Treatment-Resistant Schizophrenia: Reasons for Clozapine Discontinuation

Clozapine Better for Comorbid Schizophrenia, Cannabis Use Disorder
Clozapine Better for Comorbid Schizophrenia, Cannabis Use Disorder
Researchers in Turkey found that discontinuation of clozapine is common in patients with schizophrenia due to too many adverse effects.

Adverse effects are the most common reason that patients with treatment-resistant schizophrenia discontinue clozapine, followed by discontinuation due to noncompliance and lack of efficacy, according to a study published in Psychiatry Research.

Clozapine is more effective than other antipsychotics for the treatment of schizophrenia, but it also has a high discontinuation rate. This retrospective chart-review study investigated the reasons for clozapine discontinuation among patients with treatment-resistant schizophrenia (defined as no response to treatment with at least 2 antipsychotics at adequate doses for 6 weeks) who were prescribed clozapine and who were being treated at 6 sites in Turkey (N=396). Data were collected on duration of illness, type and number of antipsychotics and doses, and demographic characteristics. The Kruskal–Wallis test was used to compare the groups of discontinuers, and the Mann–Whitney U test was used for post hoc analysis.

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Of the total 396 patients in the study, 240 were taking clozapine, and 156 had discontinued the drug. Comparing the clinical characteristics of these patients showed that those who discontinued treatment tended to be older, had a longer disease history, and had more hospitalizations before initiating clozapine. Inadequate response to clozapine was more common among those who discontinued medication compared with those who continued taking the medication. The most prevalent reason given for discontinuation was adverse effects at 49% (n=77), followed by patient or psychiatrist decision to discontinue due to noncompliance at 29.7% (n=46), followed by discontinuation by psychiatrist due to lack of efficacy at 21.3% (n=33). The 3 most common adverse effects leading to discontinuation were

  • leukopenia,
  • sedation, and
  • seizure/myoclonic jerks.

The patients discontinuing due to adverse effects were younger with a lower maximum dose and a shorter duration of use than other patients who discontinued the drug. Limitations of this study include its retrospective design, a lack of information on discontinuation reasoning, and potentially limited generalizability.

Researchers conclude, “Our findings point out the importance of enhancing psychiatrists’ ability to handle manageable … effects in order to minimize discontinuations and maximize the benefits of clozapine in patients with treatment-resistant schizophrenia. As a next step, we are planning to study the clinical course of patients after clozapine discontinuation and the predictors of rechallenge of clozapine in a larger group of patients with schizophrenia.”


Ucok A, Yağcıoğlu EA, Yıldız M, et al. Reasons for clozapine discontinuation in patients with treatment-resistant schizophrenia [published online March 19, 2019]. Psychiatry Res. doi: 10.1016/j.psychres.2019.01.110