Use of Serotonin Reuptake Inhibitors in Pregnancy
Summary
Objective. To summarize the current state of knowledge on the use of serotonin reuptake inhibitors (SRIs) during pregnancy.
Methods. English-language reports on studies using human subjects were selected from a MEDLINE search of the literature from 1995 to April 2007 using the terms serotonin uptake inhibitors/*therapeutic use/*adverse effects, in combination with pregnancy, pregnancy trimester, first, pregnancy complications, depression/*drug therapy, pregnancy, maternal exposure/*adverse effects, infant/newborn, abnormalities, drug induced, prenatal exposure delayed effects/epidemiology, and teratogens. In addition, the Cochrane Central Controlled Trials Register was searched using the terms paroxetine, fluoxetine, sertraline, fluvoxamine, citalopram, and venlafaxine, and pregnancy. Web sites of the American Academy of Pediatrics, Food and Drug Administration, American Psychiatric Association, and American College of Obstetricians and Gynecologists also were searched for documents relevant to the use of SRIs in pregnancy. A total of 268 articles were retrieved for analysis. When high-quality systematic reviews and meta-analyses were identified, they formed the basis for evaluative statements about safety and efficacy. Additional articles were identified by manual review of the references cited in these publications.
Results. Except for paroxetine, prenatal exposure to SRIs in the first trimester is not a risk factor for major congenital malformations. Data are conflicting on whether SRI exposure increases the risk of premature delivery or decreases age-appropriate birth weight. Exposure to paroxetine modestly increases the risk for congenital and certain cardiac malformations, perhaps in a dose dependent fashion. Third trimester exposure to SRIs may increase the risk of persistent pulmonary hypertension of the newborn, and the occurrence of a neonatal behavioral syndrome with central nervous system, respiratory, gastrointestinal, and motor signs. These symptoms may be attributable either to drug withdrawal or serotonin toxicity. Long-term neurobehavioral effects are not apparent.
Conclusion. Untreated depression during pregnancy is associated with obstetrical complications and infant behavioral abnormalities. Use of SRIs in the third trimester is associated with various perinatal complications that generally are self-limiting and resolve with supportive care. Further studies are needed to establish the actual frequency of these complication, whether the symptoms represent excessive serotonergic effects or are a manifestation of drug discontinuation, and whether tapering of the antidepressant late in pregnancy is an appropriate clinical maneuver to protect infants without triggering relapse in the mother or an increase in the incidence of postpartum depression. However, if the mother is treated with SRIs, the neonate should be monitored for possible adverse effects, including during the immediate period after release from the hospital.
RECOMMENDATIONS
The following statements, recommended by the Council on Science and Public Health, were adopted by the AMA House of Delegates as directives at the 2007 AMA Annual Meeting:
- The AMA encourages further research into the treatment of depression during pregnancy, including the effects of antidepressant drugs, as well as strategies designed to best protect the health and welfare of both the mother and the child. (Directive)
- The Council on Science and Public Health will monitor the activities of relevant medical specialty societies on this issue, including development of practice guidelines or policy statements, and assist as needed in educating the physician community. (Directive)
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