A New Pharmacotherapy for Alcohol Dependence: Olanzapine
Status:
Completed
Trial end date:
2011-09-01
Target enrollment:
Participant gender:
Summary
Craving for alcohol has been related to loss of control drinking and is a major target of
biological and behavioral interventions for alcohol dependence. Our previous research has
demonstrated that olanzapine (a dopamine antagonist) attenuates craving for alcohol, that a
variant in the gene that expresses D4 receptors influences craving for alcohol, and that
olanzapine is particularly effective at reducing craving among individuals with this variant.
Pilot data from a recent 12 week trial of olanzapine indicates that olanzapine is well
tolerated and that olanzapine reduces drinking, particularly among individuals with the
aforementioned genetic variant. The objective of the present application is to examine the
effectiveness of olanzapine (5 mg/day), as compared to olanzapine (2.5 mg/day) and a placebo
control, in terms of reducing craving and alcohol use behavior among treatment seeking
alcoholics. Furthermore, the present application will examine whether the effects of
olanzapine on drinking outcomes are mediated by its effects on a specific putative mechanism
(i.e., cue-elicited craving for alcohol) and determine whether the DRD4 VNTR polymorphism is
a marker for the effectiveness of olanzapine. To that end, 202 alcohol dependent subjects
will be randomly assigned to medication group and receive 12 weeks of medication. Subjects
will complete follow-up assessments at 3 and 6 months after the end of the treatment. It is
expected that olanzapine will significantly reduce cue-elicited craving and alcohol use
behavior in a dose dependent fashion over the course of the 12 week trial and follow-up
period, as compared to the placebo condition. Furthermore, it is expected that the effects of
olanzapine on alcohol use behavior will be mediated by the effect of olanzapine on
cue-elicited craving and that the effects of olanzapine on cue-elicited craving and alcohol
use behavior will be moderated by the DRD4 VNTR, such that olanzapine will be more effective
among individuals with the 7 repeat allele. The successful completion of the proposed
research is expected to advance a new medication for alcohol dependence and advance genetic
markers that predict the effectiveness of this medication.