Depression Is Not a Chemical Imbalance: Why SSRIs Fail and What Actually Heals

For decades, the dominant explanation for depression has been deceptively simple: low serotonin causes low mood, and antidepressants correct the imbalance. This idea became so widespread that it entered common language, clinical practice, and even church conversations about mental health.

But the theory is false.

Not outdated.
Not incomplete.
False.

And continuing to treat depression as if it were true has caused profound harm. More often depression itself is a breakdown in how the nervous system communicates, regulates stress, restores itself through sleep, and adapts after prolonged strain. When these systems lose coherence, mood follows — not as the root problem, but as the visible symptom.

This distinction matters. Because when we misunderstand what depression actually is, we tend to choose tools that manage it indefinitely rather than help resolve it.

The chemical-imbalance myth

Despite how often it is repeated, no reliable biological marker has ever been identified that distinguishes a “depressed brain” from a “non-depressed brain.” Large reviews of neuroimaging, neurotransmitter levels, and post-mortem studies have consistently failed to show a reproducible serotonin deficiency in people diagnosed with depression.

Brain scans of individuals with depression do not reveal a consistent structural or chemical abnormality. There is no blood test, no imaging result, no neurotransmitter assay that can diagnose depression or confirm a serotonin deficit. This matters because medicine must be grounded in reality, not narrative.

The chemical-imbalance story did not emerge from decisive evidence. It emerged as a marketing simplification, designed to make long-term psychiatric drug use feel intuitive and inevitable.

Depression is not caused by “low serotonin” in the way diabetes is caused by low insulin. Treating it as such is not only incorrect — it is medically reckless.

What depression actually is

Most people with depression are not simply sad. They are mentally exhausted. Their thoughts loop in familiar, unproductive patterns. Sleep no longer restores them. Emotion feels either distant or overwhelming, with little middle ground. Even reflection, prayer, or quiet presence can feel clouded — not because meaning is gone, but because internal clarity has been disrupted.

Physiologically, this often involves several overlapping processes. The stress response becomes overactive, keeping the body in a state of alert long after danger has passed. Sleep cycles fragment, reducing the brain’s ability to reset emotionally. Thought patterns become repetitive, circling the same concerns without resolution. Over time, the brain’s natural adaptability — its capacity to form new connections and exit old loops — diminishes.

This adaptability is known as neuroplasticity. When it is impaired, people don’t simply feel bad — they feel stuck. Understanding this helps explain why encouragement alone rarely lifts depression, and why purely suppressing symptoms often falls short.

Depression is better understood as a state of nervous-system dysregulation, not chemical deficiency.

People with depression experience:

Persistent stress activation that does not resolve
Disrupted sleep cycles that prevent emotional reset
Rumination loops that trap attention and meaning
Reduced neuroplasticity — the brain’s ability to adapt and recover

These changes are functional, not structural. They reflect how the brain is operating, not that it is broken or missing something. This is why depression can lift suddenly after rest, repentance, environmental change, or meaningful intervention — and why no scan can reliably distinguish a depressed person from a non-depressed one.

The problem is not that the brain lacks a substance. The problem is that its regulatory systems have been overwhelmed and locked into maladaptive patterns.

Why SSRIs are dangerous by design

SSRIs do not correct a known deficiency. They force a change in signaling based on a theory that does not hold.

They work by blocking serotonin reuptake indiscriminately, increasing serotonin activity everywhere — not where it is needed, not in proportion, and not in response to actual physiological demand.

This creates several predictable harms.

First, SSRIs flatten emotional range. They reduce not only despair, but joy, motivation, grief, and conviction. Many users report feeling less human, less responsive, and less present — precisely because the medication suppresses emotional signal strength rather than restoring regulation.

Second, SSRIs disrupt sleep architecture. REM sleep and deep restorative cycles are altered, impairing the brain’s natural capacity to process emotion and consolidate meaning. This alone can perpetuate depression rather than resolve it.

Third, SSRIs create physiological dependence. Over time, the nervous system adapts to forced serotonin elevation. When the drug is reduced or stopped, withdrawal symptoms often emerge — not because depression has returned, but because normal signaling has been chemically overridden.

This is why discontinuation is frequently described as more severe than the original condition.

Finally, SSRIs block neuroplastic repair. By suppressing emotional signaling rather than resolving it, they prevent the brain from completing the very adaptations required for healing. The person may feel “stable,” but stability is achieved through suppression, not restoration.

In short: SSRIs manage distress by disabling the alarm system, not by repairing what caused it to activate.

