How do antidepressants work? We still don’t know

antidepressantillustration hero
Credit: UNC

[A]bout a third of Americans are showing signs of depression or anxiety, according to the U.S. Census Bureau. That’s about double the percentage of people who reported experiencing a depressive mood six years ago.

Though depression and anxiety can be serious and debilitating diseases, the tools we have to treat them are only partially understood by scientists and physicians… While physicians and researchers know the basics of what these medications do in the brain, they still don’t know how much of the effects are placebo and how much are real drug effects. These unknowns, along with the complex nature of the illness, mean doctors often have to try multiple antidepressants before they find one that works for each patient.

There are about 40 different antidepressants currently in use around the world, says [clinical psychiatrist] Lauren Edwards.

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[R]esearch suggests antidepressants may have both an actual pharmacological impact and a placebo effect that influences how patients feel when they start taking the drugs. For example, a recent meta-analysis concluded that antidepressants do have a statistically significant effect compared with placebo alone, says Edwards. Older research from the 1990s supports this, suggesting that 25 percent of the impact of antidepressants is due to placebo, 25 percent due to unknown factors and about 50 percent from the actual pharmacological effects from the drugs.

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