Exercise as Antidepressant: Movement That Belongs in the Prescription

Key Takeaways:

• A 2024 BMJ network meta-analysis of 218 randomized trials and 14,170 participants with depression found moderate reductions in symptoms compared with active controls for walking or jogging, yoga, and strength training, and the benefit grew with the intensity prescribed.
• The authors concluded that these forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression, while rating the certainty of the evidence as low to very low because participants in exercise trials cannot be blinded.
• A meta-analysis of 29 studies found that a single session of exercise raises brain-derived neurotrophic factor (BDNF) with a moderate effect size, and in a randomized trial of 120 older adults, a year of aerobic training enlarged the hippocampus by 2 percent, with larger volume tracking higher serum BDNF.

In the week after World Mental Health Day, it is worth putting one of the most underused treatments in medicine on the table. The case for exercise for depression does not rest on endorphins or a vague sense of accomplishment. It rests on a growth factor. Brain-derived neurotrophic factor, or BDNF, is a protein that helps neurons survive, sprout new connections, and strengthen the synapses they already have, and it is especially active in the hippocampus, a structure that sits at the crossroads of memory, stress regulation, and mood. A meta-analysis of 29 human studies found that a single bout of exercise raises circulating BDNF with a moderate effect size, that people who train regularly get a bigger surge from each session, and that regular training nudges resting levels up as well. The structural consequences show up on imaging. In a randomized trial of 120 older adults, a year of walking-based aerobic training enlarged the anterior hippocampus by 2 percent, effectively reversing one to two years of age-related shrinkage, and the growth tracked serum BDNF. In mice, voluntary wheel running alone doubled the number of surviving new neurons in the hippocampal dentate gyrus, the best-documented site of adult neurogenesis.

The clinical evidence is now large enough to take seriously on its own terms. A 2024 network meta-analysis in the BMJ pooled 218 randomized trials with 14,170 participants who met clinical criteria for major depression and compared exercise types head to head. Against active control conditions such as usual care or a placebo pill, walking or jogging produced a moderate reduction in depressive symptoms, as did yoga and strength training, with mixed aerobic exercise and tai chi or qigong close behind. Two findings matter for anyone writing an actual plan. First, the benefit was proportional to the intensity prescribed, so a brisk walk that raises the breathing rate beats a stroll. Second, strength training and yoga were the best tolerated, which matters because the best exercise is the one a person will keep doing. The effect held across people with and without other medical conditions and across different starting levels of depression. The authors’ conclusion was measured but striking: these forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments.

How should exercise for depression fit with other treatment?

It belongs alongside other care, not in place of it. The same BMJ analysis was candid about its limits. Only one of the 218 trials met the strictest criteria for low risk of bias, and confidence in the findings was rated low for walking or jogging and very low for the other forms of exercise, largely because nobody can be blinded to whether they are exercising, so expectation effects are hard to separate from biology. That does not make the benefit imaginary, but it does mean the numbers are softer than a drug trial’s. The practical message is additive. Someone who is already taking an antidepressant or working with a therapist should keep doing so and add movement; stopping a medication should always be a planned decision made with the prescriber, never a side effect of starting a running habit. A reasonable starting prescription is three sessions a week of whatever the person will actually do, whether walking, jogging, yoga, or resistance training, gradually pushed toward an effort that makes conversation harder. Autumn mornings are a good time to begin. And anyone with thoughts of self-harm needs care today, not a training plan; in the United States, calling or texting 988 reaches the Suicide and Crisis Lifeline at any hour.

References:

1. Szuhany, K. L., Bugatti, M., & Otto, M. W. (2015). A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. Journal of Psychiatric Research, 60, 56-64.
2. Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., et al. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3017-3022.
3. van Praag, H., Kempermann, G., & Gage, F. H. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neuroscience, 2(3), 266-270.
4. Noetel, M., Sanders, T., Gallardo-Gómez, D., Taylor, P., del Pozo Cruz, B., van den Hoek, D., et al. (2024). Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ, 384, e075847.