| Bree is a 40-year-old woman with recurrent major depression. She sees a therapist every 1-2 weeks and is hesitant to take medications or supplements for depression. She asks if changing her diet or exercising more could help her depression. What is the evidence for diet changes or exercise improving major depression? Diet Multiple meta-analyses show a link between a healthy diet and a reduced risk of depression among non-depressed adults (Lai 2014, Psaltopoulou 2013). The data to support a specific diet as a therapeutic intervention for depressed patients is largely limited to studies of the Mediterranean diet. Three meta-analysis/systematic reviews demonstrated a reduction in depressive symptoms among those in the Mediterranean diet intervention arm, offering early evidence that dietary interventions could help depression (O’Neil 2022, Swainson 2022, Firth 2019). These reviews relied heavily on data from 1 RCT, known as SMILES. SMILES (Jacka 2017), and a very similar study AMMEND (Bayes 2022), were small (n < 75), Australian based RCTs that found significant improvement in depressive symptoms with medium effect sizes among depressed adults with a 12-week intensive intervention that included multiple meetings with dietitians, grocery bags, and meal plans. A “control” group had meetings with a trained person who played cards or engaged the participant in neutral topics such as sports, news, or music (befriending protocol). A systematic review and meta-analysis of RCTs of dietary interventions for adults with depressive disorders published in 2025 came to the opposite conclusion. Tavakoly and colleagues included 5 RCTs investigating the Mediterranean diet (n=952), including the SMILES and AMMEND trials. They found no significant effect of short-term, intermediate-term or long-term dietary intervention on depression severity compared to active or passive controls. The certainty of evidence was low or very low (Tavakoly 2025). The authors also noted flaws in the older reviews. Overall, the current evidence to support the Mediterranean diet as a treatment for depression is very low. Despite the theoretical benefits and the positive results of 2 small RCTs (SMILES, AMMEND), we do not currently advise this dietary intervention in treating depression. Exercise Among non-depressed persons, there is an inverse dose response between physical activity and depression risk. The WHO recommends moderate intensity exercise for 150-300 minutes per week for general health. People with even half the recommended amount of physical activity had an 18% lower risk of depression than non-active adults (Pearce 2022). There is also evidence to support exercise as a treatment for depression. A 2013 Cochrane Review demonstrated a pooled standardized mean difference (SMD) of -0.62 (moderate effect size; 95% confidence interval (CI) -0.81 to -0.42) in favor of exercise versus control for the treatment of depression, albeit with substantial heterogeneity among the studies. When the analysis was limited to the 6 highest quality trials, the SMD was no longer statistically significant. When comparing exercise to psychological therapy or pharmacologic therapy, no significant differences were found (Cooney 2013). A more recent meta-analysis and systematic review found no difference between exercise, antidepressants, and the combination of exercise and antidepressants in reducing depressive symptoms compared with controls (Recchia 2022). In other words, exercise was no more or less effective than antidepressants for the treatment of depression. It is worth looking more closely at one of the included studies that compared exercise with antidepressants. Blumenthal et al conducted a randomized, parallel group, 16-week, trial of exercise (group-supervised and individual home-based) and medication (sertraline and placebo) for the treatment of MDD (Blumenthal 2007). All groups showed a clinically and statistically significant decline in depression scores (HAM-D) from baseline to 16 weeks, and both exercise and medication interventions achieved higher remission rates compared with placebo. There were no statistically significant differences between the exercise groups and antidepressant medication. The authors note, “Most of the participants in the present study enrolled with the hope that they would receive exercise treatment for their depression.” In other words, the placebo response may have been more powerful in the exercise group than the medication groups, given the participant’s expectation effects. A more recent meta-analysis and systematic review expanded the analysis to include exercise interventions like yoga and tai chi and participants with physical comorbidities. Large reductions in depression were observed across all exercise modalities with a clear dose response curve for intensity of exercise. Confidence in these effects were low due to high within-study bias (Noetel 2024). While the data for exercise is also mixed, there is a sufficiently clear signal to consider exercise as an evidence-based treatment for depression . The NICE guidelines recommend exercise as one of many potential treatment options for mild to severe depression and also as an adjuvant treatment in treatment-resistant depression. Returning to Bree You start by acknowledging and supporting Bree’s interest in lifestyle interventions to treat her depression. You explain that unfortunately there isn’t currently good evidence to use dietary changes as a treatment for depression. You encourage Bree to continue to eat a healthy diet during this difficult period. Because Bree loses weight when she is depressed due to a lack of appetite, you specifically encourage her to eat regularly, whether or not she is hungry. You also recommend that Bree start exercising again, which might help her depression. You explore what she is open to doing and help her set a goal. Bree says she’ll restart briskly walking 3-5 days a week in the evening – she used to do this with a neighbor. You are impressed with her goal and explore if she might have a friend join her or talk with her sister on the phone while walking. You also share a list of group classes she might enjoy and schedule a follow up visit in 2 weeks.  Key Points 1) Data to support the efficacy of the Mediterranean diet as a treatment for depression is currently lacking. 2) Exercise may prevent depression and improve depressive symptoms. Some studies suggest that exercise is non-inferior to first line treatments for depression. References: Bayes, J., Schloss, J., & Sibbritt, D. (2022). The effect of a Mediterranean diet on the symptoms of depression in young males (the “AMMEND: A Mediterranean Diet in MEN with Depression” study): a randomized controlled trial. The American Journal of Clinical Nutrition, 116(2), 572–580. https://doi.org/10.1093/ajcn/nqac106 Blumenthal, J. A., Babyak, M. A., Doraiswamy, P. M., Watkins, L., Hoffman, B. M., Barbour, K. A., Herman, S., Craighead, W. E., Brosse, A. L., Waugh, R., Hinderliter, A., & Sherwood, A. (2007). Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder. Psychosomatic Medicine, 69(7), 587–596. https://doi.org/10.1097/PSY.0b013e318148c19a Cooney, G. M., Dwan, K., Greig, C. A., Lawlor, D. A., Rimer, J., Waugh, F. R., McMurdo, M., & Mead, G. E. (2013). Exercise for depression. Cochrane Database of Systematic Reviews, 2013(9). https://doi.org/10.1002/14651858.CD004366.pub6 Firth, J., Marx, W., Dash, S., Carney, R., Teasdale, S. B., Solmi, M., Stubbs, B., Schuch, F. B., Carvalho, A. F., Jacka, F., & Sarris, J. (2019). The Effects of Dietary Improvement on Symptoms of Depression and Anxiety: A Meta-Analysis of Randomized Controlled Trials. Psychosomatic Medicine, 81(3), 265–280. https://doi.org/10.1097/PSY.0000000000000673 Jacka, F. N., O’Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., Castle, D., Dash, S., Mihalopoulos, C., Chatterton, M. L., Brazionis, L., Dean, O. M., Hodge, A. M., & Berk, M. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Medicine, 15(1), 23. https://doi.org/10.1186/s12916-017-0791-y Lai, J. S., Hiles, S., Bisquera, A., Hure, A. J., McEvoy, M., & Attia, J. (2014). A systematic review and meta-analysis of dietary patterns and depression in community-dwelling adults. The American Journal of Clinical Nutrition, 99(1), 181–197. https://doi.org/10.3945/ajcn.113.069880 Noetel, M., Sanders, T., Gallardo-Gómez, D., Taylor, P., Del Pozo Cruz, B., Van Den Hoek, D., Smith, J. J., Mahoney, J., Spathis, J., Moresi, M., Pagano, R., Pagano, L., Vasconcellos, R., Arnott, H., Varley, B., Parker, P., Biddle, S., & Lonsdale, C. (2024). Effect of exercise for depression: Systematic review and network meta-analysis of randomised controlled trials. BMJ, e075847. https://doi.org/10.1136/bmj-2023-075847 O’Neill, S., Minehan, M., Knight-Agarwal, C. R., & Turner, M. (2022). Depression, Is It Treatable in Adults Utilising Dietary Interventions? A Systematic Review of Randomised Controlled Trials. Nutrients, 14(7), 1398. https://doi.org/10.3390/nu14071398 Pearce, M., Garcia, L., Abbas, A., Strain, T., Schuch, F. B., Golubic, R., Kelly, P., Khan, S., Utukuri, M., Laird, Y., Mok, A., Smith, A., Tainio, M., Brage, S., & Woodcock, J. (2022). Association Between Physical Activity and Risk of Depression: A Systematic Review and Meta-analysis. JAMA Psychiatry, 79(6), 550. https://doi.org/10.1001/jamapsychiatry.2022.0609 Psaltopoulou, T., Sergentanis, T. N., Panagiotakos, D. B., Sergentanis, I. N., Kosti, R., & Scarmeas, N. (2013). Mediterranean diet, stroke, cognitive impairment, and depression: A meta‐analysis. Annals of Neurology, 74(4), 580–591. https://doi.org/10.1002/ana.23944 Recchia, F., Leung, C. K., Chin, E. C., Fong, D. Y., Montero, D., Cheng, C. P., Yau, S. Y., & Siu, P. M. (2022). Comparative effectiveness of exercise, antidepressants and their combination in treating non-severe depression: A systematic review and network meta-analysis of randomised controlled trials. British Journal of Sports Medicine, 56(23), 1375–1380. https://doi.org/10.1136/bjsports-2022-105964 Swainson, J., Reeson, M., Malik, U., Stefanuk, I., Cummins, M., & Sivapalan, S. (2023). Diet and depression: A systematic review of whole dietary interventions as treatment in patients with depression. Journal of Affective Disorders, 327, 270–278. https://doi.org/10.1016/j.jad.2023.01.094 Tavakoly, R., Moosburner, A., Anheyer, D., & Cramer, H. (2025). Effect of Different Dietary Patterns on Patients with Depressive Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 17(3), 563. https://doi.org/10.3390/nu17030563 |
