When researchers made artificial mouse muscle contract with flashing lights, nearby neurons grew four times longer. The secret? Proteins released during muscle contractions that act like 'miracle grow for the brain.'

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Now, some psychiatrists are using structured exercise protocols and creatine supplementation— often alongside traditional treatments—to harness this same muscle-to-brain communication for treating depression.

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In the latest episode of Psychiatry Tomorrow, Dr. Will Sauvé sat down with Dr. Nicholas Fabiano, a rising star in psychiatry at the University of Ottawa, who’s shaking up the field with "lifestyle psychiatry." He’s diving into how exercise is a legitmate first-line treatment for depression.

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In this episode, you’ll learn:

• Why exercise can rival antidepressants for some patients—and how to "prescribe" it right
• How creatine’s brain benefits go way beyond the gym and standard recommended dosing
• The role of myokines, proteins linking muscle movement to mood
• Warning signs when exercise becomes self-harm
• Why the future of psychiatry means treating mind and body together

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Exercise Rivals Antidepressants: The Evidence

Twenty years ago, suggesting exercise could treat depression would have earned you skeptical looks (intentional exercise was uncommon until fairly recently). Today, the evidence tells a different story. Exercise can be equally as effective as antidepressants for mild-to-moderate depression according to current randomized control trial data. Research suggests this may work through myokines—muscle proteins that promote brain growth—though the exact mechanisms are still being studied.

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But these studies face a unique challenge. Unlike medication trials, there’s no good version of placebo for exercise. "You can't really blind someone to exercising," Fabiano explains. "Even if you quite literally put a blindfold on them, they're gonna know they're exercising."

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Different studies handle control groups differently. Some compare running to no movement, others use active stretching as the control, and some pit high-intensity against low-intensity exercise. None are perfect solutions, but the consistency across different approaches strengthens the findings.

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The caveat? These are controlled trial conditions with supervision and support. "This is not necessarily real world, so adherence may be better when you have someone watching you exercise," Fabiano notes.

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The Muscle-Brain Connection: Myokines and BDNF

Muscle does more than move your body. Skeletal muscle acts as an endocrine organ, secreting proteins called myokines that communicate with the brain.

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A recent study illustrates this perfectly. Researchers created artificial muscle tissue from mice and genetically engineered it to contract when exposed to flashing lights. "They essentially simulated exercise by flashing a light over and over, which contracted that muscle over and over. And what that did was release these myokines," Fabiano explains.

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The results were striking: "When there were neurons in the presence of this myokine, they grew four times further than those that were not."

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"One of the best things that you can do for your cognitive health is exercising and really contracting your muscles," Fabiano explains. When muscles contract repeatedly, they release myokines that cross into the brain.

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The key player is BDNF (brain-derived neurotrophic factor), which "people describe that to be the miracle grow for the brain." Exercise creates structural brain changes - "we know that exercise can actually increase the size of your hippocampus," which is important for memory.

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Exercise also decreases overall body inflammation and improves metabolic markers like blood pressure—factors linked to depression pathophysiology.

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Not All Exercise Is Equal: Intensity Matters

When patients ask about the "best" exercise for depression, the research provides a clear answer: intensity matters more than type.

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"The intensity of exercise is really what is proportional to the antidepressant effect, so the higher the intensity, the greater the antidepressant effect," Fabiano says. Whether you choose aerobic, resistance, or mind-body exercise, meta-analyses show no huge differences between types. Of course, consider physical capabilities and enjoyment. "In elderly populations, usually a moderate or low intensity is better than a high intensity.”

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The most dramatic improvements happen when someone goes from 0-1. "When you look at someone going from completely sedentary and not moving to even just starting to exercise a bit... that little bout of exercise has such a significant antidepressant effect." Most importantly, adherence trumps optimization. "Making sure that it's something the patient actually wants to do" matters more than following a perfect protocol.

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The FIT Framework: How to Prescribe Exercise for Depression

Rather than telling patients to "go exercise," Fabiano advocates for the FIT framework, treating exercise like any other therapeutic intervention. "You can very realistically have a conversation with your patient and write down the FIT framework as you would for a prescription," he explains.

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The framework has four components:

Frequency: How many times per week? "Start low and go slow" (the same principle used for medications).

Intensity: Low, moderate, or vigorous? Match this to the patient's capabilities.

Type: Aerobic, resistance, or mind-body? Let patient preference guide this choice.

Time: Session duration? Begin with achievable durations rather than overwhelming commitments.

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Document the plan and follow up at each visit. "Each time you see your patient, the goal is to steadily increase a little bit. Or when you find that dose that works akin to a medication, you stay there."

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The framework, detailed in Fabiano's paper "How to Prescribe Physical Activity for Depression" in the Journal of Sports Psychiatry, transforms vague advice into actionable treatment plans.

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For Clinical Practice, here’s a quick reference guide:

• Frequency: Start with 2-3x/week, increase gradually
• Intensity: Higher intensity = greater antidepressant effect (but match to patient capability)
• Type: Patient preference trumps optimal type; adherence matters most
• Time: Begin with 10-15 minutes, build to 30-45 minutes
• Documentation: Chart like medication:  "Patient prescribed moderate intensity walking 3x/week for 20 minutes, follow-up in 2 weeks"

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Creatine for Depression: From Gym to Brain

While bodybuilders have used creatine for decades, mental health applications are increasingly compelling. The safety profile that made creatine popular in fitness translates well to psychiatric use.

