clozapine and Alcoholism

Several novel techniques were developed recently to explore neural circuit mechanisms of neuropsychiatric disorders. These techniques include the Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic tools, which represent valuable platforms for selective and non-invasive control of neural activity with a high degree of spatial resolution. Among all variants, Gq- and Gi-DREADDs are widely used by neuroscientists to dissect out the circuitry and cellular signals. This review is focused on strategies to access a specific neuronal population or circuit using the DREADD technique and summarizes the current knowledge of the DREADDs' application in alcohol use disorder research and therapeutics.

Topics: Alcoholism; Animals; Brain; Clozapine; Humans; Pharmacogenomic Testing; Receptors, Muscarinic

In recent years, there has been a growing interest in developing adequate treatments for patients with a diagnosis of schizophrenia and a comorbid substance use disorder (SUD). In the present paper we aim to critically review published reports on the use of conventional and second-generation antipsychotics in the treatment of patients with schizophrenia and comorbid SUD, to provide clinicians with a clearer view of the pharmacological treatment of this highly prevalent dual diagnosis based upon the evidence arising from the scientific literature.. A search of the relevant literature from Medline, PsycLIT and EMBASE databases, included in the Science Citation Index, and available up to November 2006 was conducted using the terms: 'schizophrenia', 'substance use disorder' and 'antipsychotics'.. While research on the use of conventional antipsychotics has remained limited, the majority of studies suggest the effectiveness of second-generation antipsychotics, particularly clozapine, for patients with schizophrenia and a comorbid substance use disorder.. In the absence of randomized controlled trials that could provide more reliable information, clinical decisions may need to rely on indirect data provided by the increasing number of case reports, open trials and retrospective studies showing a decrease in cigarette smoking, alcohol, cocaine or cannabis use and an improvement of overall psychiatric symptoms.

Topics: Alcoholism; Antipsychotic Agents; Clozapine; Cocaine-Related Disorders; Combined Modality Therapy; Comorbidity; Cross-Sectional Studies; Diagnosis, Dual (Psychiatry); Humans; Marijuana Abuse; Schizophrenia; Smoking Cessation; Substance-Related Disorders

Co-occurring substance use disorder is common among patients with schizophrenia, and its presence greatly worsens the course of schizophrenia. A number of theories have been introduced to explain the increased rate of substance use disorder in these patients. These theories include the notion that substance use could trigger psychotic symptoms in vulnerable individuals and the idea that the substances are used to self-medicate symptoms of schizophrenia. Our group and others have advanced a neurobiological hypothesis to explain this comorbidity-that a mesocorticolimbic brain reward circuit underlies the substance use disorder in patients with schizophrenia. Treatment of substance use disorder in these patients is best done with integrated treatment programs that combine psychosocial interventions with pharmacotherapy. Recent data suggest that the atypical antipsychotic clozapine and perhaps other atypical agents may lessen substance use in patients with schizophrenia. My colleagues and I have proposed that clozapine's effect in these patients may be related to its ability to decrease the brain reward circuit dysfunction. Research is continuing on the use of atypical antipsychotics in patients with schizophrenia and comorbid substance abuse. The adjunctive use of naltrexone or other agents also may be helpful. Further research on the optimal pharmacologic approach to patients with dual diagnosis is needed.

Topics: Alcohol Deterrents; Alcoholism; Antipsychotic Agents; Clozapine; Comorbidity; Diagnosis, Dual (Psychiatry); Disulfiram; Drug Therapy, Combination; Humans; Naltrexone; Narcotic Antagonists; Schizophrenia; Substance-Related Disorders; Treatment Outcome

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.

Topics: Adult; Alcoholism; Antipsychotic Agents; Clozapine; Comorbidity; Female; Humans; Male; Schizophrenia; Substance-Related Disorders; Treatment Outcome

In an open trial 25 tremor patients were treated with clozapine in small doses (18-75 mg per day). The effect was measured with a new movement analyzer. Nine of 12 essential tremor patients were greatly improved. In six of nine patients with Parkinson tremor and in two combined essential tremor/Parkinson tremor patients tremor almost disappeared. Sedation is a major side effect, but decreases in most patients with time. The risk of agranulocytosis makes blood control necessary.

Topics: Alcoholism; Clinical Trials as Topic; Clozapine; Dibenzazepines; Double-Blind Method; Humans; Parkinson Disease; Tremor

Alcohol use disorder (AUD) is a significant co-morbidity in patients with schizophrenia. Clozapine offers some benefits in treating patients with refractory schizophrenia and AUD, but co-medicating with disulfiram is also common.. We report two cases where co-medicating with disulfiram led to a significant increase in clozapine serum levels.. Clozapine serum levels decreased to one-third in Patient 1 when disulfiram was discontinued and started to increase again when disulfiram was reintroduced. Patient 2 developed toxic serum levels of clozapine during disulfiram treatment combined with heavy coffee drinking and symptoms reminiscent of neuroleptic malignant syndrome.. Clozapine and disulfiram are both metabolized by cytochrome P450 CYP1A2 and clinically relevant interaction through this shared pathway is possible.

