Prior stimulant treatment in adolescents with bipolar disorder: association with age at onset

Objectives: To compare demographic and clinical characteristics between bip olar adolescents with and without a history of stimulant treatment, we hypo thesized that adolescents treated with stimulants would have an earlier age at onset of bipolar disorder, independent of co-occurring attention-defici t-hyperactivity disorder (ADHD). Method: Thirty-four adolescents hospitalized with mania were assessed using the Washington University at St Louis Kiddie Schedule for Affective Disord ers and Schizophrenia (WASH-U-KSADS). We systematically evaluated age at on set of bipolar disorder and pharmacological treatment history. Results: Bipolar adolescents with a history of stimulant exposure prior to the onset of bipolar disorder had an earlier age at onset of bipolar disord er than those without prior stimulant exposure. Additionally, bipolar adole scents treated with at least two stimulant medications had a younger age at onset compared with those who were treated with one stimulant. There was n o difference in age at onset of bipolar disorder between bipolar adolescent s with and without ADHD. Conclusions: Our results suggest that stimulant treatment, independent of A DHD, is associated with younger age at onset of bipolar disorder. A behavio ral sensitization model is proposed to explain our findings. There are seve ral limitations to our study including the small sample size, the retrospec tive assessment of stimulant exposure and age at onset of bipolar disorder? and the inclusion of only hospitalized patients, who may be more likely to present with a severe illness. Nonetheless, future prospective longitudina l investigations that systematically assess the effects of stimulant medica tions in children with or at genetic risk for bipolar disorder are warrante d.