Here’s how psychiatrists like me think about the most promising hypotheses.
Sophi Miyoko Gullbrants
Dr. Awais Aftab is a practicing psychiatrist and writer. This is part of Therapeutic Window, a series exploring the science and the debates behind mental health diagnoses.
Oct. 27, 2026
Lately, the public conversation around antidepressants has focused largely on whether and how to quit them.
Health Secretary Robert F. Kennedy Jr. has made deprescribing, or supervised drug tapering, a focus of policy. Mr. Kennedy and other critics of antidepressants argue that the medications are overprescribed, with dangerous side effects. The medical community, however, views them as effective and necessary treatments for people with a wide range of mental disorders, including depression, anxiety and obsessive-compulsive disorder.
But underneath this debate lies a more fundamental question that science has yet to conclusively answer: How, exactly, do antidepressants work?
For decades, the public understanding of antidepressants has been stuck in a narrative popularized by pharmaceutical advertising in the 1990s: that they work by correcting a chemical deficiency in the brain.
But evidence from research studies has been clear since at least the early 2000s — if not earlier — that this is not how antidepressants work. Doctors prescribe the drugs because decades of study data and patient reports show they can relieve people’s mental health problems. But doctors and scientists don’t have a clear understanding of how they do that. That may be surprising, but it’s the case for many kinds of medications, such as acetaminophen and general anesthetics.
Even so, understanding how antidepressants work is important not only for educating the public, but also for furthering scientific research — into why the drugs are not effective for everyone, and how to develop more treatments.
Scientists today are working with several promising explanations. No hypothesis is settled science, and some may be disproved tomorrow. But together they reflect the strongest understanding medicine currently possesses.