Regulator orders drug companies to study suicide risk during trials

Andrew von Eschenbach, U.S. Food & Drug Administration commissioner, speaks to the media during a news conference in Hyderabad, India. (Racha Ramesh/Bloomberg News)

Regulator orders drug companies to study suicide risk during trials

After decades of inattention to the possible psychiatric side effects of experimental medicines, the U.S. Food and Drug Administration is requiring drug makers to study closely whether patients become suicidal during clinical trials.

The new rules represent one of the most profound changes of the past 16 years in regulations governing drug development in the United States. But since the regulator's oversight of experimental medicines is done in secret, the agency's shift has not been announced publicly.

The drug industry, however, is keenly aware of the change. For the first time, the agency is asking makers of drugs dealing with obesity, urinary incontinence, epilepsy, smoking cessation, depression and many other conditions to put comprehensive suicide assessments into their clinical trials.

In recent months, the agency has sent letters - it would not say how many - to drug makers requiring that they use such a scale. Merck, Sanofi-Aventis and Eli Lilly are all using a detailed suicide assessment in clinical trials being conducted now.

The seeds for the new U.S. effort were planted four years ago with the discovery that antidepressants might cause some children and teenagers to become suicidal. Top agency officials at first discounted the finding but commissioned researchers from the Columbia University department of psychiatry, led by Kelly Posner, to reanalyze the drugs' clinical trials. This work led the drug agency and its experts to view the risk as real.

Then it received an application for rimonabant, a much-heralded obesity drug developed by Sanofi-Aventis, the French drug giant. As agency medical reviewers pored over the drug's clinical trial data, they discovered hints that it could cause psychiatric problems, too.

Unsettled by their experience with antidepressants, agency reviewers again ordered the use of Posner's system. The assessment found that the drug doubled the risk of suicidal symptoms. In June, an agency advisory committee voted unanimously that the regulator reject rimonabant because of its psychiatric effects, and Sanofi-Aventis withdrew the application, although the drug is sold in Europe.

Just this month, published results of a trial of Merck's obesity drug taranabant showed similar psychiatric problems.

Fears have grown that drugs used to treat epilepsy, seizures and mood disorders may have similar effects. Examination of these medicines by the agency should be completed this year.

Suddenly, agency officials realized that multiple classes of medicines might cause dangerous psychiatric problems.

"Clearly we were somewhat surprised when this signal emerged in the pediatric antidepressant data," said Dr. Thomas Laughren, the drug agency's director of the division of psychiatry products. "So various groups within FDA are now looking at suicidality more broadly as a possible adverse event."