The future of depression psychopharmacology

Robert H. Belmaker

    Research output: Contribution to journalReview articlepeer-review

    33 Scopus citations


    Along with the development of selective sertonin reuptake inhibitors there has been a tremendous widening of the definition of depression and an impressive decrease in the placebo-drug difference in controlled studies. In the early 1960s, about one third of depressed patients improved with placebo and two thirds with active compounds. Current controlled studies suggest that the situation has certainly not improved. The Sequenced Treatment Alternatives to Relieve Depression Study found that response rates to new compounds after the failure of the first antidepressant are low. The monoamine hypothesis of depression was formulated in the mid 1960s based on the antidepressant efficacy of the monoamine reuptake inhibitors, monoamine oxidase inhibitors, and the depressogenic effects of reserpine as a monoamine depleter. However, no monoamine-related finding has been found that is diagnostic for depression. A second major hypothesis regarding depression has been the stress cortisol hypothesis. However, blood cortisol levels are not diagnostic of depression. Psychiatric clinicians are convinced that there are patients for whom antidepressants have made the difference between life and death. However, physicians may generalize unjustifiably based on single dramatic cases to a much larger diagnostic group. Perhaps there are many causes of different types of human sadness, and perhaps only some of these involve mechanisms related to monoamines. Thus, perhaps only some kinds of depression are responsive to monoamine affecting antidepressants.

    Original languageEnglish
    Pages (from-to)682-687
    Number of pages6
    JournalCNS Spectrums
    Issue number8
    StatePublished - 1 Jan 2008

    ASJC Scopus subject areas

    • Clinical Neurology
    • Psychiatry and Mental health


    Dive into the research topics of 'The future of depression psychopharmacology'. Together they form a unique fingerprint.

    Cite this