April 14, 2010 -- A class of drugs prescribed to treat conditions including migraines, chronic pain and bipolar disorder may increase suicidal tendencies, a large study has found.
Government officials raised concerns about the class of drugs called anticonvulsants in 2008 because they appeared to double the risk for suicide in studies compared with patients taking a placebo. But the Food and Drug Administration did not have studies to compare which anticonvulsant had greater suicide risks.
Now in an article in the Journal of the American Medical Association, doctors crunched statistics on the suicide risk of nearly 300,000 people who started taking one of 13 anticonvulsants between 2001 and 2006. They found that 180 days after starting medication, 26 of the 300,000 people in the study committed suicide and 801 people attempted suicide.
Doctors found the drugs gabapentin (brand name Neurontin), lamotrigine (Lamictal), oxcarbazepine (Trileptal) and tiagabine (Gabitril), often prescribed for pain, bipolar disorder and epilepsy, appeared to increase suicide risk significantly while topiramate (Topomax), which is commonly prescribed for migraines, increased the suicide risk but less so than the other drugs.
Researchers called the study an "exploratory analysis" but also expected the results to influence medicine.
"I would say doctors should talk with their patients about the risk of these drugs and to try to evaluate if the patient is receiving the treatment he or she needs, and balance the risk and benefits," said Dr. Elisabetta Patorno, lead author of the study and research fellow in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital in Boston.
Patorno said clear differences appeared between the drugs -- gabapentin had 40 percent higher suicide risk compared with topiramate, for example -- but that the overall risk for suicide was low enough that doctors might not pick up on it in their practice.
"I would say the risk is there, it's probably not anything to expect the practitioner on his daily basis to detect this risk, and that's why this study is so important," Patorno said.
Yet doctors tasked with treating epilepsy, pain and bipolar disorder say the study raises more questions to research than it provides answers.
Suicide Risk a Drug Issue, or a Disease Issue?
"You aren't comparing 100 percent apples with apples here," said Dr. Orrin Devinsky, director of the Comprehensive Epilepsy Center at the NYU Langone Medical Center in New York City. "Having said that, the findings are extremely interesting -- they raise flags."
Devinsky said that the results were complicated by the various conditions included in the study. Not only were the doctors comparing drugs, they were comparing patients with epilepsy to patients with migraines.
Other specialists agreed.
"What looks like it is drug-related is probably more disease-related," said Dr. James Grisolia , a neurologist with Scripps Mercy Hospital and board member of the epilepsy foundation of San Diego.
For example, Grisolia said the drug topiramate appeared to carry a low suicidal risk in the study compared with other drugs. But topiramate is primarily prescribed to migraine sufferers. People who have epilepsy or bipolar disorder would likely be given a different anticonvulsant such as lamotrigine and valproate.
"Migraines can really, really hurt but they don't increase your risk for suicide as far as we know," said Grisolia. "We know that people with bipolar have a higher risk of suicide -- I think that that's affecting this data quite a lot."
But Patorno said she believes her study took such complications into account. Indeed, the researchers were careful to select patients without a recent history of suicidal behavior, and they used mathematical modeling to account for differences between the conditions.
"We are pretty confident that we took care of the major confounding factors according to [drug] indication bias," said Patorno.
But even if the study authors accounted for every conceivable difference between epilepsy and migraines, specialists pointed out that they have to account for the mental state of individuals too.
Will Doctors Prescribe Differently?
"They [the study authors] control to a large number of factors," Dr. Timothy Lineberry, board chair of the American Association of Suicidology.
"But how do you apply that to an individual patient?" he asked. "Not treating a patient clearly has implications."
For example, a doctor will have to decide whether using a drug that works best for the patient but has a slightly higher suicide risk is better than choosing a less effective drug with lower suicide risk, or no drug at all.
Devinsky echoed that point.
"If the bipolar disorder is poorly controlled there might be other ways patients might have a bad outcome; driving under the influence, or using drugs and alcohol," said Devinsky.
Dr. Taft Parsons III, of the Henry Ford Health System in Detroit, believes the study provided at least one clear implication.
"Pretty much all the diagnoses psychiatrists treat have a risk for suicide," said Parsons, the medical director of Kingswood Hospital in the Henry Ford Health System.
But Parsons argued that this study should inspire doctors who treat pain problems or headaches to also think of the individual patient's psychological profile when prescribing drugs.
"Historically psychiatric problems have been thought of something that doesn't affect your overall [physical] health," said Parsons. "I think this study shows they do."