Cannabidiol (CBD) transdermal gel reduced focal impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS) frequency and improved quality of life, in pediatric patients with developmental and epileptic encephalopathies (DEEs), according to study results published in JAMA Network Open.

DEEs, which include Dravet syndrome and Lennox-Gastaut syndrome (LGS), are typically resistant to antiseizure medicines (ASMs), which pediatric patients struggle to take. The objective of the study was to determine whether CBD transdermal gel would provide a benefit for this patient population when it comes to 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-label, controlled, nonrandomized study. They had experienced at least 5 seizures (including FIAS and TCS) in a 28-day baseline period.


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Parents administered 4.2% topical CBD transdermal gel treatment twice daily for 6.5 months (1-month titration and 5.5-month flexible dosing maintenance period) and took daily records of seizures and erythema, which were reviewed at study visits held at weeks 2, 4, 6, 14, and 26 (6.5 months). Patients continued into a 6-month extension study or entered a taper period.

Adverse events were reported by 29% of patients during baseline and 96% of patients during treatment (60% treatment-related). Nearly all (44 of 46) treatment-related adverse events were mild or moderate.

Treatment-related adverse events included dryness and pain at the application site and somnolence. Ten patients had 15 serious adverse events (10 infections; 4 seizure-related). One case of nonconvulsive status epilepticus and 1 lower respiratory tract infection could have been related to treatment, the researchers reported.

Nearly all (92.5%) parents reported no or minimal erythema. One patient who had a history of keratosis pilaris had intense erythema, which the researchers said was due to secondary bacterial infection.

The 46 patients in the seizure frequency analysis completed at least 80% of seizure diaries and completed the treatment for at least 80 days experienced a median seizure reduction of 12.3% (range 18.6% to 46.3%). Median FIAS (44.5% reduction) and TCS (22.7% reduction) reduced the most. The 33 patients with FIAS and TCS experienced a median monthly reduction of 43.5% from baseline to 6.5 months.

Scores on the Epilepsy and Learning Disabilities Quality of Life (ELDQOL) and Sleep Disturbance Scale for Children (SDSC total score difference at 3.5 months -3.7 P =.047 at 6 months -5.1 P =.01) significantly improved. Subscores related to initiating and maintaining sleep, arousal or nightmares, and sleep-wake transitions improved significantly.

Patients’ irritability (77%) sleep (53%), cognition or concentration (47%), postictal symptoms of seizures (51%) improved, parents reported. Alertness (40%) and reduction in seizure frequency (37%) were the most frequently reported improvements.

Difficulty in applying the study medication and reactions at the application site were the most frequent complaints. Seven patients discontinued CBD because of lack of effect. One discontinued due to reaction at application site.

Study limitations included the lack of control group and possible regression toward the mean for seizure frequency reduction.

The researchers concluded: “Treatment was associated with a reduction in FIAS and TCS frequency, as well as with caregiver-reported improvements in behavior, sleep, cognition, and quality of life. These findings highlight the need for a double-masked randomized clinical trial of CBD transdermal gel.”

Disclosure: This research was supported by Zynerba Pharmaceuticals Inc. Some study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Scheffer IE, Hulihan J, Messenheimer J, et al. Safety and tolerability of transdermal cannabidiol gel in children with developmental and epileptic encephalopathies a nonrandomized controlled trial. JAMA Network Open. Published online September 3, 2021. doi:10.1001/jamanetworkopen.2021.23930