Results from the National Institute of Mental Health's Study of the Pharmacotherapy of Psychotic Depression (STOP-PD) were presented at the American Psychiatric Association's 2008 Annual Meeting by Barnett Meyers, MD, Weill Medical College of Cornell University, New York, NY, on behalf of the collaborative study group. “There's a need for alternative treatments to ECT [electroconvulsive therapy]. One of the factors that I don't think is discussed enough is that there is a significant change in Hamilton scores following the ECT procedure – scores are found to have drifted upwards at the next assessment.” There are also practical considerations, as ECT is not readily available on an out-patient basis.

To investigate the efficacy of a pharmacotherapeutic approach, STOP-PD looked at monotherapy with an antipsychotic versus an antipsychotic/antidepressant combination. In this 12-week, multicenter, placebo-controlled, double-blind trial, 259 patients with unipolar delusional depression were randomized to treatment with olanzapine/placebo or olanzapine/sertraline. Dosing regimens were initiated and then escalated as follows: olanzapine 5 mg, 10 mg, then 15 mg/day on Days 1, 4, and 7; with sertraline at 50 mg, 100 mg, and then 150 mg/day on the same schedule. Doses of 200 mg/day sertraline and 20 mg/day olanzapine were allowed for residual symptoms. Study endpoints included 2 weeks of Hamilton Rating Scale for Depression (HAM-D) 17 ≤ 10 (“remission”) to demonstrate stability, and SADS delusional item measures of “no delusion” at the 2nd or both weeks of the depression remission period.

All patients in this study were aged 19 years and older, and 142 patients who were randomized were aged ≥60 years. All patients had HAM-D 17 scores of ≥21 at study entry. Patients with suicidal ideation were excluded.

After enrollment, subject discontinuations in this trial were high: 53% in the monotherapy arm and 37% in the combination arm. “The most common reason for both groups is the subject withdrawing consent,” reported Meyers, “followed by clinical worsening.” He added that insufficient response leading to discontinuation was higher in the monotherapy arm than for the combination: 10% versus 4.7%, respectively.

After 12 weeks, results showed a superior depression remission rate of 67% in the olanzapine/sertraline arm versus 41.9% for monotherapy (p=0.036). When broken down by age, both older (≥60) and younger patients had statistically superior results for the combination versus monotherapy (p<0.02), yet within the combination arm, results for the two age groups were not statistically different. “This did not support our hypothesis that younger patients would do better with the combination. In fact, numerically, older patients had a better response.” SADS scores were reduced equivalently for both groups in both treatment arms.

The adverse events that were reported for this study did not differ significantly between the age groups, with the exception of more pedal edema seen in older patients and younger patients experiencing more weight gain. As expected, olanzapine-related weight gain was the most common adverse event overall (54.1%) and was dose-related.

When asked about weight gain concerns for patients being treated long-term, Meyers suggested that other atypical antipsychotics might be appropriate for use in this setting, cautioning, however, that little is known about the efficacy of these other atypical medications for psychotic depression or their adverse effects.