ABSTRACT
CONTEXT: Although a large number of women of reproductive age use new selective serotonin reuptake inhibitors (SSRIs) and half of all pregnancies are unplanned, no data exist on the safety of these agents for the human fetus. OBJECTIVE: To assess fetal safety and risk of fluvoxamine, paroxetine, and sertraline. DESIGN: A prospective, multicenter, controlled cohort study. SETTING: Nine Teratology Information Service centers in the United States and Canada. PATIENTS: All women who were counseled during pregnancy following exposure to a new SSRI and followed up by the participating centers. Controls were randomly selected from women counseled after exposure to nonteratogenic agents. MAIN OUTCOME MEASURES: Rates of major congenital malformations. RESULTS: A total of 267 women exposed to an SSRI and 267 controls were studied. Exposure to SSRIs was not associated with either increased risk for major malformations (9/222 live births [4.1%] vs 9/235 live births [3.8%] in the controls, relative risk, 1.06, 95% confidence interval, 0.43-2.62) or higher rates of miscarriage, stillbirth, or prematurity. Mean (SD) birth weights among SSRI users (3439 [505] g) were similar to the controls (3445 [610] g) as were the gestational ages (39.4 [1.7] weeks vs 39.4 [1.9] weeks). CONCLUSION: The new SSRIs, fluvoxamine, paroxetine, and sertraline, do not appear to increase the teratogenic risk when used in their recommended doses.
Subject(s)
Abnormalities, Drug-Induced/etiology , Antidepressive Agents/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , 1-Naphthylamine/adverse effects , 1-Naphthylamine/analogs & derivatives , Adult , Antidepressive Agents/therapeutic use , Cohort Studies , Female , Fluvoxamine/adverse effects , Humans , Infant, Newborn , Paroxetine/adverse effects , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, First , Prospective Studies , Selective Serotonin Reuptake Inhibitors/therapeutic use , SertralineABSTRACT
OBJECTIVE: To compare pregnancy outcome following first-trimester fluoxetine (Prozac) exposure with pregnancy outcome in two matched control groups. Fluoxetine is a new antidepressant used by many young women. Currently, no published data exist on its safety in pregnancy. DESIGN: We prospectively collected and followed up 128 pregnant women exposed to a mean daily dose of 25.8 mg (+/- 13 mg) of fluoxetine during the first trimester and compared pregnancy outcome with two matched groups of women exposed during the first trimester of pregnancy to either nonteratogens or tricyclic antidepressants. RESULTS: Rates of major malformations were comparable within the three groups and did not exceed those expected in the general population. Women treated with fluoxetine had a tendency for increased risk for miscarriage when compared with women exposed to nonteratogens (relative risk, 1.9; 95% confidence interval, 0.92 to 3.92). The rate of miscarriages in the fluoxetine group was comparable with the tricyclic group (13.5% and 12.2% vs 6.8% in the nonteratogens). CONCLUSIONS: Our study suggests that the use of fluoxetine during embryogenesis is not associated with an increased risk of major malformations. Women exposed to both fluoxetine and tricyclic antidepressants tended to report higher rates of miscarriage; further studies will be needed to confirm this observation and to separate the effects of the psychiatric condition from the associated drugs. Long-term studies will be warranted to rule out potential developmental teratology of fluoxetine, which affects a central nervous system neurotransmitter.
