Emerging Treatments for Depression: Beyond the Monoamine Hypothesis

Julio Licinio

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Depression is a common and complex disorder of gene-environment interactions for which there are no curative treatments. All therapeutic strategies available today, which include more than 40 FDA-approved compounds, were initially discovered by serendipity; once aspects of their mechanism of action were identified as targeting monoamines, strategies to develop increasingly refined modulators of monoaminergic neurotransmission led to the new antidepressants available today. Conceptually novel treatments have not yet reached the market but loom promisingly on the horizon. These include drugs aimed at neuropeptidergic systems that have been associated with depression for over two decades, such as CRH. Efforts are also underway to address new targets that have been explored in more depth or unveiled in the last decade, including glutamate, BDNF, CREB, and rewardrelated molecules such as opioids and cannabinoids. The field has had for nearly a century one standard, highly effective nonpharmacological approach, namely electroconvulsive therapy. Two additional new approaches are now being tested clinically: transcranial magnetic stimulation and vagal nerve stimulation. The pharmacological and nonpharmacological pipeline has interesting elements but it is not replete with excitement and opportunity. This should not be so. The World Health Organization and World Bank acknowledge depression to be a major public health problem worldwide. Depression is among the most lucrative drug targets. Basic neuroscience, molecular neurobiology, genomics, and pharmacogenomics have grown explosively in the last decade. It is a reality that at the present time, translation of such exciting new science into much-needed new therapeutic opportunities has lagged behind in the field of depression research. Recognition of key pitfalls provides a foundation for bridging the gap between fundamental science and innovative clinical research treatments in a process that facilitates the discovery and successful implementation of novel, and hopefully individualized, therapies.

Original languageEnglish
Title of host publicationBiology of Depression
Subtitle of host publicationFrom Novel Insights to Therapeutic Strategies
PublisherJohn Wiley and Sons
Number of pages20
ISBN (Print)3527307850, 9783527307852
Publication statusPublished or Issued - 29 Jan 2008


  • Biogenic amines
  • Glutamate
  • Monoamines
  • Neurotransmission
  • Therapies

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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