Correlates of Incident Bipolar Disorder in Children and Adolescents Diagnosed With Attention-Deficit/Hyperactivity Disorder

Background: The greater severity and chronicity of illness in youths with co-occurring attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder deserve further investigation as to the risk imparted by comorbid conditions and the pharmacotherapies employed.

Method: A retrospective cohort design was employed, using South Carolina’s Medicaid claims dataset covering outpatient and inpatient medical and psychiatric service claims with International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses and medication prescriptions between January 1996 and December 2006 for patients ≤ 17 years of age.

Results: The cohort included 22,797 cases diagnosed with ADHD at a mean age of 7.8 years; 1,604 (7.0%) were diagnosed with bipolar disorder at a mean age of 12.2 years. The bipolar disorder group developed conduct disorder (CD)/oppositional defiant disorder (ODD), anxiety disorder, and a substance use disorder later than the ADHD-only group. The odds of a child with ADHD developing bipolar disorder were significantly and positively associated with a comorbid diagnosis of CD/ODD (adjusted odds ratio [aOR] = 4.01), anxiety disorder (aOR = 2.39), or substance use disorder (aOR = 1.88); longer treatment with methylphenidate, mixed amphetamine salts, or atomoxetine (aOR = 1.01); not being African American (aOR = 1.61); and being treated with certain antidepressant medications, most notably fluoxetine (aOR = 2.00), sertraline (aOR = 2.29), bupropion (aOR = 2.22), trazodone (aOR = 2.15), or venlafaxine (aOR = 2.37) prior to the first diagnosis of mania.

Conclusions: Controlling for pharmacotherapy differences, incident bipolar disorder was more likely in individuals clustering specific patterns of comorbid psychiatric disorders, suggesting that there are different pathways to bipolarity and providing a clinical impetus for prioritizing prevention and preemptive strategies to reduce their hazardous influence.