The Association of Weight Gain and Olanzapine Plasma Concentrations

Abstract

Atypical antipsychotics, including olanzapine, have been associated with clinically significant weight gain in some patients. The purpose of this study was to determine if weight gain was associated with increasing plasma concentrations during olanzapine treatment in subjects with schizophrenia. This study included 39 acutely ill subjects with schizophrenia, schizoaffective disorder, or schizophreniform disorder (DSM-III-R or DSM-IV). Assessments included the Brief Psychiatric Rating Scale (BPRS), the Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a dose of 5 to 20 mg/d for 2 to 6 weeks. A 24-hour plasma concentration was obtained after 6 weeks of treatment. Analysis using a receiver operator characteristic curve identified a threshold dose-weighted plasma concentration of 20.6 ng/mL being associated with an increased likelihood of clinically significant weight gain (> or =7% baseline weight) during olanzapine treatment. The associations remained significant after adjusting for age, gender, baseline body mass index, baseline symptom severity, and symptom improvement (OR = 10.1; 95% CI, 1.3-75.0; P = 0.024). Similar analysis determined that a threshold olanzapine dose of 13.3 mg/d was associated with > or =7% weight gain. However, after adjusting for potential confounders, the results did not remain significant. The association of weight gain with plasma concentrations during treatment with olanzapine may support the utilization of plasma drug concentration as a marker for antipsychotic-induced weight gain in the treatment of schizophrenia.

Early Weight Gain as a Predictor of Substantial Weight Gain With Olanzapine/Fluoxetine Combination

“…For patients identified as most likely to experience adverse effect/s, the availability of such data may help clinicians tailor treatment options. Although some reports have suggested monitoring blood plasma concentrations of OLZ as a predictor of weight gain, 30 the calculated PPV and NPV in the present study are more clinically feasible measures because the modest PPV is greater than the proportion of patients who experienced SWG (29.1% vs 20.6%) and the NPV is greater than the proportion of patients who did not experience SWG (83.7% vs 79.4%). Monitoring weight and educating patients is less invasive than blood sampling, provides educational and health benefits to more patients, and follows National Institutes of Health weight management recommendations to the general public.…”

Antipsychotic drugs and diabetes—an application of the Austin Bradford Hill criteria

“…Moreover, the doses compared may not be the doses clinicians are most concerned about when treating patients on high doses, which commonly exceed 20 mg daily among persistently mentally ill patients [60]. When considering surrogate markers, one study has shown that the serum concentration of clozapine and the ratio of olanzapine to N-desmethylolanzapine, one of its metabolites, were correlated with insulin, C-peptide and triglycerides [61].…”

Influence of Topiramate on Olanzapine-Related Weight Gain in Women

“…1,2 Excess weight gain is associated not only with social stigma and a lower quality of life, it also has a great impact on somatic comorbidity. 3 Thus, the search for an effective method to counteract weight gain would be beneficial.…”