Antidepressants during pregnancy and lactation: defining exposure and treatment issues

The majority of psychiatric illness onsets early in an individual's life, typically before or during the reproductive years. The increased incidence of major depression, dysthymia, and panic disorder in women compared with men underscores the likelihood that the clinician will encounter the clinical dilemma of medication use during pregnancy and lactation. The emergence of specialized clinics at several academic centers specifically to investigate and address issues in Perinatal psychiatry illustrates this conundrum best. The extant literature derived from human studies suggests that maternal mental illness and stress may have an adverse impact on obstetrical outcome. These clinical investigations are complemented by a burgeoning series of laboratory studies in rodents and nonhuman primates, showing the profound deleterious impact of maternal stress during the perinatal and neonatal periods on the development of the offspring. Data obtained from pharmaceutical registries, cohort studies, toxicology centers, and case series have consistently failed to show an adverse effect associated with in utero antidepressant exposure. Despite these advances and treatment guidelines proposed by the various academic leaders, investigations describing the extent of fetal/neonatal exposure, clinical methods for minimizing such exposure, and clinical treatment guidelines that include the physiological impact of pregnancy are sparse. The available literature shows distinct pharmacokinetic profiles of the selective serotonin reuptake inhibitors in placental passage and breast milk. Preliminary animal studies have shown higher than expected central nervous system concentrations associated with exposure during pregnancy and mathematical modelling for calculating infant exposure when nursing. The clinical import of these data will require further investigations of central nervous system bioavailability in the fetus and neonate.