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OBJECTIVES: Depression is a common and treatable condition among nursing facility residents, with low body weight being a frequent concomitant concern. A common prescribing dictum is that older tricyclic antidepressants (TCAs) enhance appetite and may facilitate weight gain, while newer selective serotonin reuptake inhibitors (SSRIs) cause anorexia and resultant weight loss in older adults. Evidence is lacking on whether the small weight changes noted during short-term antidepressant efficacy trials translate into larger weight changes during prolonged treatment periods. Our main objective was to compare weight outcomes at 6 months among users of three different antidepressant groups with a control group of non-antidepressant users. A secondary objective was to determine whether antidepressant selection was associated with weight pattern before drug initiation, to capture possible prescribing bias that would affect study inferences.<br><br>DESIGN: Retrospective cohort design using the Minimum Data Set—Plus (MDS+).<br><br>SETTING: Kansas nursing facilities.<br><br>PARTICIPANTS: 1157 antidepressant users age 65 and older who started an antidepressant after admission and remained on the same single agent for at least 6 months, and 4852 persons meeting the same inclusion/exclusion criteria but not receiving an antidepressant.<br><br>MEASUREMENTS: Antidepressant use was identified by drug code data and divided into four groups for analysis: TCAs, SSRIs, others, and none. (Amitriptyline and trazodone were excluded because of frequent use for nondepression purposes.) Rates of clinically important loss and gain (assigned for a 10% change from baseline weight or presence of the significant loss or gain markers on the 6-month MDS assessment) and mean weight changes were compared across the four groups. Regression models were used to control for age, gender, baseline weight, confounding comorbidity, and functional variables related to eating. Previous weight patterns (loss, gain, neither, or unknown) before antidepressant initiation were compared across drug groups.<br><br>RESULTS: Clinically important weight loss and gain occurred at 6 months in 14.8% and 14.4% of the sample, respectively. In unadjusted analyses, an increased likelihood of loss was found for users of SSRIs (Odds Ratio 1.57; CI 1.30, 1.90) and others (OR 1.89; CI 1.18, 3.03), compared with none. In logistic models accounting for potential confounding factors, however, SSRI use showed a modest association with gain (OR 1.31, CI 1.01, 1.70) and a trend toward a similarly modest association with loss (OR 1.28; CI 0.995, 1.64). TCA use was not associated with weight gain. When weight was examined as a continuous variable, all groups demonstrated a broad range of both loss and gain with mean-unadjusted weight changes <3 pounds. Pairwise comparisons of adjusted differences in weight change at 6 months for SSRIs (mean loss of 1.6 pounds) and TCAs (mean gain of 0.4 pounds) were of marginal importance (P = .046) given the large sample size. No evidence was found for prescribing bias based on prior weight pattern.<br><br>CONCLUSIONS: TCAs do not facilitate weight gain more than other antidepressant groups and SSRIs are not associated disproportionately with weight loss when other important clinical variables are accounted for. Small but statistically significant differences in mean weight changes between groups are largely a reflection of large sample size rather than clinically important differences. Clinicians may wish to reconsider the widely held notions that TCAs facilitate weight gain and that SSRIs place depressed older nursing facility residents at disproportionate risk for weight loss.<br><br>