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Hepatitis, Interstitial Nephritis, and Pancreatitis in Association With Clozapine Treatment: A Systematic Review of Case Series and Reports.

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journal contribution
posted on 22.11.2019 by John Lally, Hana Al Kalbani, Amir Krivoy, Kieran C. Murphy, Fiona Gaughran, James H MacCabe

PURPOSE/BACKGROUND: 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.

METHODS/PROCEDURES: 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.

FINDINGS/RESULTS: 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.

IMPLICATIONS/CONCLUSIONS: 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.

History

Comments

This is a non-final version of an article published in final form in Lally J, Al Kalbani H, Krivoy A, Murphy KC, Gaughran F, MacCabe JH. Hepatitis, Interstitial Nephritis,and Pancreatitis in Association With Clozapine Treatment: A Systematic Review of Case Series and Reports. Journal Clinical Psychopharmacology. 2018;38(5):520-527.

Published Citation

Lally J, Al Kalbani H, Krivoy A, Murphy KC, Gaughran F, MacCabe JH. Hepatitis, Interstitial Nephritis,and Pancreatitis in Association With Clozapine Treatment: A Systematic Review of Case Series and Reports. Journal Clinical Psychopharmacology. 2018;38(5):520-527.

Publication Date

27/07/2018

Publisher

Wolters Kluwer

PubMed ID

30059436

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