Weight gain has often been associated with olanzapine treatment, yet little is known about the influence of patient age or cumulative dose on olanzapine-associated weight gain. The first 118 participants in the National Institutes of Mental Health Study of the Pharmacotherapy of Psychotic Depression randomized clinical trial (ClinicalTrials.gov Registration NCT00056472) completing at least 4 weeks of treatment with olanzapine were analyzed to determine the relationship between weight gain, age, and cumulative olanzapine dose. Younger (age 18-59 years) and older (age 60+ years) participants received open-label olanzapine and either sertraline or placebo for up to 12 weeks. Linear mixed effect regression modeling was used to determine the effects of age and cumulative olanzapine dose on weight gain, controlling for potential confounders. Age was observed to have a significant negative association with weight gain (P=0.01), even after controlling for differences in cumulative dose and baseline body mass index. Each 10-year increase in age was associated with a decrease in mean weight gain over 12 weeks of approximately 0.6 kg (95% confidence interval: 0.14-1.05 kg). Cumulative olanzapine dose was also significantly associated with weight gain (P<0.0001). Approximately 60% of completers of the 12-week trial experienced clinically significant weight gain (> or =7% of baseline weight).

OBJECTIVE: Practice guidelines recommend the use of a combination of an antidepressant and an antipsychotic for the pharmacologic treatment of major depressive disorder with psychotic features (MD-Psy). We assessed the extent to which the pharmacotherapy received by patients with MD-Psy under usual care conforms to these recommendations. METHOD: We assessed the pharmacotherapy received under usual care conditions by 100 patients with MD-Psy prior to enrollment in STOP-PD (Study of the Pharmacotherapy of Psychotic Depression), a 12-week randomized, controlled trial comparing olanzapine plus sertraline to olanzapine plus placebo. Our assessment took place from January 2003 to May 2004. The strength of antidepressant trials was rated using the Antidepressant Treatment History Form (ATHF). The strength of antipsychotic trials or combinations of antidepressants and antipsychotics was rated using a modified version of the ATHF. We also determined whether the strength of antipsychotic or combination trials was associated with age, the duration of the current depressive episode, medical burden, cognitive status, or the severity of depressive or psychotic symptoms. RESULTS: Most patients with MD-Psy were treated with antidepressants (N = 82, 82%) or antipsychotics (N = 65, 65%). About half of the patients (N = 48, 48%) received therapeutic doses of an antidepressant; 10% (N = 10) received an intermediate dose of an antipsychotic, and 6% (N = 6) received a high dose. Overall, only 5% (N = 5) received a combination of an adequate dose of an antidepressant and a high dose of an antipsychotic. The strength of both antipsychotic trials (p = .021) and combination trials (p = .039) was significantly associated only with a longer duration of the current depressive episode. CONCLUSIONS: These findings show a persisting low use of antipsychotics in the treatment of MD-Psy. Given the high morbidity rates associated with MD-Psy, it is important to continue to educate clinicians regarding its identification and treatment. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00056472.