WASHINGTON Cody Miller was a high school football player who was allergic to ragweed. Douglas Briggs was a doctor coping with pain from an old back injury.
Both are now dead, hanging victims driven to suicide, their families believe, when drugs prescribed to relieve physical symptoms upset their mental and emotional balance.
Federal drug regulators are investigating to see if the families could be right.
Until now, the Food and Drug Administration's attention to the suicide risks of medications has focused on psychiatric drugs, such as antidepressants prescribed to youngsters. But this year, officials unexpectedly broadened their concerns to include a medication for asthma, drugs for controlling seizures and even one for quitting smoking. Those are medical conditions not usually associated with psychiatric disorders.
Several independent experts say the safety alarms point to a gap in the FDA's knowledge of how drugs affect the brain. Even if medications are intended for physical conditions, some drugs can have unforeseen consequences if they are able to enter the brain. A group at Columbia University has developed a method for assessing the suicide risks of drugs, possibly helping identify risks before a medication goes on the market. But the FDA only requires use of such assessments on a case-by-case basis.
Drug companies say no cause-and-effect link has been established that would tie the medications under scrutiny to suicides. Also, some doctors worry that the talk of suicide may scare patients with serious illnesses away from drugs that could help. For example, depression a major risk factor for suicide is associated with physical illness, they note.
The Miller and Briggs families say their lives were turned upside down without warning.
Cody Miller, 15, began using Singulair for his allergies in the summer of 2007. He switched from a different drug after a new doctor assured his mother that once-a-day Singulair was better.
When the teenager became moody and anxious, his parents were surprised. He had no history of emotional problems. But they did not connect it to the drug. Physical reactions such as a rash or indigestion are easy to recognize; mental health side effects can be confused with everyday ups and downs.
About two weeks after he started taking his new medication, he hanged himself in an upstairs closet of the family home in Queensbury, N.Y., about 50 miles north of Albany.
Some two months later, the company that makes Singulair updated its prescribing literature to report that some patients had experienced suicidal thinking and behavior. But Merck & Co. said that only may be a coincidence because there were no such reports during controlled clinical trials with the drug.
"Singulair is a really effective drug that has been on the market 10 years and has been taken by millions of patients," said Dr. Alan Ezekowitz, an asthma expert with Merck. "In over 40 placebo-controlled trials, no reports of suicide in Singulair-treated groups have been found."
An independent study by the American Lung Association supports Merck's conclusion without completely answering the question. The research looked at measures of emotional well-being in three clinical trials sponsored by the association and found a positive effect on emotional outlook in patients taking Singulair.
But the study, set to appear Mondaytoday in the Journal of Allergy and Clinical Immunology, was not designed specifically to look for suicidal thinking or actions. "The evidence is good, but we couldn't call it perfect," said Dr. Norman Edelman, the group's chief medical officer.
Cody's mother said that if she had had any inkling of a problem, she would not have allowed her son to take Singulair. Merck and the FDA should have warned parents more forcefully, Kate Miller said. Cody was her only child. "When you don't know what to look for, it's pretty sad," Miller said.
Briggs, 54, was a family doctor practicing near Charlotte, N.C. In his 30s, Briggs had injured his back in a car crash. Three surgeries over the years failed to completely resolve his problem. But Briggs stayed active, playing tennis and basketball. In February 2004, he began taking Neurontin, an epilepsy drug also prescribed for nerve-related pain and used for chronic back trouble.
His wife and two sons noticed a change.
"He started developing uncharacteristic mood swings and irritability," said son Andrew Briggs, who works as a consultant in Washington. "He began talking about losing the desire to practice medicine, even though it was a great passion of his."
Briggs' family wondered what was going on. They did not connect the changes to Neurontin.
On Christmas Day in 2004, Briggs wanted to be alone. He urged his family to go see a movie. They picked a zany comedy. When they returned, they found he had hanged himself in the foyer of their home.
"For a guy who was such a family man to do that in a way that would basically ensure his family would be the first to find him was completely baffling," Andrew Briggs said.
Pfizer Inc., which makes Neurontin, said that since the drug was first marketed in the 1990s, the prescribing literature had listed "suicidal" and "suicidal gesture" as rarely reported adverse events seen in clinical trials. But Pfizer does not believe such reactions were connected to taking Neurontin, and the company remains confident in the drug.
"Neurontin is an important medicine that has helped millions of patients with serious conditions," Pfizer said in a statement. "Based on an extensive review of our clinical trial data for Neurontin, we see no evidence to support the claim that Neurontin causes an increased risk of suicide-related events.
After Briggs' killed himself, the family started hearing about other Neurontin patients who had committed suicide, Andrew Briggs said. The family is suing Pfizer; their lawyer said there are about 250 such lawsuits.
This summer, the FDA convened a panel of scientific advisers to evaluate the suicide risks of 11 anti-seizure drugs, including Neurontin. Crunching data from 210 clinical trials, the agency found a small increased risk: two of 1,000 patients taking the medications experienced suicidal thoughts or behavior. When millions of people are taking a drug, even such slim odds can have significant consequences.
The advisory panel accepted the FDA's findings but voted against imposing the government's strongest warning on the drugs, saying that could do more harm than good. The FDA is considering how to communicate the risks to patients.
"Even though a drug is identified as a drug for weight control, or smoking cessation, or asthma, these drugs often also get into the brain, so there is always the potential for having psychiatric side effects," said Dr. Thomas Laughren, head of the FDA's division of psychiatric products. "But we don't have any unifying hypothesis as to why very different classes of drugs have psychiatric side effects."
With mental health side effects, one of the first questions scientists ask is whether a drug can affect the brain. Not all do, because the brain is protected by a cellular barrier that keeps out many substances circulating in the blood. Neurontin does work in the human brain. With Singulair, Merck said tests on rats showed that minimal amounts enter the brain, and there is no data on humans.
The FDA has other tools to assess the suicide risks of medications. Researchers at Columbia University have developed a system for collecting and analyzing data about suicidal thoughts and actions among people who enroll in drug trials. The FDA helped pay for the research, but the agency does not require drug makers to use the system, a puzzling oversight to independent experts.
"I can't see any reason why it should not be widely and regularly used during drug development," said Larry Sasich, a professor of pharmacy practice at the Lake Erie School of Osteopathic Medicine in Erie, Pa. "It has been validated and appears to be a technique that is not expensive."
But Laughren, the FDA official, said that while many drugs can get into the brain, "there is no compelling reason to think that more than a few are associated with suicidality." With the FDA reluctant to issue a mandate for suicide screening, families who find themselves in the same predicament as the Millers and the Briggs may be left with unresolved questions.
"Whether or not any of these drugs cause suicidal thoughts and behavior is the critical question we need to answer; up to now, we have not answered that," said Kelly Posner, a Columbia researcher who led the effort to develop the screening system. "Debunking false notions of risk is just as important to the public health as knowing about risks that exist."