olanzapine and Alcoholism

Alcohol use disorder (AUD) is a common comorbidity of schizophrenia. No effective pharmacologic treatment is available for both disorders to date.. In a phase 2, double-blind study, patients with schizophrenia and AUD experiencing ≥ 10 drinking and ≥ 2 heavy-drinking days in the previous month and recent (≤ 6 mo) disease symptom exacerbation were recruited between June 2014 and March 2017. DSM-IV-TR and DSM-5 criteria were used to assign the diagnoses of schizophrenia and AUD, respectively. After a 6-week lead-in period, 234 eligible patients were randomized (1:1) to olanzapine + 10 mg samidorphan tablets (OLZ/SAM) or olanzapine + placebo tablets (olanzapine) for 36-60 weeks of treatment. The primary outcome of time to the first event of exacerbation of disease symptoms (EEDS) was evaluated using the log rank test for treatment comparison, and the Cox proportional-hazards model was used to estimate hazard ratio. Safety was assessed as adverse events and laboratory measures.. No significant difference was observed between groups in the time to first EEDS (hazard ratio = 0.91; 95% CI, 0.53-1.56; P = .746). Patients treated with OLZ/SAM vs olanzapine had numerically lower rates in 6 of 8 criteria to evaluate EEDS. Change from baseline in percentage of heavy-drinking days during the double-blind treatment period was similar in OLZ/SAM- vs olanzapine-treated patients. OLZ/SAM was generally well tolerated with a safety profile similar to olanzapine.. OLZ/SAM was not superior to olanzapine in the time to EEDS and was well tolerated in patients with schizophrenia and AUD. Further research is needed to identify effective treatments for this difficult-to-treat population.. ClinicalTrials.gov identifier: NCT02161718; EudraCT number: 2014-001211-39 ​.

Topics: Adult; Alcoholism; Antipsychotic Agents; Comorbidity; Female; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Olanzapine; Outcome Assessment, Health Care; Schizophrenia

Patients with schizophrenia and comorbid alcohol use disorder remain understudied. This post hoc analysis evaluated data from Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia study (January 2001-December 2004).. Patients without substance abuse (except marijuana use) in the month before study entry were categorized into those with a history of alcohol use disorder (SZ + AUD) within 5 years before study entry and those without alcohol use disorder (SZ-only) per DSM-IV criteria. Time to first and recurrent exacerbations and hospitalizations were compared between disease states and between olanzapine and perphenazine, quetiapine, risperidone, and ziprasidone.. A total of 1,338 patients (SZ + AUD = 22.6%; SZ-only = 77.4%) were included. Time to first exacerbation of SZ was significantly shorter in the SZ + AUD versus SZ-only population (median = 5.4 vs 6.4 months; hazard ratio [HR] = 1.20 [95% CI, 1.01-1.42]; P = .039). Similar findings were observed for first hospitalization (HR = 1.63 [95% CI, 1.20-2.22]; P = .002) and recurrent hospitalizations (HR = 1.60 [95% CI, 1.18-2.15]; P = .002). The most common reasons leading to exacerbation in both groups were an increase in symptom severity and lack of efficacy. In patients with SZ + AUD related or unrelated to marijuana, perphenazine, quetiapine, risperidone, and ziprasidone were associated with significantly shorter time to first exacerbation versus olanzapine.. This post hoc analysis confirmed that patients with SZ + AUD had a worse illness course than patients with SZ-only and suggests that olanzapine may be associated with a longer time to first and recurrent exacerbations versus other antipsychotics in this difficult-to-treat population. Further research is needed to identify effective treatments for this important yet understudied patient population.. ClinicalTrials.gov identifier: NCT00014001.

Topics: Adult; Alcoholism; Antipsychotic Agents; Comorbidity; Female; Hospitalization; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Symptom Flare Up; Thiazoles; Time Factors

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.. To clarify whether olanzapine has clinical utility in the treatment of alcohol dependence, a 12-week, double-blind, and randomized clinical trial was conducted.. 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.. 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.. 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.

