clozapine and Sleep-Initiation-and-Maintenance-Disorders

Insomnia commonly occurs in schizophrenia, and insomnia is associated with suicide risk. Clozapine has anti-suicidal properties and beneficial effects on sleep. We performed a meta-analysis of insomnia in randomized controlled trials (RCTs) of patients with schizophrenia treated with clozapine. We hypothesized that compared to clozapine there is an increased odds of insomnia in patients treated with other antipsychotics.. We systematically searched PubMed, PsycINFO, and Web of Science databases. We included RCTs, in English, with data on insomnia in patients with schizophrenia treated with clozapine versus other antipsychotics. Data were pooled using a random effects model.. Eight RCTs (1952 patients: 922 on clozapine and 1030 on other antipsychotics) met inclusion criteria. Patients treated with other antipsychotics versus clozapine had a significant increased odds of insomnia (22.3 % versus 12.4 %, OR = 2.20, 95 % CI = 1.64-2.94, p < 0.01). Olanzapine, quetiapine, risperidone, and ziprasidone were each associated with significant increased odds of insomnia compared to clozapine. In meta-regression analyses, clozapine dose, publication year, sex, trial duration, and study quality score were unrelated to the association; however, there was a significant association with age. The observed ORs for insomnia from RCTs were almost perfectly correlated with reported ORs from pharmacovigilance data.. Clozapine is associated with significantly less insomnia compared to other antipsychotics. Findings provide additional evidence for improvement in sleep as a potential pathway underlying clozapine's anti-suicidal properties. A greater mechanistic understanding of this association is needed.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Schizophrenia; Sleep Initiation and Maintenance Disorders

The purpose of this study was to compare the side effect +profiles of clozapine and risperidone.. The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports.. Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment.. In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.

Topics: Akathisia, Drug-Induced; Ambulatory Care; Clozapine; Cognition Disorders; Cross-Over Studies; Humans; Neuropsychological Tests; Pilot Projects; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Quality of life (QoL) has been always an important way to evaluate the outcomes of schizophrenia, but there have been few previous longitudinal studies and few in middle-income countries. This study aimed to explore the QoL in Chinese patients with schizophrenia treated in primary mental health care and the risk factors of QoL over time.. Patients with schizophrenia treated in primary mental health care in rural/regional areas in Luoding, Guangdong, PR China, were evaluated with an extended questionnaire including the Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) at baseline and 2-year follow-up. Bivariate and multivariate analyses were conducted including Generalized Estimated Equation analyses (GEE).. Four hundred and ninety-one patients with schizophrenia in primary care completed the 2-year follow up evaluation. The QoL physical, environmental, and social relationships domains showed improvement after the 2-year period, but the psychological domain did not. GEE results showed that earlier age of onset, older age, being employed, being unmarried, the thicker waist circumference, less use of clozapine or other SGAs, fewer hospitalizations, more frequent insomnia, more severe depressive and negative symptoms as well as worse treatment insight were independently associated with poor QoL in patients with schizophrenia.. According to our results, to improve the quality of life of patients with schizophrenia in primary care, we should pay more attention to the treatment of depression, negative and insomnia symptoms of schizophrenia, the choice and dosage of antipsychotic medication and improvement in the treatment compliance. The combined use of educational and behavioral strategies may improve treatment adherence.

Topics: Antipsychotic Agents; China; Clozapine; Cohort Studies; Humans; Mental Health; Quality of Life; Schizophrenia; Sleep Initiation and Maintenance Disorders

Insomnia associated with chronic schizophrenia and after clozapine discontinuation represents a common, but mostly not predominant, complaint and often does not respond sufficiently to classical hypnotics. We report the case of a 46-year-old patient with schizophrenia who developed a rebound insomnia confirmed by polysomnography after discontinuation of long-term treatment with clozapine and changing to sertindole therapy. Zolpidem, zolpiclone and chloral hydrate only led to short-term improvement of subjective sleep quality. An add-on therapy with 300 mg quetiapine resulted in improved subjective quality of sleep regarding sleep latency and the number of nocturnal awakenings. The combination of the two neuroleptics did not lead to increased QTc intervals (normal QTc < 450 ms) or metabolic side effects. In conclusion, the combination of sertindole and quetiapine might be a safe and effective combination in therapy-refractory insomnia after clozapine discontinuation in schizophrenia.

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Imidazoles; Indoles; Male; Middle Aged; Polysomnography; Quetiapine Fumarate; Schizophrenia; Sleep; Sleep Initiation and Maintenance Disorders

Four patients affected by severe Parkinson's disease developed leucopenia (900-1200 WBC) during treatment of psychosis (3) or untreatable insomnia (1) with clozapine (37.5-75 mg/day). Clozapine withdrawal was followed by recovery of leucopenia (4000-6000 WBC) in two weeks with no need for the administration of leucokines. After 1-6 months olanzapine was administered (increasing the dose from 2.5 to 10 mg/day) to treat persisting disturbances, but the drug induced severe worsening of parkinsonism and also this drug had to be withdrawn.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Leukopenia; Male; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Sexual Dysfunctions, Psychological; Sleep Initiation and Maintenance Disorders

Rebound insomnia has been reported upon discontinuation of benzodiazepines. We describe the first case of a sleep polygraphically documented rebound insomnia with an unusual somatic fatigue syndrome after long-term use of clozapine in a 30-year-old schizophrenic male. The withdrawal symptoms occurred the first day after drug discontinuation and could be stopped by readministering clozapine. In our opinion, the sudden occurrence of the withdrawal symptoms cannot be explained by a dopaminergic hypersensitivity or a cholinergic rebound, but indicates an involvement of GABAergic and perhaps antiglutamatergic properties of clozapine.

Topics: Adult; Antipsychotic Agents; Clozapine; Fatigue; Humans; Male; Polysomnography; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome

The case of a patient with sleep-related painful erections is described. Insomnia and a slight depressive syndrome occurred along with a long history of this disorder. No physical abnormality was found. At a baseline recording of sleep electroencephalography (EEG) and nocturnal penile tumescence (NPT), a disturbed sleep pattern and impaired NPT were recorded. Attempts to treat the disorder with diazepam, amitriptyline, trimipramine, and biperidene did not prompt a stable improvement of the disorder, but a dosage of 25 mg clozapine was sufficient to achieve normalized sleep architecture, remission of the depressive symptomatology, and normalization of NPT. It is likely that marked sedation is the mode of action of clozapine.

Topics: Administration, Oral; Adult; Clozapine; Dibenzazepines; Electroencephalography; Evoked Potentials; Humans; Male; Pain; Penile Erection; Sleep Initiation and Maintenance Disorders; Sleep Stages