DRUG BUST by Alan Cassels

It’s time for a vocabulary-building exercise. Let’s dust off a few old words you haven’t heard for a long time and take them out for a test ride. Try “phocomelia.” Savour that one and let it roll around your tongue a bit. How about “teratogenic?” Sound eerie?
What the heck is phocomelia, you ask. A handy online dictionary provides the following definition: pho·co·me·li·a [foh-koh-mee-lee-uh, -meel-yuh] n. A birth defect in which the upper portion of a limb is absent or poorly developed, so that the hand or foot attaches to the body by a short, flipper-like stump.
And “teratogenic?” What’s that about? The same online dictionary states: “A drug or other substance capable of interfering with the development of a fetus, causing birth defects.” In any conscious person, the word phocomelia should conjure horrifying images: a tangle of toes sprouting from a torso where legs should be, perfectly formed cherubic babies, perfect in every sense except there are flippers where arms should be. That’s phocomelia.
These are the deformities most closely associated with thalidomide, a prescription sedative taken by pregnant women in the 1960s that proved to be extremely teratogenic.
Many people may not know that the US, due to a defiant commissioner at the FDA who was suspicious of the drug’s safety, would not permit the company to market thalidomide in the land of the free. That didn’t stop the manufacturer from marketing it in more than 47 countries around the world, including Canada, which led to between 8,000 and 10,000 babies born with, you guessed it, phocomelia.
From the ashes of disaster, hope springs forth. After the thalidomide debacle, legislators in most countries, following the lead of the US Congress, toughened up legislation to require rigorous safety tests before a drug could be sold. It is unbelievable now, unthinkable even, that a drug for pregnant women would have been approved and prescribed to women worldwide, without ever being proven safe for the very people it was supposed to help: pregnant women.
Fast forward 40 years and thousands of new drugs later and let me pose this question: Can we be sure that any drug taken by a woman during pregnancy is safe for her and her developing fetus and that it won’t be teratogenic? Are there other thalidomides lurking in our midst right now, drugs taken during pregnancy whose risks exceed their potential benefits?
A couple of troubling examples deserve a closer look. One is a drug called isotretinoin, sold under the banner of Accutane. This teratogenic drug is prescribed to millions of young people around the world to treat the one condition that they fear almost as much as death: zits.
It is well known that the price for clear skin may be birth defects, and the manufacturer goes to great lengths to warn women who are thinking of using Accutane to take extra precautions in the birth-control department. Doctors are advised to counsel patients on effective birth control if they wish to prescribe isotretinoin. Yet between 1982 and 2003 in the US, more than 2,000 women became pregnant while taking the drug.
While most pregnancies were aborted, about 160 babies with birth defects were born. Over the years, this has caused the FDA to beef up its programs to try to ensure that female patients taking isotretinoin do not become pregnant.
Despite some baby steps taken toward ensuring pregnant women do not take unsafe drugs, there is troubling evidence that these efforts are being eroded. What quickly comes to mind is the concerted push to have women who are taking antidepressants to continue to do so during pregnancy; in some medical circles, a mother’s depression is seen as much more serious than any potential harm to the unborn fetus from the drug.
Despite the fact that flipper babies still haunt our collective consciousness, the message from the medical establishment regarding pregnancy and antidepressants could be characterized as this: “Don’t worry your pretty little head, just keep taking your pills.”
Back in August 2004, both Health Canada and the US FDA issued warnings to pregnant women to withdraw slowly from their antidepressant medication in the third trimester. There were reports of women taking SSRI antidepressants – drugs like Prozac, Paxil, Zoloft and Effexor – giving birth to newborns with withdrawal symptoms. Withdrawal? Yes. One of the major problems with all the SSRIs is that withdrawal can be extremely difficult, even excruciating for some patients. This is certainly not new. The withdrawal effects, duly noted elsewhere were simply being logically applied in a new place: in unborn children. (See Health Canada’s August 9, 2004,
advisory of potential adverse effects of SSRIs and other antidepressants on newborns at (www.hc-sc.gc.ca/english/protection/warnings/2004/2004_44.htm)
Health advisories notwithstanding, several months later reports in medical journals advised that the warnings were unnecessarily alarmist, asserting that the maternal use of SSRIs had not proven to be a problem, at least not as big a problem as depression in mothers. I have to admit I find it troubling when medical authorities imply that pregnant women who stop taking their antidepressants may be putting themselves and their unborn babies at serious risk. There is no doubt that depression can be debilitating, but the continued admonishment to “Stay on your drug” assumes that since there is incomplete evidence that SSRIs cause harm to unborn babies, the drugs are probably safe.
Let me say this politely: absence of evidence is not evidence of absence. Basically, if our medical establishment has yet to study whether certain drugs cause direct harm to pregnant women, we cannot assume the drugs are OK. Because there is no data to clearly show the problem, doesn’t mean the problem doesn’t exist. (This rationale kept people smoking because Big Tobacco constantly repeated that there was no evidence that their products were harmful.
Me? I take a different tack on this issue. In the absence of evidence, the most rational course of action is the precautionary approach, which is summed up in the Hippocratic Oath: “First, do no harm.”
One problem with the reasoning used by those who promote the use of antidepressants in pregnancy is the underlying assumption that the only way to treat depression is with medication. This ignores the effective and safer ways to treat depression that have been widely studied.
MedPage Today recently featured an article by Crystal Phend entitled, Although antidepressants may have an effect on fetuses in utero, so may the lack of the drug during pregnancy. The writer quotes a researcher claiming there is a strong link between depression and pregnancy measured by cortisol, the stress hormone.
Claiming that cortisol is a useful marker for depression, the researcher asserts that if a woman has an elevated cortisol level, it is probably difficult for the baby. The problem is that a person’s cortisol levels go up and down every day, and stress is not depression. You can be very depressed and not stressed. Or very stressed, but not depressed. So cortisol levels don’t tell you anything.
Ralph Faggotter, a general practitioner in Australia and member of Healthy Skepticism (www.healthyskepticism.org), a group which works on reducing harm from misleading drug promotion, writes: “My guess is that this [cortisol] trial was conducted specifically for the purpose of finding some ammunition to counter-attack the recent negative publicity in relation to the use of SSRIs during pregnancy.”
Faggotter says the researchers appear to have predetermined their outcome, noting, “… it is particularly clear from the way in which the data has been misrepresented and over-interpreted to produce the desired conclusion.”
The saga around the effects of SSRIs on fetuses will no doubt continue because there’s a lot of money riding on women – even pregnant ones – continuing to take their medications.
The bad news continues to pour in. In September of last year, Health Canada issued a warning that paroxetine (Paxil), a widely prescribed SSRI, causes malformations to the fetus. (For more information, visit www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/paxil_3_hpc-cps_e.html) We learn that an epidemiological study of more than 3,000 pregnant women exposed to paroxetine, compared to other antidepressants, was related to a two-fold increase in major congenital malformations, especially involving cardiovascular malformations. I take these warnings very seriously, knowing that Health Canada and a major manufacturer do not issue warnings and advisories unless there is at least some evidence of a clear and present danger.
But do doctors?
Who knows, but here’s a warning to you, dear reader: take any medical study or media report with a huge grain of salt if it reassures you that pregnancy and drugs coexist easily and safely. Unless proven safe, assume any drug can be teratogenic. Unfortunately, it is a lesson we need to relearn every year.
And if in doubt, remember one word: phocomelia.

Alan Cassels is co-author of Selling Sickness and a drug policy researcher at the University of Victoria. He is also the founder of Media Doctor Canada (www.mediadoctor.ca), which evaluates reporting of medical treatments in Canada’s media.