Associations among obesity, acute weight gain, and response to treatment with Olanzapine in adolescent schizophrenia

Objective: The purpose of this study was to investigate associations between body weight and illness characteristics, including weight gain and therapeutic efficacy, in adolescents with schizophrenia. Methods: Adolescents ages 13-17 years (n=107) with American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) schizophrenia enrolled in a 6 week, double-blind, placebo-controlled trial comparing olanzapine and placebo. Therapeutic response was assessed by the Brief Psychiatric Rating Scale for Children (BPRS-C). Secondary outcomes included the Clinical Global Impressions-Severity (CGI-S) scale and Positive and Negative Syndrome Scale (PANSS). Obesity was defined as sex-/age-adjusted body mass index (BMI)≥95th percentile. Linear regression was used to analyze the relationship between weight gain and psychiatric symptom improvement; logistic regression was conducted to identify predictors of baseline obesity. Results: Weight gain was significantly correlated with greater BPRS-C reduction among olanzapine-treated subjects (r=-0.31, p<0.01), whereas a trend was observed among placebo-treated subjects (r=-0.31, p=0.08). However, this relationship became nonsignificant when analyses were controlled for duration of olanzapine treatment (p=0.12), and a treatment by weight gain interaction did not emerge in a repeated-measures mixed model analysis that included time in the study (t=1.27, p=0.21). Additionally, weight gain ≥7% was not significantly associated with response or remission. Among 17 adolescents (16%) with obesity at study entry, obesity was not significantly associated with endpoint BPRS-C illness severity. However, girls (p=0.03), individuals hospitalized within the past year (p=0.02), and those with less severe overall (p=0.03) and negative symptoms (p=0.003) according to the CGI-S and PANSS negative subscale, respectively, were more likely to be obese at baseline. Conclusion: Baseline obesity was associated with lower illness severity, which could be mediated by greater treatment adherence, leading to more weight gain. Olanzapine-related weight gain was not independently associated with symptomatic outcome when controlling for treatment duration. Additional studies are needed to extend these findings to other disorders and medications.