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Craving; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Treatment Outcome

No large-scale randomized trial has compared the effect of different second-generation antipsychotic drugs and any first-generation drug on alcohol, drug and nicotine use in patients with schizophrenia. The Clinical Antipsychotic Trial of Intervention Effectiveness study randomly assigned 1432 patients formally diagnosed with schizophrenia to four second-generation antipsychotic drugs (olanzapine, risperidone quetiapine, and ziprasidone) and one first-generation antipsychotic (perphenazine) and followed them for up to 18 months. Secondary outcome data documented cigarettes smoked in the past week and alcohol and drug use severity ratings. At baseline, 61% of patients smoked, 35% used alcohol, and 23% used illicit drugs. Although there were significant effects of time showing reduction in substance use over the 18 months (all p < 0.0001), this study found no evidence that any antipsychotic was robustly superior to any other in a secondary analysis of data on substance use outcomes from a large 18-month randomized schizophrenia trial.

Topics: Adolescent; Adult; Aged; Alcoholism; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Comorbidity; Cross-Sectional Studies; Dibenzothiazepines; Double-Blind Method; Female; Humans; Illicit Drugs; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Smoking; Smoking Prevention; Substance-Related Disorders; Thiazoles; Young Adult

Previous studies have indicated that olanzapine decreases craving after a priming dose of alcohol, that craving after a priming dose of alcohol is greater among individuals with the seven-repeat allele of the DRD4 variable number of tandem repeats (VNTR) polymorphism, and that the effect of olanzapine (a D2/D4 antagonist) is more pronounced among individuals with this allele. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving and differentially effective as a treatment for alcohol dependence over the course of a 12-week, randomized, placebo-controlled trial among individuals with and without the seven-repeat allele. Participants who met DSM IV criteria for alcohol dependence were randomly assigned to receive olanzapine (5 mg) or a placebo over the course of the trial. After 2 weeks of treatment, participants completed a cue reactivity assessment. The results suggested that participants who were homozygous or heterozygous for the seven (or longer)-repeat allele of the DRD4 VNTR responded to olanzapine with reductions in cue-elicited craving as well as reductions in alcohol consumption over the course of the 12-week trial, whereas individuals with the shorter alleles did not respond favorably to olanzapine.

Topics: Adult; Alcohol Drinking; Alcoholism; Benzodiazepines; Case-Control Studies; Cues; Double-Blind Method; Drinking Behavior; Female; Humans; Male; Middle Aged; Minisatellite Repeats; Olanzapine; Psychiatric Status Rating Scales; Receptors, Dopamine D4; Selective Serotonin Reuptake Inhibitors; Time Factors

A 12-week, double-blind, randomized, parallel-group clinical trial, comparing olanzapine and placebo treatment together with cognitive-behavioral psychotherapy, was carried out to determine the efficacy, safety, and tolerability of olanzapine in the treatment of alcoholism.. A total of 60 alcohol-dependent patients were assigned to 12 weeks' treatment with either olanzapine or placebo. The primary variable relapse to heavy drinking rate was evaluated by means of intention-to-treat analyses. Alcohol consumption, craving, adverse events, and changes in the biochemical markers of heavy drinking and possible toxicity were also evaluated.. We did not find significant differences in the survival analysis between placebo and olanzapine-treated patients (Kaplan-Meier log rank = 0.46, df = 1, p = 0.50). Eleven (37.9%) patients treated with olanzapine relapsed compared with 9 (29%) of those receiving placebo (chi = 0.53, df = 1, p = 0.5). Although some adverse events (weight gain, increased appetite, drowsiness, constipation, and dry mouth) were found more frequently in the olanzapine group, differences did not reach statistical significance in comparison with the placebo group.. Olanzapine was well tolerated, as the rate of adverse events was low, and it was safe, because it did not interfere with the normalization of biochemical markers of heavy drinking or alter liver function markers. Alcohol-dependent patients showed good adherence and compliance with the treatment protocol, but we found no differences in relapse rate or other drinking variables when comparing olanzapine with placebo-treated patients.

