clozapine and Fatigue

Clozapine is an alternative antipsychotic medication used to control symptoms of schizophrenia and to reduce risks of suicidal behavior in patients who did not adequately respond to standard medication. Due to severe side effects including cardiomyopathy and myocarditis its clinical use is limited.. A 31-year-old man of east European descent presented to the emergency medical department with fatigue, shortness of breath and chest pain. Due to a schizoaffective disorder he was treated with clozapine and lithium. Echocardiography revealed severely impaired left ventricular systolic function. After exclusion of coronary artery disease by coronary angiography an endomyocardial biopsy was performed according to the guidelines. This confirmed the clinically suspected toxic cardiomyopathy. Therefore, antipsychotic treatment was immediately changed and state of the art heart failure medication was started resulting in a clear improvement of left ventricular function.. In patients treated with clozapine or lithium and clinical signs of heart failure, toxic cardiomyopathy should be considered.

Topics: Adult; Antipsychotic Agents; Biopsy; Cardiomyopathies; Chest Pain; Clozapine; Dyspnea; Echocardiography; Fatigue; Heart; Humans; Male; Myocardium; Psychotic Disorders; Treatment Outcome

In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.

Topics: Animals; Antipsychotic Agents; Clozapine; Cytokines; Endotoxins; Fatigue; Fatigue Syndrome, Chronic; Fibromyalgia; Humans; Inflammation Mediators; Multiple Chemical Sensitivity; Neuroimmunomodulation; Receptors, Cytokine; Sleep; Sleep Stages; Sleep Wake Disorders

Compliance with conventional antipsychotic medication is often poor, with many patients discontinuing treatment only a few months after commencing therapy. The side effects of treatment, which are not necessarily restricted solely to motor symptoms, are often considered to be responsible for this noncompliance. In contrast to conventional antipsychotics, clozapine is associated with only minimal extrapyramidal symptoms, and in most patients, its use results in significant improvements in compliance. However, clozapine does induce a variety of adverse effects, most of which are of limited duration and either preventable or manageable if a number of simple clinical procedures are followed. Clozapine therapy is associated with a beneficial risk/benefit ratio in the majority of treatment-resistant schizophrenic patients. With careful hematologic control, the risk of agranulocytosis can be minimized. The marked increase in the well-being of patients receiving clozapine should stimulate psychiatrists to broaden its use and not limit it to severely treatment-resistant individuals.

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Fatigue; Humans; Patient Compliance; Risk Assessment; Schizophrenia; Schizophrenic Psychology; Seizures; Sialorrhea; Tachycardia; Treatment Outcome

Topics: Clozapine; Dizziness; Dopamine Antagonists; Fatigue; Humans; Schizophrenia; Serotonin Antagonists

Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine. Clozapine-induced sedation can worsen cognition and impair social and occupational functioning.. To evaluate the efficacy, tolerability, and safety of modafinil for negative symptoms, cognition, and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine.. A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007, adding modafinil up to 300 mg/d to stabilized schizophrenia outpatients receiving clozapine. Psychopathology, cognition, and wakefulness/fatigue were assessed with standard rating scales.. Thirty-five patients were randomly assigned to treatment with study drug and included in the analysis. Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo. Modafinil was well tolerated and did not worsen psychosis.. Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine. However, given our limited power to detect a treatment effect and the clear possibility of a type II error, larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude.. clinicaltrials.gov Identifier: NCT00573417.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzhydryl Compounds; Central Nervous System Stimulants; Clozapine; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Fatigue; Female; Humans; Male; Middle Aged; Modafinil; Neuropsychological Tests; Pilot Projects; Placebos; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Wakefulness

The second generation antipsychotics clozapine and olanzapine frequently induce weight gain. Randomized studies investigating abnormal eating behavior (food craving, binge eating) possibly associated with weight gain are lacking. Thirty patients with schizophrenia, schizophreniform, or schizoaffective disorder were included in this randomized, double-blind, parallel study comparing abnormal eating behavior using a standardized scale, clinical efficacy using the Brief Psychiatric Rating Scale 0-6 and Clinical Global Impression-Severity scale, and tolerability of clozapine and olanzapine. In both treatment groups, the number of patients reporting food craving, binge eating, or both increased over time. The likelihood to experience food craving at any time during drug treatment showed a trend (P = 0.068) to be higher in the olanzapine group (48.9%) compared with the clozapine group (23.3%). The likelihood to experience binge eating at any time during drug treatment was numerically but not statistically significantly higher in the olanzapine group (16.7%) than in the clozapine group (8.9%). In both groups, significant baseline-to-end point improvements of clinical symptoms (Brief Psychiatric Rating Scale 0-6: clozapine, 36.6 +/- 8.8 to 15.9 +/- 13.7; olanzapine, 36.7 +/- 9.9 to 19.1 +/- 13.8) and severity of illness (Clinical Global Impression-Severity scale: clozapine, 4.7 +/- 0.6 to 2.5 +/- 1.5; olanzapine, 4.5 +/- 0.6 to 2.3 +/- 1.2) were observed. These improvements did not differ significantly between groups. Olanzapine was more tolerable than clozapine; adverse events occurred significantly (P < 0.01) less frequently than in the clozapine group. These results suggest that both clozapine and olanzapine can induce food craving and binge eating, however, olanzapine possibly to a greater extent. Findings on clinical efficacy and safety are in accordance with previous reports.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Appetite; Benzodiazepines; Blood Pressure; Body Mass Index; Bulimia; Clozapine; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Heart Rate; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Sialorrhea; Treatment Outcome; Weight Gain

To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.. Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.. Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.. Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.

