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Background: 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., Procedures: 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])., Results: 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., Conclusions: 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.

Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

Background: Cardiovascular (CV) co-morbidity is one of the major modifiable risk factors driving the excess mortality in individuals with schizophrenia or bipolar disorder. Population-based studies in this area are sparse., Method: We used Danish population registers to calculate incidence rate ratios (IRRs) for CV drug use, and mortality rate ratios comparing subjects with schizophrenia or bipolar disorder with subjects with no prior psychiatric hospitalization., Results: IRRs for CV prescriptions were significantly decreased in patients with schizophrenia or bipolar disorder compared with the general population. Among persons without previous myocardial infarction (MI) or cerebrovascular disease, persons with schizophrenia or bipolar disorder had an up to 6- and 15-fold increased mortality from all causes or unnatural causes, respectively, compared with the general population, being most pronounced among those without CV treatment (16-fold increase). Among those with previous MI or cerebrovascular disease, excess all-cause and unnatural death was lower (up to 3-fold and 7-fold increased, respectively), but was similar in CV-treated and -untreated persons., Conclusions: The present study shows an apparent under-prescription of most CV drugs among patients with schizophrenia or bipolar disorder compared with the general population in Denmark. The excess of mortality by unnatural deaths in the untreated group suggests that the association between CV treatment and mortality may be confounded by severity of illness. However, our results also suggest that treatment of CV risk factors is neglected in these patients.