Suvorexant trial investigates orexin antagonism for alcohol use disorder and stress-related drinking
Background
Alcohol Use Disorder (AUD) is a chronic relapsing brain disease characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. Current pharmacotherapies for AUD have limited efficacy and often come with significant side effects or abuse potential. Stress is a major trigger for relapse in AUD, highlighting a critical need for treatments that can modulate stress reactivity. The orexin system (also known as hypocretin) plays a crucial role in arousal, reward, and stress responses, making orexin receptor antagonism a promising target for reducing stress-related drinking and improving sleep disturbances often associated with AUD.
Study Design
This is a randomized, double-masked, placebo-controlled Phase II clinical trial (NCT06679062) enrolling approximately 76 participants with alcohol use disorder (AUD) and co-occurring posttraumatic stress disorder (PTSD) symptoms. Participants are randomized to receive either suvorexant (SUV) 10mg capsules or a matched placebo orally each night before bedtime for an 8-week duration. Study visits occur at baseline, 4-weeks (mid-point), and 8-weeks (end-point), incorporating a psychophysiological stress paradigm with electromyography (EMG) to assess stress reactivity. Daily reports on medication adherence, side effects, sleep quality, alcohol use, and mood are collected via smartphones throughout the 8-week intervention period.
Results
This is a recruiting clinical trial (NCT06679062), and as such, specific efficacy and safety findings are not yet available. The primary objectives are to determine if suvorexant is effective for alcohol use disorder (AUD) and if it can dampen stress reactivity. Researchers will analyze daily self-reported alcohol consumption, sleep patterns, and mood changes collected via smartphone. The psychophysiological stress paradigm will provide objective measures of stress response, including electromyography (EMG) data, at multiple time points to assess the drug's impact on physiological stress markers. A key exploratory aim is to develop a biomarker for suvorexant treatment response, which will involve correlating physiological, behavioral, and self-report data with treatment outcomes. The trial will compare these comprehensive outcomes between the active drug and placebo arms to identify statistically significant differences in AUD severity, stress response, and sleep quality.
Why It Matters
If successful, this trial could validate suvorexant as a novel, non-addictive pharmacological option for alcohol use disorder, particularly for individuals whose drinking is exacerbated by stress or co-occurring PTSD. This could offer a new treatment pathway beyond existing AUD medications, which often have adherence challenges or limited efficacy in stress-induced relapse. The focus on developing a biomarker for treatment response is also significant, potentially enabling personalized medicine approaches for AUD by identifying patients most likely to benefit from orexin receptor antagonism. This could lead to more targeted and effective protocols for managing AUD, especially for those struggling with sleep disturbances and stress-related cravings.
suvorexant
alcohol use disorder
aud
orexin receptor antagonist
stress
ptsd