To the Editor: The hypotheses by Dr. Wagner et al. regarding the ineffectiveness of oxcarbazepine in the article “A Double-Blind, Randomized, Placebo-Controlled Trial of Oxcarbazepine in the Treatment of Bipolar Disorder in Children and Adolescents” may need to be modified over time because of the nearly 50% of bipolar disorder I subjects comorbid for ADHD that continued taking stimulants during the study. This stimulant subgroup introduces an ambiguous diagnostic heterogeneity into the study that will hopefully be sorted out over time as ADHD symptoms become better realized as a persistently distinct disorder or as an unfolding aspect of a disorder that is inherently bipolar. The use of stimulants in this subgroup may ultimately be at pharmacological odds with the overall goal of mood stability in bipolar mania (such as the use of nortriptyline in bipolar depression). Even though a data analysis was done to adjust for diagnostic variance due to ADHD in the comparison of scores on the Young Mania Rating Scale-50% response rate (because nearly one-half of the 70+% ADHD subjects remained on stimulants), the potential for pharmacological variance exists. We are reminded of Dr. DelBello’s work associating stimulant treatment with a younger age of bipolar onset, indicating there is at least some link between stimulant use and bipolarity (1).

1.DelBello M, Soutollo C, Hendricks W, Niemeier R, McElroy S, Strakowski S: Prior stimulant treatment in adolescents with bipolar disorder: association with age at onset. Bipolar Disord 2001; 3:53–57