Researchers found that the five drugs approved since 2008 are not related to the suicide risk of patients participating in drug clinical trials.
They say these findings oppose the US Food and Drug Administration’s “blanket” warning for all anti-epileptic drugs.
“We don’t think it’s good to confuse all these drugs,” said Dr. Michael Sperling, a senior researcher and professor of neurology at Thomas Jefferson University in Philadelphia.
Antiepileptic drugs are usually used to treat epilepsy, which is a broad term for various chronic epilepsy. They are sometimes used for other conditions, including migraine and bipolar disorder.
As early as 2008, the FDA issued a warning that anti-epileptic drugs may increase the risk of suicide-suicidal thoughts and behavior. This is based on an analysis of approximately 200 clinical trials of 11 drugs, some of which are associated with an increased risk of suicide compared to placebo pills.
However, only two drugs showed a statistically significant increase in this risk. At the same time, the other two were associated with a reduced risk of suicide.
However, Sperling said, the FDA requires all anti-epileptic drugs-including drugs approved since 2008-to carry suicide warnings.
The latest research was published online on August 2 in the journal American Medical Association Neurology, His team analyzed 17 clinical trials of five of the new drugs: eslicarbazepine (Aptiom), perampanel (Fycompa), brivaracetam (Briviact), cannabidiol (CBD) and centobamate (Xcopri). In total, these trials included 4,000 patients who were randomly assigned to take antiepileptic drugs and fewer than 2,000 patients who took placebo.
The analysis found that during the trial period, patients receiving medication were less likely to consider or attempt suicide compared with placebo patients: about 0.3% of patients in the two groups had these experiences.
However, Dr. Andres Kanner, an epilepsy expert who was not involved in the study, said that this does not necessarily make the drug clear at a glance.
He explained that the problem is that recent trials excluded patients with a history of mental illness that put them at a higher risk of suicide. They are the people who are susceptible to any suicide risk caused by anti-epileptic drugs.
“So we don’t know what happens to these patients in the real world,” said Kanner, a professor of clinical neurology at the Miller School of Medicine at the University of Miami.
In other words, he agrees that there is no point in assigning a one-size-fits-all warning to every anti-epileptic drug.
Kanner added that this is also a “big problem” for patients because the label may scare away the medications they need.
Kanner pointed out that there were “methodological issues” in the FDA analysis that led to the 2008 warning. On the one hand, these trials do not systematically assess suicidal thoughts and behavior; they rely on patients to report them.
There is also the fact that these 11 drugs are associated with different effects on suicide risk, including beneficial ones.
Sperling said that complicating matters is that people with epilepsy—especially those whose seizures are difficult to control—usually suffer from depression. Therefore, it is difficult to distinguish any excessive suicide risk from the drug itself.
Nonetheless, Kanner said that since 2008, more studies have shown that certain anti-epileptic drugs are associated with a higher risk of suicide in patients who are already vulnerable due to their mental health history.
Therefore, when people start taking medications, Kanner said, doctors should take a history of mental illness and choose a drug that is not related to increasing the risk of suicide when needed. He said one example is carbamazepine (Tegretol), which seems to have a positive effect on mood.
Sperling agreed that excluding high-risk patients from recent trials is a limitation, and it is important for doctors to understand the patient’s psychiatric history.
He said that it is also important for patients taking anti-epileptic drugs to inform their doctor of any new emotional symptoms.
However, any drug-related risks should be taken in perspective. Both Sperling and Kanner said: Patients with epilepsy without suicide risk factors will not become suicidal as a result of starting treatment.
Then, Sperling said, there is a risk of uncontrolled seizures. According to the Epilepsy Foundation, about one in a thousand epilepsy patients die suddenly every year.
There is no external funding for this study. Sperling and his colleagues report that they have economic ties with multiple companies that make epilepsy drugs.