This depression theory was never proven—but everyone still believes it

My mind was actually blown when I learned this.

Hello friends!

If you tuned into Monday’s pod, you know I’ve always struggled to be happy. It’s not something I’m proud of (or thrilled about, obviously), but I am grateful that it’s led me to talk to so many incredible, world-famous experts who have dedicated their lives to studying mental health.

One of said experts, and today’s podcast guest, is also a dear friend of mine: Dr. Ellen Vora. Ellen is a board-certified psychiatrist, acupuncturist, and yoga teacher who is revolutionizing the way we understand mental health. With a BA from Yale and an MD from Columbia, she blends traditional medicine with holistic practices to address the root causes of mental health issues.

Ellen is also the author of the bestselling book “The Anatomy of Anxiety,” where she introduces groundbreaking perspective by distinguishing between "false anxiety"—rooted in physical imbalances like blood sugar fluctuations and sleep deprivation—and "true anxiety," which serves as an internal compass signaling deeper misalignments in our lives.

It probably doesn’t come as much of a surprise to know that when it comes to new science around mental health, Ellen is on the cutting edge of it—and one thing she told me in our conversation blew my mind.

The idea that depression is caused by a chemical imbalance has never actually been proven

For decades, we were told that SSRIs—think Zoloft, Lexapro, or Prozac—can help correct a “chemical imbalance in our brains” by way of delivering more serotonin. But that theory has never actually been proven. Actually, a huge 2022 review found no consistent evidence that low serotonin causes depression at all.

Wait, what?! Here’s the deal:

🤯 The serotonin theory of depression was actually rooted in research on tuberculosis drugs

This idea originated from an observation, according to Ellen, that certain tuberculosis drugs that impacted serotonin also seemed to affect mood. From there, the theory snowballed. But in 2022, psychiatrist Mark Horowitz published a massive review in Molecular Psychiatry examining all the major research angles—serotonin levels, receptors, transporter genes—and found no consistent evidence that low serotonin causes depression.

💊 But that doesn’t mean your SSRI is useless

Ellen says that while antidepressants like SSRIs do help certain people, the mechanism is more complex than simply correcting a chemical imbalance. Their effects may be due to blunting emotional highs and lows, modulating the stress response, increasing neuroplasticity, or even the placebo effect—not replenishing “low” serotonin, as we’ve long been told.

❤️‍🩹 Believing depression is only a chemical problem can actually hold you back from healing

The chemical imbalance model offers some relief from shame (“it’s not your fault”), but it can also create a sense of stuckness. If you think you’re broken biochemically, you may feel powerless to do anything about it. Ellen encourages reframing depression as a signal of deeper imbalance, often physical or psychospiritual, that can be addressed and healed.

From the episode:

“I think that the spirit behind this pursuit [of using SSRIs] was always like, let's alleviate human suffering. And now we are many decades into a gabillion-dollar pursuit of pointing to this chemical imbalance. And I think my field is having a hard time owning that right now.

We haven't been able to demonstrate it because it is not actually there.”

The takeaway: If you’re taking SSRIs and they genuinely help you, that’s great. But if you’re skeptical of how well they work or don’t notice much as a difference, try examining other potential issues that could be holding you back on your healing journey.

For more incredible insights from Dr. Ellen Vora, including why crying might be the ultimate medicine, how to tell if you're actually in SSRI withdrawal (not a relapse), and the link between inflammation and modern depression, head over to today’s episode episode of the podcast on Spotify, Apple Podcasts, or YouTube. It would also mean the world to me if you could hit the heart to “like” this post—it helps others find my Substack more easily!

Xo,

Liz

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