Risk of Sleepwalking and Parasomnias with Dual Orexin Receptor Antagonists (DORAs)
Dual Orexin Receptor Antagonists (DORAs) have a significantly lower risk of sleepwalking and parasomnias compared to benzodiazepine receptor agonists (BzRAs), making them a safer alternative for patients with insomnia who have concerns about parasomnia behaviors.
Understanding DORAs and Parasomnias
DORAs represent a newer class of medications for insomnia that work by blocking orexin receptors, which are involved in promoting wakefulness. Unlike traditional hypnotics, DORAs:
- Target the specific sleep-wake pathway without broadly suppressing central nervous system activity
- Have a different mechanism of action than benzodiazepines and non-benzodiazepine BzRAs
- Promote more physiological sleep patterns
Comparison with BzRA Hypnotics
The FDA has specifically warned about disruptive sleep-related behaviors associated with BzRA hypnotics, including:
- Sleepwalking
- Sleep eating
- Sleep driving
- Sleep-related sexual behavior 1
These warnings are notably absent for DORAs, suggesting a more favorable safety profile regarding parasomnias.
Evidence on Parasomnia Risk
BzRA-Associated Parasomnias
The American Academy of Sleep Medicine clinical guideline for insomnia clearly documents that BzRA hypnotics (including zolpidem, eszopiclone, and zaleplon) have been associated with reports of disruptive sleep-related behaviors 1. These medications carry specific warnings about:
- Risk of complex sleep behaviors
- Potential for serious injuries during sleep episodes
- Amnesia for these events
DORAs and Parasomnia Risk
In contrast to dopamine agonists (which are associated with sleep attacks and excessive daytime sleepiness) 2, 3, 4, 5, 6 and BzRAs (associated with parasomnias), DORAs have not been prominently linked to parasomnia behaviors in clinical guidelines or FDA warnings.
Risk Factors and Considerations
When considering medication options for insomnia treatment, several factors increase the risk of parasomnias:
- Combining sedative medications with alcohol
- Using higher than prescribed doses
- Sleep restriction/deprivation
- Pre-existing history of parasomnias
- Elderly patients (who are more susceptible to CNS effects)
Clinical Approach to Medication Selection
First-Line Approach
Non-pharmacological treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I) should be the first-line treatment for chronic insomnia 1
If medication is necessary:
- For patients with parasomnia concerns: Consider DORAs as they have lower risk of complex sleep behaviors
- For patients with no parasomnia history but high risk of falls/cognitive impairment: Consider low-dose doxepin (3-6mg) 1
- For patients with comorbid depression/anxiety: Consider appropriate antidepressants with sedating properties 7
Medications to Avoid
- Benzodiazepines: High risk of dependence, falls, cognitive impairment, and parasomnias 1
- Non-benzodiazepine BzRAs (if parasomnia is a concern): Despite efficacy, these carry FDA warnings about complex sleep behaviors 1
Patient Education and Monitoring
When prescribing any sleep medication, ensure patients understand:
- The importance of allowing adequate time for sleep (7-8 hours)
- The risks of combining with alcohol or other sedatives
- The need to report any unusual sleep behaviors
- The importance of sleep environment safety precautions if medication is necessary
Conclusion
For patients with insomnia who have concerns about parasomnias, DORAs represent a safer alternative to traditional BzRA hypnotics. While all medications should be used judiciously, the evidence suggests that DORAs carry a lower risk of complex sleep behaviors like sleepwalking compared to BzRAs, which have documented associations with these concerning behaviors.