Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies
BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1888 (Published 19 March 2014) Cite this as: BMJ 2014;348:g1888
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- David Taylor, professor of psychopharmacology12,
- Anna Sparshatt, senior clinical pharmacist2,
- Seema Varma, senior clinical pharmacist2,
- Olubanke Olofinjana, senior clinical pharmacist and statistician2
- 1King’s College London, Institute of Pharmaceutical Science, London SE1 9NH, UK
- 2South London and Maudsley NHS Foundation Trust, Pharmacy Department, London SE5 8AZ, UK
- Correspondence to: D Taylor, South London and Maudsley NHS Foundation Trust, Pharmacy Department, London SE5 8AZ, UK david.taylor{at}slam.nhs.uk
- Accepted 20 February 2014
Abstract
Objective To systematically review published and unpublished efficacy studies of agomelatine in people with depression.
Design Systematic review and meta-analysis.
Data sources Literature search (Pubmed, Embase, Medline), Cochrane Central Register of Controlled Trials, European Medicines Agency (EMA) regulatory file for agomelatine, manufacturers of agomelatine (Servier).
Eligibility criteria Double blind randomised placebo and comparator controlled trials of agomelatine in depression with standard depression rating scales.
Data synthesis Studies were pooled by using a random effects model with DerSimonian and Laird weights for comparisons with placebo and comparator antidepressant. The primary efficacy measure (change in rating scale score) was summarised with standardised mean difference (SMD; a measure of effect size) and secondary outcome measures with relative risks. All results were presented with 95% confidence intervals. Statistical heterogeneity was explored by visual inspection of funnel plots and by the I2 statistic. Moderators of effect were explored by meta-regression.
Results We identified 20 trials with 7460 participants meeting inclusion criteria (11 in the published literature, four from the European Medicines Agency file, and five from the manufacturer). Almost all studies used the 17 item Hamilton depression rating scale (score 0-50). Agomelatine was significantly more effective than placebo with an effect size (SMD) of 0.24 (95% confidence interval 0.12 to 0.35) and relative risk of response 1.25 (1.11 to 1.4). Compared with other antidepressants, agomelatine showed equal efficacy (SMD 0.00, −0.09 to 0.10). Significant heterogeneity was uncovered in most analyses, though risk of bias was low. Published studies were more likely than unpublished studies to have results that suggested advantages for agomelatine.
Conclusions Agomelatine is an effective antidepressant with similar efficacy to standard antidepressants. Published trials generally had more favourable results than unpublished studies.
Footnotes
Contributors: All authors contributed to the drafting and editing of the manuscript. AS performed searching and study selection, SV extracted data and assessed risk of bias. OO contributed to searching, study selection, assessment of risk of bias, data extraction, statistical plan, and analysis. DT initiated and oversaw the research, monitored the progress, prepared the draft manuscript, and is guarantor.
Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare that DT has received personal fees and grants from Servier outside the submitted work.
Ethical approval: Not required.
Data sharing: Datasets and statistical codes are available from the corresponding author.
Declaration of transparency: The lead author affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.
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