clozapine and Lupus-Erythematosus--Systemic

To identify the clinical determinants of fever in clozapine users and their impact on management of clozapine treatment.. Articles published in English or French identified with a MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search, from inception through February 2019, using the term "clozapine" in combination with "fever" OR "hyperthermia" OR "body temperature" OR "pyrexia" OR "febrile" OR "heat" OR "thermoregulation". Information extracted for each medical condition were frequency, time to onset after initiation of clozapine treatment, characteristics of fever, associated symptoms, laboratory tests used for diagnosis, course, lethality, discontinuation of clozapine. Data were synthesized narratively.. Our search yielded 394 unique hits published from 1993 to 2018. We included 73 articles in the review: two meta-analyses, 14 reviews, six epidemiological studies, 11 clinical studies and 40 case reports. During clozapine initiation, fever is most frequently benign and transient but should be closely monitored as it may be the first stage of potentially life-threatening adverse drug reactions (ADR) (agranulocytosis, neuroleptic malignant syndrome myocarditis, hepatitis, pancreatitis, nephritis, colitis, etc.). Other ADR associated with fever are independent of duration of exposure to clozapine (heat stroke, pneumonia, pulmonary embolism, necrotizing colitis). If fever is due to intercurrent infection, therapeutic drug monitoring is recommended to adjust clozapine daily dosage.. Benign causes of fever are much more frequent than life-threatening ADR during clozapine treatment. Discontinuation should not be considered as automatic in the event of fever, especially during the early phase of clozapine initiation.

Topics: Agranulocytosis; Antipsychotic Agents; Chemical and Drug Induced Liver Injury; Clozapine; Colitis; Dose-Response Relationship, Drug; Drug Monitoring; Fever; Hepatitis; Humans; Infections; Lupus Erythematosus, Systemic; Myocarditis; Nephritis; Neuroleptic Malignant Syndrome; Pancreatitis; Pneumonia; Pulmonary Embolism; Schizophrenia; Serositis

Clozapine is widely prescribed for treatment refractory patients with schizophrenia, but its use is limited by potentially life threatening adverse effects. Rechallenge after these complications has been occasionally attempted in patients with severe psychotic symptoms.. To review the outcome of clozapine rechallenge after potentially life threatening adverse effects.. Electronic, all-language, literature search (1972-2011) followed by demographic and clinical data extraction. The outcome of rechallenge was considered favorable when the lower bound of the 95% confidence interval (CI) of the proportion of patients who could continue clozapine was >50%.. Altogether, 138 patients (mean age: 36.3years, 65.7% male, 57.6% Caucasian, virtually all with schizophrenia spectrum diagnosis) underwent clozapine rechallenge after developing neutropenia (n=112), agranulocytosis (n=15), neuroleptic malignant syndrome (NMS) (n=5), myocarditis (n=4), pericarditis (n=1) and lupus erythematosus (n=1). Rechallenge strategies were heterogeneous and not systematically evaluated. Clozapine rechallenge was successful in 78/112 patients (69.6%, CI: 60.6-77.4) after neutropenia, 3/15 (20%, CI: 7.1-45.2) after agranulocytosis, 5/5 (100%, CI: 56-100) after NMS, 3/4 (75%, CI: 30-95) after myocarditis, 1/1 after pericarditis, and 0/1 after clozapine-induced lupus. Successfully rechallenged patients were followed for 16-96weeks. None of the rechallenged patients died.. Although controlled studies are clearly needed, using a priori, confidence interval-based criteria, case reports/series suggest that in refractory patients who benefited from clozapine, careful rechallenge can be considered after neutropenia and NMS, but not after agranulocytosis and myocarditis.

Topics: Adult; Antipsychotic Agents; Clozapine; Databases, Bibliographic; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Myocarditis; Neuroleptic Malignant Syndrome; Neutropenia; Young Adult

Clozapine is the most effective treatment for patients with refractory schizophrenia. Clozapine is also associated with serious and potentially lethal side effects including drug induced lupus (DIL). There have been four previous published case reports describing clozapine inducing a lupus-like syndrome including one previous case where a clozapine rechallenge was attempted without success. This case report describes a successful clozapine rechallenge in a patient with suspected DIL.

Topics: Antipsychotic Agents; Clozapine; Humans; Lupus Erythematosus, Systemic; Schizophrenia

To report a case of classic clozapine-induced systemic lupus erythematosus that also developed on rechallenge.. A 32-year-old white woman diagnosed with schizophrenia presented in 1996 with clinical characteristics and laboratory markers consistent with drug-induced lupus (DIL). Clozapine, started 1 year prior, was withdrawn, with complete biological and clinical remission within 3 months. In 2004, 1 week after rechallenge with clozapine for uncontrolled schizophrenia, the patient developed clinical and biological signs and symptoms consistent with the diagnosis of DIL. Again, discontinuation of clozapine was followed by full remission within 2-3 months.. DIL was first described more than 50 years ago, with multiple drugs implicated in the causation. Clozapine-induced lupus was reported recently, but does not meet the usual criteria for a diagnosis of DIL. We report a classic case of clozapine-induced lupus that, according to the Naranjo probability scale, demonstrates a highly probable relationship between DIL and clozapine.. DIL demands a high index of suspicion for diagnosis. Although clozapine has an extensive safety profile, DIL must be considered as one of its serious adverse effects.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Lupus Erythematosus, Systemic; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Schizophrenia, Paranoid

Topics: Adult; Clozapine; Drug Eruptions; Humans; Lupus Erythematosus, Systemic; Male; Schizophrenia, Paranoid