Why is there no warning carried with drugs that researchers say increase the risk of suicide?
Philip Fine reports.
A simple question continually nagged David Healy. For years, the psychopharmacologist had been pushing for warnings to be distributed with Prozac and all the other related antidepressants, or selective serotonin reuptake inhibitors (SSRIs), that taking them raises the risk of suicide.
In this litigious age, cautious words are found everywhere. Even those giant cardboard windscreen sun visors carry a warning not to use them while driving.
Now, why would a manufacturer not include a warning for a risk that has been suggested by several researchers? Is it not riskier for the drugs maker not to include a warning?
Healy received his answer when he found out more about what a drugs manufacturer loses once it prints a "black box" warning. "About 84 per cent of sales," he estimates. Healy discovered that a suicide warning prohibits a company such as Eli Lilly, Pfizer or GlaxoSmithKline from putting the name Prozac or Zoloft or Paxil on pens, mugs and other marketing and advertising vehicles. That leads to a fall in sales. Each major SSRI maker spends about $50 million a year on promotion.
Healy suggests a warning along the following lines: "In the first weeks of treatment, SSRI drugs can in a number of people directly cause either suicidal ideation or other disturbing thoughts in people who have no such thoughts or aggravate any pre-existing thoughts of this type. If this happens, you should stop treatment and consult your physician. This may well be a problem with your treatment rather than anything to do with your illness."
Healy is one of the few insiders willing to risk future research budgets and personal vilification by taking a stand against Big Pharma. The University of Wales professor has been one of the few academics and psychopharmacologists to challenge multinationals and tell them their drugs have been triggering suicides. Late last year, the University of Toronto rescinded the offer of a job after he gave a talk that declared "new corporate psychiatry" the big winner.
In an era where antidepressants are being prescribed for things such as stress, menopause and backaches, Healy has been sounding an alarm for people who may develop adverse reactions to SSRIs without ever having been warned. He is not alone in the non-academic world.
Donald Schell's son-in-law is claiming there should have been a warning with his father-in-law's prescription. Two years ago, Schell allegedly killed his wife, his daughter and granddaughter, and then turned a gun on himself after having been on Paxil for 48 hours. This was a man who had apparently never before shown any signs of violence.
Healy has recently been in Cheyenne, Wyoming, acting as an expert witness for the case against the makers of Paxil, GlaxoSmithKline. Included in his testimony were the results of a study he conducted last year on healthy subjects taking sertraline, better known as Zoloft. In the study of 20 people, two developed suicidal feelings. One noted that she could think only of throwing herself in front of a car. He estimates the odds of two normal people becoming actively suicidal in any two-week period during a year at 2,000-to-1 against.
Despite glowing testimonials from peers, more than 150 refereed articles and several books, Healy has been called a junk scientist by the pharmaceuticals companies.
When asked to set up an interview to put its side of the story, Eli Lilly spokeswoman Andrea Smith would say only that there was no story and that there had never been any link between Prozac and suicide. She named several studies to prove it.
One of the studies was conducted by Yevgenia Gelfin of Hadassah Hebrew University, who, like Healy, studied healthy volunteers. Fifty were given 20mg of Prozac (fluoxetine) for five weeks, with one week of placebos before and two weeks after. None of the subjects, according to the study, suffered any adverse effects that could be attributed to the Prozac.
Healy knows his healthy subject study is not the definitive statement on SSRIs, but he would like companies such as Eli Lilly to set up a study that truly measures the frequency of suicide, something they were setting up with the United States Food and Drug Administration in 1991, but decided instead to do a meta-analysis of past studies. They concluded there was no increased risk of suicide while taking Prozac.
Healy points out that only 3,067 of the approximately 26,000 patients entered into clinical trials by the company were included in the meta-analysis. Conspicuously absent was any reference to drugs that had been prescribed to minimise agitation and the 5 per cent of patients who dropped out.
"There's really nothing that directly quells suicidal thoughts reliably," Healy says. "The best kind of study would be in healthy volunteers and the companies all have lots of these - mostly unpublished. If these were made public, I believe they would demonstrate agitation and turmoil that is an antecedent of suicidality developing over the course of a few days in quite normal individuals."
Jonathan Cole, one of the first scientists to find a clear association between the ingestion of Prozac and suicidality, called as far back as 1990 for clear warnings in light of growing prescriptions that Prozac and similar drugs could precipitate suicide. He wrote in an affidavit centring on the suicide of a 13-year-old on Zoloft that no drugs company is eager to study these kinds of risks. "To my knowledge, no manufacturer of an SSRI drug has ever done a study where the primary outcome of interest was to measure treatment emergent suicidality."
Max Fink is a 78-year-old doctor who has been one of the leaders of US research into the efficacy and safety of new psychoactive drugs from the mid-1950s to the end of the 1970s. He says the best way to evaluate suicidal risk is to compare one of the SSRIs with a drug that has proven to lower suicidal thoughts, such as imipramine. "But no manufacturer wants their drug to be second best." Instead, he says, they compare its effectiveness with another SSRI.
When Fink assessed new drugs in the early 1960s, he was given about $150,000 a year for his studies. He did not have to go to drugs companies for funding. During the Vietnam war, the US government began to cut funding to independent assessors and instead issued criteria to the drugs manufacturers, which eventually hired their own investigators. "I don't care how honest, dedicated or sincere the scientists are, they are still employees of the company."
David Healy can find some solace in the decision that came down last week. On June 6, a federal court jury in Wyoming found that Paxil "can cause some individuals to commit suicide and/or homicide" and ordered GlaxoSmithKline to pay 80 per cent of an $8 million award to the two families that were affected by the homicide and suicide of Donald Schell.
A historical expert on psychopharmacology, Healy, like Fink, looks to the past for better checks and balances. He says past patent laws allowed several manufacturers to market the same drug. Now, with one manufacturer holding the rights to one drug, there is more to lose if that treatment is proven dangerous.