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

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.

Delayed initiation of clozapine may be related to poor response in treatment-resistant schizophrenia.

The aim of this retrospective chart-review study was to investigate the relationship between delayed commencement of clozapine and the level of response in treatment-resistant schizophrenia (TRS). We included 162 patients with schizophrenia who used clozapine. The mean delay until starting clozapine after fulfillment of the TRS criteria was 29 months. The delay was shorter in those who gained benefit from clozapine (P=0.04), those who were treated in a specialized psychosis outpatient unit (P=0.01), and in men (P=0.009), and it correlated with age (P<0.001). The delay in starting clozapine and the maximum clozapine dose were independent contributors toward the response to clozapine in the logistic regression analysis. Moreover, of those who gained considerable benefit from clozapine, the patients were younger (P=0.01), the duration of illness before clozapine treatment was shorter (P=0.001), and the numbers of adequate antipsychotic trials before the use of clozapine were fewer (P=0.05). Our findings suggest that efforts aimed at reducing the delay for starting clozapine may increase the effectiveness of clozapine in TRS.

Sex hormones and metabolic syndrome in children and adolescents.

Cardiovascular risk starts early in life, yet the patterns of changes in metabolic syndrome (MS) during puberty and normal development have not been completely defined. Sex hormones are shown to play a pivotal role in the modulation of insulin resistance and MS. Our aim is to clarify the relation between sex hormones and MS in normal children and adolescents. This is a cross-sectional study of 365 (8-12 and 14-18 years old) school students. We analyzed the associations of sex hormones (testosterone, free androgen index, estradiol, free estradiol index [FEI], and sex hormone-binding globulin [SHBG]) with cardiovascular risk factors and MS. Prevalence of MS varied depending on the definition, and 33 (9%) students had MS based on at least 1 definition of MS. Frequency of MS doubled among 14- to 18-year-old adolescents compared with 8- to 12-year-old children (12.4% vs 5.6%, P = .02). Adolescent boys and girls with MS had significantly lower SHBG levels compared with controls. Adolescent boys with MS also had significantly higher FEI levels compared with controls. Logistic regression analysis was performed to find the predictors of MS. Among covariates of age, estradiol, testosterone, free androgen index, and FEI, SHBG was the only significant predictor of MS (B = -0.3, odds ratio = 0.8, 95% confidence interval for odds ratio are 0.64 and 0.92, P = .005, Nagelkarke R(2) = 0.48) in adolescent boys. In conclusion, sex hormone levels and androgen/estrogen balance may play an important role in determining MS and future cardiovascular risk among children and adolescents.