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Suicide risk with selective serotonin reuptake inhibitors and other new-generation antidepressants in adults: a systematic review and meta-analysis of observational studies
  1. Michael P Hengartner1,
  2. Simone Amendola2,
  3. Jakob A Kaminski3,
  4. Simone Kindler4,
  5. Tom Bschor5,
  6. Martin Plöderl6
  1. 1Department of Applied Psychology, Zurich University of Applied Sciences, Zurich, Switzerland
  2. 2Department of Dynamic and Clinical Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Roma, Italy
  3. 3Department of Psychiatry and Psychotherapy, Charite Universitatsmedizin Berlin, Berlin, Germany
  4. 4Psychotherapist in Private Practice, Winterthur, Switzerland
  5. 5Department of Psychiatry and Psychotherapy, University Hospital, Technical University of Dresden, Dresden, Germany
  6. 6Department of Crisis Intervention and Suicide Prevention, Christian Doppler Clinic, Paracelsus Medical University Salzburg, Salzburg, Austria
  1. Correspondence to Michael P Hengartner, Department of Applied Psychology, Zurcher Hochschule fur Angewandte Wissenschaften, Zurich CH-8005, Switzerland; michaelpascal.hengartner{at}


Background There is ongoing controversy whether antidepressant use alters suicide risk in adults with depression and other treatment indications.

Methods Systematic review of observational studies, searching MEDLINE, PsycINFO, Web of Science, PsycARTICLES and SCOPUS for case–control and cohort studies. We included studies on depression and various indications unspecified (including off-label use) reporting risk of suicide and/or suicide attempt for adult patients using selective serotonin reuptake inhibitors (SSRI) and other new-generation antidepressants relative to non-users. Effects were meta-analytically aggregated with random-effects models, reporting relative risk (RR) estimates with 95% CIs. Publication bias was assessed via funnel-plot asymmetry and trim-and-fill method. Financial conflict of interest (fCOI) was defined present when lead authors’ professorship was industry-sponsored, they received industry-payments, or when the study was industry-sponsored.

Results We included 27 studies, 19 on depression and 8 on various indications unspecified (n=1.45 million subjects). SSRI were not definitely related to suicide risk (suicide and suicide attempt combined) in depression (RR=1.03, 0.70–1.51) and all indications (RR=1.19, 0.88–1.60). Any new-generation antidepressant was associated with higher suicide risk in depression (RR=1.29, 1.06–1.57) and all indications (RR=1.45, 1.23–1.70). Studies with fCOI reported significantly lower risk estimates than studies without fCOI. Funnel-plots were asymmetrical and imputation of missing studies with trim-and-fill method produced considerably higher risk estimates.

Conclusions Exposure to new-generation antidepressants is associated with higher suicide risk in adult routine-care patients with depression and other treatment indications. Publication bias and fCOI likely contribute to systematic underestimation of risk in the published literature.

Registration Open Science Framework,

  • suicide
  • depression
  • epidemiology
  • public health

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  • Twitter @HengartnerMP, @JakobKaminski, @PloederlM

  • Contributors MPH: study concept and design, supervision of literature search and full-text assessment, interpretation of data, drafting of manuscript, critical revision of manuscript. SA: literature search and full-text assessment, quality ratings, critical revision of manuscript. JAK and TB: interpretation of data, writing of manuscript, critical revision of manuscript. SK: literature search and full-text assessment, critical revision of manuscript. MP: statistical analysis, interpretation of data, writing of manuscript, critical revision of manuscript.

  • Funding JAK is supported by the Charité Clinician-Scientist Program of the Berlin Institute of Health. SA is supported by the Scholarships for Advanced Studies Abroad of the Sapienza University of Rome. The sponsors had no influence on the conduct of this study. No funding was received for this specific study.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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