Objective: The purpose of these analyses was to compare the weight and other metabolic changes between adolescents and adults during long-term (at least 24 weeks) olanzapine treatment.
Method: The adult database included 86 studies with 12,425 patients with schizophrenia, schizoaffective disorder, depression, borderline personality disorder, or bipolar I disorder; the adolescent database comprised six studies with 489 patients with schizophrenia, schizoaffective disorder, borderline personality disorder, bipolar I disorder, or prodromal psychosis. Patients who had at least 24 weeks of olanzapine exposure (N=4,280 from adult database and N=179 from adolescent database) were analyzed in this study. Weight data were collected for all patients, fasting glucose and lipids data were collected in some patients. For weight gain, data in 34.5% adults (4,280/12,425) and 36.6% adolescents (179/489) were analyzed while for glucose and lipids, data in 8.4% (1,038/12,425) adults and 24.9% adolescents (122/489) were analyzed. Adult patients were treated with oral (5-20 mg/day) or depot formulations (doses equivalent to oral doses of 5-20 mg/day) of olanzapine and adolescent patients were treated with oral olanzapine (2.5-20 mg/day). The incidences of potentially clinically significant categorical changes in weight and metabolic parameters were calculated with a 95% confidence interval (CI). Nonoverlapping 95% CIs were considered as indicating a statistically significant difference. Weight, lipid, and glucose change comparisons are summarized.
Results: The mean age for adolescents and adults was 15.8 and 38.8, respectively. The percentage of the male population was similar for both adults (58.5%) and adolescents (62.8%). The median duration of the follow-up period was 201 days for adolescent database and 280 days for adult database. The mean weight gain from baseline to endpoint in adolescents was 11.24 kg when compared with 4.81 kg in adults. The 95% CI for adolescents (10.1, 12.4) and adults (4.57, 5.04) are not overlapping, which indicates that the difference between adolescents and adults is statistically significant. The percentage of olanzapine-treated adolescents with ≥ 7% mean weight gain was 89.4% compared with 55.4% in adults (Number need to harm [NNH]=3). Mean changes from baseline to endpoint were also greater for adolescents than for adults in fasting total cholesterol (5.49 mg/dL vs. 2.06 mg/dL), LDL (5.41 mg/dL vs. 0.49 mg/dL), and triglycerides (20.49 mg/dL vs. 16.72 mg/dL), but overlapping 95% CIs were observed for all lipid parameters. Mean changes from baseline to endpoint in fasting glucose values were similar between adolescents and adults (3.13 mg/dL vs. 3.95 mg/dL). However, the incidence of treatment-emergent significant glucose changes was greater in adults. Among olanzapine-treated adults and adolescents, 8.9% and 0.9% experienced a shift from normal to high and 12.5% and 3.3% experienced a shift from normal/impaired glucose tolerance (IGT) to high fasting glucose, respectively. The incidence of IGT to high elevations in glucose was greater in adolescents, but overlapping 95% CI was observed.
Conclusions: The types of metabolic changes during the long-term olanzapine treatment in adolescents were similar to those observed in adults. However, the magnitude of changes in weight and lipid parameters was greater in adolescents. Patients should receive regular monitoring of weight, fasting blood glucose, and lipid profile at the beginning of, and periodically during, treatment with olanzapine.