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The first psychiatric signal came from a 2011 study by Lyoo et al in the American Journal of Psychiatry. "They paired it with an antidepressant over eight weeks and two weeks in, they already noticed an improved response. And then at eight weeks, the response continued to improve."

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More recently, a 2025 study in European Neuropsychopharmacology by Sherpa et al "paired creatine with cognitive behavioral therapy" over eight weeks and "found, again, a similar trend where they had improved response at the end of eight weeks and it was very well tolerated." "Risk benefit, very favorable. It's very cheap, it's very accessible," Fabiano notes. A 90-day supply costs around $35.

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But dosing for mental health differs from gym protocols. While fitness users typically take 5 grams daily, brain benefits may require higher doses. "It's looking like around 10 or even higher to really see brain benefits, mental health benefits." The reason: "95% of creatine approximately goes to your muscle and about 5% goes to the brain.” The brain has fewer creatine transporters than muscle, and saturation takes longer.

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When Exercise Becomes Self-Harm

Fabiano warns about a pattern that often goes unrecognized: exercise as self-harm, distinct from eating disorder behaviors.

"You can imagine someone that has depression or had something really bad happen in their life and to cope, they're going to the gym... but they're going with the intention to feel pain. They're going with the intention to injure themselves. They're going with the intention to transfer that emotional pain into something physical."

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This behavior gets reinforced rather than questioned. "If you went to your doctor and said, 'Hey, I've been depressed. I went through a breakup. I'm really sad. I've been in the gym six hours a day,' your doctor will be like, 'That's great. That's sublimation.'" But excessive exercise with harmful intent can perpetuate depression; red flags include excessive time and frequent injuries.

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This connects to Fabiano's meta-analyses on exercise and suicide: "We found that exercise reduced suicide attempts... but not deaths, nor ideation." One interpretation: "Perhaps the exercise is replacing the suicide attempts rather than reducing it in the form of self-harm."

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Clinical Implementation Challenges to “Prescribing” Exercise

Translating research into practice reveals significant barriers. Studies showing exercise equals medication effectiveness typically involve supervision—conditions that don't exist in most clinical settings.

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"It would be great to be able to prescribe a fitness trainer, to prescribe a gym membership," Fabiano says. "We know that supervised exercise interventions do better than non supervised from an antidepressant perspective because of the adherence side of things."

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Financial barriers compound the problem. "If that person really wants to go to the gym and it's expensive and they're already not able to afford food and rent, you're presenting an option to someone who won't be able to do it, and that can discourage them more."

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For severe mental illness, additional considerations apply. Recent guidelines for schizophrenia management "recommended lifestyle interventions at all stages, but it was more of that passive recommendation," Fabiano notes. His group wrote to Lancet Psychiatry arguing that "it's important that beyond just passively recommending you have something in place to actually have supervision."

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Combining Forces: Exercise Plus Creatine for Depression

The logical next step combines exercise and creatine, leveraging complementary mechanisms. Creatine helps muscles contract repeatedly by replenishing ATP, while contractions release beneficial myokines.

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"If you went to your gym and you asked some of these people, they're already doing it,” Fabiano notes. But formal research lags behind practice. "There's a big gap in the literature... I’d recommend pairing creatine at the doses and durations that I mentioned before with exercise and see what effect does that have on depression."

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The combination makes biological sense and might enhance therapy engagement. "I think that would even allow you engage more in therapy if you're more cognitively alert and you're able to just be more present."

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Is Lifestyle Psychiatry and Integrated Care the Future?

Fabiano's vision for psychiatry centers on eliminating artificial divisions between mental and physical health. "Removing the divide between mental and physical health that we have... we'll see better outcomes for the patient and we'll see more collaboration between discipline," he explains.

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Current practice operates in silos, missing important connections. "In mental health, a lot of our medications have really bad effects to people's metabolic health" while other specialties prescribe medications affecting mental health.

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The solution involves proactive collaboration. When starting antipsychotics known to cause metabolic problems, "there's other things like medications, like metformin or ozempic that can be paired with these" proactively.

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“Some argue metabolic dysfunction could be the root cause of mental illness from the metabolism side of things." If true, integrated care isn't just better, it's necessary.

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TL;DR Summary

• Exercise matches antidepressants for mild-to-moderate depression through muscle proteins called myokines that boost brain growth.
• Use the FIT framework (Frequency, Intensity, Type, Time) for systematic patient discussions.
• Creatine at 10g+ may enhance these effects when used alongside traditional treatments.
• Watch for exercise becoming self-harm (6+ hours daily, frequent injuries).
• The future lies in treating mental and physical health as one integrated system rather than isolated specialties.
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To learn more about lifestyle psychiatry and Dr. Fabiano’s work, follow him on X, where he summarizes and deep-dives breaking research.
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Podcast Timestamps / Shownotes

[00:00:00] Introduction - Dr. Fabiano's background and training structure in Canada

[00:04:30] Defining lifestyle psychiatry and the mind-body connection

[00:06:00] Exercise for depression - research evidence and meta-analyses

[00:09:00] Exercise study design challenges and placebo controls

[00:11:30] Exercise intensity vs. type - what matters for antidepressant effects

[00:15:00] The muscle-brain connection - myokines and BDNF explanation

[00:20:00] Creatine for mental health - from gym supplement to brain fuel

[00:26:00] Clinical implementation - the FIT framework for prescribing exercise

[00:33:00] Exercise as self-harm - warning signs and red flags

[00:40:00] Balancing productivity with self-care during medical training

[00:42:00] Future of psychiatry - removing mental-physical health divide

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