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Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials

  • Markus Koesters (a1), Giuseppe Guaiana (a2), Andrea Cipriani (a3), Thomas Becker (a1) and Corrado Barbui (a3)...
Abstract
Background

Agomelatine is a novel antidepressant drug with narrative, non-systematic reviews making claims of efficacy.

Aims

The present study systematically reviewed published and unpublished evidence of the acute and long-term efficacy and acceptability of agomelatine compared with placebo in the treatment of major depression.

Method

Randomised controlled trials comparing agomelatine with placebo in the treatment of unipolar major depression were systematically reviewed. Primary outcomes were (a) Hamilton Rating Scale for Depression (HRSD) score at the end of treatment (short-term studies) and (b) number of relapses (long-term studies).

Results

Meta-analyses included 10 acute-phase and 3 relapse prevention studies. Seven of the included studies were unpublished. Acute treatment with agomelatine was associated with a statistically significant superiority over placebo of −1.51 HRSD points (99% Cl −2.29 to −0.73, nine studies). Data extracted from three relapse prevention studies failed to show significant effects of agomelatine over placebo (relative risk 0.78, 99% Cl 0.41−1.48). Secondary efficacy analyses showed a significant advantage of agomelatine over placebo in terms of response (with no effect for remission). None of the negative trials were published and conflicting results between published and unpublished studies were observed.

Conclusions

We found evidence suggesting that a clinically important difference between agomelatine and placebo in patients with unipolar major depression is unlikely. There was evidence of substantial publication bias.

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Copyright
Corresponding author
Markus Kösters, Department of Psychiatry II, Ulm University, Ulm, Ludwig-Heilmeyer-Str. 2, 89312 Guenzburg, Germany. Email: Markus.Koesters@uni-ulm.de
Footnotes
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Declaration of interest

None.

Footnotes
References
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Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials

  • Markus Koesters (a1), Giuseppe Guaiana (a2), Andrea Cipriani (a3), Thomas Becker (a1) and Corrado Barbui (a3)...
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eLetters

Drug Licensing

Richard Braithwaite, Consultant Psychiatrist
07 October 2013

Dear Sir

Through their comprehensive meta-analysis, Koesters and colleagues highlight serious flaws in the procedures employed by the European Medicines Agency (EMA) for licensing new drugs. (1) I fear it will be sometime before these procedures are improved.

In the meantime, the EMA could start by taking heed of such meta-analyses, reconsidering its licences for medications of dubious efficacy. It is three years since Eyding et al's meta-analysis was published, showing definitively that the "antidepressant" Reboxetine does not work. (2) Yet Reboxetine remains licensed for treatment of depressive disorder. It is available to be prescribed by any doctor, exposing patients to the harms of adverse effects and untreated illness with no hope of therapeuticbenefit.

To err may be human, but the EMA's failure to admit its mistakes is nothing short of scandalous. The European public deserves better.

I beg to remain, Sir, your most obedient servant,

Dr Rich BraithwaiteConsultant Psychiatrist

Isle of Wight NHS TrustSt Mary's HospitalNewportIsle of WightPO30 5TG

1.Koesters M, Guaiana G, Ciprani A, Becker T, Barbui C. Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials. British Journal of Psychiatry 2013; 203: 179-187. doi: 10.1192/bjp.bp.112.1201962.Eyding D, Lelgemann M, Grouven U, H?rter M, Kromp M, Kaiser T, Kerekes MF, Gerken M, Wieseler B. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ 2010;341:c4737

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