Lisuride, a dopamine D2 receptor agonist, and anticraving drug expectancy as modifiers of relapse in alcohol dependence

Due to a central role of dopamine in mediating ethanol intake and dependence, the authors tested lisuride, a dopamine D2 receptor agonist, for relapse prevention in alcoholics. Psychological and neuroendocrine determinants or outcome were also assessed within the study. This double-blind, placebo-controlled randomized study comprised 120 alcoholics who were subjected to an intend-to-treat analysis (ITT). After hospital detoxification, patients received an outpatient rehabilitation program and either the study medication or placebo for 6 months and follow-up for another 6 months without medication. Pharmacological and psychological effects on relapse and times to first drink were assessed using survival analysis and multivariate analysis of variance (ANOVA). Neuroendocrine assessments were made using growth hormone (GH) response to stimulation with dopamine D2 receptor agonist apomorphine. In contrast to our hypothesis, the pharmacological effects of lisuride shortened (effect size: 0.51) and the expectation of receiving the drug (while being on medication) prolonged the latency of relapse (effect size: 0.47) in weaned alcoholics. Lisuride was associated with side effects like dizziness and hypotension. Dopaminergic responsivity to apomorphine stimulation was reduced under lisuride. This study supports the view that alcoholics may relapse due to decreased dopamine function, resulting from intake of dopamine D2 receptor agonists. In particular, our data do not support the use of lisuride for relapse prevention in alcoholics. The favorable impact of anticraving drug expectancy on outcome was unrelated to this effect. (C) 2001 Elsevier Science Inc. All rights reserved.