A recent study titled “Adverse event reports of seizure for insomnia medication from 1967 to 2023,” published in Scientific Reports in July 2025, explores the seizure risks posed by various insomnia treatments. The authors conducted this research against the backdrop of the American Insomnia Survey, which revealed that 22% of respondents met the criteria for insomnia in 2020. Despite the lack of robust randomized trials, there has been a tendency among clinicians to prescribe hypnotic medications, often due to limited access to cognitive behavioral therapy for insomnia (CBT-i).
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The authors analyzed a large dataset from reports in 140 countries covering adverse events linked to insomnia medications from 1967 to 2013. They found a significant association between seizures and medications such as benzodiazepines, Z-drugs, antidepressants, melatonin, atypical antipsychotics, and first-generation H1 antagonists. However, no association was observed between seizure risk and melatonin receptor agonists or dual orexin receptor antagonists (DORAs).
The study underscores the common occurrence of insomnia, affecting approximately 10%-12% of adults, with an additional 15%-20% experiencing occasional symptoms. Factors surrounding insomnia are particularly relevant for individuals with epilepsy (PwE), raising concerns regarding the use of hypnotic drugs that may increase seizure risk.
The authors argue that exploring the pathophysiological mechanisms behind these associations is essential. They highlight the role of orexin (hypocretin) neurons in stabilizing wakefulness and influencing the sleep-wake cycle. Given that sleep transitions are closely linked to seizures, maintaining sleep stability may reduce the risk of nocturnal seizures.
Research has suggested that DORAs, such as suvorexant, may have an anticonvulsant potential and do not raise seizure risks. Animal studies have demonstrated that orexin receptor antagonism might mitigate the neuronal excitability associated with seizures, as orexinergic activity tends to produce proconvulsant effects.
Concerning melatonin and its receptor agonists, the existing literature generally indicates no significant increase in seizure risk, and some patients with refractory epilepsy have shown improvements. The mechanisms behind melatonin's effects—including its antioxidant properties—may contribute to seizure reduction.
Despite the lack of substantial clinical evidence linking these theoretical frameworks to practice, the authors advocate for more research on the efficacy and safety of DORAs and melatonergic drugs in improving sleep and treating insomnia in individuals with epilepsy. The utilization of DORAs remains promising, while further investigation is warranted regarding melatonin’s variable effects. Current regulatory frameworks for insomnia treatments suggest that DORAs are suitable for PwE, while melatonin receptor agonists have a limited approval status across various regions.
In conclusion, while DORAs appear safe and possibly beneficial for managing chronic insomnia without increasing seizure risk, more data is required to understand fully the complexities surrounding melatonin and similar agents in the context of epilepsy.