The long-term efficacy of cannabidiol in the treatment of refractory epilepsy.

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.

Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam.

OBJECTIVE: To evaluate the efficacy of open-label, highly purified cannabidiol (CBD, Epidiolex®) in treating refractory epilepsy relative to the concomitant use of clobazam (CLB) as well as the clinical implications of changes in CLB and norclobazam (nCLB) levels. METHODS: Data were examined retrospectively, in patients who either used CBD with concomitant CLB or without concomitant CLB after two months of treatment with CBD and at the point of best seizure control within the first year of treatment with CBD. Responder rates (percentage of subjects with a 50 % or greater reduction in weekly seizures from their baseline) and mean reduction in weekly seizure frequency were calculated and compared between those who concomitantly used CLB and those who did not. The relationship between the change in CLB and nCLB levels and change in mean weekly seizure frequency was also investigated within the group of subjects using concomitant CLB and CBD. RESULTS: We analyzed data from 47 subjects between the ages of 2.5-51 years. There was no significant difference between the concomitant CLB (n = 32) and no concomitant CLB (n = 15) groups in terms of demographics (age (p = 0.4344), race (p = 1.0000), sex (p = 0.7507)) or most epilepsy characteristics (underlying condition (all p > 0.05), mean baseline seizure frequency (p = 0.6483)). There was only one significant difference between groups regarding seizure types (more subjects with epileptic spasms in concomitant CLB group (p = 0.0413)). Concomitant AED usage was not significantly different in the two groups (all p > 0.05). Mean reduction in weekly seizure frequency was greater at the best point of seizure control within the first year than at two months of treatment with CBD, regardless of concomitant CLB usage (all p > 0.05). There was no significant difference in reduction of mean weekly seizure frequency between those who took concomitant CLB and those who did not at either time point (all p > 0.05). There was a significantly greater responder rate for subjects taking CBD and CLB than those taking CBD without CLB only at the point of best seizure control within the first year of CBD treatment (p = 0.0240). There was no strong, significant correlation between change in nCLB or CLB levels and change in seizure frequency at either time point (all |p|<0.22). SIGNIFICANCE: With or without concomitant CLB, CBD can be effective in reducing seizure frequency. Changes in nCLB and CLB levels do not have a clinically significant correlation with changes in weekly seizure frequency for those taking CBD with CLB.

Availability, accessibility, and affordability of neurodiagnostic tests in 37 countries.

OBJECTIVE: To determine the availability, accessibility, and affordability of EEG, EMG, CSF analysis, head CT, and brain MRI for neurologic disorders across countries. METHODS: An online, 60-question survey was distributed to neurology practitioners in 2014 to assess the presence, wait time, and cost of each test in private and public health sectors. Data were stratified by World Bank country income group. Affordability was calculated with reference to the World Health Organization's definition of catastrophic health expenditure as health-related out-of-pocket expenditure of >40% of disposable household income, and assessment of providers' perceptions of affordability to the patient. RESULTS: Availability of EEG and EMG is correlated with higher World Bank income group (correlation coefficient 0.38, test for trend p = 0.046; 0.376, p = 0.043); CSF, CT, and MRI did not show statistically significant associations with income groups. Patients in public systems wait longer for neurodiagnostic tests, especially MRI, EEG, and urgent CT (p < 0.0001). The mean cost per test, across all tests, was lower in the public vs private sector (US $55.25 vs $214.62, p < 0.001). Each drop in World Bank income group is associated with a 29% decrease in the estimated share of the population who can afford a given test (95% confidence interval -33.4, 25.2; p < 0.001). In most low-income countries surveyed, only the top 10% or 20% of the population was able to afford tests below catastrophic levels. In surveyed lower-middle-income countries, >40% of the population, on average, could not afford neurodiagnostic tests. CONCLUSIONS: Neurodiagnostic tests are least affordable in the lowest income settings. Closing this "diagnostic gap" for countries with the lowest incomes is essential.