Topics: Alcoholism; Antipsychotic Agents; Clozapine; Cytochrome P-450 CYP1A2; Disulfiram; Humans; Schizophrenia

The widespread prevalence of coronavirus disease 2019 (COVID-19) means that inpatient psychiatric units will necessarily manage patients who have COVID-19 that is comorbid with acute psychiatric symptoms. We report a case of recurrence of respiratory symptoms and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) testing in a patient on an inpatient psychiatric unit occurring 42 days after the initial positive SARS-CoV-2 RT-PCR test, 38 days after initial symptom resolution, and 30 days after the first of 3 negative SARS-CoV-2 RT-PCR tests. Over the course of the admission, the patient was safely initiated on clozapine. Recent literature on COVID-19's potential recurrence and neuropsychiatric effects is reviewed and implications for the management of COVID-19 on inpatient psychiatric units are discussed. In the era of COVID-19 and our still-developing understanding of this illness, psychiatrists' role as advocates and collaborators in our patients' physical health care has become even more critical.

Topics: Adult; Alcoholism; Antidepressive Agents; Antipsychotic Agents; Clozapine; COVID-19; COVID-19 Nucleic Acid Testing; Depressive Disorder, Major; Hospitals, Psychiatric; Humans; Inpatients; Male; Mirtazapine; Psychotic Disorders; Recurrence; SARS-CoV-2; Sertraline; Suicide, Attempted

Topics: Aged; Alcoholism; Antipsychotic Agents; Aripiprazole; Clozapine; Comorbidity; Drug Substitution; Humans; Male; Schizophrenia

Alcohol use disorder, characterized by modest levels of alcohol use, commonly occurs in patients with schizophrenia and dramatically worsens their course. Recent data indicate that the atypical antipsychotic clozapine, but not the typical antipsychotic haloperidol, decreases alcohol drinking both in patients with schizophrenia and also in the Syrian golden hamster, an animal model of moderate alcohol drinking. The present study was designed to assess the comparative effects of clozapine and haloperidol in the alcohol-preferring (P) rat, an animal model of alcoholism. First, the study investigated the comparative effects of clozapine and haloperidol on initiation of alcohol consumption in P rats, which models the early stage of alcoholism. Second, the study assessed the comparative effects of clozapine and haloperidol on maintenance of chronic alcohol consumption in P rats to provide a clue as to whether either drug may also limit alcohol consumption in alcohol-dependent patients. Clozapine attenuated the initiation of alcohol drinking and development of alcohol preference while haloperidol did not. However, neither clozapine nor haloperidol attenuated maintenance of chronic alcohol drinking. Taken together, the current data suggest that clozapine, but not haloperidol, may be effective at reducing alcohol abuse or non-dependent drinking and the P rat, used within an alcohol initiation paradigm, and may differentiate the effects of clozapine and haloperidol on alcohol drinking.

Topics: Alcohol Drinking; Alcoholism; Animals; Antipsychotic Agents; Body Weight; Clozapine; Dose-Response Relationship, Drug; Drinking; Eating; Haloperidol; Male; Rats; Rats, Inbred Strains

To determine the prevalence rates of hepatitis C in patients with schizophrenia and schizoaffective disorder being treated with clozapine.. Clozapine-treated outpatients and inpatients were recruited from the Centre for Addiction and Mental Health Schizophrenia Program in Toronto, Canada. All subjects had liver function tests, and positive HCV status was defined as a positive qualitative HCV RNA assay. Subjects completed a self-report questionnaire assessing HCV risk factors, past history of liver disease, previous diagnosis of human immunodeficiency virus (HIV), past hepatitis B virus (HBV) infection and current alcohol use.. 110 subjects participated in the study and the HCV prevalence rate (antibody and viremia-positive) was 2.7%, compared to a 0.8% prevalence rate in Canada. All study subjects had established housing, none reported a history of HIV, and only one patient had a history of HBV infection. A total of 9% drank two or more drinks on a typical day drinking and 7% endorsed having six or more drinks on one occasion at least monthly. Two of 3HCV-viremia positive subjects had HCV risk factors, specifically intravenous drug use and intranasal cocaine use. There was no difference between HCV infected and HCV negative subjects on liver function tests.. Our study demonstrates elevated rates of HCV in clozapine-treated patients compared to the general population in Canada and are congruent with reports from United States centres. Our study highlights the importance of homelessness and patterns of high-risk behaviour when interpreting HCV prevalence rates in this sub-population of patients and should be explored in future studies.

