Benzodiazepines as antidepressants: Does GABA play a role in depression?

Frederick Petty, Madhukar H. Trivedi, Mark Fulton, A. John Rush

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Benzodiazepines, the most widely prescribed psychotropic drugs, are often used in patients with depressive disorders, either alone or in combination with standard antidepressants. This review evaluates the efficacy of benzodiazepines (alprazolam, diazepam, chlordiazepoxide) as established in acute-phase, randomized controlled trials (RCTs) in major depressive disorder. Metaanalyses using intent-to-treat, as well as adequate treatment exposure samples, revealed an overall efficacy of 47-63% and a drug-placebo difference of 0-27% for all benzodiazepines. Alprazolam, the best studied of the benzodiazepines, had a 27.1% (sd = 6.1%) greater response than placebo, which is comparable to standard antidepressants. Alprazolam, in particular, may be a useful treatment option for patients in whom standard antidepressant medications are contraindicated, poorly tolerated, or possibly ineffective. Alprazolam may have a more rapid onset of action for some patients. Benzodiazepines do not primarily affect biogenic amine uptake or metabolism, although they do augment γ-amino butyric acid (GABA) activity. The antidepressant efficacy of benzodiazepines, which are GABAA receptor agonists, is consistent with the GABA theory of depression.

Original languageEnglish (US)
Pages (from-to)578-591
Number of pages14
JournalBiological Psychiatry
Issue number9
StatePublished - Nov 1 1995


  • Alprazolam
  • GABA
  • antidepressants
  • benzodiazepines
  • depression
  • diazepam

ASJC Scopus subject areas

  • Biological Psychiatry


Dive into the research topics of 'Benzodiazepines as antidepressants: Does GABA play a role in depression?'. Together they form a unique fingerprint.

Cite this