A large body of research demonstrates that exercise is at least as good as antidepressants and psychotherapy for treating depression. Exercise lacks the harms of drug treatment and comes with other benefits for overall health. While antidepressant drugs worsen cardiometabolic health, exercise improves it. Exercise even has a preventative effect, reducing the likelihood of later depression.
A new article in Molecular Psychiatry shows that psychiatrists have noticed this positive effect, which is good to see. “There is a significant body of literature which clearly demonstrates that exercise is an equally effective treatment for non-severe depression when compared to traditional first-line measures such as antidepressants or therapy,” the authors write.
But . . . drum roll please . . . they now see an opportunity for prescribing a pill to “mimic the effects of endurance exercise.”
These pills, known as “exercise mimetics,” already exist. Drugs classed this way include diabetes drug metformin and natural remedies like omega-3s and curcumin. The problem, though, is that there is no pill to really mimic all the effects of exercise.
Obviously, there are psychosocial aspects of exercise—aspects like leaving the house, being outside or in an environment with other people, experiencing your body (imagine how impactful this could be, particularly for those who dissociate).
But even beyond the psychosocial factors, exercise impacts the various body systems in a complex way. Any pill that claims to be an “exercise mimetic” is only acting on a fraction of the systems that actual exercise impacts. (For instance, metformin acts on AMP-activated protein kinase.) Each of the proposed “exercise mimetics” acts on a different set of such systems. They don’t improve your cardiopulmonary health like actual exercise does. And, of course, these pills come with their own set of side effects.
However, there is only one question that would really sell this concept: is there evidence these pills actually work?
Not at this time, according to the authors. Their idea is based on a theory that skeletal muscle biology is the key causal feature of depression, based on a few studies in animals. “In this scenario,” they write, “muscle fibers with slow, oxidative dominance secrete amore neuroprotective complement of molecules, which may be associated with improved metabolic homeostasis, mitochondrial function and epigenetic changes, thereby contributing to long-term mood stabilization.”
But is there any evidence these drugs improve depression in humans? Well, there is one study that found an antidepressant effect: a randomized controlled trial of metformin in 58 Chinese patients with diabetes, conducted more than a decade ago.
There is also a meta-analysis of four studies on resveratrol—which failed to find a significant effect.
The researchers write, “Obviously, the current evidence of exercise mimetics in human populations is inconclusive.”
So, the evidence for mimetics is “inconclusive” at best, and the evidence for actual exercise is growing, consistent, and positive. Does that mean we should encourage people to exercise, then?
Not according to these authors, who don’t mention such an idea. Their conclusion is that we devote more resources to the “potential of exercise mimetics […] in the quest to provide novel and effective treatment avenues for improving non-severe depression.”
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Fabiano, N., Fiedorowicz, J.G., Ravel-Chapuis, A. et al. Exercise mimetics as unexplored therapeutics for treating depression. Mol Psychiatry (2026). https://doi.org/10.1038/s41380-026-03499-2 (Link)
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Editors’ note: Psychobabble is a new monthly feature of our science coverage. Readers may submit suggestions for journal articles to be featured as Psychobabble of the Month to [email protected].
Pill=nail, hammer=psychiatrist. Grow up, psychiatrists, good mental health is about living within a safe, sane, non-violent, society; having good food and good healthcare; spending time in nature, having a loving family.
‘It Is No Measure of Health To Be Well-Adjusted to a Profoundly Sick Society’ is perhaps Krishnamurti’s best-known quote. Please wake up.
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UNBELIEVABLE :-0 :-0
(I’m trying to be polite here)
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Could it be that cognizant people living in a dystopian society naturally experience depression, and not only is this natural but normal? Maybe depression is a signal that something is really wrong with the world around us, and it would serve as a motivator for change, but we’re too busy addressing the depression itself to recognize and effectively address the “systems errors” of the world?
None of the “pills” a person can take will change the depressing world around them.
When dystopian conditions are normalized, the problem may not be with those who suffer under them, but with those who no longer recognize those conditions as a problem—and think the problem must be with those suffering under them.
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So you’re saying we live in a depressing society, and that’s why so many people are depressed? That’s a depressing thought!
But seriously, I agree 100%. If you’re not upset by what is going on around you today, you’re either asleep or dead!
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Or delusional
Are we all living with cognitive dissonance ? Some cope with it and some don’t.
Compartmentalized lives that CAN switch on and off and not bleed into one another. ?
The evolution of a non-conscience perhaps.?
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Hello Mad in America. Hi Steve. I don’t use MIA as much these days but I will always check back from time to time.
Thank you for existing. This place was literally all I had during the worst phases of my life and the only place I could express myself freely. I’d have gone truly insane without this place.
People coming on here newly will not realise how much of an achievement this place truly is, especially when it started sometime in 2012 when the internet, when it comes to Psychiatry, was dominated by places like CrazyMeds and everyone who criticised Psychiatry was shouted down as a scientologist or an anti-vaccine crank. Some people still do that of course. But this place has also permanently changed things. It gave a voice to the voiceless. I am so grateful for it.
