Five decades of work on antidepressant drugs have not made them more likely to lift people out of depression. Medications and psychotherapies help some people with the disease, but fail many others. In a stud1 conducted in real clinical settings, a common antidepressant produced a response in just under half of the participants, and achieved full remission in only 28%.

Failures to improve efficacy reflect continued ignorance of the molecular mechanisms of depression. Progress in other disorders, such as autism and schizophrenia, suggest that the best hope for insights is to identify specific genetic variants associated with the disease. However, success in depression will require studies of much larger collections of human DNA samples than in other diseases if statistically significant signals are to come through. The investments will be well worth it.

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