Conference Coverage

Geriatric depression, pain respond to various drugs


 

EXPERT ANALYSIS FROM THE AAGP ANNUAL MEETING

ORLANDO – Duloxetine for the treatment of late-life depression missed its primary end point in a recent large randomized trial, but it did result in consistently significant clinical improvement, compared with placebo across numerous secondary outcome measures.

The results overall provide a suggestion of antidepressant efficacy along with evidence of a meaningful reduction in pain in this elderly patient population, Dr. David C. Steffens observed at the annual meeting of the American Association for Geriatric Psychiatry.

Dr. David C. Steffens

This was a multicenter, double-blind, placebo-controlled 24-week study. It included 296 patients age 65 or older with major depressive disorder, a Montgomery-Asberg Depression Rating Scale score of 20 or above indicative of at least moderately severe depression, and a Mini-Mental Status Examination score of 20 or more. Participants were randomized 2-to-1 to duloxetine (Cymbalta) at either 60 mg/day, 120 mg/day, or placebo.

The primary end point was change in the Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12, compared with placebo. The difference fell short of statistical significance at week 12, which was surprising given that the difference was significant at weeks 4, 8, 16, and 20. Moreover, significantly greater improvement in depressive symptoms as measured by the Geriatric Depression Scale was seen in the duloxetine group at weeks 2, 4, 8, 16, 20, and 24 – but once again, not at week 12, which was the point when the study allowed for dose adjustment from 60 mg/day to 120 mg/day, noted Dr. Steffens, professor and chairman of the department of psychiatry at the University of Connecticut, Farmington.

Participants had baseline mild to moderate pain as reflected in their scores on the Brief Pain Inventory and Pain Numeric Rating Scale. The duloxetine-treated group showed significant improvement in pain severity and interference, compared with controls. That’s an important finding given that close to two-thirds of patients with geriatric depression have comorbid pain that typically compounds their mood disorder.

Prior trials of duloxetine have been shorter. In this one, the remission rate, as defined by a HAMD-17 score of 7 or less among patients on duloxetine at 60 mg/day for the full 24 weeks, was 66% by week 12 and 65% at week 24. Thus, if a patient wasn’t in remission after 12 weeks at 60 mg/day, it was unlikely to happen with another 12 weeks on that regimen, and a dose increase to 120 mg/day may be warranted.

Five patients discontinued duloxetine for serious adverse events, compared with one placebo-treated control. The most prominent duloxetine-related side effects were diarrhea and dizziness. Duloxetine-treated patients showed a small increase in heart rate and a modest decrease in blood pressure, issues that need to be borne in mind in an elderly population at increased cardiovascular risk. One patient on duloxetine fell and sustained a hip fracture (Am. J. Geriatr. Psychiatry 2014;22:34-45).

Dr. Steffens, who didn’t participate in the duloxetine trial, highlighted another encouraging development in the treatment of late-life depression: a pooled subgroup analysis he and other investigators conducted using the data from three similar 14-week, prospective, randomized, double-blind trials of adjuvant aripiprazole (Abilify), compared with second-line antidepressant therapy in patients with major depressive disorder who had an incomplete response to standard antidepressant therapy. Their analysis included 679 patients under 50 years of age and 409 others aged 50-67 years. The older group was further subdivided by age: 50-55, 56-60, and 61-67 years.

"Our goal was to generate some preliminary data. Industry has been less and less interested in thinking about atypical antipsychotics in the elderly because of the black box warnings. Our reasoning was any data that we can get that might support further study in this population of older adults makes sense," the psychiatrist explained.

Older patients on aripiprazole showed significantly greater improvement on the Montgomery-Asberg Depression Rating Scale at week 14 than placebo-treated controls. Their remission rate was 33%, compared with 27% in younger aripiprazole-treated patients (Int. J. Geriatr. Psychiatry 2011;26:564-72).

These data are "as good as we have in terms of this particular research issue. We showed people are not keeling over from this therapy. We can at least say that among the few elderly patients we have here, we have preliminary data that this may be helpful and can be tolerated. There are some signals here. Subsequent studies looking at the older population are needed," according to Dr. Steffens.

In response to an audience question, Dr. Steffens said that in the 10 or 12 patients with late-life depression where he has tried using aripiprazole off-label at a starting dose of 1 or 2 mg/day he has had a fair degree of success.

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