These findings imply that MDD exposure and SSRI treatment yield similar reproductive outcomes (including preterm birth). Because the preterm birth rate in the United States is 12.5% and is the leading cause of perinatal morbidity and mortality, clarification of an association between SSRI and/or MDD and preterm birth is crucial.35
Late-gestational SSRI-exposed neonates have a 3-fold higher risk of neonatal behavioral syndrome—characterized by difficulty in feeding and sleeping, irritability, prolonged crying, tremors, and seizures—compared with infants with only early or no exposure.35 Most neonatal signs resolve within 2 weeks of birth, and follow-up results of affected infants have been normal.36,37
The risk of neonatal syndrome (transient CNS, motor, respiratory, and GI signs) in infants with prenatal serotonin reuptake inhibitor exposure may be moderated by infant genotype.38 The highest reported rates for neonatal syndrome after in utero SSRI exposure were 31% in a sample of infants who had been exposed only to fluoxetine(Drug information on fluoxetine), and 30% in a sample in which 62% had been exposed to paroxetine(Drug information on paroxetine) and 20% to fluoxetine.32,39
Chambers and colleagues40 found a relative risk of 6.1 for persistent pulmonary hypertension in neonates exposed after 20 weeks’ gestation. In line with the use of absolute risks, this translates into a rate of 6 to 12 per 1000 births in SSRI-exposed infants compared with 1 to 2 per 1000 births in the general population. The investigators hypothesized a continuum of respiratory problems in SSRI-exposed neo-nates in adapting to extrauterine oxygenation. Other reports of increased risk of neonatal respiratory distress after SSRI exposure have been published34,41,42; however, a recent study did not replicate this association.43
Use of the lowest effective dose to achieve remission during pregnancy reduces residual symptoms and exposure to the underlying disorder. The SSRI dosage may need to be increased to maintain clinical effectiveness because of the increased clearance during pregnancy. Sit and colleagues44 found that 4 of 5 patients who received citalopram(Drug information on citalopram)/escitalopram and 5 of 6 patients who received sertraline(Drug information on sertraline) had declining serum drug level/dose ratios between 20 weeks’ gestation and birth. By 12 weeks postpartum, the level/dose ratios were similar to those detected at 20 weeks’ gestation. Systematic clinical response monitoring is crucial during pregnancy.
ECT is a reasonable choice for the treatment of severely depressed pregnant women. Preparation for ECT during pregnancy should include obstetrical consultation and fetal monitoring, intravenous hydration, administration of a nonparticulate antacid, and elevation of the woman’s right hip to avoid compression of the great vessels.46
Although morning bright light therapy is widely appreciated as a treatment for seasonal affective disorder, it is also effective for nonseasonal MDD.47-49 Light therapy is perceived as physiologically natural, with mild and easily correctable adverse effects (eg, mild headache and eye irritation, slight nausea); therefore, it is appealing to pregnant women and their physicians. Oren and colleagues50 performed an open trial of bright light therapy in an A-B-A design in 16 pregnant women with MDD. After 3 weeks of treatment, the mean depression ratings improved by 49%.
This work was further explored in a double-blind, placebo-controlled pilot study by Epperson and colleagues.51 Ten pregnant women with MDD were randomly assigned to a 5-week clinical trial with a 7000 lux (active) or 500 lux (placebo) light box. Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in a longer, 10-week trial, the active light produced a clear benefit (P = .001); the effect size (0.43) was similar to that seen in antidepressant drug trials. Successful treatment with bright morning light was associated with phase advances of the melatonin(Drug information on melatonin) rhythm, which was assessed with serial saliva samples. These findings provide additional evidence for efficacy of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.