Topics: Acute Disease; Adult; Aged; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatigue; Female; Humans; Huntington Disease; Male; Middle Aged; Placebos; Severity of Illness Index; Sleep Stages; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Biopsy; Clozapine; Computed Tomography Angiography; Coronary Angiography; Diagnosis, Differential; Dyspnea; Electrocardiography; Fatigue; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Myocarditis; Myocardium; Nausea

Research has shown that individuals with schizophrenia use caffeine at higher rates than the general population; however, no qualitative research has been undertaken investigating problematic caffeine use and its effects on this population. This article explores the role of caffeine consumption in the lives of people with schizophrenia through a narrative analysis of the attitudes and beliefs associated with this practice, and how these, in turn, influence caffeine consumption.. A qualitative study was undertaken with individuals who had previously scored in either a 'moderate' or 'high' risk category for caffeine use on the Alcohol, Smoking and Substance Involvement Screening Tool (ASSIST). In-depth interviews were undertaken with 20 individuals, and transcripts were analysed thematically to identify prominent perspectives.. Consistent with previous literature, participants' caffeine consumption was driven largely by its stimulating properties; however, participants also identified 'cravings' as an important motivating factor. Participants' behaviours related to caffeine consumption seemed to be tempered by their previous experiences of consumption; if participants had experienced positive effects such as alertness or relaxation in the past, their use was maintained at a similar level or increased. Conversely, participants who anticipated negative consequences often altered their patterns of caffeine consumption; for example, by substituting caffeinated drinks that minimised or ceased their experience of negative side effects for those that directly caused such impacts. Overall, participants largely identified caffeine consumption as a highly meaningful activity, which provided structure to their day and facilitated opportunities for social interaction.. The inconsistencies between individuals' beliefs about their health and the actual risk of harm associated with health-related behaviours present significant and ongoing challenges for the implementation of relevant and effective strategies for health promotion among individuals diagnosed with mental illness. As a starting point, it would be worthwhile for services engaging with people diagnosed with mental illness, and in particular schizophrenia, to consider implementing caffeine-related health literacy strategies to educate consumers about the risk of excessive caffeine consumption and the interactions between caffeine and antipsychotic medications.

Topics: Adult; Antipsychotic Agents; Clozapine; Coffee; Fatigue; Female; Humans; Male; Middle Aged; Qualitative Research; Schizophrenia; Sleep Stages; Smoking

Clozapine, an atypical antipsychotic, depends mainly on cytochrome P4501A2 (CYP1A2) for its metabolic clearance. CYP1A2 is inducible by smoking, and lower plasma concentrations of clozapine are measured in smokers than in nonsmokers. Case reports have been published on the effects of discontinuing smoking in patients receiving clozapine, which might lead to elevated plasma concentrations and severe side effects. We present 2 cases on the consequences of smoking cessation in patients receiving this drug. In the first patient, smoking cessation resulted, within 2 weeks, in severe sedation and fatigue, with an approximately 3-fold increase of plasma clozapine concentrations. In the second patient, a very high plasma concentration of clozapine (3004 ng/mL) was measured 6 days following a 16-day stay in a general hospital, during which smoking was prohibited. In the latter patient, the replacement of omeprazole, a strong CYP1A2 inducer, by pantoprazole, a weaker CYP1A2 inducer, could have contributed, in addition to smoking cessation, to the observed strong increase of plasma clozapine concentrations. Genotyping of the 2 patients revealed that they were carriers of the AA genotype for the -164C>A polymorphism (CYP1A2*1F) in intron 1 of CYP1A2 gene, which has previously been shown to confer a high inducibility of CYP1A2 by smoking. Thus, at the initiation of clozapine treatment, smoking patients should be informed that, if they decide to stop smoking, they are encouraged to do so but must inform their prescriber beforehand. Also, because of the increased use of no-smoking policies in many hospitals, studies examining the consequences of such policies on the pharmacokinetics/pharmacodynamics of drugs metabolized by CYP1A2, taking into account different CYP1A2 genotypes, are needed.

Topics: Adult; Antipsychotic Agents; Clozapine; Cytochrome P-450 CYP1A2; Fatigue; Female; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Psychotic Disorders; Schizophrenia, Paranoid; Smoking Cessation; Treatment Outcome

Topics: Adult; Citalopram; Clozapine; Confusion; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Fatigue; Humans; Male; Psychotic Disorders; Sialorrhea; Sleep Wake 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