Can Xcopri (Cenobamate), Brivaracetam, or Aptiom (Eslicarbazepine) cause hypersomnolence?

Hypersomnolence Risk with Xcopri (Cenobamate), Brivaracetam, or Aptiom (Eslicarbazepine)

Yes, all three medications - Xcopri (Cenobamate), Brivaracetam, and Aptiom (Eslicarbazepine) - can cause hypersomnolence, with Aptiom (Eslicarbazepine) having the most clearly documented risk.

Aptiom (Eslicarbazepine)

Aptiom has the most clearly documented risk of hypersomnolence among these medications:

• The FDA drug label for eslicarbazepine explicitly lists hypersomnia as part of the somnolence and fatigue-related adverse reactions 1
• Eslicarbazepine causes dose-dependent increases in somnolence and fatigue-related adverse reactions (including specifically hypersomnia, sedation, and lethargy) 1
• In controlled adult adjunctive epilepsy trials, somnolence and fatigue-related events were reported in 13% of placebo patients, 16% of patients receiving 800 mg/day eslicarbazepine, and 28% of patients receiving 1,200 mg/day eslicarbazepine 1
• These adverse effects were serious in 0.3% of eslicarbazepine-treated patients and led to discontinuation in 3% of eslicarbazepine-treated patients 1

Xcopri (Cenobamate)

Xcopri can cause somnolence, which may manifest as hypersomnolence:

• In real-world studies, fatigue and somnolence were the most commonly reported adverse events with cenobamate 2
• Three-fourths of patients reported at least one side effect, with fatigue and somnolence being the most common 2
• Adverse events most commonly emerged at cenobamate doses of ≥250 mg/day 2
• A 2025 review confirmed that somnolence, dizziness, and fatigue were the most frequently reported treatment-emergent adverse events with cenobamate 3

Brivaracetam

Brivaracetam can also cause somnolence, though it may have a better tolerability profile:

• Clinical trials have reported somnolence as one of the most common adverse reactions to brivaracetam 4
• Somnolence with brivaracetam is typically mild to moderate, transient, and often improves during the course of treatment 4
• In a review of clinical trial data, somnolence was one of the treatment-emergent adverse events significantly associated with brivaracetam 5
• Brivaracetam may have a more favorable safety and tolerability profile compared to first-generation antiepileptic drugs 6

Management Considerations

When managing hypersomnolence associated with these medications:

• Initial management requires treatment optimization of any underlying medical, neurologic, or psychiatric disorder 7
• Careful withdrawal of sedating medications or substances, if possible, is prudent 7
• Ensuring adequate opportunity for nighttime sleep is important to exclude sleep deprivation as a cause of excessive sleepiness 7
• Behavioral modifications can be beneficial, including good sleep hygiene techniques and maintaining a regular sleep-wake schedule 7
• Consider two short 15-20 minute naps, one scheduled around noon and another around 4:00-5:00 pm, to alleviate some sleepiness 7

Diagnostic Approach

If hypersomnolence occurs with these medications:

• Obtain history from both the patient and bed partner if possible 7
• Questions should address excessive daytime sleepiness, symptom response to napping, and presence of dreaming during naps 7
• Establish onset, frequency, and duration of the sleeping episodes 7
• Consider laboratory tests to rule out other medical conditions that may cause excessive sleepiness (thyroid function tests, liver function tests, complete blood count, serum chemistry) 7
• For severe or persistent cases, consider overnight polysomnography followed by a multiple sleep latency test (MSLT) 7

Alternative Medication Options

If hypersomnolence is problematic with these medications:

• Modafinil is recommended as first-line medication for patients with idiopathic hypersomnia who also have a seizure disorder 8
• Modafinil has demonstrated clinically significant improvements in excessive daytime sleepiness 8
• The American Academy of Sleep Medicine recommends modafinil for the treatment of hypersomnia secondary to medical conditions 7
• For elderly patients, a starting dose of modafinil at 100 mg once upon awakening in the morning is recommended, with increases at weekly intervals as necessary 8

Remember that medication-induced hypersomnolence should be managed under the guidance of both a sleep specialist and the patient's primary care physician who knows the patient's medical problems and current medications 7.