Cannabidiol (CBD) transdermal gel reduced the frequency of partial seizure impaired seizures (FIAS) and tonic-clonic seizures (TCS) and improved quality of life in pediatric patients with developmental and epileptic encephalopathies (DEEs), according to study results published on the JAMA Network Open .
DEEs, which include Dravet syndrome and Lennox-Gastaut syndrome (LGS), are typically resistant to anti-epileptic drugs (ASMs), which are difficult for pediatric patients to take. The aim of the study was to determine whether transdermal CBD gel is beneficial for this patient population in terms of seizure frequency, sleep, and quality of life.
Forty-six patients (mean age 10.5 years) in Melbourne, Australia and Wellington, New Zealand were included in the open, controlled, non-randomized study. They had suffered at least 5 seizures (including FIAS and TCS) in a 28-day baseline period.
Parents received 4.2% topical CBD gel treatment twice daily for 6.5 months (1 month titration and 5.5 month flexible dose maintenance period) and kept daily records of seizures and erythema from study visits during week 2 , 4 were checked. 6, 14 and 26 (6.5 months). The patients continued a 6-month extension study or entered a phase-out phase.
Adverse events were reported by 29% of patients at baseline and 96% of patients during treatment (60% treatment-related). Almost all (44 out of 46) treatment-related side effects were mild or moderate.
Treatment-related side effects included dryness and pain at the application site and drowsiness. 15 serious adverse events occurred in 10 patients (10 infections; 4 related to seizures). One case of non-convulsive status epilepticus and 1 lower respiratory tract infection could be treatment-related, the researchers reported.
Almost all (92.5%) parents reported no or minimal erythema. One patient with a history of keratosis pilaris had severe erythema, which the researchers said was due to a secondary bacterial infection.
The 46 patients in the seizure frequency analysis completed at least 80% of the seizure diaries and completed treatment for at least 80 days. Median FIAS (44.5% reduction) and TCS (22.7% reduction) decreased the most. In the 33 patients with FIAS and TCS, there was a median monthly reduction of 43.5% compared to the initial value to 6.5 months.
The scores on the epilepsy and learning disability quality of life (ELDQOL) and the sleep disorder scale for children (SDSC total score difference after 3.5 months -3.7 P = 0.047 after 6 months -5.1 P = 0.01) improved significantly. Subscores related to induction and maintenance of sleep, arousal or nightmares and sleep-wake transitions improved significantly.
The patients’ irritability (77%) sleep (53%), cognition or concentration (47%), postictal seizure symptoms (51%) improved, the parents reported. Alertness (40%) and reduction in seizure frequency (37%) were the most commonly reported improvements.
Difficulties in applying the study medication and reactions at the application site were the most common complaints. Seven patients discontinued CBD due to lack of effect. One was canceled due to a reaction at the application site.
The limitations of the study included the lack of a control group and possible regression towards the mean for reducing seizure frequency.
The researchers concluded, “Treatment was associated with reductions in FIAS and TCS incidence, as well as caregiver-reported improvements in behavior, sleep, cognition, and quality of life. These results underscore the need for a double-blind randomized clinical trial with transdermal CBD gel. “
Disclosure: This study was supported by Zynerba Pharmaceuticals Inc. Some study authors stated links with biotech, pharmaceutical, and / or device manufacturers. For a full list of specifications, see the original reference.
Scheffer IE, Hulihan J, Messenheimer J, et al. Safety and tolerability of transdermal cannabidiol gel in children with developmental and epileptic encephalopathies a non-randomized controlled study. JAMA network open. Published online September 3, 2021. doi: 10.1001 / jamanetworkopen.2021.23930