clozapine and Pancreatitis

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 the criterion standard in treatment-resistant schizophrenia. We sought to review data on several inflammatory effects associated with clozapine, specifically interstitial nephritis, hepatitis, and pancreatitis.. We conducted a systematic review to identify studies, published up until December 2017, describing clozapine-induced hepatitis, nephritis, and pancreatitis. The primary objective was to characterize the clinical characteristics associated with each of the specific inflammatory reactions to clozapine.. We identified 42 cases of inflammatory reactions associated with clozapine treatment- 20 :cases of clozapine-induced hepatitis, 11 cases of nephritis, and 11 of pancreatitis. The mean (SD) age was 38.8 (11.9) years. The mean (SD) dose of clozapine used was 252.4 (133.7) mg. Time to onset of pancreatitis (17.9 [11.2] days; range 4-35 days) was shorter than that for hepatitis (34.2 [20.1] days; range, 12-90 days) and nephritis (27.9 [27.0]; range, 8-90 days) but was not statistically significant (F = 2.267, P = 0.117). The mean (SD) time to recovery was shorter for cases of pancreatitis (15.7 [18.4] days) compared with cases of hepatitis (25.9 [16.5] days) and nephritis (24.5 [18.9] days). Three cases with hepatitis died. Seven of the cases had a clozapine rechallenge (hepatitis [n = 3], nephritis [n = 1], pancreatitis [n = 3]), with 5 having a recurrence at a mean (SD) onset of 3.5 (2.5) days (range, 1-7 days); 2 hepatitis cases were successfully rechallenged.. Clozapine-induced hepatitis, nephritis, and pancreatitis are uncommon adverse events, reflected in the paucity of case studies in the literature. Early recognition of the signs and symptoms of clozapine-associated hepatitis, nephritis, and pancreatitis is important, as when identified, clozapine should be urgently discontinued. Clozapine is associated with evidence of benign inflammatory processes; the extent to which hepatitis, and other inflammatory reactions, may be on a continuum with these more benign and self-limiting reactions is unclear, and this can only be resolved by prospectively following cohorts of clozapine-treated patients.

Topics: Antipsychotic Agents; Chemical and Drug Induced Liver Injury; Clozapine; Humans; Nephritis, Interstitial; Observational Studies as Topic; Pancreatitis; Treatment Outcome

Besides the well-known adverse effects of clozapine, such as granulocytopenia, tiredness and hypersalivation, acute pancreatitis is known to be a very rare complication of the drug. In the literature a total of five case reports have been published so far. We report a case of asymptomatic pancreatitis subsequent to clozapine treatment at therapeutic doses in a 38-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient was rehospitalized after an acute exacerbation of the psychosis subsequent to an attempt to change medication on an outpatient basis. Treatment with clozapine was initiated again. During phases of progressively increasing the clozapine dose, serum levels of amylase and lipase were increased; after maintaining daily doses of clozapine of 300 mg and/or 600 mg the pancreatic enzymes normalized quickly within a few days. The patient did not report any pancreas-related complaints, nor did specific diagnostic studies produce any indicative result, only a minor thickening of the head and body of the pancreas in the ultrasound. It is assumed that the phenomenon of subclinical, asymptomatic pancreatitis during increasing dosage of clozapine occurs more often than previously supposed. The monitoring of serum amylase levels during slow increase in clozapine is recommended; if leukocytosis or eosinophilia is present, the possibility of even a subclinical and asymptomatic pancreatitis should be considered.

Topics: Adult; Amylases; Antipsychotic Agents; Chronic Disease; Clozapine; Drug Monitoring; Hallucinations; Humans; Lipase; Male; Pancreatitis; Recurrence; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Clozapine; Humans; Neutropenia; Pancreatitis

Acute pancreatitis is a rare but recognised complication of clozapine leading to termination of treatment.. We present the case of a 39-year-old man with treatment-resistant schizoaffective disorder and a history of recurrent acute pancreatitis attributed to clozapine. After 15 years of unremitting symptoms with disruptive and aggressive behaviour, he was admitted for a clozapine rechallenge. Despite experiencing two further episodes of acute pancreatitis during clozapine treatment that led to its temporary withdrawal, clozapine was successfully re-established under gastroenterology consultation with close monitoring which resulted in progressively marked improvement of his mental state.. This case demonstrates that patients who develop pancreatitis during clozapine treatment may be cautiously rechallenged with specialist gastroenterology support.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pancreatitis; Psychotic Disorders

