No, Your Depression Isn’t Just a Serotonin Imbalance

You have low serotonin. Your brain needs this tablet to top it up. You will feel better in a few weeks.

If you have ever been in a South African general practitioner’s office and walked out with an antidepressant, there is a reasonable chance something like that was said to you — or strongly implied. And if you have ever watched a wellness influencer on TikTok explain depression as a simple deficiency, the same framing appeared there too. It is tidy. It is intuitive. And it is wrong.

The myth that took over popular culture

The “chemical imbalance” theory — the idea that depression is caused by low serotonin levels, and that selective serotonin reuptake inhibitors simply restore them — was never a settled scientific finding. It was a marketing-adjacent simplification that hardened into conventional wisdom through pharmaceutical advertising in the 1990s and 2000s, patient leaflets, and a thousand well-meaning general practitioners who needed a way to explain a complex condition in a ten-minute consultation.

The umbrella review published in Molecular Psychiatry in July 2022 by Joanna Moncrieff and colleagues concluded there was no consistent evidence of a relationship between serotonin and depression. The new review — an overview of existing meta-analyses and systematic reviews — suggested that depression is not likely caused by a chemical imbalance, and called into question what antidepressants actually do.

The paper was downloaded over one million times. Social media declared antidepressants a fraud. Neither reaction was justified.

What the 2022 review actually found — and what it didn’t

Before you flush your fluoxetine, read past the headline.

The claims of the authors were bold, and they merited careful consideration.

But “no consistent evidence that low serotonin causes depression” is not the same as “serotonin is irrelevant” or “antidepressants don’t work.”

What Moncrieff’s team examined was whether studies could demonstrate that people living with depression consistently have lower serotonin activity than people who are not depressed. Across multiple lines of evidence — serotonin levels, serotonin transporter studies, and gene studies — the data were not consistent. In experiments that deliberately lowered serotonin production by depleting tryptophan (the raw material the body uses to make serotonin), most healthy participants did not become depressed.

But many people who responded well to antidepressants, including selective serotonin reuptake inhibitors, did not show measurable serotonin abnormalities before treatment.

The honest summary: serotonin is part of a vastly more complex picture than the “low tank, top it up” model suggests. Crucially, the review does not prove antidepressants are ineffective — it undermines the explanation for why they help some people.

No local South African data exists on how widely the chemical imbalance model is communicated in public-sector consultations. But given the acute time pressure on general practitioners in community health centres — where a consultation may last under eight minutes — a simplified explanation is easy to understand how it persists.

What depression actually involves

Depression is a multi-system condition. Current evidence points to overlapping biological, psychological, and social contributors rather than a single chemical deficiency:

• Neuroinflammation:

Research has shown that excessive activation of pro-inflammatory cytokines — including interleukin-1 beta, tumour necrosis factor alpha, and interleukin-6 — is closely associated with the development of many central nervous system disorders, including depression. These inflammatory mediators contribute to depressive symptoms by affecting brain tissue and modulating neurotransmitter systems.

• Stress-system dysregulation: Chronic activation of the body’s cortisol stress response alters brain structure over time, particularly in regions governing mood and memory.
• Neuroplasticity: Depression is associated with reduced growth of new connections in the brain — and some researchers now think antidepressants may help partly by promoting that growth, not primarily by adjusting serotonin levels.
• Social and structural factors: Job insecurity, trauma, intimate partner violence, poverty, and grief all substantially raise the risk of a depressive episode. These are not “psychological weaknesses” — they have measurable biological effects.

For South African women, this last point carries particular weight.

Mental health problems, particularly depression and anxiety, are common in women and young girls living with human immunodeficiency virus, especially in low- and middle-income countries where vulnerability to psychiatric symptoms is heightened by intersectional stressors such as stigma and intimate partner violence.

South Africa carries one of the world’s largest human immunodeficiency virus burdens, and the psychological weight of that diagnosis — layered onto pre-existing poverty and gender-based violence rates — creates a risk environment that no serotonin top-up can address alone.

