SSRIs for Depression in Elderly: Are They Associated With Falls?

Is the treatment of major depression in the elderly with selective serotonin reuptake inhibitors (SSRIs) associated with falls and related injuries?

Yeates Conwell, M.D.

A recent review of literature suggests that there is insufficient evidence of such an association and that—despite current recommendations from the American Geriatric Society advising physicians to refrain from prescribing SSRIs to the elderly—physicians should not be deterred from prescribing these medications to patients experiencing late-life depression.

“The field of geriatric psychiatry has for a long time been calling for more inclusion of older adults in RCTs (randomized, controlled trials) of antidepressant drugs,” Yeates Conwell, M.D., director of the geriatric psychiatry program and the University of Rochester Medical Center Office for Aging Research and Health Services, told Psychiatric News. “It is a problem that one cannot rely on existing clinical trial data to answer this question—and many other unanswered questions regarding treatment of depression in later life—because so many trials [have] excluded people over age 65 or with the conditions that are comorbid with depression in later life and put the patient at increased risk for falls.”

In a paper appearing in the October American Journal of Geriatric Psychiatry, Marie Ann Gebara, M.D., of the Department of Psychiatry at the University of Pittsburgh and colleagues described how they systematically searched PubMed/MEDLINE, EMBASE, the Cochrane Library, PsycInfo, and ClinicalTrials.gov for studies that explored the association between SSRIs and falls in the elderly.

Among the 26 studies they identified, only one was a randomized, controlled trial. The rest were observational studies that offered no evidence of a temporal association between use of medication and falls—that is, whether the use of SSRIs preceded falls or whether falls were experienced by individuals with untreated major depression who were later treated with SSRIs.

The one randomized, controlled trial that Gebara and colleagues found suggested that patients who took sertraline were no more likely to fall than those who took placebo, but the fact that the study was “underpowered”—having too few participants—made it difficult to rule out the possibility that such a relationship might exist.

Of the nine observational studies that found a positive association between SSRI use and falls, the researchers noted that those who took SSRIs also had other risk factors that may have contributed to increased frailty, including being among the oldest participants in the study and/or having multiple comorbidities, higher numbers of medications, and baseline higher rates of falls.

“We conclude from our systematic review that there is insufficient evidence to support clinical guidelines or policy changes recommending the avoidance of SSRI use in older adults based on fall risk,” Gebara and colleagues wrote. “Given the available evidence, we do not think that clinicians should be deterred from using SSRIs life depression.”

Yet their findings fly in the face of the “2012 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.” For falls and a history of falls among elderly people, the Beers criteria lists SSRIs as potentially inappropriate (along with anticonvulsants, antipsychotics, benzodiazepines, nonbenzodiazepine hypnotics, and tricyclic antidepressants), stating that “these drugs can cause fainting and falls and make it hard to coordinate movements.”

So what is good advice for clinicians treating older adults for major depression? In their paper, Gebara and colleagues offered three recommendations:

• In cases of mild depression or subclinical depressive symptoms, cognitive-behavioral therapy and problem-solving therapy are some of the evidence-based psychosocial treatment approaches for older adults that may be considered as first-line treatment. In cases of at least moderately severe depression, however, antidepressants have adequate evidence for efficacy.

• Clinicians and policymakers should be mindful of the hazard of shifting prescribing toward agents with less evidence for efficacy in older adults and less information regarding potential risk, as is the case with serotonin-norepinephrine reuptake inhibitors and the conflicting data with respect to falls.

• The current literature does not address the question of falls and SSRIs given the limitations of observational studies; thus, there is a need for large, long-term, and appropriately powered RCTs similar to those seen in other fields of medicine. The high public health importance of this question justifies their cost.

Davangere Devanand, M.D., director of geriatric psychiatry at Columbia University Medical Center, applauded the methodological rigor of the analysis by Gebara and colleagues and broadly agreed with their recommendations. “The authors did an exceptionally careful analysis,” he said. “There are really no good prospective randomized, controlled trials that would give us much better evidence than we have now.”

Devanand said that though the Beers criteria represent consensus opinion based on the available evidence, however weak or strong, most clinicians will heed the Food and Drug Administration, which has not indicated that SSRIs should not be prescribed because of the risk of falls.

He added that a host of comorbid medical conditions, as well as dementia, can contribute to falls, and these need to be factored into the calculus of risk associated with medication. Additionally, the risk of falls can be affected by the absence of health aides and other social supports for an elderly person living alone.

“My advice is to avoid medication to the extent possible, but when there is clear evidence of major depression, clinicians who prescribe SSRIs should ‘start low and go slow’ in increasing the dose,” he said.

Conwell concurred. “Treatment of depression in frail older adults is complex and good clinical care requires highly individualized judgments in any event,” he said. “How at risk for falls is the older person due to all other causes? What alternatives are there to an SSRI? How acceptable are they to the patient? How able is the person to take added precautions against falls while the time passes necessary for the antidepressant response to kick in? These are not black and white decisions. But [Gebara and colleagues’] point is an important one—drugs do have a place and previous reports of the risk of falls should not preclude their use, especially since the evidence is weak.”

An editorial accompanying the Gebara analysis in the Journal of Geriatric Psychiatry by Carl Salzman, M.D., of the Department of Psychiatry at Massachusetts Mental Health Center, concluded, “Given the destructive nature of late-life depression on duration and quality of life as well as physical health, withholding treatment of a true late-life depression for fear of antidepressant side effects is probably more harmful both acutely and over time than antidepressant side effects, especially when doses are low and carefully prescribed to avoid drug interactions.” ■