Concerns regarding antidepressant drug use during pregnancy.

I read with attention the concerns of Dr. Urato regarding my peer-reviewed editorial on depression, the use of antidepressant medications in pregnancy and breast feeding1 recently published in the Journal of Psychiatry and Neuroscience. According to Dr. Urato's analysis, I “failed” to adequately deal with 5 crucial issues. I would first like to reiterate, as in the conclusion of my editorial, that an illness during pregnancy can be far worse than the medication used to treat it. It is certainly best not to give any medication during pregnancy, but before depriving a woman and her unborn child a protection from a potential life-threatening illness, the risks and benefits must be carefully evaluated. After a thorough interview aimed at identifying the number of prior episodes of depression and duration, the degree of treatment resistance, the presence of residual symptoms and the medication(s) used, a clear recommendation must be made to the patient. Above all, the patient must not be left with a specter of a catastrophe haunting her during the pregnancy and the years to come if she uses antidepressant drugs. Dr. Urato seemed to be very concerned about decisions taken by regulatory agencies, sometimes in concert with the pharmaceutical firms, on the basis of published manuscripts in prestigious journals. There are numerous examples of manuscripts published in first class journals that were flawed and yet made it past the peer-review process. Perhaps one of the most notorious was the paper on the “memory of water” published in Nature in the late 1980s.2,3 Dr. Urato deemed lengthy and “inadequate,” without stating why, my discussion of the paper on persistent pulmonary hypertension published in the New England Journal of Medicine.4 The journal published the paper and, of course, they stood by it. However, I was not the only one to doubt the importance of the purported association of this severe pathology and the use of antidepressant drugs during pregnancy. Dr. David Rubinow, a world-renowned scientist in neuroendocrinology of psychiatric disorders from the National Institute of Mental Health, with 195 papers listed in the National Library of Medicine (Pubmed), also expressed concerns over this problematic publication in an editorial of the American Journal of Psychiatry, the official journal of the American Psychiatric Association.5 My editorial was not meant to be a complete and exhaustive discussion of all the possible outcomes of antidepressant medication use during pregnancy and childbirth. The main goal of my analysis was to make physicians and the public realize that abstaining from using antidepressant drugs during pregnancy and allowing depression to occur (reoccur or continue) during pregnancy can lead to long-term damages to the mothers and children that may far outweigh the potential ill effects of the medications. We are now in an era where not all medications during pregnancy are evil. Can some antidepressant drugs taken during pregnancy produce discontinuation phenomena in newborns? Certainly. Can these be lethal or produce irreversible damage? I certainly have failed to find compelling evidence supporting the latter. There are indeed several studies suggesting that antidepressant drug use during pregnancy may have some deleterious effects, two of which were published after my editorial was in press.6,7 Such retrospective studies on large populations with unconfirmed diagnoses are important, but not without problems. For instance, in mothers exposed to selective serotonin reuptake inhibitors versus control subjects, a statistically significant increase in seizures (0.4% v. 0.1%) and fetal deaths (1.1% v. 0.4%) was noted in the exposed population; however, also noted in this population was a 10% higher use of social assistance (marker of poverty), a 1.8% versus 0.4% frequency of drug dependence, greater maternal age, higher parity and a higher rate of multigestation.6 In this study, in contrast to some others also mentioned by Dr. Urato, there was no increased risk of birth defects. On the other hand, there are numerous studies showing the ill effects of depression, or of allowing a relapse or recurrence to take place, when antidepressant drugs are not used or are stopped during pregnancy.1 To the family of a woman who committed suicide or killed her baby, how could a clinician justify a recommendation to stop an antidepressant on the basis of the above-mentioned differences of less than 1%?