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Suicide Risk Spikes Early In Treatment, Study Verifies

Aug 16, 2004 |

It's the kind of cautionary tale told to generations of therapists in training:

A new patient seemed better after his third therapy session.

Then "the guy went home and blew his brains out," recalled Kenneth France, a psychology professor at Shippensburg University, who heard of this case from a fellow therapist just out of grad school.

The idea that depressed patients may be at highest risk just after they begin treatment possibly because they're feeling strong enough to do something about their bleak thoughts has been taught in medical schools for decades, psychiatrists say. It predates the modern antidepressant drugs that have drawn such controversy lately because of their possible connection to suicides or suicidal ideas.

While there is anecdotal evidence for belief in this vulnerable period, it is largely what one doctor called a "clinical pearl," an observation that has not been thoroughly tested.

A study published recently in the Journal of the American Medical Association provides the "first relatively compelling evidence that this opinion is not only correct, but it's a major factor," said Hershel Jick, a Boston University epidemiologist who heads the Boston Collaborative Drug Surveillance Program.

Jick's team studied suicide and suicidal thoughts among British patients who had taken one of four antidepressants. Two were tricyclics, an older class of drugs, and two Prozac and Paxil were SSRIs (selective serotonin reuptake inhibitors), drugs that have been widely prescribed since the 1990s. The team found no differences in behavior among those taking the different drugs and concluded, Jick said, that suicide "has something to do with the nature of the people who get these drugs rather than the drugs themselves."

But the team also found something that surprised Jick. The risk of committing suicide or thinking about it was much higher soon after patients started treatment with any of the drugs. The risk for suicide was a whopping 38 times higher during the first nine days of treatment than it was after three months. For suicidal behavior attempts and thoughts the risk was four times greater during those first nine days. (Overall, suicide risk among this group of first-time antidepressant users was tiny: 17 suicides out of about 120,000 patients.)

Jick thought of two possible reasons: "Either these people came in when they were really at their wits' end to get their first drug and it just didn't do anything, or the alternative was that all these drugs make them worse." He said the idea that the drugs caused the suicides is "not very likely." The study did not look at depressed people who did not take medicines.

Douglas Jacobs, a Harvard University psychiatrist who chaired the American Psychiatric Association's treatment guidelines on suicide, said the vast majority of people who kill themselves suffer from depression, alcoholism or schizophrenia. Of the 14 million people who have a depressive episode each year, about 20,000 0.1 percent kill themselves.

"The overwhelming majority of patients who are in treatment and improve don't commit suicide," Jacobs said.

The Food and Drug Administration in March said it is not clear whether SSRIs can cause suicides, but asked makers of 10 such drugs to strengthen warnings on their labels. It said patients of all ages should be watched carefully for signs of worsening depression or suicide.

An FDA advisory panel is scheduled to meet next month to revisit the contentious issue of whether SSRIs increase the risk of suicide by children and teenagers. In both the United States and Britain, Prozac is the only drug of this type approved for use by depressed children. Both countries have specifically said that one of the SSRIs, Paxil (paroxetine), should not be prescribed for children because it has not proven effective and is associated with suicidal thoughts and behavior.

An FDA analysis of antidepressant studies in children to be discussed at the September meeting reportedly has found that children on the drugs had greater risk of suicidal thoughts and behavior than those taking placebo pills. The new study has not been released publicly, but the Washington Post and Wall Street Journal have reported this month on some of its findings.

In June, New York Attorney General Eliot Spitzer filed a civil lawsuit accusing GlaxoSmith Kline, which has a headquarters in Philadelphia, of failing to disclose negative information from tests of Paxil in children and misinforming its sales staff about Paxil's effectiveness.

In Jick's study, no one aged 10 through 19 who was taking any of the four antidepressants committed suicide. There were 15 suicides recorded between 1993 and 1999 among the approximately 1.2 million people in the database his group used; none was on an antidepressant.

The standard explanation for heightened risk for suicide early in treatment is that really depressed people are so sick they can barely do anything. "What is commonly taught is that when individuals are profoundly depressed, they are unable to organize themselves to commit suicide, and as they respond to treatment they become physically more active and therefore better able to act on suicidal feelings," said Joseph Coyle, a professor of psychiatry and neuroscience at Harvard Medical School.

Patients begin feeling better physically they have more energy and sleep and eat better before their dark feelings dissipate. "The cognitive aspects of depression are the last to respond to treatment," Coyle said.

Other psychiatrists said both tricylics and SSRIs can cause agitation. That could increase energy levels or anxiety before mood improves.

Some people may find it especially hard to accept the early side effects of the drugs on top of their depression. "When you're depressed, it's hard to imagine you'll ever get better," said John Mann, a Columbia University psychiatrist who is president of the American Foundation for Suicide Prevention.

Early in treatment, patients also have not yet formed a strong bond with their therapist, which many believe is a suicide deterrent.

Experts said depressed patients need to be warned that the early course of their treatment may be bumpy. They need frequent contact with therapists or doctors.

Moira Rynn, a child psychiatrist at the University of Pennsylvania, tells patients, "You're not going to feel better right away and, in fact, you might feel worse." Her patients, and their parents, often have unrealistic expectations. "I make sure I really do educate patients a lot that your brain doesn't get fixed fast," Rynn said.

From the start, France, of Shippensburg University, discusses emergency procedures with patients.

And Michael Vergare, chair of psychiatry at Thomas Jefferson University Hospital, tells people they may feel better, then worse again. "It isn't necessarily a sign that you're regressing back to ground zero," he tells them, "but I need to talk to you."

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