A randomized, double-blind, placebo-controlled proof-of-concept study of ondansetron for bipolar and related disorders and alcohol use disorder.

Bipolar disorder is associated with high rates of alcohol use disorder. However, little is known about the treatment of this dual diagnosis population. Previous studies suggest that ondansetron decreases alcohol use, particularly in people with specific single nucleotide polymorphism (SNP) alleles. A 12-week, randomized, double-blind, placebo-controlled trial of ondansetron was conducted in 70 outpatients with bipolar spectrum disorders and early onset alcohol use disorder. Outcome measures included alcohol use, assessed with the Timeline Followback method, Penn Alcohol Craving Scale (PACS), Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self-report, and Young Mania Rating Scale. SNPs rs1042173, rs1176713 and rs1150226 were explored as predictors of response. Participants had a mean age of 44.9 ± 9.4 years, were mostly men (60.0%), and African American (51.4%). Mean ondansetron exit dose was 3.23 ± 2.64 mg. No significant between-group differences in alcohol use measures were observed. However, a significant reduction in HRSD scores was observed (p = 0.045). Inclusion of SNPs increased effect sizes for some alcohol-related outcomes and the HRSD. Ondansetron was well tolerated. This proof-of-concept study is the first report on ondansetron in bipolar people with bipolar disorders and alcohol use disorder. Alcohol use did not demonstrate a significant between-group difference. However, the findings suggest that ondansetron may be associated with reduction in depressive symptom severity in persons with bipolar illnesses and alcohol use disorder. A larger trial is needed to examine the effects of ondansetron on bipolar depression.