Melancholia is a severely debilitating illness with a high death rate and high potential for suicide. Its consequences were so dire that the introduction of even so intrusive a treatment as induced seizures was hailed as a remarkable advance. Over the past half-century, medications effective in ameliorating melancholia were developed and the fears that melancholia engendered in earlier centuries lessened.

Our present therapeutic ideal is to select treatments based on scientific study, defined as evidence-based medicine. Randomized controlled clinical trials form the foundation of evidence-based medicine, and the literature assessing the benefits of antidepressant and mood-stabilizing drugs is widely accepted. Reviews of this evidence conclude that all antidepressant medications have equal efficacy for major depression, differing only in side-effects. These conclusions influence clinical guidelines.

Present teaching, as expressed by an expert National Institutes of Mental Health (NIMH) panel states that: “The SSRIs [selective serotonin reuptake inhibitors] are clearly the drug treatment of choice for all forms of depression in the United States … These drugs are approximately equivalent to each other and to TCAs [tricyclic antidepressants] in efficacy … The SSRIs have a much more benign side effect profile than TCAs and, largely for this reason, have replaced TCAs as first line therapy.”