The Effect of Suvorexant on Fear Extinction Recall: A Double-Blind Randomised Controlled Pilot Trial in Healthy Individuals.

Post-traumatic stress disorder (PTSD) is a highly debilitating condition that develops after trauma exposure. Dysregulation in extinction memory consolidation (i.e., the ability to remember that trauma-related stimuli no longer signal danger) is proposed to underlie PTSD development. Disruptions in rapid eye movement (REM) sleep are thought to be the key contributor to this dysregulation, as REM sleep is suggested to play a vital role in the processing of emotional memories. While previous literature has investigated the role of natural REM sleep variations or REM sleep disruptions on extinction recall capacities, none have attempted to increase REM sleep to improve extinction recall. In this pilot, randomised controlled trial, we investigated the effect of 20 mg suvorexant to increase REM sleep, 20 mg temazepam to decrease REM sleep, and a placebo on extinction recall in 30 healthy adults (age: M = 26.93 years, SD = 7.54). Overall, no difference in REM percentage (p = 0.68, η 2 = 0.0.03, small effect), nor in extinction recall (p = 0.58, η 2 = 0.04, small effect) was observed between the drug conditions. However, increased REM percentage was associated with decreased conditioned fear response at recall, indicating better extinction recall (β = -0.71, p = 0.03, η p 2 = 0.10; moderate effect) across the sample. These findings suggest that increasing REM sleep in populations with REM disruptions such as PTSD to optimal levels could improve extinction recall. This underscores the potential of enhancing REM sleep as a therapeutic target for improving PTSD outcomes, warranting further investigation of suvorexant in clinical populations where REM sleep deficits are prevalent.