Venlafaxine and Duloxetine: Pooled Analysis Shows No Increase in Risk of Malformations

Venlafaxine and Duloxetine: Pooled Analysis Shows No Increase in Risk of Malformations

Women face difficult choices when deciding whether or not to continue psychiatric medications during pregnancy.  This choice can be especially difficult for women taking newer medications which lack adequate reproductive safety data.  While we have adequate data regarding the reproductive safety of most of the selective serotonin reuptake inhibitors (SSRIs), there has been less information available on the serotonin norepinephrine reuptake inhibitors (SNRIs):  venlafaxine (Effexor) and duloxetine (Cymbalta).  A recent article, pooling data from 8 large cohort studies, provides reassuring information regarding the reproductive safety of both venlafaxine and duloxetine.

Using the PRISMA guideline for systematic reviews, the authors performed a systematic search for the risk of major congenital malformations after first-trimester exposure to venlafaxine or duloxetine. Eight cohort studies were identified, including 3186 exposed to venlafaxine and 668 exposed to duloxetine.

Of the 3186 venlafaxine-exposed infants, the majority (n=2763) come from a single study published earlier this year.  In the venlafaxine-exposed group, there were 107 major malformations, which translates into a 3.36% risk of major malformations and a relative risk estimate of 1.12 with a 95% confidence interval of 0.92-1.35.   (The researchers did not have a specific unexposed control group but they estimated relative risk using a reference value of 3% for the prevalence of major malformations in the general population.)

They analyzed data from 668 duloxetine-exposed infants and observed 16 major malformations (2.33%), resulting in a relative risk estimate of 0.80 (95% confidence interval of 0.46-1.29).

Based on these data, we can conclude that first-trimester exposure to venlafaxine is not associated with an increased risk of major congenital malformations. For duloxetine, the amount of data is considerably smaller but does not suggest a clinically important increase in risk.

Ruta Nonacs, MD PhD

Lassen D, Ennis ZN, Damkier P.  First-trimester pregnancy exposure to venlafaxine or duloxetine and risk of major congenital malformations: a systematic review.  Basic Clin Pharmacol Toxicol. 2015 Oct 5.

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