Yes, Xcopri (cenobamate) is a controlled substance. The DEA classified it as a Schedule V drug in March 2020, placing it in the lowest tier of controlled substances under federal law. This means it has a recognized but relatively low potential for abuse compared to drugs in higher schedules.
Why Xcopri Is Classified as Schedule V
Xcopri earned its controlled status because of how it affects the brain. The drug works partly by enhancing the activity of GABA receptors, the same system targeted by benzodiazepines like alprazolam and midazolam. That overlap raised questions about whether people might misuse it for its sedative or euphoric effects.
To find out, the FDA ran a formal abuse potential study in 53 healthy volunteers who had experience using sedative drugs recreationally. At the highest prescribed dose (400 mg), Xcopri produced “drug liking” scores of about 69 on a 100-point scale, compared to 52 for placebo and 85 for alprazolam (a Schedule IV benzodiazepine). In other words, people noticed pleasurable effects from Xcopri, but those effects were significantly weaker than what a well-known benzodiazepine produced. At the lower 200 mg dose, drug liking scores were not significantly different from placebo.
Animal studies told a similar story. Rats self-administered cenobamate, but at lower rates than they self-administered midazolam. The overall picture pointed to real but modest abuse potential, which is exactly the profile Schedule V is designed for.
How Schedule V Compares to Other Seizure Medications
Most epilepsy medications are not controlled substances at all. Common drugs like levetiracetam, lamotrigine, carbamazepine, valproic acid, and topiramate carry no DEA scheduling. You can typically get refills without extra regulatory hurdles.
Among seizure drugs that are controlled, Xcopri sits in the lowest category alongside a handful of others:
- Schedule III: Perampanel
- Schedule IV: Clobazam, clonazepam, diazepam, phenobarbital
- Schedule V: Xcopri (cenobamate), lacosamide, pregabalin, brivaracetam, ganaxolone
If you’ve been prescribed lacosamide or pregabalin before, the prescription process for Xcopri will feel familiar.
What This Means for Your Prescription
Because Xcopri is a controlled substance, your pharmacy may handle it slightly differently than a non-controlled medication. Some states impose their own rules on Schedule V drugs, including limits on refills or requirements for more frequent prescriber visits. In practice, Schedule V drugs face the fewest restrictions of any controlled category, and most patients find the process straightforward.
One thing to be aware of: clinical studies in healthy subjects showed that Xcopri can cause physical dependence. When the drug was stopped abruptly, withdrawal symptoms included insomnia, decreased appetite, depressed mood, tremor, and memory problems. For this reason, the prescribing guidelines call for tapering the dose gradually over at least two weeks rather than stopping suddenly. Abrupt withdrawal also raises the risk of increased seizure frequency or status epilepticus, which is true of most epilepsy medications.
Side Effects Related to Its Controlled Status
The same brain effects that give Xcopri its abuse potential also drive its most common side effects. In clinical trials, drowsiness, dizziness, and fatigue were the top complaints, and all three got worse at higher doses. At the 400 mg dose, 37% of patients experienced drowsiness (compared to 11% on placebo), 33% reported dizziness, and 24% had fatigue. At the 100 mg dose, those numbers dropped closer to 19%, 18%, and 12%.
A small percentage of patients at the highest dose reported euphoric mood (2%), which aligns with the drug’s mild abuse potential. Balance problems, coordination difficulties, and confusion also appeared more often at higher doses.
The Slow Titration Requirement
Xcopri has an unusually long dose-ramping schedule that takes at least 11 weeks to reach the standard maintenance dose. You start at just 12.5 mg daily and increase every two weeks. This gradual approach exists primarily because of a serious allergic reaction called DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), which caused one death during early clinical development when the drug was increased more rapidly. In a later study of over 1,300 patients using the slower two-week titration, no cases of DRESS occurred.
This titration schedule is separate from the controlled substance classification, but it’s worth knowing because it means Xcopri takes longer to reach a therapeutic dose than many other seizure medications. Your prescriber will likely write a series of prescriptions at increasing strengths over those first several weeks.