Can Exercise Cure Depression?

She came to me with a label. Depression. Her PHQ-9 and GAD-7 scores (these are not diagnostic, but are used to to score mental health issues) were high enough to justify it. An SSRI had already been started. On paper, everything looked appropriate. Symptoms present, diagnosis made, treatment initiated.

Then why did she come to me?

She wasn’t collapsing, but she wasn’t herself either. Flat. Foggy. Slightly disconnected from life. The scores nudged down a little, but not enough to explain the lived experience. And buried in her history was something that mattered: post‑pregnancy hypothyroidism, something that loves to blur the line between physical illness and mental distress.

I asked her if she was OK to stop her meds. I warned her of the risks, especially after her treating doctor refused to stop it. She was waiting for someone to tell her this.

And then I asked her to move. Like literally.

Not extreme exercise. No gym heroics. Just an hour a day of circuit‑style movement: light weights, lots of transitions, sustained motion. Enough to breathe harder. Enough to sweat. Enough to remind her nervous system that the body still worked.

She came back a week later feeling dramatically better.

She felt cured, but confused. How did this happen? Can exercise cure depression?

When the Story Sounds Like Voodoo

A journalist later wanted to write about preventive and wellness medicine and wanted to speak to some of my patients. When she heard the story from her, she declined to write.

“This sounds like voodoo,” she said. “Depression can’t be cured in a week.”

While she didn't say it to my face, she probably thought I was a quack too!

She wasn’t wrong.

Depression shouldn’t be trivialised. Mental health conditions are real, serious, and at times life‑threatening. And anything that looks and sounds like a quick fix deserve skepticism.

But here’s the nuance that gets lost: the claim was never that exercise cured depression. The observation was that a subset of people who meet criteria for depression improve rapidly when movement is introduced, sometimes far more than we expect.

That difference matters.

The Duck Problem

There’s a saying we all love: If it looks like a duck, walks like a duck, and quacks like a duck, then it must be a duck.

That logic works beautifully in many places. It works terribly for biology.

Chest pain is a perfect analogy. Chest pain does not always mean a heart attack but every chest pain must be taken seriously, because the cost of missing one is too high.

Mental health is similar. Low mood, anxiety, fatigue, poor motivation, sleep disturbance these symptoms demand attention. They should never be dismissed.

But attending to symptoms is not the same as assuming a single cause.

One Label, Many Biologies

In most areas of medicine, we accept heterogeneity without argument. Fever isn’t always infection. Fatigue isn’t always iron deficiency. Shortness of breath isn’t always asthma.

Yet mental health often gets compressed into a single bucket.

If the duck quacks loud enough, we call it depression. And the default response is usually the same.

Sometimes that works. Often, it helps meaningfully. And sometimes, frustratingly, it barely moves the needle.

What Poor Response Started Teaching Me

Early in my practice, a pattern emerged. Some patients responded beautifully to antidepressants. Others barely improved, maybe 10 to 20 percent. Enough to change scores, not enough to restore life. Some felt emotionally blunted. Others sedated. Many stopped treatment not because it didn’t work at all, but because it didn’t feel right.

That inconsistency was my first clue.

Over time, I stopped viewing this as treatment failure. I started seeing it as information.

What If It’s Not Just a Serotonin Story?

Let’s be clear: serotonin matters. Medication saves lives. This is not an anti‑psychiatry argument.

But biology rarely runs on a single pathway.

If low serotonin were the dominant mechanism in all depression, we’d expect antidepressants to work far more consistently than they do.

Which opens a different question, something that makes some people uncomfortable:

What if, in a subset of patients, the primary issue isn’t mood chemistry, but energy regulation?

How exactly did exercise help her?

Bear with me if this feels too much like a biology class, I'll keep it brief.

The brain is one of the most energy‑hungry organs in the body. When energy production falters, mood, motivation, focus, and resilience are often the first casualties.

Chronic inflammation can push certain amino acids down metabolic pathways that generate compounds like quinolinic acid (QUIN). In excess, QUIN can disrupt neuronal signalling and divert resources away from producing NAD+, a molecule essential for cellular energy and repair.

The fuel is there, but it’s not reaching where it’s needed.

Here’s where exercise becomes interesting.

Movement doesn’t just release endorphins. It upregulates (fancy word for wake up and push) enzymes like QPRT, nudging metabolism away from QUIN accumulation and back toward usable energy. It improves mitochondrial efficiency, inflammatory signalling, and neural plasticity, all without a prescription pad.

For some people, that shift is fast. For others, it barely registers. And that variability is the point.

While we are in this topic, exercise is not the only thing that pushes up the QPRT enzyme. Fasting does too, but what works for whom is a topic for another day.

Why Exercise Helps Some But Fails Others

Exercise isn’t a cure. It’s a biological probe.

When someone improves rapidly with movement, it suggests the dominant driver may be metabolic, inflammatory, endocrine, or deconditioning‑related.

When it doesn’t, it tells us something else is in charge.

Neither outcome invalidates the diagnosis. Both inform the strategy.

So… Can Exercise Cure Depression?

That question is too blunt to be useful.

A better one is: what biology is driving this person’s symptoms and what intervention matches it best?

For some, medication is essential. For others, movement is transformative. For many, the answer is layered and sequential.

The danger isn’t using antidepressants. The danger is assuming the duck must always be the same species.

The Takeaway

Mental health conditions are real. They deserve seriousness, urgency, and compassion.

But seriousness doesn’t require simplicity. Sometimes the most responsible thing we can do is resist neat answers, tolerate complexity, and ask better questions.

Because when it comes to the brain, what looks like a duck may be a nervous system asking for a very different kind of care.