The purpose of this study is to examine the effects of sertraline treatment of depression in older adults on gait stability, balance recovery reactions, and markers of bone metabolism. This is a pilot study that will determine feasibility and generate hypotheses for a larger definitive study.

Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant medication frequently used to treat depressive and anxiety disorders in the elderly. Although widely considered to be a safe option, several observational studies have found that SSRIs have as strong an association with falls as other psychotropic medications including tricyclic antidepressants and benzodiazepines. However, the potential mechanism for a link between SSRIs and falls is unclear. Compared to other psychotropic medications, SSRIs have lower rates of side effects that could contribute to falls, including sedation, orthostatic blood pressure changes, and anticholinergicity. Interestingly, SSRIs have also been associated with fractures, more so than other classes of antidepressants, in both administrative database studies and prospective cohort studies that control for falls history. Serotonin is known to play a role in regulating bone mass and some studies have found a loss of bone mass in individuals on SSRI treatment.

The association of SSRIs with falls and fractures is confounded by depression which is itself associated with falls, gait instability, bone loss and fractures. The goal of this study is to disentangle the contribution of the disease versus the treatment to risk of falls and fractures. As a first step towards this goal, this pilot study will: i) estimate effect sizes for statistical power calculations for an adequately powered study; and ii) examine the feasibility of timely recruitment of older patients with major depression who have not taken antidepressant medication for a minimum of 2 weeks prior to entering the study.

To address our research question, we have designed a prospective observational pilot study. Older adults with depression will be assessed at baseline, and then 3,6, and 12 weeks after initiation of sertraline antidepressant therapy. A non-depressed comparison group will be used to control for the learning effects of repeated assessment. The outcomes of interest are changes in gait, static balance, and dynamic balance recovery reactions. Our primary outcomes are the short-term changes in these variables at 3 weeks, but we will also perform a longitudinal analysis to assess change over 12 weeks.

Depressed group

Inclusion Criteria:

• Clinical diagnosis of Major Depression
• English-speaking
• If currently on an antidepressant, willing to undergo a 2 week washout.

Exclusion Criteria:

• Lifetime bipolar disorder
• Current psychotic disorder or substance use disorder
• Dementia
• Poor baseline mobility or baseline severe gait disorder
• On treatment with fluoxetine or mood stabilizer
• Severe renal impairment, bleeding disorder, recent gastric bleeding or hemorrhagic stroke in past 3 months
• Poor response or serious adverse event with sertraline in the past.

Comparison group

Inclusion Criteria:

- English-speaking

Exclusion Criteria:

• Lifetime diagnosis of depression or dementia
• Currently on antidepressant medication or mood stabilizer
• Poor baseline mobility or baseline severe gait disorder