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Olanzapine may benefit patients with psychotic depression in remission

Continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk for relapse over 36 weeks among adults with psychotic depression in remission, study findings published in JAMA showed.

“Once an episode of major depression responds to antidepressant medication, the antidepressant needs to be continued to prevent relapse and recurrence of depression,” Alastair J. Flint, MB, of Toronto General Hospital, and colleagues wrote. “However, it is not known whether antipsychotic medication needs to be continued once an episode of psychotic depression has responded to combined antidepressant-antipsychotic treatment.”

Researchers reported the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination antidepressant and antipsychotic treatment in a 36-week randomized clinical trial (the STOP-PD II trial).

Participants who experienced an episode of psychotic depression were included if they received treatment 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 prior to beginning the clinical trial. Flint and colleagues randomly allocated adult participants to either continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62) while still taking sertraline to determine the risk of relapse as well as change in weight, waist circumference, lipids, serum glucose and hemoglobin A1c (HbA_1c).

The median dosage of sertraline was 15 mg per day, and the median olanzapine dose was 15 mg per day.

Of 114 participants with psychotic depression in remission who completed the trial, 13 randomized to olanzapine (20.3%) and 34 randomized to placebo (54.8%) relapsed (HR = 0.25; 95% CI, 0.13-0.48).

Flint and colleagues also reported a higher daily rate of anthropometric and metabolic measures in the olanzapine group than in the placebo group for weight (0.13 lb; 95% CI, 0.11-0.15), waist circumference (0.009 inches; 95% CI, 0.004-0.014) and total cholesterol (0.29 mg/dL; 95% CI, 0.13-0.45), but not for LDL or HDL cholesterol, triglyceride, glucose or HbA_1c levels.

The results showed that six of 13 participants who relapsed in the olanzapine group and 11 of 34 who relapsed in the placebo group required psychiatric hospitalization due to the relapse.

“As hypothesized, continuation of olanzapine was more effective than placebo in reducing relapse, with a number needed to treat of 2.8,” the investigators wrote. “This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain.”

Based on these results, William H. Coryell, MD, from the department of psychiatry, University of Iowa, suggested in a related editorial that no changes should be made during the first 4 months after relapse in patients with psychotic depression who have responded to combination treatment

“It may be that the need for continuation of adjunctive antipsychotic agents in this population becomes apparent much earlier than does the need for antidepressant continuation in depressive disorder generally,” he wrote. “This observation, together with evidence that the resumption of antipsychotic agents for patients with schizophrenia in medication discontinuation trials is followed by a rapid improvement in symptoms suggests a strategy in which an antipsychotic agent is gradually tapered with close monitoring and reintroduced at the first definite sign of relapse, including any signs of suicidal ideation.” – by Savannah Demko

Disclosures: The authors report numerous relevant financial disclosures, please see the full study. Coryell reports no relevant financial disclosures.