ondansetron with olanzapine for the treatment of alcohol dependence: a preliminary clinical trial

Conditions: Alcohol Dependence

Summary: this study would like to test whether the combination of ondansetron and olanzapine will be superior to placebo at decreasing self-reported heavy drinking among early onset alcoholics.

target population: we will enroll male and female who meet dsm iv criteria for alcohol dependence and who are currently drinking equal or more than 21 alcohol units/week for women and equal or more than 28 alcohol units/week for men in the 7 day period prior to enrollment. this is a double-blind placebo-controlled study. eligible subjects will be randomized to ondansetron (4 ug/kg) and olanzapine (9, 18, 36 ug/kg) vs placebo. all subjects will participate in a 9 week regimen of weekly bbcet and outpatient medication treatment.

Eligibility criteria:
inclusion criteria: * males and females who have given written informed consent * aged 18 years and above and weighing ≥40 kg and ≤140 kg * drinking on average ≥21 and ≥28 drinks/week for women and men, respectively, in the 7-day period prior to enrollment * dsm-iv-r diagnosis of alcohol dependence * good physical health as determined by a complete physical examination, electrocardiogram (ekg) within normal limits and laboratory screening tests within acceptable range * negative pregnancy test at intake. * literate in english and able to read, understand, and complete the rating scales and questionnaires accurately, follow instructions, and make use of the behavioral treatments * willing to participate in behavioral treatments for alcoholism * answer an advertisement in the newspaper/radio/television, and express a wish to stop drinking * provide evidence of stable residence in the last month prior to enrollment in the study, and have no plans to move in the next three months exclusion criteria: * any current axis i dsm-iv psychiatric disorder other than alcohol or nicotine dependence that warrants treatment or would preclude safe participation in the protocol * severe alcohol withdrawal symptoms that, in the physician's opinion, require inpatient treatment * serious medical comorbidity requiring medical intervention or close supervision, or any condition that can interfere with the receipt of ondansetron or olanzapine * severe or life-threatening adverse reactions to the ondansetron or olanzapine medications in the past or during this clinical trial * female subjects who are pregnant, lactating, or not adhering to an acceptable form of contraception at any time during the study * received inpatient or outpatient treatment for alcohol dependence within the last 30 days * significant medical illness (including hypertension) as determined by history and/or complete physical examination. * gross neurological disease * mental retardation * pyrexia of unknown origin * diagnosis or suspicion of alzheimer's disease * clinically significant abnormalities on the ekg that will preclude safe participation * recent (last 3 months) history of ischemic heart disease or myocardial infarction. * current infective hepatitis as evidenced by clinical manifestations. if hepatitis is suspected, a hepatitis antibody/antigen screen will be done. * participation in a clinical study within the last 30 days * elevation of liver enzymes * history of any severe or life-threatening reaction to olanzapine or ondansetron * past or current history of seizures disorder * past or current history of diabetes * being treated with any medication with potential for clinically significant interactions with alcohol or olanzapine and/or ondansetron. these include:, serotonin antagonists (e.g., ritanserin or buspirone), dopamine antagonists (e.g., haloperidol), or compounds with actions similar to disulfiram (antabuse®). * pending imprisonment

Keywords: alcohol dependence alcohol abuse drinking alcohol