I recently wrote an article, which appears in the November issue of Elle, looking into the aggressive marketing of antidepressants to pregnant women by some doctors and psychiatrists — despite a growing body of scientific research that one popular type of antidepressant, selective serotonin reuptake inhibitors or SSRIs, is associated with adverse birth outcomes. Working with The Investigative Fund, I followed the case of Lyam Kilker, who went into cardiac arrest when he was only six weeks old and eventually had two open-heart surgeries. His mother had taken the commonly prescribed antidepressant Paxil while she was pregnant.
Such stories may soon become more common.
Because of Paxil’s risks, in 2005 the FDA had requested that the drug’s manufacturer, GlaxoSmithKline, change the drug’s pregnancy-use classification from Category C ("potential benefits may warrant use of the drug in pregnant women despite potential risks") to Category D ("positive evidence of human fetal risk") — a clear warning for doctors. But next year, as a result of pharmaceutical industry lobbying, the letter categories will be dropped altogether. Instead of seeing a Category D on Paxil’s label, doctors will find a long summary of the medical literature.
Critics of the new labeling fear that doctors won’t read the detailed summaries, and the FDA seems to acknowledge that the new system may lead doctors to more readily prescribe risky medications to pregnant women. But Melissa Tassinari, PhD, a team leader in pediatric and maternal health at the FDA’s Center for Drug Evaluation and Research, defended the change — while acknowledging that labeling is “one of the huge debates.”
“Right now making a presumptive decision based on a letter isn’t serving [patients] well,” she said. But note that Tassinari worked for Pfizer, the makers of Zoloft, a huge-selling SSRI, for 18 years on global regulatory affairs. Such cross-pollination between government regulators and the industries they’re charged with policing is increasingly common. And this is only the beginning of how drug-makers influence the decisions facing pregnant women.
For example, one study often cited by drug industry reps and by physicians who advocate for drug treatment of depression in pregnant women shows that the rate of relapse into depression among pregnant women who discontinued their medications was five times higher than those who remained on them. But the Journal of the American Medical Association, which published the study, was forced to print a correction after it was revealed that the study’s authors, including lead author Lee Cohen, MD, a psychiatry professor at Harvard Medical School, had multiple undisclosed conflicts of interest, having received grants from the likes of Eli Lilly, maker of Prozac, consulted for the likes of GlaxoSmithKline, the makers of Paxil, and a paid speaker for Pfizer, the maker of Zoloft, and many other major drug firms.
Cohen is just one example; high-profile physicians like him are routinely paid by pharmaceutical companies to give talks promoting their drugs, act as consultants, conduct clinical trials, or sit on advisory boards for their drugs. (This is when drug companies recruit physicians, often to a hotel or resort, to give their impressions of promotional materials for their medicines and offer advice about how best to influence consumers and other physicians.) Drug companies refer to them as “opinion leaders,” and the most influential physicians, often found at top universities and hospitals, are called key opinion leaders, or KOLs. Cohen is a KOL for such major drug companies as Pfizer, GlaxoSmithKline, Eli Lilly, AstraZeneca, Berlex, Wyeth, Janssen, and Forest Labs.
Last July, the Department of Justice reached a $3 billion settlement against GlaxoSmithKline, after finding that the firm had, among other fraudulent practices, skewed scientific data in favor of drug safety and efficacy — something that is often accomplished by means of KOLs. Both skewing data and failing to disclose potential conflicts of interest — a common problem with KOLs — are considered scientific misconduct.
Researcher Kara Driscoll, MD, a psychiatrist at Northwestern Memorial Hospital in Chicago who specializes in treating depressed expectant mothers, insists that untreated depression is dangerous to unborn babies, and screens all her pregnant patients, regardless of whether they present with symptoms of depression or not.
But the evidence is thin. The studies Driscoll cites, which show a higher incidence of low birth weight and pre-term birth among mothers with depression, do not control for whether or not the woman was taking an SSRI, meaning they don’t establish whether the poor outcomes were due to the depression or the medication. In fact, the only study controlling for use of SSRIs found a significant increase in low birth weight and pre-term birth among women who took the drugs compared with women with untreated depression.
Driscoll herself doesn’t appear to have any conflicts of interest, but she works directly under Katherine Wisner, who has worked for Pfizer, GlaxoSmithKline and Eli Lilly. And Wisner’s conflicts of interest are all too common, even among prominent experts in the field of fetal health.
Gideon Koren, MD, a toxicologist and pediatrician who runs Motherisk in Toronto, the world’s largest research and counseling program for pregnant women, told me he sits on advisory boards for drug companies, and his CV indicates that he has received vast amounts of research funding from them. Koren would not give specifics about the amount of money he receives from drug companies for sitting on advisory boards and other non-research activities, and when queried about how much of Motherisk's funding is derived from the pharmaceutical industry, he said, “Not enough.”
“This hospital has hundreds of — not hundreds but in excess of $80 million a year from industry from different countries,” Koren said. “And no one can tell us not to publish. [The companies] have a right to see the paper a month before and make some comments but we will not change results.”
Koren had been criticized for his close ties with pharmaceutical companies in the past. In the late 1990s, he was involved in a scandal after Nancy Olivieri, his research partner on a project to study a drug produced by Canada’s largest generic drug manufacturer, Apotex, exposed him for distorting data in favor of the firm. According to a probe by the College of Physicians and Surgeons of Ontario Olivieri’s colleagues received anonymous hate mail about her, which was later tied to Koren through DNA evidence from saliva on an envelope. The incident resulted in Koren being suspended by the College of Physicians and Surgeons.
Yet in 2007, GlaxoSmithKline involved Koren in performing a meta-analysis of Paxil studies that the company could use to bolster its defense in a birth defects case that was about to go to trial. (The plaintiffs’ attorney, Sean Tracey, filed a motion to disqualify Koren, and GSK later settled the case.)
“I hope to get more from industry, much more than we do,” Koren told me. “Because it doesn’t do anything. It doesn’t affect the way we do science.”
Another prominent researcher in the field riven by conflicts of interest is Anthony Scialli, MD, who studies the causes of birth defects and runs Reprotox, a widely used database that compiles the effects of drug exposures in pregnancy. “I don’t have any connections to the drug industries,” Scialli told me for the Elle piece. “I don’t do a lot of prescribing because I work in labor and delivery, but I do some and I only prescribe generic drugs, which are not promoted, and I don’t meet with drug reps and I don’t read drug advertising and I don’t go to pharmaceutical company-sponsored programs. So I suppose I could be influenced but it would be kind of hard. They’d probably have to put a billboard up outside my apartment.”
Perhaps not. Scialli is actually an expert witness for GlaxoSmithKline, and has given two or three depositions per year for the past quarter century for various drug and chemical companies, including in birth defects cases. In a majority of these depositions, he testified that the drug or pesticide in question was not the cause of a child’s birth defects. Not once did he lay the blame on fetal exposure to a drug. Though Scialli no longer gives talks on behalf of drug companies, he was a key opinion leader while heading the residency program at Georgetown University’s Medical School.
Scialli was also vice-president of Tetra Tech Sciences, a firm that consults for more than 50 corporations in the chemical and pharmaceutical industries. “Litigation support” and “environmental audits” are two of the first services listed on its web site. In fact, Scialli himself has consulted for at least two-dozen major pharmaceutical and chemical companies, yet he maintains that the work he does for these industries does not influence his analyses of their drugs. (Shortly after my article appeared in Elle, the website for Tetra Tech Sciences, www.sciences.com, was taken down.)