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Correlates of Clozapine Use after a First Episode of Schizophrenia: Results From a Long-term Prospective Study

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Abstract

Background

Earlier commencement of clozapine has been related to a better response in treatment-resistant schizophrenia.

Objectives

To identify variables that predict clozapine use after a first episode of schizophrenia (FES).

Methods

Patients with FES and ≤15 days of lifetime antipsychotic treatment were followed up during naturalistic treatment, and the patients who were initiated on clozapine were compared with those receiving non-clozapine antipsychotics for ≥24 months regarding demographic and clinical baseline characteristics, adherence, and relapse patterns during follow-up. Treatment-resistant schizophrenia was defined as two or more antipsychotic trials of adequate dose for ≥6 weeks.

Results

Twenty-eight patients who used clozapine and 77 non-clozapine antipsychotic users were included. Clozapine was initiated after a mean of 2.5 ± 1.1 adequate antipsychotic trials. Eight of the 28 clozapine-treated patients (28.6 %) began their clozapine treatment during the first 12 months of follow-up (mean 7.1 ± 3.3 months) and their premorbid childhood adjustment was significantly worse than those who started clozapine later (mean 78.5 ± 43.0 months). Compared with non-clozapine users, patients who started clozapine had significantly more relapses in the first 6 months of follow-up prior to clozapine use (35.7 vs. 11.7 %, p = 0.005), and were significantly more likely to have a first relapse despite treatment adherence (38.1 vs. 73.3 %, p = 0.01). In the multivariate analyses, antipsychotic polypharmacy and first relapse despite adherence to antipsychotic treatment independently predicted subsequent clozapine use.

Conclusions

Clozapine use after a FES was predicted by a first relapse while being adherent to non-clozapine antipsychotics, especially if the first relapse occurred within the first 6 months. Developmental childhood difficulties predicted significantly earlier clozapine use.

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Authors and Affiliations

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Correspondence to Alp Üçok.

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Funding

This work was supported by the Scientific Research Projects Coordination Unit of Istanbul University (Project No. BYP-2016-20507).

Conflict of interest

Dr. Correll has been a consultant and/or advisor to or has received honoraria from: Alkermes, Forum, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, Medavante, Medscape, Otsuka, Pfizer, ProPhase, Sunovion, Supernus, Takeda, and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen, and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck and Pfizer. He received grant support from Takeda. Alp Üçok, Ugur Çıkrıkçılı, Ceylan Ergül, Öznur Tabak, Ada Salaj, and Sercan Karabulut declare that they have no conflict of interest related to this study.

Ethical approval

The study protocol was approved by the Istanbul Faculty of Medicine Ethical Committee. All procedures were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All patients gave written informed consent.

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Üçok, A., Çıkrıkçılı, U., Ergül, C. et al. Correlates of Clozapine Use after a First Episode of Schizophrenia: Results From a Long-term Prospective Study. CNS Drugs 30, 997–1006 (2016). https://doi.org/10.1007/s40263-016-0358-z

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