Ondansetron for Bipolar Disorder and Alcohol Use Disorders

Study ID
112013-075

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • UT Southwestern-Other
  • Parkland Health & Hospital System

Contact
Collette Bice
214/645-6954
collette.bice@utsouthwestern.edu

Principal Investigator
Edson Brown, M.D., Ph.D.

Official Title

Ondansetron for Bipolar Disorder and Alcohol Use Disorders

Brief Overview


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).
The investigators will also use blood samples to determine if the genotype for the serotonin
transporter gene is associated with response to ondansetron.

Summary


A total of 70 outpatients with alcohol use disorder and BPD will be enrolled in a 12-week,
randomized, double-blind, parallel-group, placebo-controlled study of ondansetron.
Participant will receive either ondansetron or a placebo for 12 weeks. He or she has an
equal chance of receiving ondansetron or placebo.

Randomization will be stratified based on > 4 or ≤ 4 drinking days per week at start of the
study. Ondansetron or placebo will be given at 0.5 milligrams twice a day for the first 4
weeks. At weeks 4, 8 and 10 the dose may be increased to 1.0, 2.0 or 4.0 milligrams twice a
day, respectively, if significant reductions in depression and alcohol use are not observed
and the participant is not experiencing any side effects. Blood will be drawn for routine
laboratory analyses including a complete blood count (CBC), liver panel, and CDT at baseline
and weeks 4, 8 and 12.

Each participant will return for weekly follow-up visits and repeat outcome measures. Pill
counts will be conducted, and a list of current medications and doses will be recorded at
each visit. Participants will be compensated at each appointment with a bus pass, gift
cards, and a monetary incentive for compliance. Participants will be evaluated by both the
research assistant (RA) and principal investigator (PI) at each visit.

The HAMD and Timeline Followback will be given at each visit as the primary outcome
measures. Cognitive assessments will be performed at baseline and week 12.

Participant Eligibility


Inclusion Criteria:

- Outpatient men and women age 18-65 years old with bipolar I, II, or NOS disorder

- Current depressed mood state

- 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

- Current mood stabilizer therapy (lithium, anticonvulsant, atypical antipsychotic)
with stable dose for at least 14 days prior to randomization

Exclusion Criteria:

- Baseline YMRS or HAMD scores ≥ 35 to exclude those with very severe mood symptoms

- Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar
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 or ALT > 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)