Widely used anticonvulsant drugs, including Pfizer's Neurontin and Novartis' Trileptal, may increase the risk of suicide, attempted suicide and violent death in patients taking them for the first time, U.S. researchers said on Tuesday.

Compared with Johnson & Johnson's generic epilepsy drug topiramate or Topamax, the team found an increased risk for suicide in new users of Neurontin, sold generically as gabapentin, GlaxoSmithKline's Lamictal or lamotrigine, Novartis' Trileptal or oxcarbazepine and Cephalon's Gabitril or tiagabine.

In one analysis, the team also found an increased risk of suicide with the drug valproate sold by Sanofi-Aventis as Epilim and as Depakine in the United States by Abbott Laboratories Inc.

In 2008, the U.S. Food and Drug Administration required that all drugs in the anticonvulsant class carry a warning that they double the risk of suicidal thoughts and behaviors, based on a so-called meta-analysis of nearly 200 clinical trials.

But the analysis was not large enough to show which drugs in the class were risky. And they are prescribed for a range of conditions.

"We all know the range of uses of these medications is very, very wide," said Dr. Elisabetta Patorno of Brigham and Women's Hospital and Harvard Medical School in Boston, whose study appears in the Journal of the American Medical Association.

Anticonvulsant drugs are chiefly used for patients with epilepsy, but the drugs have been aggressively promoted, in some cases for conditions they are not approved to treat, such as bipolar disorder, pain and migraine headaches.

While doctors are free to prescribe medicines as they see fit, drugmakers are only allowed to promote them for uses approved by the FDA.

RISK PRECEDES BENEFIT

Last month, a Boston jury found Pfizer guilty of improperly marketing Neurontin. And in January, Novartis said it would plead guilty to violating U.S. laws relating to potential off-label marketing and promotion of Trileptal.

To study the risks of suicidal thoughts and acts, Patorno and colleagues analyzed prescription and clinical data on nearly 300,000 patients 15 and older who had been given an anticonvulsant drug for the first time between July 2001 and December 2006.

"We found increased risk for suicidal acts beginning within the first 14 days after treatment initiation, opening the possibility that anticonvulsant medications could induce behavioral effects prior to the achievement of their full therapeutic effectiveness," Patorno and colleagues wrote.

The study identified 827 suicidal acts, including 801 attempted suicides and 26 completed suicides. They also found an additional 41 violent deaths.

They said compared with topiramate, the risk of suicidal acts was higher in those who took gabapentin, lamotrigine, oxcarbazepine, tiagabine and valproate.

Among these, the risks were "pretty much even," Patorno said in a telephone interview. "It's not easy to draw conclusions about which one is the most risky," she said.

Patorno said patients should continue taking their medications, but the findings do suggest that patients need to be watched carefully, and doctors need to consider whether the benefits of the drug outweigh the risks, particularly when given for an unapproved use.