A RARE case report suggests that high dose perampanel may trigger compulsive nocturnal food cravings, with symptoms aligning closely to peak drug concentration levels. Perampanel, a non-competitive AMPA receptor antagonist, is widely prescribed for focal and generalized epilepsy, yet its off-label use at higher doses raises important safety concerns.
The case involved a 26-year-old man with pharmaco-resistant focal epilepsy who was titrated to 24 mg perampanel daily. Shortly after dose escalation, he began experiencing compulsive nocturnal food cravings, waking during the night to eat excessively. The behavior coincided with peak serum levels, which were shown to increase by 26% between near-trough and peak concentration. Upon dose reduction, the symptoms completely resolved, strengthening the association between perampanel exposure and the observed behavior.
This observation underscores the importance of clinician awareness of atypical adverse events in epilepsy management. While perampanel has demonstrated therapeutic benefit in seizure control, tolerability at higher doses can be problematic. Importantly, patients may not readily disclose behaviors such as compulsive eating due to embarrassment or concerns about jeopardizing seizure treatment. This highlights the need for direct questioning by healthcare professionals, particularly when managing patients on high-dose or off-label regimens.
The case also raises the question of whether rechallenge with perampanel may be appropriate in some situations where the drug has proven efficacy but produces challenging behavioral side effects. Careful monitoring and individualized dose adjustments may help balance seizure control with tolerability.
For clinicians, this report reinforces the value of vigilance when prescribing antiseizure therapies, particularly in the context of dose escalation and off-label use. Subtle behavioral changes may represent early signs of adverse effects and should be investigated proactively to optimize patient safety and treatment outcomes.
Reference:
Vassallo P, Sande JW. Emptying the fridge syndrome: a case of nocturnal food craving associated with peak perampanel concentration. Epilepsy & Behavior Reports. 2025;32:100821.
