Bipolar disorder is a severe, persistent, and common psychiatric illness that is associated with a staggering 46% lifetime prevalence of alcohol-related disorders. Alcohol use disorder in patients with bipolar disorder is associated with numerous adverse consequences including increased hospitalization, poor outcome during hospitalization, violence towards self and others, and treatment nonadherence. Thus, the development of effective treatments for patients with bipolar and alcohol use disorder is a major public health concern. However, to date, few placebo-controlled trials have been conducted in patients with bipolar disorder and alcohol use disorder. Our group conducts clinical trials in persons with bipolar disorder and substance use disorders. A particularly promising medication that we have investigated is the atypical antipsychotic aripiprazole. A 12-week, randomized, double-blind, placebo-controlled study of aripiprazole is proposed in 132 outpatients with bipolar I or II disorder (depressed or mixed mood state) and alcohol use disorder, with active alcohol use. Alcohol use will be the primary outcome, with alcohol craving and mood symptoms as secondary outcomes. To reflect the diversity of our geographic region, both English- and Spanish-speaking participants will be included. The study design includes a 12-week acute phase with a maximum aripiprazole dose of 15 mg/day. A 4-week extension phase for completers with at least one heavy drinking day at week 12 will explore an aripiprazole titration up to 30 mg/day. To standardize management of other psychotropic medications (e.g. mood stabilizers, antidepressants), concomitant medication changes will be managed in both groups using a treatment algorithm. Relationships between changes in alcohol use and changes in mood will be explored. Outcome measures will include alcohol use assessed with the Timeline Followback method, Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology?Self-report, Young Mania Rating Scale, Penn Alcohol Craving Scale, as well as liver enzyme and carbohydrate deficient transferrin levels. Side effects, including those associated with antipsychotics, will be monitored. Additionally, blood samples will be obtained for genotype analysis, as well as laboratory values including blood sugar and lipid levels. A research team with extensive experience in dual diagnosis, mood disorders, clinical trials, statistics, and alcohol research will conduct the trial.
