Journal
ARCHIVES OF GENERAL PSYCHIATRY
Volume 66, Issue 8, Pages 838-847Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/archgenpsychiatry.2009.79
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Funding
- US Public Health Service [MH 62446, MH 62518, MH 62565, MH 62624]
- National Institute of Mental Health [MH069430, MH067710, P30 MH068368]
- National Center for Research Resources [M01- RR024153, RR000056, CTSC UL1RR024996]
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Context: Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features. Objectives: To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age. Design: Twelve-week, double-blind, randomized, controlled trial. Setting: Clinical services of 4 academic sites. Patients: Two hundred fifty-nine subjects with MD with psychotic features randomized by age (< 60 or >= 60 years) (mean [standard deviation (SD)], 41.3 [10.8] years in 117 younger adults vs 71.7 [7.8] years in 142 geriatric participants). Intervention: Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day. Main Outcome Measure: Remission rates of MD with psychotic features. Results: Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47; P < .001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy (X-1(2) = 9.53, P =.002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P=.02) and older (OR, 1.34; 95% CI, 1.09-1.66; P=.01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean [SD], 6.5 [6.6] kg vs 3.3 [4.9] kg, P=.001). Conclusions: Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features. Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks.
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