Objective

Adolescents with bipolar disorder (BD) are more likely to develop substance use disorders (SUDs) than adolescents without psychiatric disorders; however, to our knowledge, specific risk factors underlying this relationship have not been prospectively examined. The purpose of this study was to identify predictors of developing SUDs after a first manic episode.

Method

Participants aged 12 to 20 years and hospitalized with their first manic episode associated with bipolar I disorder (BP-I) were recruited as part of the University of Cincinnati First-Episode Mania Study and prospectively evaluated for patterns of substance use. Follow-up ranged between 17 and 283 weeks (mean = 113 weeks, SD = 71.9 weeks). Demographic and clinical variables were compared between adolescents with and without SUDs.

Results

Of the 103 adolescents with BD, 49 (48%) either had a SUD at baseline or developed one during follow-up. Of the 71 participants who did not have a SUD at study entry, 17 (24%) developed one during follow-up (median = 40 weeks). Later onset of BD, manic (versus mixed) mood episode, and comorbid disruptive behavior disorders were associated with an increased risk of developing a SUD in univariate analyses. Adolescents treated with psychostimulant treatment before their first manic episode were significantly less likely to develop a SUD independent of attention-deficit/hyperactivity disorder (ADHD) diagnosis. Comorbid posttraumatic stress disorder (PTSD) and psychotic symptoms were the strongest predictors of SUD development.

Conclusion

Our results confirm high rates of SUD in adolescents with BD. In addition, our findings identify potential risk factors associated with SUDs in adolescents with BD. These data are preliminary in nature and should be explored further in future studies.

Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12-17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.