Research published in 2024 also links load-shedding-related disruptions — including darkened streets, alarm failures, and the relentless uncertainty of unplanned power cuts — to compounding stress and anxiety responses in South African communities already under pressure.

Antidepressants still matter — but so does everything else

Here is the nuanced truth the 2022 review does not change:

antidepressants can still help, even if the precise mechanism is not fully understood.

For moderate to severe depression, selective serotonin reuptake inhibitors and other antidepressants have a meaningful evidence base for reducing symptoms. Stopping medication abruptly because of a social media video is dangerous.

What the science does argue against is the idea that a tablet alone is a complete treatment for most people.

Combined antidepressants with individual cognitive behavioural therapy appear more efficacious than either treatment alone for adults with a new episode of depression

, according to a 2024 network meta-analysis published in eClinicalMedicine. For less severe presentations,

group cognitive behavioural therapy appears efficacious even in cases where antidepressants do not show evidence of effect.

The practical implication: if your general practitioner hands you a prescription without any discussion of therapy, follow-up, or the social factors in your life, you are receiving an incomplete response to a complex condition — not because the doctor is careless, but because the system is overstretched.

Getting help in South Africa: what to expect

In the public sector, your first point of contact is your nearest community health centre or clinic. A general practitioner can prescribe a first-line antidepressant such as generic fluoxetine or sertraline, both available at public sector facilities. Referral to a district hospital psychiatrist is possible but comes with long waiting times —

there are only approximately 217 public sector psychiatrists in South Africa, and in the public sector, South Africa has only 0.31 psychiatrists and fewer than one psychologist per 100,000 people, with most resources locked up in hospitals rather than accessible at community or primary care level.

The South African Society of Psychiatrists has called for strengthening community mental health centres to reduce this gap.

In the private sector,

a session with a clinical or counselling psychologist costs approximately R1,100 to R1,900, while a registered counsellor or clinical social worker charges R550 to R750 per session. A psychiatrist consultation runs R1,800 to R3,400, with a first appointment sometimes reaching more.

Generic fluoxetine (20 mg per day) is available at most pharmacies for under R150 per month, making medication significantly more accessible than specialist consultations for most South Africans.

Medical aid coverage: Depression is listed as a prescribed minimum benefit condition under the Medical Schemes Act 131 of 1998, meaning your medical aid is legally required to cover the diagnosis, treatment, and care of major depression — regardless of which option you are on. In practice, the number of therapy sessions covered varies sharply between schemes. Check with your scheme administrator whether your plan covers psychology sessions under the mental health benefit or the day-to-day benefit, as the difference affects your out-of-pocket cost significantly.

Practical barriers and workarounds: Load-shedding affects telehealth platforms and after-hours clinic access. Several South African therapists now offer WhatsApp-based check-ins between sessions, which use less data and are more resilient to power interruptions. The South African Depression and Anxiety Group (SADAG) runs a free, phone-based counselling line that does not require an appointment or a medical aid card — call 0800 567 567 any time.

When to see a doctor or mental health professional

Seek help urgently if you are experiencing thoughts of self-harm or suicide, have stopped eating or sleeping for several days, or are unable to care for yourself or your children. Go to your nearest emergency department or call the Suicide Crisis Line on 0800 567 567 or Lifeline on 0861 322 322. If you are on antidepressants and thinking of stopping, speak to your prescribing doctor first — stopping abruptly can cause withdrawal symptoms and destabilise your mood.

Bottom line

• The idea that depression is simply low serotonin, and that antidepressants top it up, has no consistent scientific support — a 2022 umbrella review in Molecular Psychiatry confirmed this across multiple lines of evidence.
• Antidepressants can still work, likely through mechanisms science has not fully mapped yet — stopping prescribed medication without medical guidance is dangerous.
• Depression involves overlapping biological, psychological, and social factors; in South Africa, these include human immunodeficiency virus comorbidity, gender-based violence, poverty, and chronic stress.
• A prescription without a conversation about therapy, lifestyle, and social stressors is an incomplete response — push your general practitioner for a more complete plan, or ask for a referral.
• Free support is available now: call the South African Depression and Anxiety Group on 0800 567 567. You do not need a medical aid card or an appointment.