A randomized, placebo‐controlled trial of paroxetine in nursing home residents with non‐major depression

Abstract

Depression is common across a broad spectrum of severity among nursing home residents. Previous research has demonstrated the effectiveness of antidepressants in nursing home residents with major depression, but it is not known whether antidepressants are helpful in residents with less severe forms of depression. We conducted a randomized double-blind placebo-controlled 8-week trial comparing paroxetine and placebo in very old nursing home residents with non-major depression. The main outcome measure was the primary nurse's Clinical Impression of Change (CGI-C). Additional outcome measures were improvement on the interview-derived Hamilton Depression Rating Scale (HDRS) and Cornell Scale for Depression (CS) scores. Twenty-four subjects with a mean age of 87.9 were enrolled and twenty subjects completed the trial. Placebo response was high, and when all subjects were considered, there were no differences in improvement between the paroxetine and placebo groups. Two subjects that received paroxetine developed delirium, and subjects that received paroxetine were more likely to experience a decrease in Mini Mental State Exam scores (P =.03). There were no differences in serum anticholinergic activity between groups. In a subgroup analysis of 15 subjects with higher baseline HDRS and CS scores, there was a trend toward greater improvement in the paroxetine group in an outcome measure that combined the CGI-C and interview-based measures (P =.06). Paroxetine is not clearly superior to placebo in this small study of very old nursing home residents with non-major depression, and there is a risk of adverse cognitive effects. Because of the high placebo response and the trend towards improvement in the more severely ill patients, it is possible that a larger study would have demonstrated a significant therapeutic effect for paroxetine as compared with placebo. The study also illustrates the discordance between patient and caregiver ratings, and the difficulties in studying very elderly patients with mood disorders.

A Systematic Review of Antidepressant Placebo-Controlled Trials for Geriatric Depression: Limitations of Current Data and Directions for the Future

“…The two studies in medical in-patients both failed to differentiate active drug from placebo (Tan et al, 1994;Evans et al, 1997). The two studies in nursing home populations found differing results (Katz et al, 1990;Burrows et al, 2002), but this was complicated as one examined minor rather than major depression (Burrows et al, 2002).…”

“…A pooled analysis reported that advanced age does not appear to affect antidepressant response rates or time to remission (Gildengers et al, 2002). However, most of these placebocontrolled trials report a mean age in the 60s, although a few studies report mean ages in the 70s (Schweizer et al, 1998;Schneider et al, 2003) or 80s (Katz et al, 1990;Evans et al, 1997;Burrows et al, 2002). Both studies with samples who had a mean age in their 70s demonstrated a superiority of active agent over placebo, and also exhibited comparable response rates compared with other trials of drugs in their class (Tables 3 and 4).…”

“…Placebo responses for each measure were similarly comparable between studies. There was one trial of paroxetine in residential elderly subjects with DSM-IV-defined minor depressive disorder (Burrows et al, 2002). A total of 20 subjects were examined; entrance criteria required a minimum age of 80 years, an MMSE410, and a score above 3 on the seven-item depression subscale of the Cornell Scale.…”

“…More studies reported outcomes of improved on CGI-I (Kane et al, 1983;Cohn et al, 1984;Merideth et al, 1984;Katz et al, 1990;Nair et al, 1995;Tollefson et al, 1995;Schweizer et al, 1998;Schneider et al, 2003) than outcomes of response or remission on HAM-D (Nair et al, 1995;Tollefson et al, 1995;Evans et al, 1997;Schweizer et al, 1998;Schneider et al, 2003). We did not include the study of minor depression (Burrows et al, 2002) in these analyses. We also did not include buspirone as an antidepressant, although we did include data from the imipramine and placebo arms of that study (Schweizer et al, 1998).…”

Depression in older people living in residential homes

“…It is also challenging to treat them effectively. Some antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), may have limited efficacy in residents with comorbid dementia (Burrows et al, 2002). In addition, some residents may not be able to participate effectively in psychotherapy because of their limited cognitive function (Kallenbach and Rigler, 2006;Carlson and Snowden, 2007).…”