Can the double orexin receptor antagonist suvorexant increase rapid eye movement (REM) sleep and improve sleep-dependent processing of emotional memories in healthy adults?
A randomized placebo controlled trial to investigate the effect of suvorexant on REM sleep and fear extinction recall in healthy volunteers.
The University of Melbourne
60 participants
Jan 21, 2020
Interventional
Conditions
Summary
Dysregulated fear memory processing as well as disrupted sleep (particularly rapid eye movement sleep) are important factors in the development of posttraumatic stress disorder. Sleep is one of the few modifiable variables in the aftermath of a traumatic event, which might be utilized to prevent PTSD onset. Therefore, the aim of this project is to examine the effect of two insomnia drugs that alter REM sleep (suvorexant and temazepam) on processing of fear extinction learning and emotional memory consolidation compared to placebo in healthy individuals. Impairments in fear conditioning and extinction is the prevailing model of mechanisms involved in the development of PTSD. We hypothesize that suvorexant increases REM sleep and adaptive emotional memory processing compared to temazepam and placebo.
Eligibility
Inclusion Criteria3
- Aged between 18 – 50 years’ old
- Physically and mentally healthy
- Proficient in English
Exclusion Criteria7
- Diagnosis of psychiatric disorder including personality disorder and bipolar disorder and/or total score on PTSD Checklist-5 greater or equal to 30 (Weathers et al., 2013), subscores on Depression, Anxiety Stress Scale 21 greater or equal to 7 (Depression), greater or equal to 6 (Anxiety) and/or greater or equal to 10 (Stress; Henry & Crawford, 2005)
- Physical disorders including severe hepatic or renal impairments, neurological disorders including narcolepsy, epilepsy or seizures and/ or cardiac disorders, including hypotension or hypertension (blood pressure outside 90/60mmHg - 140/90mmHg)
- Sleep disorders and/or sleep disturbances including jetlag or shift work.
- Currently taking any medication that interacts with the study drugs or the central nervous system (e.g. sedatives). Contraceptive pills are ok.
- Regular smokers (social smokers are ok)
- BMI (body mass index) outside of 18.5 – 30kg m2
- Women only: pregnant, breastfeeding and/or trying to get pregnant
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Interventions
This Randomized Controlled Trial (RCT) investigates whether the double orexin receptor antagonist suvorexant increases rapid eye movement (REM) sleep and improves fear extinction recall compared to an active control condition (temazepam) and placebo control. Participant will be recruited and randomly assigned to the double-blinded drug condition. The intervention group receives one dose of 20mg suvorexant orally about 30 minutes before bedtime. On the test day, participants will complete a standardized and well-validated fear conditioning and extinction task which examines their capacity to acquire conditioned fear (via recording skin conductance response [SCR] reflecting physiological arousal to stimuli paired with a mild electric shock) and extinguishing fear. For the fear acquisition phase, they will look at visual images of a scene containing a desktop lamp which lights up with a color. One color will be associated with a mild electrical shock (the CS+), the other colored circle is never associated with shock (the CS-). This will be followed immediately by the fear extinction phase in which they will look at both colored lights which will never be followed by shock. This paradigm is adapted from Milad, Orr, Pitman, & Rauch (2005). SCR will be recorded to reflect sympathetic arousal. SCR amplitude typically increases to the CS+ compared to the CS- in the acquisition phase, and then gradually reduces over the extinction phase. The slope of decline of SCR over the fear extinction phase reflects how well an individual can inhibit/regulate their fear and reflects their capacity for fear extinction learning. Next, participants view emotive and neutral images selected from the International Affective Picture System (IAPS). Then, participants will take the drug and sleep at the lab while polysomnography (PSG) records sleep including REM sleep during the test night. This is followed by a recovery night at home to allow full drug washout (an ambulatory PSG records REM sleep during the recovery night). The participants return to the lab the next morning for the follow up. First they are asked to remember, recognized and rate the IAPS images they have seen two days before. Then, they complete the extinction phase again while SCR is recorded to measure recall of fear extinction. The extent that their fear returns reflects how well they remember the fear extinction from the first test day. The following week, participants record any intrusive memories that they have of the IAPS images.
Locations(1)
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ACTRN12619001694101