Predictors of Nonhospitalization and Functional Response in Clozapine Treatment: A Nationwide, Population-Based Cohort Study

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Clozapine remains the only evidence-based treatment for treatment-resistant schizophrenia, and prediction of clozapine response is important in developing stratified treatment. We studied potential predictors of clozapine response, applying functional assessments as well as service use.


We performed a nationwide cohort study among all individuals diagnosed with schizophrenia in Denmark after 1995 (age, ≥18 years) who initiated clozapine treatment between 2004 and 2011 with a Global Assessment of Functioning (GAF-F) score registered at clozapine initiation. During up to 2-year follow-up, clinical response was defined as (a) no further hospitalization with schizophrenia or (b) improvement in GAF-F score (moderate improvement: increase, ≥10; substantial improvement: increase, ≥20; and GAF-F, ≥50). We performed Cox regression analysis and report adjusted hazard rate ratios (HRRs; 95% confidence intervals [95% CIs]).


Among 502 clozapine users with a registered GAF-F score, 232 (46.2%) remained out of hospital, 96 (19.1%) achieved moderate functional improvement, and 29 (5.8%) substantial functional improvement. Of all potential predictors, voluntary status at clozapine initiation showed borderline statistical significance with nonhospitalization (HRR, 1.61; 95% CI, 0.97–2.67). Regarding functional improvement, living with a partner was the strongest predictor with an almost threefold increased HRR (2.78; 95% CI, 1.07–7.23). Female sex was only nonsignificantly associated with functional improvement, whereas the chance of substantial improvement decreased by 15% (HRR, 0.85; 95% CI, 0.72–1.00) for each year delay in clozapine initiation among females.


Living with a partner was the strongest predictor of functioning after clozapine initiation in this study. Although potentially indicating better premorbid functioning, this finding stresses the need and importance of social support during the course of the treatment independent of clinical factors.

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