Associations Among Obesity, Acute Weight Gain, and Response to Treatment with Olanzapine in Adolescent Schizophrenia

Abstract

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. 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. 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. 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.