Moderation of antidepressant and placebo outcomes by baseline severity in late-life depression: A systematic review and meta-analysis

• Studies in mixed-aged depression indicate an advantage of antidepressants over placebos with increasing baseline severity.
• This severity hypothesis could not be confirmed in late-life depression.
• However, placebo responses are large and meaningful in the treatment of depressed elderly people.
• Psychosocial interventions should be considered initially followed by antidepressants.

BackgroundBaseline severity is a crucial moderator of trial outcomes in adult depression, with the advantage of antidepressants over placebo increasing as severity increases. However, this relationship has not been examined in late-life depression.MethodsPubMed, Embase, Web of Science, PsycINFO, and Cochrane were searched for studies published through September 2014. Randomized, acute phase, and double-blind studies comparing an antidepressant group with a placebo group in depressed elderly patients were included.ResultsNineteen studies met all inclusion criteria. Within-group effect sizes revealed significant improvement in antidepressant groups (g=1.35, p<.000), as well as in placebo groups (g=.96, p<.000). Change in depressive symptoms assessed by Hamilton Depression Rating Scale (HDRS) was moderated by baseline severity in antidepressant groups (Z=2.67, p=.008) and placebo groups (Z=4.46, p<.000). However, this would be expected as a result of regression toward the mean, and mean differences between groups did not increase (r=.19, p=.469) as a function of baseline severity.LimitationsLimited to published data and information was only analyzed at the level of treatment groups.ConclusionBaseline severity was not associated with an antidepressant–placebo difference and placebo responses are large in the treatment of depressed elderly people. We propose a stepwise approach, i.e., to initially offer elderly depressed patients psychosocial interventions and only consider antidepressants if patients do not respond.