FROM JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY

A reasonable number of patients with treatment-resistant epilepsy experienced a decrease in the frequency of seizures when treated with pharmaceutical-grade cannabidiol, according to findings from a systematic review.

The review, published online March 6 in the Journal of Neurology, Neurosurgery and Psychiatry , centers on 36 studies testing the use of cannabinoids as adjunctive treatments for treatment-resistant epilepsy, including six randomized controlled trials involving a total of 555 patients and 30 observational studies involving 2,865 patients.

Two randomized, controlled trials representing a total of 291 patients (one with 120 patients with Dravet syndrome and another with 171 patients with Lennox-Gastaut syndrome) found cannabidiol (CBD) treatment was 74% more likely than placebo to achieve a greater than 50% reduction in seizures. In the observational studies, nearly half (48.5%) of the 970 patients across a range of epilepsy subtypes achieved a 50% or greater reduction in seizures.

Emily Stockings, PhD , of the National Drug and Alcohol Research Centre at the University of New South Wales, Sydney, and her coauthors estimated that eight patients would need to receive CBD treatment to achieve a 50% reduction in seizures in one person. However, they also pointed out that the quality of the evidence was mixed.

“There is insufficient evidence from moderate-quality or high-quality studies to assess whether there is a treatment effect of Cannabis sativa, CBD:THC combinations, or oral cannabis extracts,” they wrote.

There were three randomized, controlled trials that also looked at complete seizure freedom, finding a sixfold higher likelihood of total seizure freedom with CBD, compared with placebo. However, the number needed to treat to achieve this was 171, and again, the quality of evidence was described as “mixed.”

Just over half of patients treated with CBD reported improved quality of life, and significantly more parents and caregivers of those treated with CBD said the patient’s overall condition had improved. The pooled estimates from observational studies suggested that 55.8% of patients experienced improvements in their quality of life when using cannabinoids.

Studies involving patients with Dravet syndrome reported the greatest improvements in quality of life, compared with studies involving a mix of epilepsy syndromes. However, the authors noted that the studies that involved Dravet syndrome patients were all case series in which every patient responded and suggested they should be interpreted with caution.

The authors said they were more confident of the benefits of CBD in children than in adults, because the more recent, larger, and better-conducted randomized, controlled trials focused on children and adolescents.

“In RCTs, and most of the non-RCTs, cannabinoids were used as an adjunctive therapy rather than as a standalone intervention, so at present, there is little evidence to support any recommendation that cannabinoids can be recommended as a replacement for current standard [antiepileptic drugs].”

The review also looked at the number of withdrawals, which they said could serve as an indicator of the tolerability and effectiveness of a treatment. The randomized, controlled trials showed no difference in withdrawal rates between patients on CBD and those on placebo, although CBD patients were more likely to withdraw because of adverse events.

There was a small but significant increase in the risk of adverse events with CBD, compared with placebo: particularly drowsiness, diarrhea, fatigue, and changes in appetite. There also was a higher incidence of serious adverse events (AEs), including status epilepticus and elevated aminotransferase levels.

“The fact that more patients withdrew or experienced AEs when receiving CBD than placebo indicates the need for clinicians and patients to weigh the risks and benefits of adding CBD to other AED [antiepileptic drug] treatment,” the authors wrote.

The study was supported by the Commonwealth Department of Health, the New South Wales Government Centre for Medicinal Cannabis Research and Innovation, the Victorian Department of Health and Human Services, and the Queensland Department of Health. Four authors were also supported by National Health and Medical Research Council grants. Three authors declared grants from the pharmaceutical industry, and one author has provided evidence to parliamentary committees on medical uses of cannabis in Australia and the United Kingdom, and is on the Australian Advisory Council on the Medicinal Use of Cannabis. No other conflicts of interest were declared.

cnnews@frontlinemedcom.com

SOURCE: Stockings E et al. J Neurol Neurosurg Psychiatry. 2018 Mar 6. doi: 10.1136/jnnp-2017-317168

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