As more research is conducted within the field of women’s mental health, there are times when recommendations may change depending on the available data.   We will discuss a case here to illustrate this point.

The patient is a 32 year old woman with a history of anxiety who was first evaluated by this clinician in early 2007 for a pre-pregnancy perinatal psychiatry outpatient consultation around medication issues.  She had a long history of doing well on paroxetine but had some concerns about potential weight gain. She was switched to venlafaxine and did well, but also felt she may have had weight gain on this medication.  Since she and her husband were thinking about pregnancy planning, she came off the venlafaxine but within a few weeks, her anxiety symptoms returned.  Given the extent of her symptoms, she was placed back on her original dose of paroxetine 20 mg by her outpatient psychiatric clinician. She responded well to paroxetine again, and was well preceding the consultation.

At that time of her initial perinatal psychiatry consultation in early 2007, there was concern that paroxetine may have an increased risk of cardiovascular malformations among infants exposed to paroxetine in utero, as reported by GlaxoSmithKline in 2006.

Given that concern, and fact that there was and continues to be sparse data on venlafaxine in pregnancy, the recommendation was for the patient to switch from paroxetine to a medication with a better established safety profile in pregnancy, such as fluoxetine.  She eventually changed to fluoxetine 20mg and did relatively well, but felt that it was never as effective as paroxetine 20mg.  She continued the fluoxetine until she discovered she was pregnant and decided to discontinue psychiatric medication altogether and stopped the fluoxetine.

The patient presented for her second perinatal psychiatry consultation earlier this year during her second trimester and reported that she is doing relatively well off the fluoxetine. While her anxiety was currently manageable and she did not have a history of depression, she was concerned about the postpartum period in terms of anxiety and potential postpartum depression.  She stated that she would like to consider going back on an antidepressant either before or after delivery.   She inquired whether she should go back on fluoxetine, her most recent medication, or paroxetine, the medication she felt was most efficacious for her.

Since the time of her initial consult, there has been new, reassuring information about the previously raised issue regarding paroxetine and cardiovascular defects.  A 2008 assessment by the Motherisk Program in Toronto reported the outcomes of over 3000 paroxetine-exposed infants and it did not find association between paroxetine exposures and increased cardiovascular birth defects.  Also, this finding was repeated by Gentile (2008), who conducted a systematic review and did not find any increased risk with paroxetine use.

Considering that the first trimester is the time considered most critical for exposures and birth defects, including cardiovascular malformations and defects associated with other organ development, it may be reasonable to reintroduce a medication later in pregnancy, even if first-trimester concerns were consistently reported in the literature.  Also, other factors in the risk-benefit analysis are those of late pregnancy exposure and SSRI use, involving inconsistently reported risk of persistent hypertension of the newborn (PPHN) and poor neonatal adaptation.  At this time, we do not have good evidence to determine which antidepressants might pose most risk in late pregnancy.  Theoretically, given paroxetine’s short half life and known withdrawal effects established in adults, we discussed that it is possible that her baby may have more symptoms of neonatal distress syndrome than if she were to go on fluoxetine prior to delivery, but we also discussed that data regarding poor neonatal adaptation consistently demonstrate that if these were to occur they typically go away within a few days postpartum and usually are mild. Another possibility would be to manage her symptoms with a low dose benzodiazepine on an as needed basis during pregnancy and to start paroxetine after delivery.  Benzodiazepines, like other drugs, also might introduce possible complications with the baby, such as withdrawal, but this would not be expected with a low dose.

If this patient was not currently pregnant but instead on paroxetine and in the pre-pregnancy planning stage, as she was in her initial consult, my recommendation at this time would be to remain on paroxetine if she wanted to remain on an antidepressant.

As with any field of medicine, it is essential to be aware of new research that may impact decisions concerning recommendations. We invite you to leave comments on this case.

Betty Wang, MD

Einarson A, Pistelli A, DeSantis M et al. Evaluation of the Risk of Congenital Cardiovascular Defects Associated With Use of Paroxetine During Pregnancy. Am J Psychiatry 2008 Apr 1.

Gentile S.  Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine. The Journal of Clinical Psychiatry, February 2009.

From our blog: New Study Does Not Find Link Between Paroxetine and Cardiovascular Defects SSRIs in Pregnancy and Neonatal Distress Syndrome