Effect of sertraline on risk of falling in older adults with psychotic depression on olanzapine: results of a randomized placebo-controlled trial

Abstract

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 × 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.

Trial registration: ClinicalTrials.gov NCT00056472.

Keywords: Selective serotonin reuptake inhibitor; aged; depression; falls; randomized controlled trial.

Conflict of interest statement

Conflicts of Interest:

AJF has receives grant support from the NIMH, the Canadian Institutes of Health Research, and Lundbeck and has received honoraria from Janssen-Ortho, Lundbeck Canada, and Pfizer Canada. BHM currently receives research support from the Canadian Institutes of Health Research (CIHR), the US National Institute of Health (NIH), Bristol-Myers Squibb (medications for a NIH-funded clinical trial), and Pfizer (medications for a NIH-funded clinical trial). He directly own stocks of General Electric (less than $5,000). Within the past three years, he has also received some travel support from Roche. In the more distant past he has received honorarium and consulting fees from Pfizer. AJR has received grant support from the National Institute of Mental Health (NIMH), Cyberonics, Takeda, and St. Jude Medical and has served as a consultant to Allergan, GlaxoSmithKline, Eli Lilly, Noven Pharmaceuticals, Pfizer, Shire Pharmaceuticals, and Sunovian. BSM receives research support from the NIMH. He is receiving medication donated by Pfizer and Eli Lilly for his NIMH trial. During the last three years he has provided legal consultation to AstraZeneca and research consultation for Forest Laboratories. EMW has received research support from the NIMH, the National Institute of Child Health and Human Development (NICHD), the Department of Defense (DOD) and through a Small Business Innovation Research (SBIR) grant from Fox Learning Systems / National Institute of Neurological Disorders and Stroke (NINDS). AI has no conflicts to report.

Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.