Introduction

As there is lack of clinical data and definite guidelines for choosing a particular drug as add-on antiseizure medicine (ASM) in epilepsy patients, the practice is varied among clinicians. Add-on clobazam has shown some promise in drug-resistant epilepsy. However, its long-term efficacy as add-on therapy in a large group of patients with various epilepsy syndromes has not been well studied.

Aim

To evaluate the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy.

Patient Profile

• 429 patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy

Method

Study Design

• Prospective, multicenter, observational study
• Patients were initiated on clobazam 10 mg as a single dose daily (5 mg in very young children) at night
• Follow-up at 1, 3, 6, 9, and 12 months

Endpoints

• Seizure control
• Adverse events (serious and non-serious) with clobazam until one year of follow-up

Results

Efficacy

• Clobazam achieved sustained seizure freedom in >70% of the patients at one-year follow-up; 83.4% patients in the study and 73.9% patients of the evaluable population remained seizure free (Figure 1)
• At one year therapy with clobazam, seizure was reported for the first time in only 0.8% patients
• On adding clobazam in patients with a history of epilepsy from 1 to 5 years, 84.9% patients achieved seizure-free status at one year
• The seizure freedom rate at 6 months and 12 months were similar in patients with different seizure types like focal (aware, impaired awareness and bilateral tonic-clonic), myoclonic and tonic ones.
• In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment

Figure 1: Effect of add-on clobazam on seizure freedom

Safety 

• Add-on clobazam was well tolerated with majority of patients reporting mild-to-moderate adverse events (AEs)
• No serious AEs reported within the one-year study period; no record of any aggravation of seizures after adding clobazam
• A total of 22.6% patients experienced at least one AE which included 20.6% patients who experienced 386 episodes of seizures
• The most common AEs were dizziness, behavioral problems, and somnolence. Sedation, somnolence, dizziness, seizure, asthenia, generalized edema, weight gain, anorexia, and psychotic disorder that were considered to be related to clobazam were seen in 1.6% patients
• Clobazam withdrawal occurred in one (0.2%) patient due to generalized edema of mild intensity and in another due to excessive weight gain

Conclusion

• Clobazam was effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy
• The study has a pragmatic design mimicking real-life clinical practice

Epilepsy Behav 2022; 130: 108671