Do antidepressants really work, or are they just short‑term symptom masks? A deep dive into the science behind the hype.
In this livestream podcast, Nasiragami breaks down what “antidepressants” actually do. He argues the term is misleading and prefers “monoamine agonists.” Across more than 500 randomized trials, these drugs improve depression scores modestly—about a two‑point advantage on the MADRS scale, translating to a Cohen’s d of ~0.3, below the FDA’s threshold for a clinically meaningful effect. The benefit shows up mainly in severe depression; mild cases see virtually no difference from placebo, and the placebo effect itself accounts for much of the improvement.
Long‑term prevention claims are also questioned. Most maintenance studies enroll only patients who already responded, then randomize them to stay on the drug or switch to placebo. Benefits disappear after roughly six months, suggesting monoamine agonists are short‑term symptom relievers, not disease‑modifying agents. For bipolar depression, the evidence is even weaker, with effect sizes near zero and risks of triggering mania. The only proven long‑term mood stabilizer is lithium.
For the full meta‑analysis details see:
https://www.thelancet.com/article/S0140-6736(17)32802-7/fulltext
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0050045
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-5618.2008.00639.x
https://www.sciencedirect.com/science/article/pii/S0149291811007703
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