Definitive causality for medication-induced illnesses is difficult to determine, as often there are other causes for the condition. Additionally, for disease management there are often alternative treatment paths, and it is therefore clinically unnecessary to re-challenge with the suspected drug causing an adverse reaction; however, that was not the case in this clinical situation. Providers augmented treatment for this patient, but returned to the only therapy that controlled her condition, clozapine, as there appeared to be limited suitable alternatives. As outlined in this medical case, because the patient clinically responded only to clozapine, this forced providers to order multiple de-challenges and re-challenges resulting in confirmed drug-induced pancreatitis. Through courses of re-challenge, they were forced to find an effective dose and timing to maximize options for care using the drug despite inducing pancreatitis. At the time of this submission, providers had resumed a tolerated lower dose of clozapine without inducing pancreatitis. This case adds to the literature of drug-induced pancreatitis confirmation due to clozapine therapy being de-challenge and re-challenge.
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Topics: Antipsychotic Agents; Clozapine; Female; Humans; Pancreatitis

Topics: Acute Kidney Injury; Antimanic Agents; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Humans; Male; Middle Aged; Pancreatitis; Psychotic Disorders; Valproic Acid

Topics: Adolescent; Antipsychotic Agents; Clozapine; Disease Management; Humans; Male; Metformin; Pancreatitis; Schizophrenia; Weight Gain

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Pancreatitis; Schizophrenia; Seizures

Topics: Adult; Antipsychotic Agents; Clozapine; Cytochrome P-450 CYP1A2; Female; Genotype; Humans; Hyperglycemia; Pancreatitis; Schizophrenia, Paranoid

This report concerns the case of a 29-year-old male patient suffering from severe psychotic illness who had been satisfactorily treated with clozapine for 4 months. Clozapine had also been successfully administered during a psychotic episode 5 years previously. Though symptoms of psychosis were successfully controlled following the most recent psychotic episode, a medical consultation assessed that exacerbation of pancreatitis warranted discontinuation of the current antipsychotic treatment regime. Following a series of unsuccessful courses of neuroleptic medication, a magnetic resonance cholangiopancreaticography (MRCP) revealed marked cholecystolithiasis suggesting a biliary pancreatitis. Clozapine treatment was readministered following cholecystectomy. After 4 weeks of antipsychotic treatment the patient was discharged from hospital on clozapine monotherapy.

Topics: Adult; Antipsychotic Agents; Cholangiopancreatography, Magnetic Resonance; Cholecystectomy; Cholecystolithiasis; Clozapine; Humans; Male; Pancreatitis; Psychotic Disorders; Withholding Treatment

Topics: Adult; Amylases; Antipsychotic Agents; Blood Cell Count; Clozapine; Follow-Up Studies; Humans; Lipase; Male; Pancreatitis; Schizophrenia

Topics: Adolescent; Antipsychotic Agents; Clozapine; Humans; Male; Pancreatitis; Pericardial Effusion; Schizophrenia, Paranoid

Clozapine, the first atypical antipsychotic, is indicated for the treatment of therapy-resistant schizophrenia. It needs to be monitored closely because of its well-known potential side-effects, especially agranulocytosis. We present a case of a middle-aged woman with chronic schizophrenia, who was treated with clozapine and developed a clinical syndrome of asymptomatic pancreatitis and eosinophilia within the fifth week of treatment. Asymptomatic pancreatitis has rarely been reported up to now and is not recognized as a typical side-effect of clozapine. In our opinion, pancreatic enzymes should be monitored especially in the first 6 weeks of clozapine treatment.

Topics: Adult; Amylases; Antipsychotic Agents; Clozapine; Eosinophilia; Female; Humans; Pancreatitis; Pancrelipase; Schizophrenia

Topics: Clozapine; Female; Humans; Middle Aged; Pancreatitis; Suicide, Attempted

Topics: Adolescent; Clozapine; Eosinophilia; Female; Humans; Pancreatitis

Topics: Acute Disease; Adult; Clozapine; Humans; Male; Pancreatitis; Psychotic Disorders