Ondansetron for Bipolar Disorder and Alcohol Use Disorders

Inclusion Criteria: * Outpatient men and women age 18-70 years old with bipolar I, II, or Not Otherwise Specified (NOS) disorders, schizoaffective disorder (bipolar type), cyclothymic disorder, or major depressive disorder with mixed features * Current diagnosis of alcohol use disorder (DSM V terminology) with onset ≤ age 25 * Alcohol use (by self-report) of at least 15 drinks in the 7 days prior to intake * IF diagnosis of Bipolar I, II, or NOS Disorder: Current mood stabilizer therapy (lithium, anticonvulsant, atypical antipsychotic) with stable dose for at least 14 days prior to randomization * IF diagnosis of Schizoaffective disorder (bipolar type): Current atypical antipsychotic therapy with stable dose for at least 14 days prior to randomization * IF diagnosis of Major Depressive Disorder with mixed features: Current antidepressant therapy with stable dose for at least 14 days prior to randomization Exclusion Criteria: * Baseline Young Mania Rating Scale (YMRS) or Hamilton Rating Scale for Depression (HAMD) scores ≥ 35 to exclude those with very severe mood symptoms * Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar (Clinical Institute Withdrawal Assessment of Alcohol Use-Revised) score of ≥ 10 * Therapy in past 14 days with naltrexone, acamprosate, disulfiram, or topiramate * Vulnerable populations (e.g. pregnant, breastfeeding, incarcerated, cognitively impaired (e.g. dementia, mentally challenged)) * High risk of suicide defined as \> 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded * Intensive outpatient treatment (defined as ≥ 3 visits each week) for substance abuse (AA, NA meetings, or less intensive counseling at baseline will be allowed) * Severe or life-threatening medical condition (e.g., hepatic cirrhosis) or laboratory or physical examination findings consistent with serious medical illness (e.g., dangerously abnormal electrolytes) * AST (aspartate aminotransferase ) or ALT (alanine transaminase) \> 3 times the upper limit of normal * History of severe side effects or allergic reaction with prior ondansetron therapy (e.g. for vomiting) or use of medications with significant drug-drug interactions with ondansetron (phenytoin, carbamazepine, and rifampicin, apomorphine, tramadol)