FDA to hear views on drugs' suicide link

As a nurse, she said, she had heard that such drugs could raise the risk of suicide in young people, and her son already suffered from low self-esteem. But the psychiatrist had said Lexapro could do some good. So she paced, "for fear that if I go to sleep, he's not going to be awake when I wake up."

Confusion and concern about whether Paxil and other Prozac-generation antidepressants increase suicidal tendencies in some children and teenagers have become so widespread among parents, doctors, and researchers that the Food and Drug Administration will convene a public hearing tomorrow to take testimony and review the evidence.

The agency is not expected to reach a conclusion until this summer about whether the drugs increase the risk of suicide among children and teenagers.

Estimates vary, but perhaps as many as 1 million American young people take the drugs, known as selective serotonin reuptake inhibitors or SSRIs. In Massachusetts, about 1.3 percent, more than 5,000 in all, of children and teens on Medicaid take them, according to the only state records on prescriptions.

Concerns that Prozac might make some adults suicidal were first raised publicly in 1990 but were set aside a year later when the FDA found the drug safe. Now, events and disclosures in the last few months have infused the suicide debate with new urgency.

Last summer, reports emerged that in clinical trials, Paxil and another drug, Effexor, were linked to heightened suicidal tendencies in youngsters. British authorities warned against Paxil's use in young people, citing new data indicating that among 1,100 children given Paxil, those on the drug were up to three times more likely to have suicidal thoughts as those on a placebo.

Then in December, British authorities warned doctors not to prescribe SSRIs -- except Prozac -- for children, saying the risks outweighed the benefits.

In the United States last fall, the FDA warned doctors to use caution and carefully monitor young patients on SSRIs. Prozac is the only SSRI the FDA has approved for treating depression in children, but doctors are free to prescribe the others as well. Children are particularly difficult to treat, psychiatrists say, because it is harder to diagnose them and determine the right dosages for medication.

Meanwhile, those who question the suicide connection have also been gaining impetus. On Jan, 21, a task force of psychiatric pharmacologists convened by the American College of Neuropsychopharmacology issued a report concluding that SSRIs do not appear to increase the risk of suicide in teens and children. They based their conclusion on a review of the data on about 2,000 young people who had enrolled in clinical trials of the drugs.

The American Psychiatric Association has reached a similar conclusion, said Dr. David Fassler, a Burlington, Vt., psychiatrist and specialist on child depression who is scheduled to speak on behalf of the association at the FDA hearing.

Based on the association's review of the available literature on SSRIs, he said, "There is not a clear and convincing association with an increased risk of suicidal thinking or behavior."

The FDA now faces a serious dilemma. A memo it issued in advance of tomorrow's hearing defines the issue in stark terms: If, as it sorts through the data, the agency overlooks a pattern of increased risk of suicidal tendencies, then doctors treating pediatric depression could feel "greater comfort than is warranted in the safety of these drugs."

But if the agency decides prematurely that there is increased risk, the drugs could be used too conservatively or become unavailable altogether, and patients with serious and even life-threatening cases of depression would have fewer treatment options.

Many psychiatrists sound a similar note. They worry that they could lose a drug that has often proven effective in fighting depression in their young patients.

"I'm somewhat concerned that all the attention around this issue may frighten some parents away from getting help for their kids, and that would be a tragedy because we really can help most of these kids," said Fassler.

Psychiatrists also argue that suicidal tendencies tend to be relatively common among teenagers and that in 15 countries, the advent of SSRIs has coincided with a drop in the rate of suicide among young people. In the United States, the suicide rate among young people ages 15 to 24 has dropped since the mid-1990s from about 13 to 10 per 100,000 people.

On the other hand, anecdotal evidence abounds that the SSRIs can trigger agitation that can turn suicidal. Leah Harris, a 28-year-old Washington, D.C., writer who was put on Prozac when she was 12, plans to offer herself as an example at today's hearing.

She had been introverted as a child but never suicidal, she said. But, "as soon as I went on the drugs -- bam! -- I started having suicidal thoughts," thoughts like, "killing yourself might be a good idea."

She also began cutting herself and suffering from anxiety and insomnia. When she told psychiatrists of her turmoil, she said, "They would say, `Oh, you're getting worse, let's give you more.' " At 18, she said, she went off the drugs and has been fine ever since.

"You get enough anecdotes, and it starts to add up," said Harris, who is working on a memoir.

A spate of lawsuits in recent years has revolved around the argument that Prozac and other antidepressants can trigger suicide.

Patient advocacy groups also have entered the fray, arguing that the drug companies that make the antidepressants have purposely hidden clinical trial results that indicate that the drugs are ineffective or that they can induce suicidal tendencies.

The FDA has failed in its duty to warn the public of the drugs' dangers, said Vera H. Sharav, president of the Alliance for Human Research Protection. Doubts also remain as to whether today's panel will correct that, she said, because it may be stacked with researchers "who have huge financial interlocking interests with the drug companies that manufacture these drugs."

The drug companies acknowledge that they have not published all their results, but that is not the only problem. The methodology in many of the trials has been flawed, said Dr. Martin Teicher, head of the Developmental Biopsychiatry Research Program at McLean Hospital in Belmont. It was not designed to catch suicidal tendencies, and the trials may not have been big enough to catch a relatively rare side effect.

The FDA is now trying to reanalyze the data from 20 trials of nine SSRI drugs, totaling more than 4,000 patients, to try to catch subjects whose suicidal tendencies increased.

If there is anything close to a consensus on the topic, all sides agree that more research would help.

Meanwhile, psychiatrists say, no one should abruptly drop taking an SSRI; it should always be done under medical supervision.

The key in prescribing SSRIs to young people is to start with a low dose, go slowly and carefully, and treat them at the same time with a sedative or psychotherapy, said Dr. Alexander Bodkin, chief of clinical psychopharmacology research at McLean.

"If you're doing all these things then they're great," he said. "But if you're prescribing to 100 people a day that you don't even know, and just handing the stuff out -- and kids are more impulsive anyway -- then you would expect more of these kinds of `surprises.' "

Carey Goldberg can be reached at goldberg@globe.com