What Antidepressants Do to the Brain — and Why Something Happens When You Stop

The core mechanism behind all the effects

SSRIs block the serotonin transporter (SERT) — preventing serotonin from being taken back up out of the synaptic cleft. The synapse floods with serotonin. The brain responds by reducing the sensitivity of its own receptors, reducing serotonin production, and triggering a cascade of adaptations.

Serotonin acts as a brake on dopamine via GABAergic interneurons in the ventral tegmental area. Chronically elevated serotonin therefore simultaneously lowers dopamine tone. This is the actual cause of most side effects users report: emotional blunting, loss of libido, reduced motivation, weight gain, cognitive fog.

At the same time, serotonin affects oxytocin release, disrupts the hypothalamic-thyroid and gonadal axes, and reopens a critical period of brain plasticity (BDNF). These effects persist long after the drug itself is discontinued.

Main effects according to published research

Emotional blunting — 71% of 1,431 users in Read & Williams (2018) reported emotional blunting, 66% a feeling of "not feeling like myself." Cause: suppression of dopamine tone via a chain of serotonergic interactions.

Sexual dysfunction — 66% in the same survey; the Montejo (2001) study reports 58–73%. Some individuals develop PSSD (Post-SSRI Sexual Dysfunction) — persistent impairment of sexual function long after discontinuation (formally recognized by the EMA in 2019).

Weight gain — a BMJ study of over 300,000 patients (Gafoor 2018) found a 21% increased risk of gaining ≥5% of body weight over 5 years. Mechanisms: dopamine suppression, disrupted satiety, reprogramming of fat cells.

Protracted withdrawal — the Davies & Read (2019) systematic review found that more than half of users experience withdrawal effects, and nearly half describe them as severe. Hengartner (2020) describes an average duration of protracted symptoms of 37 months.

Neuroplastic changes — Maya Vetencourt (Science, 2008) showed that fluoxetine reactivates a critical period of plasticity in the adult brain. Receptor changes remain measurable on average 29 months after discontinuation (up to 60 months in some cases).

Why "discontinuation" isn't a switch you flip off

The common medical claim that antidepressant withdrawal resolves within 1–2 weeks is not supported by the evidence. The drug molecule itself clears the body within weeks to a few months, but the neuroplastic changes it caused persist independently.

An analogy: if you break your arm and wear a cast for 2 years, you can take the cast off in 5 seconds. But the muscle atrophy takes months to heal. The cast is gone, but the damage it caused is still there.

This distinction is crucial. Many people are incorrectly diagnosed with "relapse" after discontinuation — when in fact the brain is still healing. Return of function can take months to 1–2 years, and it tends to arrive in waves ("windows and waves").

What can be done — from a referral service's perspective

PsyLab is not a medical practice. We can't and don't want to tell you whether or not to stop your medication. That decision belongs solely to you and your treating physician.

What we can offer: a 45-minute educational consultation (€75), where you and a consultant go through your symptoms, any biotype test results (Pyroluria, Histamine, Cortisol), and get oriented for the next step. The consultation is a supplement to your medical care — not a replacement for it.

The full review, with 20 sections and all PubMed citations, is available on a dedicated page: Antidepressants and the Brain — a Scientific Review.