Key PointsQuestionWhat percentage of patients with severe depression experience improvement with antidepressant therapy and by how much?FindingsIn this pooled secondary analysis of data from the US Food and Drug Administration that included 57 313 participants with severe depression from 232 randomized clinical trials of antidepressants for major depressive disorder, all quantiles of depression response were more favorable among drug-assigned participants, by 3% to 14%. These findings depend heavily on statistical assumptions.MeaningThese findings suggest that antidepressants may improve depression severity for a broad range of patients with severe depression, but for many patients, the magnitude of the reduction may be small.