Drug or Exercise for Geriatric Depression?
It Depends

Jake Remaly

August 02, 2021

Among older adults with mild-to-moderate depressive disorder diagnosed during a primary care visit, antidepressant medication or supervised group exercise sessions may decrease symptoms to a similar degree during the first month of treatment, a randomized trial shows.

At 3 and 6 months, however, medication may have greater benefit.

Each intervention has its advantages, risks, and limitations and may play a role in clinical practice, researchers said.

The findings suggest that "while exercise by itself may not be as potent as an antidepressant in treating depression, it certainly seems to be a good augmentation strategy to antidepressants," commented Lauren Gerlach, DO, MSc, a geriatric psychiatrist at Michigan Medicine in Ann Arbor, who was not involved in the study.

Jesús López-Torres Hidalgo, MD, and colleagues published the results of the DEP-EXERCISE trial in Annals of Family Medicine. Hidalgo is affiliated with the University of Castile-La Mancha and Albacete Zone VIII Health Center in Albacete, Spain.

The researchers found that adverse effects were more common among patients who received antidepressants, whereas more participants in the exercise group withdrew from the study. Nevertheless, participants in both groups reported that the interventions were satisfactory and improved their health.

To compare the effectiveness of physical exercise vs antidepressant drugs for the treatment of depression in older adults, Hidalgo and colleagues recruited 347 patients from multiple primary care clinics in Albacete, a city of 170,000 people in eastern Spain. All participants were aged 65 years or older with a clinically significant depressive episode. The investigators randomly assigned participants to a supervised exercise program or to antidepressant medications prescribed by their general practitioner.

Participants had an average age of 72 years, and approximately 80% were female. Mean Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline was 15.1 in the physical activity group and 15.9 in the antidepressant treatment group.

In all, 66 participants in the physical activity group and 93 in the medication group completed follow-up.

At 1 month, participants in the two groups were similarly likely to have reduced symptoms, defined as a MADRS score less than 10, in an intention-to-treat analysis. At that time, 48.1% of participants in the physical activity group and 54.2% in the antidepressant treatment group had improved.

At 3 months, those in the antidepressant group were significant more likely to show continued improvement than those in the exercise group (60.6% vs. 45.6%). A similar pattern was seen at 6 months (49.7% vs. 32.9%).

Moreover, at 6 months, MADRS scores had decreased from baseline by an average of 5.8 points in the antidepressant treatment group compared with 4.04 points in the physical activity group.

However, when the researchers restricted their analysis to those participants who completed follow-up, the results did not significantly differ between the groups at any point.

Antidepressants used during the trial included sertraline (26.5%), trazodone (14.8%), paroxetine (12.9%), mirtazapine (9%), escitalopram (8.4%), venlafaxine (7.7%), and duloxetine (5.8%).

More participants who received antidepressants experienced adverse side effects vs those in the exercise group (22.5% vs. 8.9%). Medication side effects included dizziness (6.5%), epigastric pain (5.2%), and daytime drowsiness (3.2%).

In the exercise group, 14 participants reported adverse effects such as osteomuscular pain, mild contusions, or dizziness. "The most severe adverse effects were a fracture of the radius after a fall and fainting with spontaneous recovery," the researchers report.

"A Lot of Exercise"

The trial incorporated "a lot of exercise," especially for participants who may not have been exercising previously, said Mijung Park, PhD, MPH, RN, an associate professor of family health care nursing at University of California, San Francisco who studies depression in older adults. Park was not involved in the DEP-EXERCISE trial.

The exercise intervention incorporated two 1-hour group sessions per week run by qualified instructors, in which participants performed aerobic, strength, flexibility, and balance exercises. They also learned ways to exercise regularly outside of the supervised sessions.

Adherence to the exercise program was limited. Participants in the physical activity group attended an average of about 19 sessions. It is possible that the intention-to-treat analysis underestimates the intervention's benefits, given the poor adherence, the authors noted. The number of participants who withdrew from the trial was greater in the physical activity group at 3 months (39.2% vs. 22.6%) and at 6 months (58.2% vs. 40%).

Health problems or functional limitations "common to older adults might have negatively influenced adherence" to the physical activity program, the researchers said.

The investigators excluded patients with physical or mental limitations that could prevent participation, contraindications for physical exercise, severe depressive disorder, and those already taking antidepressants.

Participants knew which intervention they received, which could have biased the results, the authors say.

Exercise potentially could reduce depression symptoms by distracting from negative thoughts, facilitating social contact, and producing physiologic effects that improve mood, the researchers wrote. Nevertheless, the effectiveness of exercise for treating depression is uncertain, and older adults have not been well represented in depression treatment trials, according to the authors.

An Augmentation Strategy?

Clinicians often think about depression in older adults using a holistic, multifaceted approach, University of Michigan's Gerlach said.

First, Gerlach considers medical conditions that might contribute to a patient's symptoms, such as underlying obstructive sleep apnea, a hormone imbalance, or congestive heart failure that is not optimally managed.

"We'll also think about any psychosocial or social stressors that are going on," and ways to increase support at home and in the community, she said. "And then we will be thinking about their level of activity. Exercise is always something that I am thinking about when I am thinking about nonmedication options for treating depression. We know that exercise has huge health benefits on its own."

Pharmacologic treatments for depression take time to achieve their full effect, sometimes 4-12 weeks. Meanwhile, sustaining motivation for any kind of physical activity can be challenging. In that sense, it is not surprising that outcomes with these interventions may diverge over time, Gerlach said.

One key benefit of an exercise program may be the accompanying routine that gets people out of the house and physically active again, she added.

UCSF's Park said the study supports the idea that not everybody has to take an antidepressant initially. "We can start with a nonpharmaceutical treatment regimen first" and achieve a similar effect, Park said.

For older adults, avoiding an extra drug may be particularly important. Yet, for some patients, psychotherapy and pharmaceutical approaches still would be expected to play important roles, Park said.

For patients with mild depression where clinicians are not sure whether antidepressant medication is indicated, psychotherapy referrals and addressing lifestyle factors may be a reasonable place to start, Gerlach said. Recommending exercise or encouraging physical activity can be one element of that picture.

With moderate or severe depression, pharmacotherapy may be needed. "For those folks, I probably wouldn't be recommending exercise alone, but I think it can be an additional treatment strategy to add to the overall plan," Gerlach said.

The study received funding from the Carlos III Institute of Health. The researchers, Gerlach, and Park had no relevant financial disclosures.

Ann Fam Med. Published online July 12, 2021. Full text

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