Quinolone antibiotics and suicidal behavior: analysis of the World Health Organization’s adverse drug reactions database and discussion of potential mechanisms
- 566 Downloads
Several case-reports suggest that the use of quinolones may increase the risk of psychiatric adverse reactions such as suicidal behaviors.
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.
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.
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.
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.
KeywordsPsychopharmacology Adverse drug reactions Suicidal behaviors Suicide Quinolones
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.
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.
Compliance with Ethical Standards
Conflict of interest
This study was not funded. The authors declare that they have no conflicts of interest.
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.
- Barthélémi L, Lebrun J (2015) Completed suicide and fluoroquinolones: a possible association. 19th Annual Meeting of French Society of Pharmacology and Therapeutics., 21–23 April 2015 Caen., France. Fundam Clin Pharmacol 29(suppl 1):65Google Scholar
- Behera C, Krishna K, Singh HR (2014) Antitubercular drug-induced violent suicide of a hospitalised patient. BMJ Case Rep. 2014 published online Jan 6. doi: 10.1136/bcr-2013-201469
- Dukes MNG (2006) Fluoroquinolones. In: Meyler’s side effects of drugs: the international encyclopedia of adverse drug reactions and interactions, 15th edn. Elsevier Science, Amsterdam, pp 1396–407Google Scholar
- European Medicines Agency (EMEA) (2008) EMEA restricts use of oral norfloxacin drugs in UTIs. EMEA. www.who.int/medicines/publications/newsletter/2008news3.pdf
- European Medicines Agency (EMEA) (2008) EMEA recommends restricting the use of oral moxifloxacin-containing medicines. EMEA. www.who.int/medicines/publications/newsletter/2008news3.pdf
- Lindquist M (2008) VigiBase, the WHO global ICSR database system: basic facts. Drug Inf J 42:409–19Google Scholar
- Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, Hammad TA, Temple R, Rochester G (2009) Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ 339:b2880CrossRefPubMedPubMedCentralGoogle Scholar
- Uppsala Monitoring Centre (2008). Uppsala Report 40: New import processs for ICSR. Uppsala Monitoring Centre. http://www.who-umc.org/graphics/24360.pdf
- WHO Collaborating Centre for Drug Statistics Methodology (2013) Guidelines for ATC classification and DDD assignment 2013. http://www.whocc.no/filearchive/publications/1_2013guidelines.pdf