Effect of flunitrazepam as an oral hypnotic on 24-hour blood pressure in healthy volunteers

Daniele Bosone, Roberto Fogari, Annalisa Zoppi, Angela D’Angelo, Natascia Ghiotto, Giulia Perini, Matteo Cotta Ramusino, Alfredo Costa

Research output: Contribution to journalArticlepeer-review


Purpose: The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. Materials and methods: Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 females) between 21 and 30 years were randomized to receive either flunitrazepam 1 mg or placebo (both administered once a day in the evening) for 4 weeks in two cross-over periods; each separated by a 2-week placebo period. At the end of each study period, non-invasive 24-h BP and HR ambulatory monitoring was performed. Results: Flunitrazepam produced a significant decrease in nighttime systolic blood pressure (SBP) (− 6.4 mmHg) and diastolic blood pressure (DBP) (− 4.1 mmHg) (both P < 0.05 vs placebo) without affecting nocturnal HR. During the morning hours, significantly higher values of SBP (+ 7.4 mmHg, P < 0.01), DBP (+ 3.4 mmHg, P < 0.05) and HR (+ 3.9 beats/min, P < 0.05) were observed in the flunitrazepam group compared to the placebo-treated group. No significant differences were noted between the two groups during afternoon and evening hours. Conclusions: These results suggest that chronic oral administration of 1 mg flunitrazepam as a hypnotic agent causes a significant nocturnal fall in BP and a transient rebound increase of both BP and HR at awakening in the morning. Mechanisms underlying these cardiovascular effects remain unclear, although the direct vasodilatory effect, which is typical of flunitrazepam (with consequent reflex counter-regulatory responses), and the attenuation of baroreflex sensitivity are likely to play a major role.

Original languageEnglish
Pages (from-to)995-1000
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Issue number8
Publication statusPublished - Aug 1 2018


  • Blood pressure
  • Circadian rhythm
  • Flunitrazepam
  • Heart rate

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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