Dataset Information

Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission: The STOP-PD II Randomized Clinical Trial.

ABSTRACT:

Importance

Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission.

Objective

To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent.

Design, setting, and participants

Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017.

Interventions

Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline.

Main outcomes and measures

The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c).

Results

Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016).

Conclusions and relevance

Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain.

Trial registration

ClinicalTrials.gov Identifier: NCT01427608.

SUBMITTER: Flint AJ

PROVIDER: S-EPMC6704758 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder.The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome.This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders.

Project description:ObjectiveTo examine the effect of older versus younger age on change in anthropometric and metabolic measures during extended treatment of psychotic depression with sertraline plus olanzapine.MethodsTwo hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo. Weight, waist circumference and plasma lipids, glucose, HbA1c, and insulin were measured at regular intervals during the acute, stabilization and randomized phases of the study. Linear mixed models were used to analyze the trajectories of anthropometric and metabolic measures.ResultsParticipants aged 60 years or older experienced less weight gain and less increase in cholesterol during the combined acute and stabilization phases of the study compared with those aged 18-59 years. At the acute-stabilization termination visit, mean weight in older participants was 6.5 lb. less than premorbid weight, whereas it was 17.9 lb. more than premorbid weight in younger participants. In the RCT, there was a significant interaction of treatment and age group for the trajectory of weight, but the post hoc tests that compared age groups within each treatment arm were not statistically significant. There were no clinically significant differences between younger and older participants in glycemic measures.ConclusionOlder patients with psychotic depression experienced less increase in weight and total cholesterol than their younger counterparts during acute and stabilization treatment with sertraline plus olanzapine. In the older group, weight gained during the acute and stabilization phases appeared to be partial restoration of weight lost during the index episode of depression, whereas weight gain in younger participants was not.