Safety of pregabalin in pregnancy

Abstract

In different parts of the world, pregabalin is an approved treatment for neuropathic pain syndromes, fibromyalgia, partial-onset seizures, and generalized anxiety disorder. Few studies have examined the safety of pregabalin exposure during pregnancy. Among 4 studies identified through a PubMed search conducted in September 2018, one small study (exposed n = 30) recorded a major malformation rate of 3.3%, which was similar to that in unexposed controls. Another small study (exposed n = 30) recorded increased rates of spontaneous abortion (23.3%), preterm birth (25.0%), and major malformations (7.7%), none of which reached statistical significance even in unadjusted analyses. A third study (exposed n = 116) identified a significantly increased rate of major malformations (6.0%) but no increase in the rates of other adverse birth outcomes. The fourth and largest study (exposed n = 477 and n = 174; 2 datasets), which also presented the best statistical analysis, found no increase in the major malformation risk associated with pregabalin exposure. A subjective conclusion is that there is no clear signal that pregabalin exposure during pregnancy is associated with adverse gestational outcomes; however, this conclusion is limited by the consideration that all analyses were underpowered. Pregabalin use in pregnancy is therefore best restricted to circumstances in which the risk-benefit ratio is clearly favorable, and then, only after shared decision-making.