From monoamines to genomic targets: A paradigm shift for drug discovery in depression

Ma Li Wong, Julio Licinio

Research output: Contribution to journalReview articlepeer-review

183 Citations (Scopus)


Depression, a complex psychiatric disorder that affects ∼15% of the population, has an enormous social cost. Although the disorder is thought to be the outcome of gene-environmental interactions, the causative genes and environmental factors underlying depression remain to be identified. All the antidepressant drugs now in use - the forerunner of which was discovered serendipitously 50 years ago - modulate monoamine neurotransmission, and take six to eight weeks to exert their effects, but each drug is efficacious in only 60-70% of patients. A conceptually novel antidepressant that acted rapidly and safely in a high proportion of patients would almost certainly become the world's bestselling drug. Yet such a drug is not on the horizon. Here, we cover the different phases of antidepressant drug discovery in the past, present and future, and comment on the challenges and opportunities for antidepressant research.

Original languageEnglish
Pages (from-to)136-151
Number of pages16
JournalNature Reviews Drug Discovery
Issue number2
Publication statusPublished - Feb 2004

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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