Obesity Associated With Symptomatic Remission in Clozapine-Treated Individuals With Treatment Resistant Schizophrenia

Background Clozapine, indicated for use in treatment resistant schizophrenia (TRS), comes with notable weight gain and metabolic side effects. Prior studies have suggested a link between weight gain and antipsychotic efficacy in schizophrenia. Aims & Objectives In this study, we seek to explore the relationship between obesity and clinical outcome in TRS on clozapine treatment. The study extends the investigation of obesity to include other measures of metabolic health. Method The data used in this study was collected from a cross-sectional study conducted at the Institute of Mental Health investigating clinical outcomes in patients on clozapine. Participants enrolled were diagnosed with schizophrenia or schizoaffective disorder and were between ages 21 to 80. They had to have been on clozapine for at least 12 weeks and maintained stable medication doses for at least 2 weeks before enrolment. Data was collected through a research interview and review of medical records. Symptoms were assessed on the Positive and Negative Syndrome Scale. Anthropometric measures including weight, height, waist circumference and blood pressure were measured during the visit. A blood sample for lipids and glucose was obtained after an 8-hour fast. Univariate regression analysis was used to identify significant factors amongst BMI and components of metabolic syndrome associated with remission status, which were further studied in a multiple logistic regression analysis. Results: Univariate and multiple logistic regression on remission status Out of 159 patients enrolled, 154 patients were included in the final analysis as five were missing data for PANSS and/or metabolic syndrome. 37 patients (24.0%) achieved symptomatic remission (see Table 1). The remitter group had significantly higher BMI as compared to the non-remitter group (26.6 kg/m2 vs 24.2 kg/m2, p = 0.007). Univariate analyses identified BMI, waist circumference and blood pressure as possible metabolic factors associated with remission. In the multivariate model, BMI was the only statistically significant predictor of remission status (OR = 1.147, p-value = 0.020). Discussion & Conclusions Our study found that obesity was associated with remission in TRS patients on clozapine. This lends support to existing evidence proposing a metabolic threshold for clozapine. Further investigations are needed to study the mechanisms underpinning weight gain and clozapine efficacy.