A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD)

Randomized Controlled Trial

Barnett S Meyers et al. Arch Gen Psychiatry. 2009 Aug.

Erratum in

Arch Gen Psychiatry. 2011 Jun;68(6):626

Abstract

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 > 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 (chi(2)(1) = 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.

Trial registration: clinicaltrials.gov Identifier: NCT00056472.

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Figures

Figure 1

CONSORT CHART

Figure 2

Remission Rates in the ITT sample of 259 Subjects Randomized To Olanzapine Plus Placebo Versus Olanzapine Plus Sertraline At Each Assessment *Statistically significant using the Hochberg alpha-level adjustments with a two-sided family-wise alpha level = 0.05 from chi-square analysis.

Figure 3

Ham-D Scores during the Trial in Olanzapine plus Placebo versus Olanzapine plus Sertraline Subjects Overall treatment effect: F(1,1722)=14.32, p<.001 *Statistically significant using the Hochberg alpha-level adjustments with a two-sided family-wise alpha level = 0.05 from post-hoc t-tests.

Figure 4

Metabolic Values at Baseline and Week 12 or Termination in Young Adult and Older Subjects *Glucose: Young Time Effect: t=2.76, df=205, p=.006 *Triglycerides: Old Time Effect: t=2.88. df=201, p=.004; Young Time Effect: t=3.73, df=201, p<.001. Statistics performed after log transformation due to non-normality. *Cholesterol: Old Time Effect: t=3.73, df=205, p=.002; Young Time Effect: t=4.58, df=205, p<.001 *Weight: Old Time Effect: t=7.28, df=221, p<.001; Young Time Effect: t=10.98, df=221,p<.001; Statistics performed after log transformation due to non-normality. +Interaction between time and age group: F=11.1, df=1,221, p=.001

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