Dose specific effects of olanzapine in the treatment of alcohol dependence

Rationale: It is well established that the rewarding effects of alcohol are modulated by the mesolimbic dopaminergic system. Olanzapine, a D₂ dopamine antagonist, has been shown to reduce alcohol craving and consumption. Objective: To clarify whether olanzapine has clinical utility in the treatment of alcohol dependence, a 12-week, double-blind, and randomized clinical trial was conducted. Methods: One hundred twenty-nine treatment-seeking alcohol-dependent adults were randomly assigned to 12 weeks of olanzapine (5 vs. 2.5 mg) or placebo. Outcomes examined were average drinks per drinking day (DDD), proportion of drinking days (PDD) to total days in treatment, alcohol craving, and impaired control over alcohol use. Mixed models were used to examine medication effects during the course of treatment on specified outcomes. Results: All of the analyses indicated a main effect for time, such that there were reductions in alcohol use and craving and an increase in control over alcohol use across treatment conditions. Dose-response analyses indicated that, in comparison to placebo, participants in the 5 mg group experienced reduced craving for alcohol and participants in the 2.5 mg group decreased in PDD and increased in their control over alcohol use. Better control over alcohol use remained significant 6 months post-treatment for the 2.5 mg group. Subjective experiences of the medication suggest that 2.5 and 5 mg were equally well tolerated. Conclusions: Results provide some support for the notion that dosage is an important consideration in relation to effectiveness; however, the cost-benefit balance does not support the clinical utility of olanzapine in treating alcohol dependence.