Topiramate for co-occurring alcohol use and bipolar disorders in adolescents

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DESCRIPTION (provided by applicant): There is a bidirectional overlap between alcohol use and bipolar disorders, with a particularly severe illness course for individuals with both conditions. Specifically, patients with co-occurring alcohol use and bipolar disorders exhibit slower recovery, worse treatment adherence, increased suicidality, and higher rates of relapse of both illnesses compared with individuals with either illness alone. Adolescents with co-occurring alcohol use and bipolar disorders have a poorer outcome of both disorders than even occurs in similar adults. However, adolescents with co-occurring alcohol use and bipolar disorders are routinely excluded from controlled pharmacological treatment studies of either condition. Thus, clinicians have no evidence-based guidance on how to treat these adolescents. Research on the treatment of adolescents with co-occurring alcohol use and bipolar disorders is critical because adolescence may be the best time to interrupt the progression of these illnesses into lifelong alcohol dependence and treatment refractory bipolar disorder, both of which are associated with significant morbidity and mortality. Topiramate is an antiepileptic agent with a dual mechanism of action that leads to reduction of midbrain dopamine neurotransmission, and therefore, may be useful to reduce the reward and craving associated with alcohol use. Indeed, topiramate has been found to be safe and efficacious for reducing alcohol consumption and craving in adults. Our preliminary work suggests that topiramate also may be effective for the treatment of mania in adolescents with bipolar disorder. However, the efficacy of topiramate as a treatment for alcohol use disorders in bipolar adolescents has not been explored. Therefore, the goal of this two-year exploratory R21 proposal is to conduct a double-blind placebo-controlled, 12-week pilot study examining the efficacy and tolerability of topiramate as a treatment for reducing alcohol consumption in adolescents with co-occurring alcohol use and bipolar disorders. In order to accomplish this goal, we will randomize a total of 50 bipolar adolescents (ages 12-20 years) with an active alcohol use disorder to topiramate or placebo. All adolescents will also receive quetiapine and a manual-driven Cognitive Behavioral Therapy, as standard treatments for bipolar and alcohol use disorders, respectively. Change in alcohol consumption is the primary outcome measure. We will also examine the efficacy of topiramate in combination with quetiapine for the treatment of manic and depressive symptoms and explore the relationship between changes in alcohol use and mood symptoms. The proposed study would be the first to examine a pharmacological intervention for the treatment of alcohol consumption in adolescents with alcohol use and bipolar disorders. The preliminary data from this pilot project will inform and guide the design of future larger, more definitive, controlled studies of topiramate as a treatment for adolescent alcohol use disorders.