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Megan Sarashinsky, PharmD, BCPP

This session can be purchased in CPNP University

Available literature regarding the safety of treatment of anxiety, sleep, and mood disorders during pregnancy is conflicting. Guidance has been needed to navigate the literature in order to better create pharmacotherapeutic regimens and to answer patients’ questions about how to continue therapy with the most benefit and least amount of harm to the patient and fetus when they learn of their pregnancy.

Dr. Marlene Freeman, Associate Professor of Psychiatry, Harvard Medical School, and Associate Director, MGH Center for Women’s Mental Health, presented a riveting clinical application series session at the 2018 CPNP Annual Meeting where she shared her expertise regarding these current controversies with psychotropic use in pregnancy. She focused on contrasting the safety and efficacy of anxiolytic treatment with the risk of untreated anxiety/insomnia during pregnancy, evaluating the risk of neurobehavioral complications secondary to pre-pregnancy and prenatal exposure to antidepressants and mood stabilizers, and comparing the risk of prenatal antidepressant and mood stabilizer exposure syndrome to the risk of untreated mood disorders during pregnancy.

To begin the presentation, Dr. Freeman delineated potential risks of untreated antenatal depression, including negative effects on maternal weight gain, less adherence to prenatal care, increased risk of low birth weight, prematurity, and small for gestational age, and increased neonatal irritability. She also described evidence that demonstrated untreated maternal anxiety increased risk for attentional problems in the offspring. She then reviewed the challenges with interpreting pregnancy and lactation information provided in the prescribing information as well the challenges of interpreting the risks of the use of antidepressants during pregnancy from clinical trials. Dr. Freeman then reviewed the American Psychiatric Association/American College of Obstetricians and Gynecologists joint recommendations, which include psychotherapy for mild to moderate depression and medication management for pregnant women with severe depression. Also included was the importance of taking into account patient preferences and previous illness course(s).

Next Dr. Freeman transitioned into discussing the use of selective serotonin reuptake inhibitors (SSRI) during pregnancy. She noted that reproductive safety data with SSRI use exceeds information about most other medicines used in pregnancy. She summarized available literature by illustrating the absolute risk of SSRI exposure in pregnancy is consistently small, including the risk of cardiac defects with SSRI exposure in pregnancy. She noted that most available literature does not suggest major long-term adverse effects from prenatal antidepressant exposure on infant/child neurobehavioral development. Dr. Freeman next presented later pregnancy considerations with antidepressant use during pregnancy. She discussed reductions in associated risk of persistent pulmonary hypertension of newborn and cardiac effects with SSRI exposure were appreciated as confounding variables were better controlled in clinical trials.

Changing topics, Dr. Freeman reviewed the safety of using sleep medications in pregnancy. She highlighted that the majority of women experience sleep dysregulation during pregnancy, and some may have an impact on functioning. Of the sleep medications, benzodiazepines have been the best studied. Inconsistent findings have been seen with first-trimester benzodiazepine exposure; possible neonatal withdrawal, sedation, hypotonia, and cyanosis have been reported with late pregnancy exposure. She then discussed the available literature regarding safety of non-benzodiazepine hypnotics, melatonin, sedating antihistamines, tricyclic antidepressants, trazodone, and mirtazapine during pregnancy, noting that the lack of literature should not be mistaken as an endorsement for safety.

To conclude her presentation, Dr. Freeman discussed the risks of mood stabilizer and atypical antipsychotic use during pregnancy. One takeaway message was that valproic acid is the worst known teratogen amongst psychotropic medications and is associated with lower intelligence quotient (IQ) scores. Dr. Freeman ended by requesting providers to refer pregnant patients receiving psychotropic medications to national pregnancy registries.

Take Home Points

  • Untreated antenatal depression and anxiety can lead to negative effects for both the mom and the offspring.
  •  Reproductive safety data with SSRI use exceeds information about most other medicines used in pregnancy; the absolute risk of SSRI exposure in pregnancy is small is a consistent conclusion from available literature.
  • Majority of women experience sleep dysregulation during pregnancy, and some may have an impact on functioning.
  • Of the sleep agents, benzodiazepines have been the best studied. Inconsistent findings have been seen with first-trimester exposure; possible neonatal withdrawal, sedation, hypotonia, and cyanosis have been reported with late pregnancy exposure.

References

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  11. Brown et al. The association between antenatal exposure to selective serotonin reuptake inhibitors and autism: a systematic review and meta-analysis. J Clin Psychiatry 2017;78(1):e48-58.
  12. Huybrechts et al., Antidepressant use and the risk of persistent pulmonary hyptertension of the newborn. JAMA 2015;313(21):2142-51.
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