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Disappointed to see an AI slop here
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Nikita, to whom are you referring as “an AI slop”?
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AI will pretty soon be telling us all what we want to hear. We will start living in a closed loop with ourselves and not recognise this based on the belief that the information we receive is true and good and correct and accurate and complete.
Dan, maybe we like the mirroring and reflection that we receive from AI; something that we don’t get from real live real time humane beings.
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Dismissing ideas because an LLM helped express them is a form of the genetic fallacy—judging an idea by its source rather than its merit.
I often use AI to help shape what I write. Not to generate an idea, but to help express something I’ve been thinking about writing about, some of those things for decades to no avail. It’s not that I’m a poor writer, I’m a decent writer. But I write like I read: very slowly.
Although I’ve published well-reasoned, well-written articles in magazines and journals all over the world—all with a good message offering value, and all before AI was even a thing—I’ve yet to see any of what I’ve written make any difference to anyone.
I’ve spent years trying to communicate ideas about our “system errors” driving immeasurable misery and distress. And offering ideas of an alternative. But writing has never been the most natural medium for me. I can think things through, I can feel when something is off, and I can write. But translating ideas into clear, readable language is something that takes me lots of time.
So I often use AI to help organize and phrase what I’m saying. And it’s not like anyone is paying me for it. I’m merely trying to communicate ideas. People writing for credit or pay might be more concerned about using AI, but I’m just a guy trying to get ideas across. If good ideas are rejected out-of-hand because AI is suspected of creating or coming up with the ideas, then some good ideas might be rejected because of their delivery. That happens all the time (even without AI).
So, even if AI did originate ideas, or create or generate written pieces entirely, does that mean the ideas are wrong or unworthy of consideration? Do matters of taste, form, delivery or personal preference lead earnest thinkers to reject good ideas?
Using AI to help express an idea or viewpoint doesn’t make an idea itself artificial, or invalidate a viewpoint, and it doesn’t mean there isn’t lived experience or real human thought behind it. It might just mean a tool is being used to communicate clearly in a reasonable amount of time.
But dismissing it as “AI slop” (or dismissing a person on that basis) skips over the substance entirely, and that’s the part potentially worthy of discussing. Over the years, I’ve found people are very good at finding all kinds of reasons to reject good ideas. Someday (and it could be soon), people might be more willing to entertain good ideas regardless of their delivery or source. We’re not quite there yet, though.
Honestly, if someone wants my real “human voice,” that’s something that really only comes through in conversation. Writing, like public speaking, is always a one-way form of communication. You lose the back-and-forth, the ability to adjust in real time, the tone, the context. Rising to the occasion to make a point more understandable. But with writing or public speaking, you don’t get to address people in the audience as individuals. So the message is couched in terms that are most widely understood or appropriate for the audience, even sometimes at a cost of sacrificing clarity.
So when I use tools to help with writing, part of that is just trying to compensate for the limits of the medium itself. And I tend to get passionate about certain topics. Sometimes my passionate delivery becomes the focus of my arguments. AI can help with my tone and pacing, and sometimes AI offers viewpoints and facts and ideas that I hadn’t considered. So AI serves as a valued collaborator at times, too.
If someone actually wants to understand where I’m coming from, a conversation will always get closer than a comment, essay, or speech ever can. That’s where a “human voice” can be heard.
Finally, let’s not think that everyone who has something to say or who has lived experience to share is a good enough writer to publish (even just comments), or one with time enough to polish phrasing that may well have no impact, anyway.
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I was actually referring to the ugly meaningless picture (and as you may see, I’m still bad with articles, so no issue with using LLMs for editing).
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Glad to hear it, thanks. I wish everyone were as forgiving for using LLMs for editing. I’ve had good work rejected on that basis.
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How so Nikita. Maybe your comment was deliberately left open for interpretation allowing you to further comment based on the feedback? Genuine? Authentic? True?
A transparent comment would have communicated clearly.
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Thanks, Steve.
It seems we tend to pathologize natural individual coping behaviors while ignoring the artifactual systemic forces that create the conditions people are coping with in the first place—and those systemic forces are what scale into real global harm (and real individual harms, too).
The addictions we should be focusing on are the addictions to money and concentrated power. Those are the addictions that will threaten humanity at large. Those are the addictions creating fundamental problems that increasingly make life miserable—for some more than others.
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“The addictions we should be focusing on are the addictions to money and concentrated power. Those are the addictions that” are threatening humanity at large. “Those are the addictions creating fundamental problems that increasingly make life miserable” for the majority.
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If you were looking for proof that attempts to reform psychiatry are doomed, look no further. Proof that exercise helps depressed people leads to concluding that we need drugs to mimic exercise! What is wrong with these people?
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Of all the drugs in the world they chose Metformin, the one that lowers folate.
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