Anti-seizure drugs may increase the risk of suicidal thoughts or behaviour, the Food and Drug Administration warned Thursday in an alert to doctors.
Meanwhile, Health Canada says it is aware of the FDA's latest findings and that new information will be made public to Canadians and Canadian health care professionals as soon as it is available.
The FDA began an investigation into epilepsy drugs in 2005, analyzing almost 200 studies of 11 anti-seizure drugs -- some that have been on the market for decades. The studies tracked almost 28,000 people given the medications and another 16,000 given placebo pills.
The review found that drug-treated patients faced about twice the risk of experiencing suicidal thoughts or behaviour, but the overall risk was still relatively low.
They found 0.43 per cent of drug-treated patients experienced suicidal thoughts or behaviour, compared with 0.22 per cent of placebo-takers. So for every 1,000 patients, about two more drug-treated patients experienced suicidal thoughts than placebo-takers, FDA concluded.
Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups.
The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks.
The findings affect more than just epileptics. Anti-seizure drugs are prescribed for a variety of illnesses, including migraines, certain nerve-pain disorders, and psychiatric diseases such as bipolar disorder. Each of those illnesses themselves carry a risk of suicide.
The FDA found drug-treated patients were at increased risk no matter their diagnosis, but that the risk was highest for epilepsy sufferers.
The drugs investigated included:
- Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
- Felbamate (marketed as Felbatol)
- Gabapentin (marketed as Neurontin)
- Lamotrigine (marketed as Lamictal)
- Levetiracetam (marketed as Keppra)
- Oxcarbazepine (marketed as Trileptal)
- Pregabalin (marketed as Lyrica)
- Tiagabine (marketed as Gabitril)
- Topiramate (marketed as Topamax)
- Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
- Zonisamide (marketed as Zonegran)
"Although only the drugs listed above were part of the analysis, the FDA expects that all medications in the antiepileptic class share the increased risk of suicidality," the agency noted.
The FDA is now asking manufacturers to add a warning to their product labels. It's also asking doctors to tell patients and their families about the risk so they can be aware of changes in mood. As well, doctors should be aware of the possibility of the emergence or worsening of depression, suicidal thoughts, or any unusual changes in behavior.
"Patients who are currently taking antiepileptic medicines should not make any changes without first talking to their health care provider," the FDA advisory warns, noting that skipping epilepsy medication can result in seizures.
Patients and family members of patients taking these medications should be aware of common warning signs that might be a signal for risk of suicide, including:
- Talking or thinking about wanting to hurt yourself or end your life
- Withdrawing from friends and family
- Becoming depressed or having your depression get worse
- Becoming preoccupied with death and dying
- Giving away prized possessions
Health Canada says its experts are currently reviewing this new information, and have been working with manufacturers of anti-epileptic drugs in Canada to develop "class labelling," which will ensure all drugs used in the treatment of epilepsy contain the same warnings.
"Health Canada anticipates that the class label wording will be finalized in approximately one month, at which point it will be incorporated into the labelling of all drugs used in the treatment of epilepsy," the agency said in a statement emailed to CTV.ca.
It also advises patients using these medications do not stop their drugs or switch products without consulting their physician, to avoid serious harm.
