Weak evidence comparing duloxetine to other antidepressants, says new Cochrane review

Antipsychotics can help with the neuropsychiatric symptoms of dementia, but they are also associated with a range of serious adverse events.

There are many different antidepressants to choose from when treating acute depression, so it’s always helpful to see a systematic review that looks at the efficacy, acceptability and tolerability of the different drugs.

This new Cochrane review compares duloxetine hydrochloride (one of the newer drugs) with other antidepressants and finds little high quality evidence upon which to base treatment decisions.

Along with escitalopram and desvenlafaxine, duloxetine is one of the few antidepressants that remains on patent. Many of the included studies in this review are therefore sponsored by the drug industry, so it’s worth considering sponsorship bias and the fact that the results are likely to overestimate the true treatment effect.

As always, the Cochrane reviewers performed a systematic search to find randomised controlled trials to include in their analysis. They found 16 trials with 5,735 patients in total, comparing duloxetine to SSRIs, newer antidepressants and antipsychotics also used as antidepressants.

Here are the results of their analysis:

  • There were no significant differences in efficacy when comparing duloxetine to other antidepressants
  • When compared with escitalopram or venlafaxine, there was a higher rate of drop out due to any cause in the patients randomised to duloxetine (odds ratio (OR) 1.62; 95% confidence interval (CI) 1.01 to 2.62 and OR 1.56; 95% CI 1.14 to 2.15, respectively)
  • No studies were found comparing duloxetine with tricyclic antidepressants

The reviewers concluded:

Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. No differences in terms of efficacy were found, even though duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability.

Overall, this is an emerging area of evidence, as is often the case with newer drugs where only a small number of (mostly industry sponsored) trials have been produced. We will have to wait for further studies before we can make any definitive judgements about duloxetine.


Cipriani A, Koesters M, Furukawa TA, Nosè M, Purgato M, Omori IM, Trespidi C, Barbui C. Duloxetine versus other anti-depressive agents for depression. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.: CD006533. DOI: 10.1002/14651858.CD006533.pub2.

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Andre Tomlin

André Tomlin is an Information Scientist with 20 years experience working in evidence-based healthcare. He's worked in the NHS, for Oxford University and since 2002 as Managing Director of Minervation Ltd, a consultancy company who do clever digital stuff for charities, universities and the public sector. Most recently André has been the driving force behind the Mental Elf and the National Elf Service; an innovative digital platform that helps professionals keep up to date with simple, clear and engaging summaries of evidence-based research. André is a Trustee at the Centre for Mental Health and an Honorary Research Fellow at University College London Division of Psychiatry. He lives in Bristol, surrounded by dogs, elflings and lots of woodland!

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