In March, drugmaker GlaxoSmithKline agreed to pay $6.2 million to settle a class-action lawsuit on behalf of children born with congenital defects whose mothers used GSK’s blockbuster drug Paxil while pregnant. Just days before the agreement was announced, an updated analysis of the Quebec Pregnancy Cohort in BMJ Open, an online journal, showed that for the period 1998-2009, antidepressant use during pregnancy in the study population more than doubled, and the rate of major congenital malformations increased as well, by more than 50 percent. The rate of maternal depression in the study population also went up — odd, given that these drugs are supposed to be relieving depression.
The study reconfirmed the well-established link between paroxetine (the active ingredient in Paxil) and congenital heart defects, and also showed a link between venlafaxine (the active ingredient in Effexor) and congenital lung defects. In fairness, it should be pointed out that the absolute increase in risk is modest, on the order of one in a hundred — although this is cold comfort for mothers of babies born with holes in their hearts or unable to breathe on their own.
Moreover, these figures no doubt underestimate the true numbers of pregnancies affected since they omit those that end in spontaneous abortion, and those that end in therapeutic abortion after detection of fetal abnormalities via ultrasound. Antidepressants during pregnancy have been linked to increases in both spontaneous abortions and therapeutic abortions.
Is anyone surprised? These drugs inhibit the uptake of serotonin, an evolutionarily ancient signaling molecule that predates the origin of animal life itself and which plays an essential role in the development of the heart, the lungs, the brain, and probably every other organ in the body. It’s no wonder monkeying with serotonin uptake during development occasionally turns out badly. And could these children with major birth defects be just the tip of the iceberg? What about more subtle effects that may take years to manifest themselves?
We don’t know for certain, but studies on rodent models give us a hint. When researchers gave antidepressants to mice during the developmental period corresponding to the third trimester of pregnancy in humans, they found the mice as adults were reluctant to explore new environments, preferring to hide in the dark rather than walk in the clear light of day. They lost interest in eating and were slow to move to avoid a painful electric shock or to escape when imprisoned in a cylinder full of water. In short, the mice appeared fearful and despondent — precisely those conditions for which antidepressants are prescribed to humans. These effects could not be replicated by giving antidepressants to adult mice, indicating the effects are exerted during a specific time window during development.
David Healy, professor of psychiatry at Bangor University and the author of “Pharmageddon,” told me “The usual rule of thumb is that if a drug causes a gross birth defects like a cardiac defect, it will cause behavioral changes, also.”
A study by Finnish researchers published last year supports this. They examined national health care records and found offspring exposed to antidepressants during gestation had a threefold increase in the incidence of depression, compared to those whose mothers discontinued antidepressant use before pregnancy. Compared to offspring of mothers with a psychiatric diagnosis who never took antidepressants, the increase was fourfold.
Are the drug companies grooming the next generation of customers in the womb?
Why do doctors prescribe these drugs to pregnant women — or anyone, for that matter? Because they are safe and effective remedies for depression, of course.
Or are they? Last January BMC Psychiatry published the most comprehensive meta-analysis ever of antidepressants for major depression, reviewing 131 studies involving 27,422 patients. Researchers found that antidepressants reduced patient scores on the 52-point Hamilton Rating Scale for Depression by less than two points — an improvement far too puny to be noticeable in a face-to-face assessment of global functioning by a trained clinician. They also found that every one of the studies was at a high risk for bias, that the bias most likely favored the drug over placebo, and that antidepressants caused a 37 percent increase in the rate of serious adverse events. Moreover, only six trials reported data for suicides, and only eight for suicidality — odd, given that suicide prevention routinely is used as justification for dispensing these drugs.
This is getting close to saying the emperor has no clothes. Why do we even call these substances “medicines”? Perhaps what our society needs is less “mental health care” and more plain old-fashioned care.
Patrick D. Hahn is an affiliate professor of biology at Loyola University Maryland and a freelance writer. He can be reached at firstname.lastname@example.org.