Ms. A is a 27-year-old woman who is seven weeks pregnant and is currently taking duloxetine (Cymbalta).  She has a history of recurrent major depressive disorder (MDD) and has had a good response to duloxetine at 60 mg per day.  She has had four previous episodes of major depressive disorder (most untreated) and has been in remission for one year.  Past episodes have lasted up to six months and caused difficulty with functioning at work and in relationships, although she was not diagnosed and treated until one year ago.

Ms. A is concerned about her baby’s exposure to medication, but she also is afraid that she will experience a recurrence if she stops her medication.  Here are some factors to consider in advising this patient:

Higher rates of relapse are observed in pregnant women who discontinue antidepressants versus those who maintain treatment.  For women with histories of MDD, the rate of relapse with medication discontinuation was observed to be 68% compared to 26% of pregnant women who remained on antidepressant (Cohen et al, 2006).

There have been no published peer-reviewed data on the use and safety of duloxetine (Cymbalta) in pregnancy.  It is probable that some of the general risks seen with other antidepressants should apply to duloxetine, and are in fact included in Cymbalta’s package insert, but systematic study of pregnancy outcomes with Cymbalta are needed.  It is unclear how much the data from SSRIs inform the use of duloxetine, as duloxetine has some shared proposed mechanisms of action and some different effects, and has not received specific study.  At this time, we know more about the short- and long- term outcomes with other antidepressants.

In contrast, the selective serotonin reuptake inhibitor (SSRI) antidepressants have received a substantial amount of study in pregnancy regarding safety outcomes.  Most studies do not show any increased risk of birth defects with SSRIs or tricylics (a class of older antidepressants).

Recently attention has focused on a range of transient neonatal distress syndromes associated with exposure to (or withdrawal from) antidepressants in uteroThese syndromes appear to affect up to 25% of babies exposed to antidepressants in utero, although some studies have failed to use raters blinded to whether babies were exposed to medication or not, and many reports have not taken into consideration the contributing factors of maternal anxiety and depression.  Although duloxetine has not received specific study in this area, these data regarding neonatal adaptation are likely to pertain to its use as well.

Persistent pulmonary hypertension of the newborn (PPHN), a rare condition which has been reported as having an increased association with SSRI use in late pregnancy (Chambers 2006).  More recent studies have demonstrated lower risk of PPHN than initially reported or absent (Källén and Olausson 2008; Andrade 2009).  PPHN was not specifically reported with duloxetine use, nor has it been included for analysis in the published studies.

Please think about what you would advise Ms. A as her health care provider or friend.  What recommendations would you make to Ms. A?

Marlene P. Freeman, MD

Cohen, L. S., L. L. Altshuler, et al. (2006). “Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment.” JAMA 295(5): 499-507.

Chambers, C. D., S. Hernandez-Diaz, et al. (2006). “Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn.” N Engl J Med 354(6): 579-87.

Källén B, Olausson PO. Maternal use of selective serotonin re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf. 2008 Aug;17(8):801-6

Andrade SE, McPhillips H, et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf. 2009 Mar;18(3):246-52.