Why “benefit” is the wrong metric

SSRIs are often defended by pointing to short-term symptom reduction. But reduced distress is not the same as healing. If a medication numbs pain while preventing recovery, it cannot be considered therapeutic — only palliative. This is why long-term outcomes on SSRIs are so poor, why relapse rates remain high, and why many people remain medicated for years without resolution.

A medicine that must be taken indefinitely to maintain baseline function has failed its purpose.

A fundamentally different approach

Before SSRIs dominated psychiatry, some treatments worked upstream — supporting the brain’s ability to regulate itself rather than overriding it. One such approach involved reversible MAO-A modulation, which gently slows the breakdown of mood-related neurotransmitters without forcing their release or suppressing emotional processing. This distinction is critical.

Reversible MAO-A support does not flatten emotion. It does not induce intoxication. It does not bypass conscience or agency. Instead, it reduces internal noise, softens rumination, and supports sleep and neuroplastic recovery.

One traditional example of this — when used soberly, without admixtures or ceremony — is the vine of Banisteriopsis caapi prepared as an alcohol tincture. In this form, it supports regulation rather than suppression and clarity rather than escape.

The difference is not subtle. One approach seeks control. The other seeks restoration.

Why this matters spiritually

From a Christian perspective, medicines must be evaluated not only by symptom reduction, but by what they do to presence, agency, and conscience. A substance that dulls conviction, numbs emotional response, and encourages passive dependence undermines repentance, growth, and discernment — even if it reduces distress. Depression does not require emotional erasure. It requires restoration of function.

A medicine that helps someone re-enter life, prayer, responsibility, and relationship serves healing. A medicine that suppresses these capacities does not.

The conclusion modern medicine avoids

Depression is not evidence of a broken brain. It is evidence of a system under prolonged strain. SSRIs treat this strain by chemically silencing the system. That is not healing. It is containment — and often permanent containment.

There are better ways. They are quieter. They require education, participation, and patience. They do not promise instant relief. But they respect the body’s design and the soul’s integrity. Healing does not come from overriding the system. It comes from removing what prevents it from regulating itself.

Closing thought

A good medicine does not numb a person into compliance.
It restores their ability to feel, discern, and respond.

Anything less is not treatment.
It is surrender dressed as care.

Resources & Studies

🧠 The Chemical-Imbalance Hypothesis — Lack of Evidence

“No evidence that depression is caused by low serotonin levels” — A comprehensive umbrella review finds no consistent evidence linking serotonin levels or serotonin activity with depression, challenging the foundational claims behind the “chemical imbalance” model.
🔗 UCL Review – No clear evidence depression is caused by low serotonin
https://www.ucl.ac.uk/news/2022/jul/no-evidence-depression-caused-low-serotonin-levels-finds-comprehensive-review University College London

Systematic analysis of serotonin studies — A detailed scientific article surveying multiple lines of research on serotonin and depression shows that the evidence does not support the idea that depression is caused by low serotonin or its metabolites.
🔗 Nature Article: The serotonin theory of depression — umbrella review
https://www.nature.com/articles/s41380-022-01661-0 Nature

📉 Historical Critique of the Serotonin Hypothesis

Serotonin research history and limitations — An NIH-hosted paper reviewing 50 years of research explains how the serotonin hypothesis originated and why it has failed to yield consistent, reproducible evidence linking serotonin to depression.
🔗 NIH Paper: Fifty years on — Serotonin and depression
https://pmc.ncbi.nlm.nih.gov/articles/PMC10076339/ PMC

🧠 The Chemical Imbalance Belief as a Cultural Phenomenon

“Chemical imbalance” as a social narrative — A peer-reviewed paper explores how the chemical-imbalance explanation became widespread in public understanding of depression, largely due to pharmaceutical marketing narratives rather than solid scientific validation.
🔗 ScienceDirect Article: Is the chemical imbalance an ‘urban legend’?
https://www.sciencedirect.com/science/article/pii/S266656032200038X ScienceDirect

🧪 Advertising vs Evidence

SSRIs and serotonin imbalance messaging — A classic PLOS Medicine paper from ongoing research shows how SSRI advertising historically framed depression as caused by a chemical imbalance and marketed drugs as correcting it — even though this link is scientifically unproven.
🔗 PLOS Medicine: Serotonin and Depression Advertising Claims
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0020392 PLOS

🧠 Psychiatric Criticism of Antidepressants

Antidepressants do not correct chemical imbalance — In this article from PMC, researchers argue that antidepressants have mind-altering effects and that there is no evidence they work by fixing a chemical imbalance in depression.
🔗 PMC