Cannabidiol Drug Approved For Rare and Severe Types of Epilepsy

October 29, 2018 · Posted in Current Treatments · Comment 

epidiolex

In June, the US Food and Drug Administration (FDA) for the first time approved a drug derived completely from the cannabis plant. The drug, Epidiolex, a syrup, contains cannabidiol, the cannabis component that has been found to treat certain ailments. In a news release, the FDA stated that cannabidiol does not cause intoxication or a ‘high’. Tetrahydrocannabinol, or THC, is the cannabis component that makes people high, impairs cognition, and can induce paranoia.

The approval led, in September, to the Drug Enforcement Agency re-classifying FDA-approved drugs containing cannabidiol derived from cannabis and less than 0.1% THC as schedule V controlled substances. So far only Epidiolex meets these criteria. Cannabis had previously been classified as a schedule I controlled substance, in the same legal category as heroin, LSD, or ecstasy.

Epidiolex is now approved to treat two rare, severe types of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients aged two years and older. It is the first FDA-approved treatment for Dravet syndrome, a genetic condition that appears in the first year of life when babies develop fever-related seizures. Other types of seizures, even including a continuous seizure state, can occur later.

Lennox-Gastaut syndrome also develops in young children, usually between the ages of three and five. They have multiple types of seizures with debilitating consequences.
In three randomized, double-blind, placebo-controlled clinical trials that included a total of 516 patients with either Lennox-Gastaut syndrome or Dravet syndrome, the drug reduced the frequency of patients’ seizures compared to placebo.

Side effects of Epidiolex include sleepiness, sedation and lethargy; elevated liver enzymes; decreased appetite; diarrhea; rash; fatigue, malaise and weakness; insomnia, sleep disorder and poor quality sleep; and infections. The FDA also warned in its approval that “[a]s is true for all drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression and panic attacks.” The drug is produced by GW Pharmaceuticals, which has already gained approval outside the US for a cannabis-based drug to treat multiple sclerosis.

Editor’s Note: It is important for readers to know that most marijuana available in the US contains mostly THC with minimal cannabidiol.

Birth Defects from Valproate Lower in Bipolar Disorder than in Epilepsy

August 30, 2017 · Posted in Current Treatments · Comment 

pregnancyThe anticonvulsant valproate increases the risk of serious birth defects in fetuses exposed to it. However, a 2017 report by ANSM, France’s agency for health and product safety, and its national insurance fund for employed workers shows that these risks are lower for women taking valproate for bipolar disorder than for women taking valproate for epilepsy.

In France, the risk of a major fetal malformation was 10.2 per 1000 women in the general population, about twice that (22.2 per 1000) in women taking valproate for bipolar disorder, and about 4 times higher (46.5 per 1000) in women taking valproate for epilepsy. The authors suggest that treatment for bipolar disorder may be more likely to be interrupted during pregnancy, and this could explain the different levels of risk by diagnosis.

Among the risks of defects in the fetuses of women being treated with valproate for epilepsy, the risk of a ventricular septal defect (a hole in the wall separating the lower heart chambers) was 11.2% compared to 2.7% in fetuses not exposed to valproate, while risk of an atrial septal defect (a hole in the wall separating the upper heart chambers) was 19.1% in the fetuses of those prescribed valproate for epilepsy compared to 1.9% in unexposed fetuses. Risk of hypospadias (placement of the urethra opening on the underside of the penis rather than its end) was 22.7% compared to 4.8% in the general population.

Risks of a major malformation were dose dependent in those with epilepsy (but interestingly, not in those with bipolar disorder), meaning the more valproate patients with epilepsy took, the higher their risk of a fetus with birth defects.

The only birth defects that were more common in the fetuses of women taking valproate for bipolar disorder than in fetuses not exposed to valproate were hypospadias (17.5% risk compared to 4.8% in the general population) and craniostenosis, a deformity of the skull (4.2% risk compared to 0.4% in the general population).

The relative safety of valproate in women being treated for bipolar disorder compared to those being treated for epilepsy is good news for some. However, fetal exposure to valproate has also been linked to deficits in cognitive development.

The risk of spina bifida, which causes lifetime paralysis, in a fetus may no longer be such a catastrophic  issue for women taking valproate for bipolar disorder (where the risk did not exceed that of the general population), as was once assumed based on data from women with epilepsy (where the risk is usually 2-4%, but was 8% in this French study). This may be of some comfort to women with bipolar disorder who require valproate treatment to remain stable and wish to become pregnant or in those who experience an unplanned pregnancy.