The long‐term efficacy of cannabidiol in the treatment of refractory epilepsy

Abstract

Objective: Cannabidiol (CBD) has been shown to reduce seizures among patients with refractory epilepsies of various etiologies in recent clinical trials and an expanded access program (EAP). Most studies report efficacy over short time periods (<1 year), with little published on longer term efficacy. Here, we investigate the efficacy of CBD for a treatment period of up to 60 months (median = 45.5 months). Methods: We conducted a retrospective review of patient-reported seizure logs and medical records for 54 subjects with refractory epilepsy who enrolled in the Massachusetts General Hospital's open-label EAP for CBD as a new treatment for epilepsy. We analyzed the effect of CBD on seizure frequencies and concomitant antiepileptic drug (AED) use at 1 year after starting treatment and the most recent study visit. Results: Our results indicate that CBD maintains its efficacy for controlling seizures from Year 1 to the most recent study visit. The percentage of seizure responders remained similar at these time points (41.7%-42.6%), and the seizure response rate was also maintained (p = .12). Efficacy was also seen over a broad dose range, and up to 50 mg/kg/day. CBD was particularly effective for controlling seizures in the setting of tuberous sclerosis complex and for reducing epileptic spasms and absence seizures. Although CBD use did not lead to an overall decrease in concomitant AEDs, most subjects reduced the dose of at least one concomitant AED compared to baseline. CBD was generally well tolerated, with drowsiness and diarrhea as the primary adverse reactions. Significance: This study demonstrates CBD does not lose its efficacy in controlling seizures over a treatment period of up to 60 months. Taken alongside other results on the efficacy and tolerability of CBD in the treatment of refractory epilepsies, our results provide evidence that CBD is an effective, safe, and well-tolerated AED for long-term use.

Long‐term efficacy and safety of cannabidiol in patients with treatment‐resistant epilepsies: Four‐year results from the expanded access program

“…The initial EAP data showed a median reduction of 36.5% in monthly motor seizure frequency and a favorable adverse events (AEs) profile 13 . Several subsequent EAPs have reported similar efficacy and safety profiles 14–16 …”

“…13 Several subsequent EAPs have reported similar efficacy and safety profiles. [14][15][16] Previously, in a safety and efficacy update of this EAP, pooled results for safety outcomes up to 144 weeks and efficacy outcomes up to 96 weeks in more than 600 patients treated through December 2016 showed that add-on CBD can be an efficacious, long-term treatment option for TRE. 14 Here, we report the Year 4 update of the efficacy and safety results from the EAP.…”

Use of cannabidiol in the treatment of epilepsy

“…Despite the broad dose range (up to 50 mg/kg/day), CBD was well-tolerated and safe. The greatest therapeutic benefits were experienced by patients with TSC and patients with absence seizures and epileptic spasms [32]. Park et al reached similar conclusions proving the long-term efficacy and safety of CBD in children with treatment-resistant epilepsy who were ineligible to participate in randomised controlled trials [33].…”

A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication

“…Cannabidiol was also associated with improvements in overall condition assessed using the Caregiver Global Impression of Change, as well as increases in seizure-free days. Longer term efficacy and safety (up to 3 years) has been determined in an open-label extension of the pivotal phase III trials [ 67 , 68 ], and importantly from an expanded access programme confirming its efficacy in real-world clinical practice [ 69 – 72 ].…”