GLAXO IS ASKING COURT TO SET ASIDE JUDGMENT IN LAWYER’S SUICIDE
ior in children, teens and young adults under age 25.
The warning labels also stipulate that the suicide risk has not been seen in short-term studies in anyone over age 24, but it urges close monitoring of all patients initiating drug treatment.
“The scientific evidence does not establish that paroxetine causes suicide, suicide attempts, self-harm or suicidal thinking in adult populations,” Frances Defranco, a company spokeswoman, said in an email. “Any suicide is a tragedy, and a reminder that depression and other mental illnesses can be fatal.”
Dolin’s lawsuit, however, has lifted the curtain on data from early clinical trials of Paxil, renewing concerns that older adults, who use antidepressants in far greater numbers than young people, may also be at greater risk of self-harm when taking the drugs.
The documents indicate that several suicides and suicide attempts in early clinical trials that were attributed to patients on a placebo — and which made Paxil look safer by comparison — should not have been counted, and that an FDA reviewer told the company as much. Glaxo later reanalyzed its data, and in 2006 enhanced the warning on Paxil, cautioning that among adults of all ages with major depressive disorder, “the frequency of suicidal behavior was higher in patients treated with paroxetine compared with placebo” — 6.7 times higher.
But that label was replaced a year later, in June 2007, by the Fda-mandated warning now carried on all antidepressants, which says only that the increased risk has been seen among people under age 25.
A delicate risk calculation
Some 325 million prescriptions for antidepressants were filled last year in the United States, including 15 million for Paxil and paroxetine, according to IMS Health, a health care information company.
But while one in 10 Americans aged 12 and older has filled an antidepressant prescription, one in seven adults aged 40 and over has done so, including nearly one in five middle-aged women, according to the National Center for Health Statistics.
Many psychiatrists say the benefits of antidepressants far outweigh the risks, even for younger patients, and that the drugs are highly effective. Several prominent experts have been critical of what they say is excessive attention to the dangers, which they say could potentially dissuade people who could benefit from treatment from accessing care.
The issue is complicated by the fact that depression and other mental illnesses can themselves lead to suicide.
“Antidepressants prevent more suicides than they cause, probably by a large multiple,” said Dr. Peter Kramer, a psychiatrist and clinical professor emeritus at Brown University and the author of several books about antidepressants, including “Listening to Prozac.”
Kramer, who was not involved in the Dolin litigation, says he urges patients to contact him right away if they have a bad reaction during the first weeks after starting treatment with the drugs, especially in the first five days.
“When I put people on medication for the first time, I say we’re going to be very cautious in the early going,” he said.
The prescribing information on antidepressants specifically warns that patients should be monitored for symptoms like anxiety, agitation, panic attacks, mania and akathisia. “There is concern that such symptoms may represent precursors to emerging suicidality,” the labels say, especially if they were “abrupt in onset” or “not part of the patient’s presenting symptoms.”
Akathisia is, by definition, a drug-induced syndrome. The word comes from Greek and means “not to sit,” referring to an inability to sit still. Akathisia is characterized by anxiety, restlessness and a compulsion to move or walk about; patients may pace, or fidget endlessly in their chairs.
It may develop when a patient, adult or younger, begins treatment, but it can also emerge when the dosage of the drug is increased, decreased or discontinued. Patients who have tolerated a drug in the past may develop akathisia when they start a new course of treatment, experts say.
Akathisia is a fairly common and well-known side effect of antipsychotic medications, commonly used to treat disorders like schizophrenia but increasingly given for a variety of mental health complaints, including depression. But the association with antidepressants is not as well recognized, experts say, and incidence rates are hard to pin down.
A group of psychopharmacologists who reviewed over 100 studies found the reported rate of what they broadly called “jitteriness/ anxiety syndrome” — which they defined as a worsening of anxiety, agitation and irritability — ranged from 4 percent to 65 percent among patients initiating treatment with selective serotonin reuptake inhibitors, or S.S.R.I.S, the popular class of antidepressants to which Paxil belongs.
Psychiatrists linked S.s.r.i.induced akathisia to suicidal behavior in a 1991 paper describing three patients who survived violent suicidal attempts shortly after they had started fluoxetine or had the dose increased.
The patients were removed from the drug but agreed to try another course of treatment with fluoxetine under close observation. All three became extremely agitated and had a recurrence of suicidal thoughts.
“This is exactly what happened the last time I was on fluoxetine, and I feel like jumping off a cliff again,” one of the patients reportedly said. Another said she had tried to kill herself “because of these anxiety symptoms. It was not so much the depression.”
Dr. Anthony J. Rothschild, one of the study’s co-authors, has since disavowed the paper, saying it was an observation that has been disproved by subsequent drug company clinical trials. He testified as an expert witness for Glaxo in the Dolin trial.
Akathisia symptoms so closely resemble symptoms of anxiety and depression that it may be hard for a doctor to distinguish between the underlying illness and what could be a side effect of the drug used to treat it, said Dr. Joanna Gedzior, an assistant clinical professor of psychiatry at the Fresno Medical Education Program of the University of California, San Francisco.
If a doctor thinks the patient’s condition is deteriorating, he or she may increase the dose, which could be disastrous if the drug itself is causing the problem.
“We have to be very careful about this and ask, ‘Is it something I’m giving the patient that’s causing this?’” said Gedzior, who wrote a paper on akathisia.
During the Dolin trial, a therapist testified that Stewart Dolin had called to schedule a sameday session on July 14, the day before his suicide. But Dolin was unable to sit still during their meeting, shifted nervously in his chair, and could not calm down.
The therapist was so worried that she called him at work the next day — the day of his suicide — to urge him to ask his doctor for anti-anxiety medication.
Dolin is convinced her husband was not suicidal until he developed akathisia as a side effect to paroxetine. Her husband was having “one of his best years ever,” she said. The couple were high school sweethearts who had been married for 36 years, and had adult children who were thriving and a large circle of friends.
“Stewart occasionally had stress and anxiety associated with being a high-powered attorney, but he had great coping skills, and he would seek counseling and move on,” said Dolin, who has started an organization called Missd to raise awareness about the warning signs of akathisia.
“The only thing different this time was that he had started Paxil.”