on psychiatric and educational outcomes of patients diagnosed with ADHD at age 6-18 and followed for 10 years. Children who received stimulants had better outcomes than children not treated with stimulants. Our concern is twofold: the disregard of pitfalls of drawing causal inferences from observational studies of treatment effects and misrepresentation of the study as a case-control.
Treatments administered in the course of usual care are influenced by differences across patients[2]. These differences are likely to be strongly related to outcomes, leading to a common type of confounding in observational studies of treatment effects: confounding by indication[3]. Typically, confounding by indication leads to associations of treatment with poor outcome, because more severe cases receive treatment.
In this study, confounding by indication is likely to work in the opposite direction because comorbidity of ADHD with conduct, depressive and/or anxiety symptoms is the most likely reason physicians decided against stimulant therapy. Notably, 33% of those not treated with stimulants were treated with anti-depressants. These comorbid conditions in children are strongly associated with subsequent onset of adult psychopathology[4]. It is likely that patients treated with stimulants were less severe than those not treated with stimulants.
Biederman et al convey the misleading impression that the results are based on a case-control design, when in fact they are from a case series. The analysis is limited to information on cases. Data on controls are not used. The fact that the case series was originally compiled as part of a case-control study is irrelevant.
We agree that treatments for ADHD should be evaluated in well executed RCTs; there already exists sufficient support for such investments. This study neither strengthens nor weakens the evidentiary base on the effects of stimulant treatment.
REFERENCES
1. Biederman J., Monuteaux M. C., Spencer T., Wilens T. E., Faraone S. V. Do stimulants protect against psychiatric disorders in youth with ADHD? A 10-year follow-up study. Pediatrics. 2009;124(1):71-78.
2. Wang P. S., Schoenbaum M. Invited Commentary: Assessing Treatment Effects by Using Observational Analyses-Opportunities and Limitations. American Journal of Epidemiology. 2009;170(3):286-287.
3. Psaty B. M., Koepsell T. D., Lin D., Weiss N. S., Siscovick D. S., Rosendaal F. R., et al. Assessment and control for confounding by indication in observational studies. J Am Geriatr Soc. 1999;47(6):749-754.
4. Kim-Cohen J, Caspi A, Moffitt TE, Harrington H, Milne BJ, Poulton R. Prior juvenile diagnoses in adults with mental disorder: developmental follow-back of a prospective-longitudinal cohort. Arch Gen Psychiatry. 2003;60(7):709-717.
Conflict of Interest:
None declared