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. 2020 Sep;217(3):498-505.
doi: 10.1192/bjp.2019.267.

In the aftermath of clozapine discontinuation: comparative effectiveness and safety of antipsychotics in patients with schizophrenia who discontinue clozapine

Jurjen J Luykx  1 , Noraly Stam  2 , Antti Tanskanen  3 , Jari Tiihonen  4 , Heidi Taipale  5
Affiliations

In the aftermath of clozapine discontinuation: comparative effectiveness and safety of antipsychotics in patients with schizophrenia who discontinue clozapine

Jurjen J Luykx et al. Br J Psychiatry. 2020 Sep.

Abstract

Background: Although clozapine is often discontinued, there is a paucity of guidelines and evidence on treatment options after clozapine discontinuation. Moreover, it is currently unknown whether reinstating clozapine in patients formerly using clozapine should be avoided.

Aims: To compare the real-world effectiveness of antipsychotics after clozapine cessation.

Method: From Finnish registry data (1995-2017), we identified 2250 patients with schizophrenia who had been using clozapine for ≥1 year before treatment cessation. The primary analysis consisted of adjusted within-individual analyses of psychiatric ward readmission owing to psychosis and treatment failure. Secondary analyses concerned between-individual mortality differences.

Results: Compared with no use of antipsychotics, risk of psychiatric ward readmission was lowest for reinitiation of clozapine (adjusted hazard ratio (aHR) 0.49; 95% CI 0.40-0.61; P < 0.0001), oral olanzapine (aHR 0.58; 95% CI 0.48-0.71; P < 0.0001) and antipsychotic polypharmacy (aHR 0.62; 95% CI 0.53-0.72; P < 0.0001). Risk of treatment failure was lowest for aripiprazole long acting injectable (aHR 0.42; 95% CI 0.27-0.65; P < 0.0001), reinitiation of clozapine (aHR 0.49; 95% CI 0.43-0.57; P < 0.0001) and oral olanzapine (aHR 0.69; 95% CI 0.61-0.77; P < 0.0001). Mortality risk was lowest for reinitiation of clozapine (aHR 0.18; 95% CI 0.09-0.36; P < 0.0001) and oral olanzapine (aHR 0.26; 95% CI 0.17-0.40; P < 0.0001).

Conclusions: Clozapine and olanzapine are the most effective and safest treatment options in those discontinuing clozapine for undefined reasons. Clozapine should therefore be reconsidered in patients with schizophrenia who previously discontinued this compound.

Keywords: Schizophrenia; antipsychotics; clozapine; discontinuation; psychiatric ward readmission.

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Conflict of interest statement

Declaration of interest: J.T., H.T. and A.T. have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their employing institution. J.T. reports personal fees from the Finnish Medicines Agency (Fimea), European Medicines Agency, Eli Lilly, Janssen-Cilag, Lundbeck and Otsuka; is a member of advisory board for Lundbeck and has received grants from the Stanley Foundation and Sigrid Jusélius Foundation. The other authors report no conflict of interest.

Figures

Fig. 1
Fig. 1
Risk of psychiatric ward readmission for use of antipsychotics compared with non-use of antipsychotics after clozapine discontinuation, within-individual model.
Fig. 2
Fig. 2
Risk of treatment failure for use of antipsychotics compared with non-use of antipsychotics after clozapine discontinuation, within-individual model.
Fig. 3
Fig. 3
Risk of all-cause mortality for use of antipsychotics compared with non-use of antipsychotics after clozapine discontinuation, between-individual model.
See this image and copyright information in PMC

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