Ondansetron for Bipolar Disorder and Alcohol Use Disorders
Condition: Bipolar Disorder; Alcohol Use Disorder; Dual Diagnosis
MeSH terms: Alcoholism; Bipolar Disorder; Alcohol Drinking
Intervention: Ondansetron; Placebo
Intervention description: Ondansetron is a serotonin receptor antagonist that is FDA-approved to treat nausea and vomiting caused by cancer therapy and surgery.; Inactive ingredient matching the active medication in appearance
Intervention MeSH terms: Ondansetron
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Bipolar Disorder; BPD; Alcohol Use Disorder; Alcohol Abuse; Alcohol Dependence; Ondansetron; Cognition; Mood

Summary:

      The purpose of the study is to determine if ondansetron, as an add-on therapy, is associated
      with reduced depressive symptoms and alcohol use in outpatients with bipolar disorder (BPD),
      cyclothymic disorder, schizoaffective disorder (bipolar type) and major depressive disorder
      (MDD) with mixed features. The investigators will also use blood samples to determine if the
      genotype for the serotonin transporter gene is associated with response to ondansetron.
    

Eligibility criteria:

        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)