The Effects of Clozapine on Alcohol and Drug Use Disorders Among Patients With Schizophrenia

Abstract

Several case studies indicate that clozapine use is associated with reductions in the use of nicotine, alcohol, or illicit drugs. Although not designed to assess clozapine, this study explored a posteriori the effects of clozapine on alcohol and drug use disorders among schizophrenia patients. Among 151 patients with schizophrenia or schizoaffective disorder and co-occurring substance use disorder who were studied in a dual-disorder treatment program, 36 received clozapine during the study for standard clinical indications. All participants were assessed prospectively at baseline and every 6 months over 3 years for psychiatric symptoms and substance use. Alcohol-abusing patients taking clozapine experienced significant reductions in severity of alcohol abuse and days of alcohol use while on clozapine. For example, they averaged 54.1 drinking days during 6-month intervals while off clozapine and 12.5 drinking days while on clozapine. They also improved more than patients who did not receive clozapine. At the end of the study, 79.0 percent of the patients on clozapine were in remission from alcohol use disorder for 6 months or longer, while only 33.7 percent of those not taking clozapine were remitted. Findings related to other drugs in relation to clozapine were also positive but less clear because of the small number of patients with drug use disorders. This study was limited by the naturalistic design and the lack of prospective, standardized measures of clozapine use. The use of clozapine by patients with co-occurring substance disorders deserves further study in randomized clinical trials.

Olanzapine Reduces Craving for Alcohol: A DRD4 VNTR Polymorphism by Pharmacotherapy Interaction

“…The study with olanzapine is consistent with previous work indicating that consumption of alcohol increases craving and that a traditional dopamine antagonist (ie haloperidol), that acts on D 2 and D 4 receptors, reduces alcohol-elicited craving (Modell et al, 1993). In addition to these laboratory studies on dopamine antagonists and alcohol craving, recent clinical reports have suggested that clozapine, a D 4 receptor antagonist that is similar to olanzapine, reduces substance abuse among patients with comorbid substance abuse/ dependence (Green et al, 1999) and specifically, alcohol use (Drake et al, 2000). Thus, research with humans suggests that selective targeting of dopamine receptor subtypes may be useful for developing pharmacotherapies that reduce craving.…”

The Effect of Olanzapine on Craving and Alcohol Consumption

“…Thus, the effect of alcohol and alcohol cues on the activation of these dopamine pathways represents a target that may prove to be useful in terms of pharmacotherapy development, and genetic variants that alter the functioning of these pathways may prove to be important in terms of predicting the success of such a pharmacotherapy. Other research has suggested that clozapine, a D 4 receptor antagonist that is somewhat similar to olanzapine, reduced substance abuse among patients with comorbid substance abuse/dependence (Green et al, 1999) and, specifically, alcohol use (Drake et al, 2000). Thus, clinical research also supports an important role for the D 2 family of receptors, and specifically the D4 receptor.…”

Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia

“…There are higher rates of alcohol use disorders (AUD) in schizophrenia than in the general population (Drake et al, 2000) and AUDs have a negative impact on the course and outcome of schizophrenia (Drake et al, 1989(Drake et al, , 1996Cuffel and Chase 1994). However, little is known about why there is an elevated risk for AUDs in this population.…”