The Elusive Fit: Why Antidepressants Don’t Work for Everyone

Antidepressants have helped some people for decades, but research shows they often provide only modest relief overall, with no reliable way to predict who will benefit. The history traces from iproniazid and imipramine to SSRIs and beyond, while meta-analyses indicate small improvements over placebo and low remission rates for many drugs. Ketamine offers rapid relief for some with treatment-resistant depression, challenging the idea that depression is a simple chemical imbalance. Precision psychiatry aims to tailor treatments via blood tests and genetic or neural markers, but this approach is still years away from routine practice. The field continues to wrestle with what depression actually is and how to best help the millions affected.