Antidepressant use continues to rise. In England, 96 million antidepressant prescription items were dispensed to an estimated 9.1 million patients in 2025 to 2026. These medicines are prescribed for depression and other conditions, including anxiety and some forms of pain.

Antidepressants can take several weeks to work fully, can cause unwanted side effects and do not help everyone sufficiently. But there is another potential problem: a treatment that initially works can sometimes appear to lose its effect.

This is known as antidepressant tachyphylaxis: someone initially improves while taking an antidepressant, but their symptoms later return or worsen despite continuing the same medicine at the same dose. It has also been called antidepressant “poop-out” or “breakthrough depression”.

Tachyphylaxis describes a different pattern from treatment-resistant depression. While definitions vary, treatment-resistant depression generally means that someone has not improved sufficiently after trying at least two antidepressants, taken at suitable doses for long enough to assess their effect. With tachyphylaxis, the person initially benefited before apparently losing that improvement.

Why might an antidepressant stop helping?

Exactly why this happens is unclear. One possibility is that the brain gradually adapts to prolonged exposure to........

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