Effects of doxylamine and acetaminophen on postoperative sleep

The separate and combined effects of doxylamine succinate (25 mg) and acetaminophen (1 gm) on sleep were studied by interview procedures and information from medical records of 2,931 postoperative patients. The sample contained 1,617 patients with mild or moderate pain and 1,314 who were free of pain. Each received either doxylamine alone (S), acetaminophen alone (A), a combination of both drugs (C), or placebo (P). Drug treatment was double blind and randomized separately for the pain and pain‐free subsamples. Twelve measures of sleep were determined. C was more beneficial than S or A, and S and A were each superior to P. For all 12 sleep measures, the effect of the combination (C – P) approximated or exceeded the sum of the two separate effects (S – P) + (A – P). The presence of either drug tended to enhance the sleep benefit of the other. The sedative and analgesic benefits to sleep were at least additive, and some outcome measures suggested synergism. In the total sample, the contributions of sedative and analgesic were similar. Among patients with pain, contributions of the analgesic surpassed those of the sedative. For patients free of pain, the sedative was better, but even pain‐free patients had enhanced sleep after the analgesic. The analgesic, but not the sedative, reduced pain; the analgesic induced the feeling of being well rested and not tired; the sedative induced a feeling of being drugged. Nondrug variables (e.g., pain, sex, age, and sleep expectations) influenced sleep outcome at least as much as drugs, but randomization and the large sample prevented those extraneous variables from biasing drug comparisons. Clinical Pharmacology and Therapeutics (1985) 37, 549–557; doi: 10.1038/clpt.1985.87