Effect of Sertraline on Risk of Falling in Older Adults with Psychotic Depression on Olanzapine: Results of a Randomized Placebo-Controlled Trial

Objective: Observational studies report that selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with an increased risk of falls in the elderly, but these studies may overestimate drug-specific risk because of confounding. A randomized controlled trial (RCT) is the optimal way to assess the causal relationship between use of an SSRI and falls. We therefore analyzed data from a RCT of the treatment of psychotic depression, to examine whether combined olanzapine and sertraline interacted with older age to increase the risk of falling compared with olanzapine plus placebo. Design: Double-blind placebo-controlled RCT. Setting: Four academic medical centers. Participants: Two hundred fifty-nine patients with major depressive disorder with psychotic features (N = 117 aged 18-59 years and N = 142 aged 60 years or older). Intervention: Twelve weeks of randomized double-blind treatment with olanzapine plus sertraline or olanzapine plus placebo. Measurements: Proportion of participants who fell at least once. Results: Older participants were significantly more likely than younger participants to fall. Among older participants, the odds ratio of falling with olanzapine plus sertraline versus olanzapine plus placebo was 1.56 (95% confidence interval: 0.63-3.83). There was not a statistically significant treatment effect or treatment x age interaction with respect to the proportion of participants falling. These negative results may have been due to low statistical power. Conclusion: Evaluating the association between SSRIs and falls in a RCT is limited by the large sample size that is required. An alternative approach is to examine the effect of an SSRI on measures of postural stability and gait that are valid markers of risk of falling.