Utility of Saccadic Eye Movement Analysis As an Objective Biomarker to Detect the Sedative Interaction Between Opioids and Sleep Deprivation in Opioid-naive and Opioid-tolerant Populations

Analysis of saccadic eye movements (SEMs) has previously been used to detect drug- and sleep-deprivation-induced sedation, but never in combination. We compared the effects of sleep deprivation and opioids on 10 opioid-naive with nine opioid-tolerant participants. The naive-participant study evaluated the effects of sleep deprivation alone, morphine alone and the combination; the tolerant-participant study compared day-to-day effects of alternate-daily-dosed buprenorphine and the combination of buprenorphine on the dosing day with sleep deprivation. Psychomotor impairment was measured using SEMs, a 5-minute pupil adaptation test (PAT), pupil light reflex (PLR) and alertness visual analogue scale (AVAS). The PAT and PLR did not detect sleep deprivation, in contrast to previous studies. Whilst consistently detecting sleep deprivation, the AVAS also detected buprenorphine in the tolerant study, but not morphine in the naive study. SEMs detected morphine alone and sleep deprivation alone as well as an additive interaction in the naive study and the effect of sleep deprivation in the tolerant study. The alternate-day buprenorphine dosing did not alter SEMs. The current study revealed greater SEMs, but not AVAS impairment in tolerant versus naive participants. The current study demonstrates that objective measures provide additional information to subjective measures and thus should be used in combination.