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Pharmacopsychiatry 2022; 55(04): 181-192
DOI: 10.1055/a-1811-7318
Review

Clinical Outcomes after Clozapine Discontinuation in Patients with Schizophrenia: A Systematic Review

Gentaro Miura
1   Oizumi Hospital, Tokyo, Japan
,
Kouhei Tanaka
2   Yamanashi Prefectural Kita Hospital, Yamanashi, Japan
,
Takashi Kemuriyama
3   Asaka Hospital, Fukushima, Japan
,
Fuminari Misawa
2   Yamanashi Prefectural Kita Hospital, Yamanashi, Japan
,
Hiroyuki Uchida
4   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
,
Masaru Mimura
4   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
,
Hiroyoshi Takeuchi
4   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
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Abstract

Introduction Clozapine is the gold standard of treatment for patients with treatment-resistant schizophrenia. However, approximately 60% of those patients do not respond to clozapine; moreover, clinical outcomes after clozapine discontinuation are unclear so far. Therefore, we conducted a systematic review to clarify the outcomes after clozapine discontinuation.

Methods A systematic literature search was conducted, using MEDLINE and Embase with the following keywords: (clozapine AND (cessation* OR cease* OR withdraw* OR discontinu* OR halt* OR stop* OR switch*) AND (schizophreni* OR schizoaffective)).

Results A total of 28 clinical studies from 27 articles were identified and included in this systematic review. Three randomized controlled trials reported worsening of psychiatric symptoms. In 10 single-arm studies, the results of worsening and improving psychiatric symptoms were inconsistent. In one large retrospective cohort study, clozapine rechallenge, olanzapine, and antipsychotic polypharmacy had lower rehospitalization rates compared to no medication after clozapine discontinuation. In the other 14 retrospective studies, the vast majority showed worsening of clinical status after clozapine discontinuation. Among five studies on clinical outcomes after clozapine rechallenge, four reported improvements in clinical status in more than half of patients who rechallenged clozapine. The remaining study reported that the clozapine discontinuation-rechallenge group had a worse remission assessment score than the clozapine discontinuation-no rechallenge group.

Discussion Clinical outcomes generally worsen after clozapine discontinuation. Clozapine rechallenge and olanzapine may be considered following clozapine discontinuation. The outcomes after clozapine discontinuation in clozapine non-responders remain inconclusive; therefore, well-designed studies are warranted.

Key words

cessation - clozapine - discontinuation - schizophrenia - treatment-resistant schizophrenia


Publication History

Received: 24 January 2022
Received: 12 March 2022

Accepted: 14 March 2022

Article published online:
05 May 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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