Comorbidities and concurrent medications increasing the risk of adverse drug reactions: prevalence in French benzodiazepine users

Eur J Clin Pharmacol. 2016 Jul;72(7):869-76. doi: 10.1007/s00228-016-2044-y. Epub 2016 Mar 29.


Purpose: To estimate benzodiazepine prevalence of use and to quantify, in benzodiazepine users, the prevalence of comorbidities and concurrent medications increasing the risk of adverse drug reactions (ADRs).

Methods: Cross-sectional study performed using data from the French national healthcare insurance system. The prevalence of use was estimated by considering as users, patients who had at least one benzodiazepine reimbursement during the year 2013. Patients at increased risk for benzodiazepine ADRs were those who had (i) drug-drug interactions at risk for central nervous system and respiratory depression and (ii) comorbidities at risk for adverse respiratory effects, or for falls or fractures.

Results: Overall, the prevalence of benzodiazepine use in 2013 was estimated to be 13.8 %; it was higher among women and increased with age. This prevalence was 10.6 % for anxiolytic benzodiazepines, and 6.1 % for hypnotic benzodiazepines. Approximately half of the benzodiazepine users (48.1 %) were at increased risk for benzodiazepine ADRs; this proportion increased with age. Drug-drug interactions represented the most prevalent condition (39.3 % of benzodiazepine users). The drugs most frequently involved were opioids: analgesics (15.9 %) and antitussives (6.8 %). Overall, 11.3 % of benzodiazepine users had comorbidities at increased risk for adverse respiratory effects (13.9 % in those aged 65-79), and 7.0 % comorbidities at increased risk for falls or fractures (13.4 % in those aged ≥80).

Conclusions: This study found that benzodiazepine use remained high in France, and that roughly half of the users presented with comorbidities and concurrent medications increasing the risk of ADRs. These findings are of concern, given that benzodiazepines are frequently used, and especially among the elderly.

Keywords: Benzodiazepines; Drug utilization; Insurance health reimbursement; Pharmacoepidemiology.

MeSH terms

  • Accidental Falls
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Anxiety Agents / adverse effects*
  • Benzodiazepines / adverse effects*
  • Central Nervous System Diseases / epidemiology
  • Comorbidity
  • Cross-Sectional Studies
  • Drug Interactions
  • Drug Utilization / statistics & numerical data
  • Female
  • Fractures, Bone / epidemiology
  • France / epidemiology
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Male
  • Middle Aged
  • Polypharmacy*
  • Prevalence
  • Respiration Disorders / epidemiology
  • Young Adult


  • Anti-Anxiety Agents
  • Hypnotics and Sedatives
  • Benzodiazepines