FDA pours oil on troubled waters

In the midst of conflicting evidence about SSRI/suicide link, the FDA asks pharma companies to add warning labels

By Chris Williams

Everything seemed to be going so well for Cecily Bostock. The 25-year-old Stanford graduate had found a job, just had a big raise, and was in a loving relationship with her boyfriend. Then one night she got out of bed, went to the kitchen and stabbed herself to death with a large kitchen knife. She'd been taking paroxetine for two weeks. Was there a connection?

In light of shocking stories like these, the US Food and Drug Administration (FDA) has taken the step to ask drug manufacturers to add warning statements to the labelling of 10 antidepressants, and is recommending close observation of adult and pediatric patients for worsening depression or suicidal thoughts.

The American College of Neuropsychopharmacology � a group of psychiatrists and pharmacologists � convened its own task force in January to independently investigate the issue. Their review of the literature did not turn up a strong enough link between SSRIs and suicide to justify discouraging doctors from prescribing the drugs to depressed teens and children.

The FDA, which has also been closely reviewing the results of antidepressant studies in children since June 2003, says it's unsure whether behaviours reported in the studies they looked at represented actual suicide attempts. But for the moment they're not taking any chances.

At the February meeting, called by the FDA themselves, government scientists reported that among 25 studies of the suspect medications involving 4,000 children and teens, there were no completed suicides, though 109 patients engaged in possibly suicide-related behaviours or attempts. The studies varied dramatically on what was considered suicidal behaviour � for example, among 19 patients classified as cutting themselves, almost all were superficial, with little bleeding.

The lack of suicides reported in these studies doesn't match what the families are saying. There were many stories like Cecily Bostock's at the public meeting, and several families openly blamed SSRI antidepressants for their loved ones' suicides.

NOT JUST THE KIDS
Although the FDA's original concerns all centred on pediatric use of antidepressants, the authority has issued an advisory that cautions physicians to closely monitor both adults and children with depression, especially at the beginning of treatment, or when the doses are increased or reduced. The FDA plans to update its advisory this summer.

In the meantime, the agency is advising that these patients be observed for certain behaviours that are known to be associated with these drugs, such as anxiety, agitation, panic attacks, and insomnia, and that physicians be particularly vigilant in patients who may have bipolar disorder.

"We think this is good advice whether the drugs increase the risk or not," says FDA medical policy chief Dr Robert Temple. "There's a reason people are put on therapy � their depression is worse or somebody's worried about it. Maybe that's what drives reports of suicides, or maybe it's the drugs. In either case, you really need to pay attention in the early days."

Britain already acted last summer, when its Medicines and Healthcare Products Regulatory Agency advised that paroxetine should not be prescribed for children or adolescents at all.

Meanwhile, Canada's Thera- peutic Products Programme convened a meeting in February to address the issue and came to the same conclusion as the FDA � that labelling changes are the best solution until better data is forthcoming. They have yet to decide what the new labelling will say.