The US Food and Drug Administration is ordering companies that make epilepsy drugs to add warning about increased risks of suicide to their products, the agency said Tuesday on its Web site.

The order is based on the agency’s review of 199 clinical trials of 11 epilepsy drugs, which showed that patients taking those drugs had almost twice the risk of suicidal behavior or thoughts than patients taking a placebo. Out of about 43,000 patients studied, about four patients on the drugs and none taking placebo completed suicide, while 30 patients on anti-epileptic drugs attempted to kill themselves, compared to only six of the placebo group.

The review was made public in January. In July, the agency’s outside experts voted 20-0 that all epilepsy drugs increase the risk of suicide. However, they voted 14-4  against adding a new boxed warning to the drugs’ prescription information, saying that a prominent discussion of the risks may cause millions of people to shun needed treatment. The risk of suicide linked to epilepsy drugs is extremely low compared to the potential danger of leaving patients untreated, members of the American Epilepsy Society said in a statement last week, considering the FDA findings “flawed.”

The FDA now ordered the warnings to be written on the drugs’ label but not outlined in a black box, the agency’s strictest caution.

The list of drugs to be added the warning includes: Carbatrol, Klonopin, Tranxene, Depakote, Zarontin, Peganone, Felbatol, Neurontin, Lamictal, Vimpat, Keppra, Mesantoin, Celontin, Trileptal, Dilantan Suspension, Lyrica, Mysoline, Gabitril, Topamax, Tridione, Zonegran. The review showed risk of suicide was only significant for Topamax and Lamictal.

The above-mentioned drugs are used to treat psychiatric disorders, migraines, and other conditions as well as epilepsy. Sales of these drugs topped $10.2 billion last year, on about 102 million prescriptions, according to the research firm IMS Health Inc. Lamictal and Topamax saw roughly $2.1 billion sales, while Lyrica reached nearly $1.1 billion.

Moreover, the FDA said patients, family members and caregivers should pay close attention to any unusual day-to-day changes in mood, behavior and actions like becoming depressed or becoming preoccupied with death and dying. According to the agency, roughly 11 million patients take epilepsy drugs.

On the other hand, “patients who are currently taking an antiepileptic medicine should not make any treatment changes” without talking to a doctor, Russell Katz, director of neurology drugs at the FDA, said in a statement.

Epilepsy, a chronic neurological disorder, is characterized by recurrent unprovoked seizures, caused by abnormal, excessive or synchronous neuronal activity in the brain. There are five drug pathways, which can alleviate epilepsy symptoms: sodium channel blockers, calcium channel blockers, drugs that potentiate the effect of GABA and drugs which decrease the excitatory transmission.