Clobazam is a benzodiazepine medication primarily used to help control seizures in people with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy. It is FDA-approved as an add-on treatment for seizures associated with LGS in patients 2 years of age and older. In practice, it is also prescribed for other seizure types and, in some countries, for anxiety disorders.
Its Primary Use: Lennox-Gastaut Syndrome
Lennox-Gastaut syndrome is a rare, serious epilepsy disorder that typically begins in childhood and causes multiple types of seizures, including “drop seizures” where a person suddenly loses muscle tone and falls. These seizures are notoriously difficult to control, and most patients need more than one medication. Clobazam is not used alone for LGS. Instead, it’s added to a patient’s existing seizure medication regimen to reduce how often seizures occur.
Clinical trial data shows meaningful results. In studies, about half of patients taking clobazam experienced at least a 50% reduction in both drop seizures and total seizure frequency. Among patients with the least severe baseline seizure rates, 33% achieved complete freedom from drop seizures on clobazam, compared to just 7% on placebo. Even in the most severely affected patients, 5% became completely free of drop seizures, versus none on placebo. These results held regardless of whether patients were also using a vagus nerve stimulator, a device sometimes implanted to help manage seizures.
Off-Label and International Uses
While the FDA approval is specific to LGS, clobazam is widely used in clinical practice for many different seizure types beyond that diagnosis. Neurologists may prescribe it as an add-on therapy for focal seizures, generalized seizures, or other epilepsy syndromes that haven’t responded well to first-line medications.
Outside the United States, clobazam has a longer history and broader range of approved uses. In Europe, Asia, and Australia, it has been found effective for treating anxiety, including generalized anxiety and social anxiety. An open-label pediatric trial through the American Epilepsy Society explored treating both anxiety and epilepsy with clobazam simultaneously, reflecting growing interest in its dual potential for patients who experience both conditions.
How Clobazam Works
Like other benzodiazepines, clobazam works by enhancing the activity of GABA, the brain’s main calming chemical messenger. When GABA binds to its receptor on a nerve cell, it slows that cell’s activity. Clobazam doesn’t activate the receptor on its own. Instead, it acts as an amplifier, making the receptor more responsive when GABA is already present. This reduces the excessive electrical activity in the brain that triggers seizures.
Clobazam has a slightly different chemical structure compared to more familiar benzodiazepines like diazepam (Valium) or clonazepam (Klonopin). This structural difference is thought to contribute to its somewhat different side effect profile, particularly when it comes to sedation.
How It Compares to Other Benzodiazepines
One of clobazam’s practical advantages is its tolerability relative to other benzodiazepines used for epilepsy. A UK database study comparing clobazam and clonazepam found an important difference in dosing over time. The median clobazam dose stayed the same from the start of treatment through the last follow-up visit, while clonazepam doses increased by 25% in adults and 50% in children. Rising doses over time can signal that a medication is losing its effectiveness, a phenomenon called tolerance. The fact that clobazam doses remained stable suggests it may maintain its seizure-controlling effects more consistently. Despite this difference, both medications kept patients on treatment for similar durations, with comparable retention rates out to 10 years.
Common Side Effects
The most frequently reported side effects of clobazam include drowsiness, coordination problems (unsteadiness or shakiness when walking), fever, and difficulty swallowing. These effects tend to be most noticeable when first starting the medication or after a dose increase.
Other common but generally less serious side effects include irritability, aggression, decreased appetite, constipation, drooling, vomiting, and cold-like symptoms such as a runny nose, congestion, or sneezing. In children especially, behavioral changes like irritability and aggression are worth watching for, as they can affect daily life and may require a dosage adjustment.
Because clobazam is a benzodiazepine, it carries the same class-wide risks of physical dependence with long-term use. Stopping it abruptly can trigger withdrawal symptoms or a rebound increase in seizures, so any dose changes should be made gradually.
Drug Interactions to Be Aware Of
Clobazam is broken down in the liver, and its active byproduct (which also helps control seizures) is processed through a specific enzyme pathway called CYP2C19. This matters because many common epilepsy medications affect that same pathway. Felbamate and oxcarbazepine inhibit CYP2C19, which can cause the active byproduct to build up in the body and potentially intensify side effects. Meanwhile, medications like valproic acid, phenobarbital, phenytoin, and carbamazepine speed up the breakdown of that byproduct, potentially reducing clobazam’s effectiveness.
People who are genetically “poor metabolizers” at CYP2C19, meaning their body processes drugs through this pathway more slowly than average, may experience higher levels of the active byproduct and stronger effects from the same dose. Genetic testing for CYP2C19 status is sometimes done to help guide dosing, particularly if side effects are unexpectedly strong.