Topics: Adult; Alcoholism; Analysis of Variance; Benzodiazepines; Chi-Square Distribution; Cognitive Behavioral Therapy; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine

Topics: Alcoholism; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cocaine-Related Disorders; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Substance-Related Disorders

Topics: Adult; Aggression; Alcoholism; Antipsychotic Agents; Brazil; Humans; Male; Mental Disorders; Olanzapine; Social Isolation

Topics: Alcoholism; Benzodiazepines; Clonazepam; Depressive Disorder; Dibenzothiazepines; Disulfiram; Female; Fluoxetine; Foreign Bodies; Hallucinations; Humans; Middle Aged; Movement Disorders; Olanzapine; Pharynx; Quetiapine Fumarate; Tetrabenazine; Tongue Habits

Clinical evidence suggests that atypical antipsychotic drugs might reduce alcohol drinking and help to maintain abstinence. This study aimed to compare the effects of two widely used atypical antipsychotic drugs clozapine and olanzapine on alcohol intake in alcohol-preferring AA (Alko, Alcohol) rats that were taught to drink 10% alcohol in a 4 h limited access paradigm. Effects of acute clozapine (0, 0.3, 1.0 and 5.0 mg/kg) and olanzapine (0, 0.1, 0.5 and 1.25 mg/kg) treatments on the limited access alcohol drinking were studied. In repeated treatment experiment, clozapine (1.0 mg/kg) or olanzapine (0.5 mg/kg) was administered once daily, before limited access alcohol drinking session, over 5 successive days. To reveal any effect of the drugs selective for alcohol drinking, alcohol was exchanged with 0.1% saccharin solution for the 4 h limited access, and acute treatments were repeated. Effects of the drugs on ambulatory locomotor activity were tested with doses that were used in the acute experiments. Acute clozapine treatment had no effect on either alcohol or saccharin drinking, but olanzapine significantly reduced 4 h alcohol drinking. Repeated olanzapine treatment significantly reduced 4 h alcohol drinking when compared with vehicle or clozapine, but a tolerance developed to this effect. Repeated clozapine treatment produced no significant effect compared with vehicle. Both drugs significantly reduced locomotor activity. In conclusion, the atypical antipsychotic olanzapine non-selectively reduced alcohol drinking, while clozapine failed to do so, even if both were administered at pharmacologically effective doses.

Topics: Alcohol Drinking; Alcoholism; Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Drug Tolerance; Male; Motor Activity; Olanzapine; Rats; Time Factors

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Citalopram; Delusions; Depressive Disorder, Major; Diagnosis, Differential; Drug Therapy, Combination; Hospitalization; Humans; Male; Marijuana Abuse; Olanzapine; Patient Readmission; Psychotic Disorders; Spouses

Stalking behavior has been associated with several mental disorders, both psychotic and non-psychotic. The most frequently associated condition appears to be an individual with primitive personality psychopathology regardless of co-occurring psychotic symptomatology. Among the psychotic symptoms, erotomanic, and jealousy delusions may be the most clinically and torensically relevant. However, delusional jealousy has not been well appreciated in the psychiatric literature as an important contributor to stalking behavior. In this article, we explore the psychiatric, psychosocial, and forensic aspects of stalking in the context of delusional jealousy. We use a case example to highlight important issues in this area.

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Dangerous Behavior; Delusions; Humans; Jealousy; Male; Olanzapine; Pirenzepine; Schizophrenia, Paranoid; Sexual Behavior; Spouses

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

Topics: Alcoholism; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 1; Dyskinesia, Drug-Induced; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone