Should Exercise be Prescribed for Depression and Anxiety?

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Exercise is an antidepressant.

A new meta-analysis of 26 randomized controlled studies found that both aerobic and resistance training significantly reduced symptoms of depression and anxiety, often rivaling standard treatments like medication and therapy. Although both modes were beneficial, aerobic exercise had a slightly greater impact on depression, while resistance training showed a modest edge for anxiety.

Why does it work? Exercise influences key biological systems, reducing inflammation, enhancing neuroplasticity through BDNF, and rerouting kynurenine metabolism to protect the brain from damage.

For those with depression or anxiety, movement is powerful medicine. And the dose needed might be smaller than you think. Many of the included studies didn't even meet the minimum weekly physical activity recommendations for aerobic or resistance exercise, and even then, reduced depressive and anxiety symptoms significantly.

Today's email will break down the study and delve into why exercise helps in the prevention and treatment of depression, as well as the mechanisms behind the mood-enhancing effects of physical activity.

Exercise–In All Forms—Reduces Depression and Anxiety

For this latest study on exercise for depression and anxiety, researchers meta-analyzed a total of 26 randomized controlled trials that compared either aerobic exercise, resistance exercise, or combined training to a control intervention—usually a standard of care such as medication, cognitive behavioral therapy (CBT), counseling, or health education.

A majority of the studies (21) used an aerobic exercise-only intervention, while just 3 of them used resistance training and 6 used combined aerobic and resistance exercise…a glaring indication that we have much more to learn (and more studies to conduct) on resistance exercise as it relates to depression.

Exercise had a large benefit for reducing depressive symptoms, and importantly, this didn't depend on the mode of exercise—both aerobic and resistance exercise reduced depressive symptoms. Aerobic exercise did have a numerically greater effect (a 1.6-point reduction in standardized depression scores) than resistance exercise (a 0.89-point reduction), but the difference between them wasn't statistically significant.

Exercise also helped moderately reduce anxiety symptoms, again with both aerobic (a 0.56-point reduction in standardized depression scores) and resistance exercise (a 0.83-point reduction) showing benefits. This time, resistance exercise had a numerically (but not statistically significant) advantage compared to aerobic exercise, hinting at its potentially greater effectiveness for anxiety outcomes.

The effects of exercise on depression symptoms.

Why Exercise Helps with Depression

The claim that "exercise cures depression" is a bold and controversial one.

That's because—despite observational studies showing a link between higher levels of physical activity and lower levels of depression—some argue that this is a classic case of reverse causality. Maybe it's not that physical activity fights depression per se, but rather, that more depressed people just exercise less.

We have to acknowledge that this is a possibility. Adults with major depressive disorder are less active and more sedentary than adults without depression, and nearly 70% of them don't meet the recommended physical activity guidelines, putting them at a much higher risk of cardiovascular disease, metabolic syndrome, and overall mortality.

Exercising less isn't a matter of laziness or willpower. Depression creates several barriers to participating in physical activity including depressive symptoms themselves which hamper motivation, a higher body mass index and other physical comorbidities that make physical activity challenging, and reduced self-efficacy.

However, two things can be true. Yes, depression creates a landscape less conducive to physical activity, but physical activity per se has also been causally linked to depression. Mendelian randomization studies show that people genetically inclined to be less active tend to have higher rates of depression, suggesting that physical inactivity isn't just associated with—but actually contributes to—depressive symptoms.

There is also robust mechanistic evidence supporting a link between exercise and depression.

Mechanisms Linking Exercise to Depression

One biological pathway linking exercise and mental health involves kynurenine—a metabolite produced from the amino acid tryptophan. Under stress and inflammatory conditions, tryptophan metabolism is diverted away from serotonin production toward the kynurenine pathway, resulting in increased formation of quinolinic acid, a neurotoxic compound linked to depression and neurological disorders.

Exercise positively modulates this pathway, shifting it toward neuroprotection. Specifically, endurance exercise stimulates muscles to produce higher levels of kynurenine aminotransferase (KAT), an enzyme that converts kynurenine into kynurenic acid rather than quinolinic acid. Kynurenic acid is neuroprotective and, importantly, cannot cross the blood-brain barrier. This enzymatic shift significantly reduces the availability of kynurenine to form quinolinic acid in the brain, thereby lowering the neurotoxic burden.

This "kynurenine hypothesis" has substantial scientific backing. Individuals experiencing depression typically show an unfavorable shift—characterized by elevated ratios of kynurenine to tryptophan and increased quinolinic acid levels. Conversely, experimental studies in animal models demonstrate that enhancing KAT enzyme activity offers protection against stress-induced depression. Furthermore, endurance athletes consistently exhibit higher concentrations of KAT in muscle tissue, supporting exercise's role in promoting mental resilience through this biochemical mechanism.

Want to learn how to use exercise to boost memory and creativity? I took a deep-dive into the mechanisms in Premium Member Q&A #24.

8:04 - Can just 15 minutes of exercise before learning improve short-term memory?
9:46 - Does exercising after learning enhance long-term memory retention?
10:15 - Why exercise always pays off in productivity (despite the time commitment)
11:18 - How exercise boosts cognition by improving tryptophan delivery to the brain
12:46 - Does boosting serotonin through exercise stimulate neurogenesis?
13:43 - How serotonin from exercise promotes brain neuroplasticity

Inflammation is another key pathway connecting exercise to mental health. While chronic inflammation is known to play a causative role in depression, the transient inflammation induced by exercise has beneficial effects. Every exercise session triggers a "myokine pulse," releasing hundreds of muscle-derived signaling molecules—known as myokines—into circulation. One especially important myokine in this context is interleukin-6 (IL-6).

Acute increases in IL-6 following exercise initiate a robust anti-inflammatory response in the subsequent hours, lowering chronic inflammation with training and shifting baseline physiology toward conditions less detrimental to mood-regulating brain circuits. Additionally, IL-6 and other myokines actively promote microglia in the brain toward a restorative, anti-inflammatory state rather than the harmful pro-inflammatory phenotype often observed in depression. Reduced inflammation driven by IL-6 also positively impacts the kynurenine pathway by limiting the diversion of tryptophan away from serotonin production.

Lower levels of BDNF are frequently observed in depression, with depressed individuals often displaying BDNF concentrations 10–20% lower than healthy counterparts. Successful antidepressant treatment commonly normalizes BDNF levels, highlighting its central role in mood regulation through neuroplasticity. Disruptions in neural plasticity—often driven by stress and adverse environmental stimuli—contribute significantly to the onset and progression of depressive symptoms. By stimulating neuroplasticity, elevated BDNF can reverse or mitigate these detrimental changes. Notably, no intervention has proven more effective at increasing BDNF levels than strenuous aerobic exercise.

Finally, there are endocannabinoids and endorphins. Endocannabinoids are naturally produced compounds that bind to receptors throughout the brain and immune system—the same receptors activated by cannabinoids like THC and CBD. These molecules play a significant role in generating the euphoric sensations often felt during moderate- to vigorous-intensity aerobic exercise.

Additionally, exercise triggers the release of beta-endorphins, the body’s own opioids that help reduce pain and enhance mood, famously associated with the "runner's high." Together, the endocannabinoid and endorphin systems contribute significantly to the mood-boosting effects of exercise, although they likely play a more supportive role when it comes to reducing depressive symptoms—a distinction likely reserved for kynurenine, BDNF, and inflammatory signaling.

Final Thoughts

The mood-elevating effects of a hard workout are what initially drew me to exercise, and I still find that high-intensity exercise is one of the best ways to sharpen my thinking and raise my spirits for several hours. I like to think of it as my "brain pill."

Of course, simple mood elevation is not the same as resolving symptoms of clinically diagnosed depression or anxiety, but they do share similar pathways.

It's clear based on the evidence that exercise should become a standard treatment for depression and anxiety. However, it remains underused and undervalued. Hopefully that will change as medical professionals, therapists, and other mental health experts become increasingly aware of exercise's powerful effects on its own or when combined with other pharmacological or behavioral therapies.

The biggest question often on people's minds is: "Ok then, how much do I need to exercise?"

The answer to this question might be less than you think.

I am an advocate of moving as much (and as vigorously) as possible—at least 150 minutes and up to 300 minutes or more per week. But for depression, the benefits might start at an even lower dose. In fact, the authors of the study noted that "Despite the findings from this review favoring the use of exercise to reduce symptoms of depression and anxiety, only three studies met the WHO weekly physical activity guidelines (volume and intensity) for both aerobic and resistance exercise."

For people with depression—or even those just seeking mood elevation—movement is the best medicine.

Warm regards

— Rhonda and the FoundMyFitness team

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Exercise–In All Forms—Reduces Depression and Anxiety

Why Exercise Helps with Depression

Mechanisms Linking Exercise to Depression

Final Thoughts