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The effect of acute morphine on sleep in male patients suffering from sleep apnea: Is there a genetic effect? An RCT Study
Author(s) -
Rowsell Luke,
Wu Justin GuangAo,
Yee Brendon J.,
Wong Keith K.H.,
Sivam Sheila,
Somogyi Andrew A.,
Grunstein Ronald R.,
Wang David
Publication year - 2021
Publication title -
journal of sleep research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.297
H-Index - 117
eISSN - 1365-2869
pISSN - 0962-1105
DOI - 10.1111/jsr.13249
Subject(s) - anesthesia , crossover study , medicine , sleep (system call) , sleep onset latency , morphine , obstructive sleep apnea , placebo , slow wave sleep , sleep apnea , polysomnography , opioid , sleep stages , electroencephalography , sleep onset , apnea , pharmacology , insomnia , computer science , operating system , alternative medicine , receptor , pathology , psychiatry
Questionnaire‐based studies have suggested genetic differences in sleep symptoms in chronic opioid users. The present study aims to investigate if there is a genetic effect on sleep architecture and quantitative electroencephalogram (EEG) in response to acute morphine. Under a randomized, double‐blind, placebo‐controlled, crossover design, 68 men with obstructive sleep apnea undertook two overnight polysomnographic studies conducted at least 1 week apart. Each night they received either 40 mg of controlled‐release morphine or placebo. Sleep architecture and quantitative EEG were compared between conditions. Blood was sampled before sleep and on the next morning for genotyping and pharmacokinetic analyses. We analysed three candidate genes ( OPRM1 [rs1799971, 118 A > G], ABCB1 [rs1045642, 3435 C > T] and HTR3B [rs7103572 C > T]). We found that morphine decreased slow wave sleep and rapid eye movement sleep and increased stage 2 sleep. Those effects were less in subjects with HTR3B CT/TT than in those with CC genotype. Similarly, sleep onset latency was shortened in the ABCB1 CC subgroup compared with the CT/TT subgroup. Total sleep time was significantly increased in ABCB1 CC but not in CT/TT subjects. Sleep apnea and plasma morphine and metabolite concentration were not confounding factors for these genetic differences in sleep. With morphine, patients had significantly more active/unstable EEG (lower delta/alpha ratio) during sleep. No genetic effects on quantitative EEG were detected. In summary, we identified two genes ( HTR3B and ABCB1 ) with significant variation in the sleep architecture response to morphine. Morphine caused a more active/unstable EEG during sleep. Our findings may have relevance for a personalized medicine approach to targeted morphine therapy.