USE OF VENLAFAXINE IN PREGNANCY

Venlafaxine is a serotonin and noradrenaline reuptake inhibitor (SNRI) indicated for the treatment of depression, anxiety and panic disorders.

Data from cohort studies on the use of venlafaxine in human pregnancy do not indicate an increased risk of congenital malformation overall. However, evidence regarding the risk of specific malformations is currently conflicting. A small number of retrospective case-control studies, which may be influenced by various methodological biases, have shown associations with specific anomalies such as hypospadias, gastroschisis, cleft palate, and limb and heart defects (both for any heart defect and specific heart defects). Single prospective cohort studies have described associations with non-severe cardiac malformation (approximate absolute risk of 1.5 to 1.8%, relative to a background risk of 0.9%), hypoplastic left heart syndrome (approximate absolute risk of 0.4%, relative to a background risk of 0.025%) and respiratory malformation (approximate absolute risk of 0.1%, relative to a background risk of 0.05%). Given the data for some of these associations are conflicting, and with other prospective cohort studies not replicating the findings, it is currently unclear if these anomalies are truly associated with venlafaxine use or whether the associations have been described due to methodological bias and/or data confounding. The benefits of venlafaxine use in pregnancy in preventing depression and its associated effects are likely to outweigh the small absolute risks of these specific defects.

An increased risk of miscarriage has been reported in a small number of studies. However, the data are inconsistent and likely confounded by indication and other factors, with better quality studies not identifying increased risks. A single study has suggested a possible association between venlafaxine use and preterm delivery. Current data do not suggest an increased risk of intrauterine death or small for gestational age (SGA) infants following gestational venlafaxine exposure; however, the data are insufficient for an increased risk to be excluded.

Neonatal complications observed in infants exposed to venlafaxine in utero are similar to those reported with selective serotonin reuptake inhibitors (SSRIs) and include respiratory problems, low Apgar score and convulsions. Use of centrally acting drugs throughout pregnancy or around the time of delivery is associated with an increased risk of poor neonatal adaptation syndrome (PNAS). Monitoring of the neonate post-delivery is therefore advised.

As in utero SSRI exposure is associated with an increase in the occurrence of persistent pulmonary hypertension of the newborn (PPHN), there are theoretical concerns that in utero venlafaxine exposure could also result in PPHN. Although there are no published data which identify an association, data are insufficient to disprove this theory. An increased risk of PPHN cannot be excluded, although the absolute risk is likely to be low.

Reports of lower than average IQ in children exposed to antidepressants in utero have been published; however, the effects of venlafaxine exposure on neurodevelopment have not been widely studied. Preliminary findings suggest that children exposed to antidepressants in utero, including venlafaxine, and children of untreated depressed women have lower IQs and exhibit more behavioural problems than children of non-exposed, non-depressed women.

Where maternal treatment with venlafaxine is clinically indicated, the benefits of treatment are likely to outweigh both the risks that have been described in the available evidence and the risks of leaving the patient untreated.

At present there is insufficient evidence to warrant additional fetal monitoring for congenital malformations. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when considering the need for additional pregnancy monitoring. Discussion with UKTIS is recommended in all cases.