Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Schizophrenia: Reinitiating clozapine can be considered in patients who have previously discontinued it

Key clinical point: Reinitiation of clozapine therapy is the most effective and safest therapeutic option for most patients who discontinue clozapine.

Major finding: Risk for psychiatric ward readmission was significantly lower for the use of clozapine (adjusted hazard ratio [aHR], 0.49), oral olanzapine (aHR, 0.58), and antipsychotic polypharmacy (aHR, 0.62) compared with nonuse of an antipsychotic (P less than .0001 for all). Risk for treatment failure was significantly lower for the use of aripiprazole long-acting injectable (aHR, 0.42) and reinitiation of clozapine (aHR, 0.49) and oral olanzapine (aHR, 0.69) vs nonuse of an antipsychotic (P less than .0001 for all). Risk for all-cause mortality was significantly lower for reinitiation of clozapine (aHR, 0.18), antipsychotic polypharmacy (aHR, 0.23), quetiapine (aHR, 0.24), and oral olanzapine (aHR, 0.26) vs nonuse of an antipsychotic (P less than .0001 for all).

Study details: The data come from the Finnish registry involving 2,250 patients with schizophrenia who had been using clozapine for at least 1 year before the cessation of treatment.

Disclosures: This study was funded by the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. Heidi Taipale received a grant from the Academy of Finland for the study. Jari Tiihonen, Heidi Taipale, and Antti Tanskanen participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their employing institution. Jari Tiihonen received personal fees/grants from various pharmaceutical companies and research institutions. The remaining authors reported no conflicts of interest.


Clozapine is unique among antipsychotic drugs for its efficacy in treatment resistant schizophrenia. In spite of this significant advantage, clozapine is challenging to use due to multiple potential adverse effects and that the fact that ongoing blood monitoring is required during the entire duration of treatment. This could help explain that fact that many individuals who start clozapine end up stopping treatment. This study investigated the comparative effectiveness of a broad range of antipsychotics in patients who, for any reason, terminated clozapine treatment. Clozapine and oral olanzapine were consistently associated with the best outcomes. Study findings appear to support the notion that clinicians should consider re-initiating clozapine therapy among their patients who have stopped drug as long as there are no significant and obvious safety contra-indications.”

Martha Sajatovic, MD

Professor of Psychiatry and of Neurology

Willard Brown Chair in Neurological Outcomes Research

Director, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center

Case Western Reserve University School of Medicine


Luykx JJ et al. Br J Psychiatry. 2020;217(3):498-505. doi: 10.1192/bjp.2019.267.