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Quinolone antibiotics and suicidal behavior: analysis of the World Health Organization’s adverse drug reactions database and discussion of potential mechanisms

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Abstract

Rationale

Several case-reports suggest that the use of quinolones may increase the risk of psychiatric adverse reactions such as suicidal behaviors.

Objectives

The aim of this study is to investigate whether there is a safety signal for quinolone-related suicidal behaviors in a global adverse drug reactions database.

Methods

All antibiotic-related adverse reactions were extracted from VigiBase, the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database. Disproportionality analyses were performed to investigate the association between reports of suicidal behavior and exposure to quinolones, in comparison with other antibiotics.

Results

From December 1970 through January 2015, we identified 992,097 antibiotic-related adverse reactions. Among them, 608 were quinolone-related suicidal behaviors including 97 cases of completed suicides. There was increased reporting of suicidal behavior (adjusted reporting odds ratios [ROR] 2.78, 95 % CI 2.51–3.08) with quinolones as compared to other antibiotics. Candidate mechanisms for quinolone-induced suicidal behaviors include GABAA antagonism, activation of NMDA receptors, decreased serotonin levels, oxidative stress, and altered microRNA expressions.

Conclusions

We found a strong safety signal suggesting an increased risk of suicidal behaviors associated with quinolone use. Plausible psychopharmacological mechanisms could underlie this association. Further investigations are urgent to confirm and better understand these findings.

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Acknowledgments

The Uppsala Monitoring Centre has provided the data, but the study results and conclusions are those of the authors and not necessarily those of the Uppsala Monitoring Centre, National Centres, or WHO.

Contributors

All authors participated in the study design. JLF acquired the data. JS did the statistical analyses and wrote the initial draft. All authors critically revised the manuscript.

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Authors and Affiliations

  1. Department of Medical Pharmacology and Toxicology, CHU Montpellier University Hospital, Montpellier, France

    Julie Samyde, Dominique Hillaire-Buys & Jean-Luc Faillie

  2. Department of Psychiatry, CHU Montpellier University Hospital, Montpellier, France

    Pierre Petit

  3. INSERM U1058, Faculty of Medicine, University of Montpellier, Montpellier, France

    Dominique Hillaire-Buys

  4. Laboratory of Biostatistics, Epidemiology and Public Health (EA 2415), Faculty of Medicine, University of Montpellier, Montpellier, France

    Jean-Luc Faillie

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  1. Julie Samyde
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Corresponding author

Correspondence to Jean-Luc Faillie.

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Conflict of interest

This study was not funded. The authors declare that they have no conflicts of interest.

Research ethics

Since this study did not include individual patients and only studied the data of an existing and anonymously recorded database, ethical approval was not needed.

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Samyde, J., Petit, P., Hillaire-Buys, D. et al. Quinolone antibiotics and suicidal behavior: analysis of the World Health Organization’s adverse drug reactions database and discussion of potential mechanisms. Psychopharmacology 233, 2503–2511 (2016). https://doi.org/10.1007/s00213-016-4300-3

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  • DOI: https://doi.org/10.1007/s00213-016-4300-3

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