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Extended Olanzapine Treatment May Lower Risk of Psychotic-Depression Relapse

August 22, 2019

By Reuters Staff

NEW YORK—Extending olanzapine treatment beyond remission of psychotic-depression symptoms may lower relapse rates, according to findings from the STOP-PD II randomized clinical trial.

Patients with major depressive disorder who respond to antidepressant medication need continued treatment to prevent relapse and recurrence of the depression, researchers write in the August 20 issue of JAMA.

Whether antipsychotic medication needs to be continued once an episode of psychotic depression has responded to combined antidepressant-antipsychotic treatment remains unclear, add Dr. Alastair J. Flint of Toronto General Hospital, in Canada, and colleagues.

The team assessed the risks and benefits of continuing olanzapine in 126 patients with psychotic depression who responded to treatment with sertraline plus olanzapine in the STOP-PD trial.

Relapse, the primary outcome, was defined broadly, the researchers explain: "Declaring relapse required at least 1 of the following: (1) enough Structured Clinical Interview for the DSM(SCID)–rated symptomsto meet criteria for aDSM-IV major depressive episode; (2) 17-itemHDRS score of 18 or higher; (3) SCID-rated psychosis (delusions or hallucinations); or (4) other significant clinical worsening, defined as having a suicide plan or attempting suicide, developing SCID-rated symptoms of mania or hypomania, or being hospitalized in a psychiatric unit."

Relapse occurred in significantly fewer participants in the sertraline-olanzapine group than in the sertraline-placebo group (20.3% vs. 54.8%).

In multivariable analysis, the risk of relapse was 75% lower in the group that received extended olanzapine (P<0.001), which translates into a number needed to treat with sertraline plus olanzapine to prevent one relapse of 2.8.

Compared with placebo, olanzapine treatment led to significantly increased weight gain, waist circumference and total cholesterol. There were nearly twice as many patients reporting falls in the olanzapine group (31.3% vs. 17.7%), and reports of weight loss, sleepiness or sedation and orthostatic dizziness were more common with olanzapine continuation.

Akathisia developed in 4.7% of sertraline-olanzapine patients and 4.8% of sertraline-placebo patients, and the incidence of tardive dyskinesia was 0% and 3.2%, respectively.

Serious adverse event rates were similar in the sertraline-olanzapine group (18.8%) and in the sertraline-placebo group (19.4%).

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

"What is unclear is how much longer combined treatment offers substantially more protection than does monotherapy," writes Dr. William H. Coryell of the University of Iowa, in Iowa City, in a linked editorial. "Should combined treatment be prescribed indefinitely? As the authors note, the study to answer this question would require many more participants to achieve adequate power, and it is unlikely that such a study will ever be conducted."

"It seems likely then that judicious discontinuation of antipsychotic agents followed by close vigilance over the subsequent several months is likely to be an effective strategy," he concludes. "For those patients who tolerate antipsychotic medications well, longer periods taking combined treatment may be preferable."

Dr. Flint did not respond to a request for comments on this report.

Eli Lilly provided olanzapine and matching placebo, and Pfizer provided sertraline, but neither company provided funding for the study.


JAMA 2019.

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