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