Topics: Administration, Intranasal; Adult; Alcoholism; Antipsychotic Agents; Canada; Clozapine; Cocaine-Related Disorders; Cohort Studies; Female; Hepacivirus; Hepatitis C; Humans; Male; Middle Aged; Prevalence; Psychotic Disorders; Risk Factors; Risk-Taking; Schizophrenia; Substance Abuse, Intravenous; Surveys and Questionnaires

Topics: Akathisia, Drug-Induced; Alcoholism; Antipsychotic Agents; Aripiprazole; Clozapine; Cocaine-Related Disorders; Comorbidity; Delayed-Action Preparations; Diabetic Ketoacidosis; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Middle Aged; Molindone; Piperazines; Quinolones; Schizophrenia, Paranoid; Substance Withdrawal Syndrome

Clozapine is known to be effective in treating schizophrenia patients with comorbid alcohol use disorders (AUD). However, few prospective studies have examined the effect of clozapine on community survival of the patient, which is one of the most important indicators of success for patients with schizophrenia. In this prospective, naturalistic, observational, community-survival-analysis study, we compared the effect of clozapine and risperidone on two-year psychiatric hospitalization rate and time to hospitalization in the treatment of patients with schizophrenia and comorbid AUD. We found that the clozapine treated patients were readmitted to hospital significantly later (mean survival=526.5 days, n=25 patients) than the risperidone treated patients (mean survival=420.4 days, n=36 patients). The survival curve for the clozapine-treated patients was significantly different from that of the risperidone treated patients (log-rank test, df=1, p=.045). At the end of the two-year study period, 75% of the risperidone treated patients had been admitted to the hospital, compared to only 48% of the clozapine treated patients. These findings suggest that clozapine should be considered for the treatment of schizophrenia patients with comorbid AUD. However, due to the limitations of this study, further studies will be required to confirm these findings.

Topics: Adolescent; Adult; Alcoholism; Antipsychotic Agents; Clozapine; Diagnosis, Dual (Psychiatry); Female; Humans; Male; Middle Aged; Patient Readmission; Prospective Studies; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Socioeconomic Factors; Survival Analysis

Topics: Alcoholism; Amisulpride; Antipsychotic Agents; Behavior, Addictive; Blood Glucose; Clozapine; Comorbidity; Diabetes Mellitus; Diagnosis, Dual (Psychiatry); Drug Therapy, Combination; Humans; Male; Middle Aged; Schizophrenia; Sulpiride

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

The beneficial effect of clozapine on polydipsia and water intoxication in patients with schizophrenia has been demonstrated many times. The authors report a successful clozapine treatment of polydipsia, intermittent water intoxication, and delusional jealousy of an alcoholic. This is a rare case of clozapine treatment of a non-schizophrenic patient affected by polydipsia.

Topics: Adult; Alcoholism; Antipsychotic Agents; Clozapine; Drinking Behavior; Feeding and Eating Disorders; Humans; Male; Schizophrenia, Paranoid; Water Intoxication

A man affected by schizoaffective disorder and alcohol abuse presented priapism after eleven years of clozapine treatment. After surgical intervention and resolution of priapism, he continued clozapine treatment at the same dose without problems. Clozapine withdrawal is not mandatory in patients who develop priapism in the course of treatment.

Topics: Adult; Alcoholism; Antipsychotic Agents; Clozapine; Humans; Male; Priapism; Psychotic Disorders; Treatment Outcome

Comorbid alcohol dependence is common in patients with schizophrenia and is associated with a variety of serious adverse consequences. Although case reports exist concerning the positive impact of lamotrigine addition on clozapine treatment in resistant schizophrenia, a review of the literature fails to document any evidence regarding a combination of the two in the treatment of patients with schizophrenia and comorbid alcohol dependence. In the present study, we present three cases in which patients with resistant schizophrenia and comorbid alcohol use disorder were given lamotrigine to augment clozapine. Our findings suggest that clozapine plus lamotrigine may be helpful in reducing alcohol consumption and craving among patients with schizophrenia and comorbid alcohol dependence.

Topics: Adult; Alcoholism; Antimanic Agents; Antipsychotic Agents; Clozapine; Diagnosis, Dual (Psychiatry); Drug Resistance; Drug Therapy, Combination; Humans; Lamotrigine; Male; Schizophrenia; Schizophrenic Psychology; Triazines

Topics: Adult; Alcoholism; Clozapine; Disulfiram; Drug Therapy, Combination; Humans; Male; Schizophrenia

Topics: Activities of Daily Living; Alcoholism; Clozapine; Female; Humans; Middle Aged; Psychotherapy; Rehabilitation, Vocational; Schizophrenia; Schizophrenic Psychology; Sick Role

Topics: Adult; Alcohol Deterrents; Alcoholism; Antitubercular Agents; Clozapine; Humans; Male; Middle Aged; Tuberculosis, Pulmonary