Nonsteroidal anti-inflammatory drugs affect normal sleep patterns in humans

Physiol Behav. 1994 Jun;55(6):1063-6. doi: 10.1016/0031-9384(94)90388-3.


Previous studies have demonstrated that some nonsteroidal anti-inflammatory drugs (NSAIDs), specifically aspirin and indomethacin, have acute negative effects on sleep in humans and animals. Whether this finding can be replicated and extended to other NSAIDs, particularly the widely used over-the-counter drugs ibuprofen and acetaminophen, was the focus of the present investigation. Thirty-seven male and female subjects slept in the sleep laboratory on 2 consecutive nights; sleep was polygraphically recorded on the second night. Three doses of a prostaglandin-inhibiting drug (i.e., aspirin, acetaminophen, or ibuprofen) or placebo were administered, one each at 2300 h on the day prior to sleep recording, and at 0815 h and 2300 h on the day sleep was recorded. Subjects slept from 2400-0800 h both nights. Aspirin and ibuprofen disrupted sleep in comparison to placebo by increasing the number of awakenings and percentage of time spent in stage wake, and by decreasing sleep efficiency. Ibuprofen also delayed the onset of the deeper stages of sleep. Acetaminophen did not differ significantly from placebo on any measure of polygraphically recorded sleep. However, every index of objective sleep reflected slight, albeit nonsignificant, sleep disruption for each drug group relative to placebo. The mechanisms of sleep disruption after NSAID administration may relate to direct and indirect consequences of inhibiting prostaglandin synthesis, including decreases in prostaglandin D2, suppression of nighttime melatonin levels, and changes in body temperature.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / pharmacology
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspirin / pharmacology
  • Body Temperature Regulation / drug effects
  • Body Temperature Regulation / physiology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Ibuprofen / pharmacology
  • Male
  • Melatonin / physiology
  • Polysomnography / drug effects
  • Prostaglandin D2 / physiology
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Sleep Stages / drug effects*
  • Sleep Stages / physiology
  • Sleep, REM / drug effects
  • Sleep, REM / physiology
  • Wakefulness / drug effects
  • Wakefulness / physiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen
  • Melatonin
  • Aspirin
  • Prostaglandin D2
  • Ibuprofen