If the foregoing was the "bad news," is there any good news regarding these putative risks? Let's start with the data on paroxetine(Drug information on paroxetine) and cardiac risks. Recently, Wulsin and Ignatowski9 critically examined the FDA advisory and concluded that it "flunks as evidence-based medicine." These authors reviewed 8 published studies of SSRI use during pregnancy--including 5 involving paroxetine--and concluded that there is no significant increase in birth defects with SSRIs, notwithstanding the data cited by the FDA and unpublished retrospective data from the manufacturer. The conclusion from Wulsin and Ignatowski is in agreement with that of Newport.5 In this writer's view, if there is a "signal" of teratogenicity coming from the SSRIs, it is a weak one. But in the absence of randomized, prospective data--sorely lacking in this area of study--we must still be wary.
What about the PPHN risk? Chambers' study7 found a 5- to 6-fold increase in risk among SSRI-exposed neonates. However, since PPHN occurs in only about 2 per 1000 live births, the absolute number of PPHN cases should still be quite small among neonates exposed to SSRIs--probably no more than 12 per 1000 births.10 That may be an acceptable risk level for many mothers facing the rigors of intrapartum or postpartum major depression.
With regard to the neonatal abstinence syndrome associated with SSRIs, this is generally a mild, self-limited condition, lasting just a few days and requiring only supportive care. (There are scattered reports of seizures as part of this syndrome, according to FDA sources,11 but the nature of the FDA's adverse event reporting system makes these claims difficult to evaluate.) It is possible that tapering and discontinuing the antidepressant during the last 7 to 10 days of gestation might be a way of mitigating withdrawal effects, but more research on that issue is needed. By itself, this withdrawal syndrome is surely no reason to withhold antidepressant treatment in mothers at high risk for intrapartum or postpartum major depression.Back to mom
So what, precisely, do you advise your pregnant, 32-year-old patient with the horrendous history of suicidal depression? First, I would recommend a calm and reassuring "risk-benefit" discussion, ideally involving the patient's gynecologist (Table). This is not the time for knee-jerk reactions, such as the immediate discontinuation of paroxetine (which could precipitate a nasty withdrawal syndrome). Even the FDA advisory noted that "the benefits of continuing paroxetine may out- weigh the potential risk to the fetus" in some cases.6 If this patient stays on paroxetine, it is advisable, in my view, to obtain a fetal echocardiogram around week 16 of gestation, similar to guidelines for lithium(Drug information on lithium) use in pregnancy.
What about switching to another SSRI, or perhaps, to a nonserotonergic antidepressant, such as bupropion (Wellbutrin, Zyban)? This might be reasonable and is worth discussing with the patient, but there is very little solid evidence demonstrating that such a move would increase the safety or well-being of the average patient in this predicament. The decision might turn, in part, on whether the patient has been successfully treated with other agents (besides paroxetine) in the past--if not, the risks of switching are significant.12 Indeed, if the patient in our scenario had done poorly with other antidepressants, I would favor keeping her on the same regimen at this point. Of course, electroconvulsive therapy remains a viable option for severely depressed pregnant patients, although it is usually difficult to persuade patients of its benefits.
Whatever the decision, the clinician should always write a detailed chart note indicating that the appropriate options have been discussed with the patient (and her gynecologist); that the patient understands the nature and consequences of these options; and that the risks and benefits of available treatments have been thoroughly explained. Some physicians encourage the patient to sign a statement or chart note to this effect.9
Recently, Dr Lee Cohen has presented data showing that relapse rates are very high in euthymic pregnant women with a history of major depression who discontinue antidepressant treatment.13 Indeed, the risk of relapse during pregnancy increases about 5-fold with discontinuation--contrary to the old saw that pregnancy is always a time of emotional well-being. Of course, psychosocial support of the depressed pregnant patient is important; indeed, when maternal depression is (or historically has been) relatively mild, psychotherapy alone might be the treatment of choice. But given the risks of resurgent major depression to both mother and infant, the benefits of continuing antidepressant treatment during pregnancy probably outweigh the risks in most cases.
Dr Pies is clinical professor of psychiatry at Tufts University. His most recent books include Creeping Thyme, a collection of poetry (Brandylane Publishing); Zimmerman's Tefillin, a short story collection (PublishAmerica); and Handbook of Essential Psychopharmacology, 2nd edition, from American Psychiatric Publishing.