Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex.

OBJECTIVE: Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder with highly variable expression. The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment-resistant epilepsy. Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol (CBD), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of TSC. METHODS: Eighteen of the 56 patients who have enrolled in our current expanded-access study of cannabidiol for patients with treatment-resistant epilepsy carry a diagnosis of TSC. After an initial baseline period of 1 month, patients began treatment with CBD. The initial dose of 5 mg/kg/day was increased by 5 mg/kg/day every week up to a maximum dose of 50 mg/kg/day, if tolerated. Weekly seizure frequencies, percent change in seizure frequencies, and responder rates were calculated during the 2nd, 3rd, 6th, 9th, and 12th month of treatment with CBD. RESULTS: The median weekly seizure frequency during the baseline period was 22.0 (interquartile range [IQR] 14.8-57.4), which decreased to 13.3 (IQR 5.1-22.1) after 3 months of treatment with cannabidiol. The median percent change in total weekly seizure frequency was -48.8% (IQR -69.1% to -11.1%) after 3 months of treatment. The 50% responder rates over the course of the study were 50%, 50%, 38.9%, 50%, and 50% after 2, 3, 6, 9, and 12 months of treatment with CBD, respectively. In patients taking clobazam concurrently with CBD (n = 12), the responder rate after 3 months of treatment was 58.3%, compared to 33.3% in patients not taking clobazam (n = 6). Twelve (66.7%) of 18 patients in this study experienced at least one adverse event thought possibly related to CBD; the most common adverse events were drowsiness (n = 8, 44.4%), ataxia (n = 5, 27.8%), and diarrhea (n = 4, 22.2%). SIGNIFICANCE: Although double-blind, placebo-controlled trials are still necessary, these findings suggest that cannabidiol may be an effective and well-tolerated treatment option for patients with refractory seizures in TSC.

Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis complex.

Lacosamide (LCS) was approved by the United States Food and Drug Administration (FDA) in 2008 as adjunctive therapy to other anti-epileptic drugs (AEDs) to treat focal-onset seizures, with or without secondary generalization. Its role in the treatment of epilepsy in individuals with tuberous sclerosis complex (TSC) has yet to be determined. This study evaluates LCS treatment of focal-onset refractory epilepsy in patients with TSC. From November 2009 to June 2014, 46 TSC patients followed by a single neurologist were treated with LCS. Forty-eight percent were responders (seizure reduction ≥50%). No significant differences between responders and non-responders in demographic characteristics were found. LCS appears to be an effective and safe treatment of refractory focal onset seizures in TSC. Determining the long-term tolerability and efficacy of LCS in TSC patients requires additional clinical experience.

Clobazam therapy of refractory epilepsy in tuberous sclerosis complex.

Clobazam (CLB) was recently approved by the FDA, but has not been evaluated in tuberous sclerosis complex (TSC). We retrospectively reviewed a cohort of patients with TSC and refractory epilepsy who started CLB over a 5-year period. Clinical characteristics and number of tubers on MRI were assessed. Duration of therapy, therapeutic response and adverse events were recorded. CLB was prescribed in 29 adults and children of whom 72% were cognitively impaired, with a median age at seizure onset of 5 months. Mean duration of CLB therapy was 17.3 months with a 12 and 24-month estimated retention rate of 82% and 68%, respectively. Twenty patients (69%) reported a good response (>50% seizure reduction) at the end of the titration, and six patients (21%) remained good responders after 12 months of CLB therapy. Adverse events occurred in 13 patients, predominantly somnolence and behavioral disorders. One quarter of the responders reported improvement in behavior. No predictive factor for a good response could be identified. CLB appears to be a well-tolerated and valuable option for treatment of refractory epilepsy in TSC.