Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.
PROSPERO registration number CRD42017055412.
- dravet syndrome
- lennox-gastaut syndrome
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Contributors MW, SN and LD devised the search strategy and data extraction tool, and ES and MW ran the literature searches. ES, DZ, GC and MW screened studies for inclusion, and extracted study data. DZ and GC conducted GRADE assessments, and ES resolved conflicts. ES conducted the data analysis. ES, GC, DZ, MW, WDH and LD wrote the manuscript, and SN, GKH and MF provided substantial comments on iterations of the draft. All authors approved the final version for submission.
Funding Funding was received from the Commonwealth Department of Health, the NSW Government Centre for Medicinal Cannabis Research and Innovation, the Victorian Department of Health and Human Services and the Queensland Department of Health. GC, ES, SN and LD are supported by NHMRC research fellowships (#1119992; #1104600; #1013803 and #1041472). The National Drug and Alcohol Research Centre at the University of NSW is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund.
Competing interests SN, MF and LD have all been investigators on untied investigator-driven educational grants funded by Reckitt Benckiser. MF and LD have received an untied educational grant from Mundipharma for postmarketing surveillance studies of Reformulated OxyContin. SN, MF and LD have been investigators on untied investigator-driven educational grants funded by Indivior. WDH provided evidence to parliamentary committees on medical uses of cannabis in Australia and the UK, and is on the Australian Advisory Council on the Medicinal Use of Cannabis. MW, WDH, MF and LD have previously published manuscripts on the topic of therapeutic use of cannabis.
Provenance and peer review Not commissioned; externally peer reviewed.