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February 2010

Second-Generation Antipsychotics: New Information
Second-generation antipsychotics differ from each other, offering options for patients.

Cognitive Effects of Antipsychotic Drugs: Are All Created Equal?
First- and second-generation antipsychotics appear comparable in their ability to lessen cognitive dysfunction associated with schizophrenia.

In Brief
Long-acting Injectable Olanzapine Approved in US; High-potency Cannabis May Increase Risk of Psychosis

Olanzapine and Sertraline Combined for Psychotic Depression
In a short-term trial, sertraline (Zoloft and others) combined with olanzapine (Zyprexa) was more efficacious than olanzapine plus placebo for psychotic depression in both young and elderly patients.

Olanzapine and Sertraline Combined for Psychotic Depression

February 2010

Between 15% and 20% of patients with major depression may have psychotic features; in elderly depressed patients, the estimate climbs to almost 50%!1 When psychosis accompanies major depression, patients often take longer to recover from acute episodes and have worse short-term outcomes, greater residual disability, and increased mortality compared to depressed patients without psychosis. The most commonly recommended treatments for psychotic depression are electroconvulsive therapy (ECT) or antipsychotic and antidepressant medications combined. Most studies of the medication combination have used tricyclic antidepressants. In the elderly, the efficacy of combining antidepressants and antipsychotics has not been established, and the combined therapy appears to be more poorly tolerated than antidepressants alone.

With funding from the National Institutes of Health, Meyers and collaborators conducted a 12-week, double-blind, randomized, controlled trial of newer medications in patients with psychotic depression.1 Two hundred fifty-nine patients with major depression with psychotic features were enrolled at four academic centers. All patients received olanzapine (Zyprexa), with targeted doses between 15 and 20 mg/day. They were randomly assigned to receive either placebo or sertraline (Zoloft and others), 150 to 200 mg/day, concomitantly. At the end of the study, patients were taking an average of over 14 mg of olanzapine and almost 170 mg of sertraline daily.

The antipsychotic-antidepressant treatment was associated with higher remission rates during the trial than antipsychotic plus placebo and showed superior efficacy between weeks 8 and 12. Of 129 participants who received olanzapine plus sertraline, 54 (41.9%) were in remission at their last assessment. By contrast, only 31 (23.9%) of 130 patients taking olanzapine monotherapy achieved remission. Contrary to the authors’ hypothesis, the combination therapy was as statistically superior to olanzapine plus placebo in patients over age 60 as it was in younger adults. Moreover, the treatments’ tolerability was relatively similar across age groups.

All subjects in this trial took olanzapine, and both younger and older patients had significant increases in cholesterol and triglyceride concentrations. Glucose, however, increased only in younger adults. Older patients had a greater frequency of pedal edema but were no more likely than younger patients to experience falls or sedation/somnolence or to have more extrapyramidal symptoms. Younger patients tended to gain more weight with olanzapine than older patients. Overall attrition was significantly (P = .01) greater in the olanzapine-placebo group than in the olanzapine-sertraline group.

Metabolic effects and weight gain are well-known side effects of olanzapine. Presumably, these particular reactions would be lower with other antipsychotics, but the efficacy and overall safety of other antipsychotics for psychotic depression remain to be established. The authors suggest that future studies compare antidepressant monotherapy with combined antipsychotic-antidepressant treatment and also determine the optimal duration of continued combined treatment for patients in remission.

ECT remains an excellent treatment for major depression with psychotic features. Less well-established are amoxapine (Asendin) and mifeprestone (Mifeprex). The combination of an antipsychotic and an antidepressant is an evidence-based intervention. This study shows good benefit for the combination of olanzapine and sertraline throughout a broad age spectrum, albeit with noted adverse effects.

1Meyers BS, Flint AJ, Rothschild AJ, Mulsant BH, Whyte EM, Peasley-Miklus C, Papademetriou E, Leon AC, Heo M; STOP-PD Group: 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). Arch Gen Psychiatry 2009;66:838-847.