What’s New in Perinatal Psychopharmacology?

“Between a rock and a hard place” or “Between Scylla and Charybdis” is how some have described the risk/risk assessment involved in prescribing psychotropic drugs to pregnant women with psychiatric illness. Each year, more and more studies confirm the widely held belief that “happy mommy = healthy baby.” Although double-blind placebo-controlled studies are limited, and in many ways impossible, a wealth of large retrospective reviews, registry databases, and improved research methodology has enriched our fund of knowledge, helping direct clinical decision making in this complex area. Below are some highlights to bring you up to date on what is new in the field, and a list of resources and references which are updated regularly with the most current findings.¹

Untreated psychiatric conditions in pregnancy are not benign

Women who abruptly discontinue antidepressant therapy at the onset of pregnancy have a 5-fold increased risk for symptom recurrence compared to women who continue with treatment.² Active psychiatric symptoms during pregnancy are associated with poor prenatal care, substance abuse, preterm delivery, low birth weight, and other obstetric/neonatal complications.

As a group, antidepressants do not increase the risk of congenital malformations above the baseline risk of 2% to 4% in the general population.³ Concerns about septal defects and PPH have been raised, but absolute risk remains low. Antidepressant exposure is not associated with increased risk of autism or other neurodevelopmental problems, although women who take antidepressants may have other risk factors for these problems in their offspring.³  Given the comorbidity of psychiatric illnesses with each other and with substance use disorders, multiple factors likely contribute.

Bipolar disorder

The rate of recurrence of bipolar illness during and after pregnancy is high; thus the risk of untreated symptoms may exceed medication-linked risks in individual cases. Valproic acid is strongly contraindicated in pregnancy due to the 1% to 6% risk of neural tube defects and higher rates of impaired neurocognitive development. Carbamazepine also is associated with multiple teratogenic effects including a 1% risk of neural tube defects. Lithium has a 0.05% to 0.1% increased risk for Ebstein’s anomaly with exposure during the first trimester, much lower than that with valproate or carbamazepine, and much lower than previously reported. Lamotrigine has no known increased risk of congenital anomalies after antenatal exposure. Reports of an association with oral cleft defects are conflicting. There are limited data on gabapentin, oxcarbazepine, tigabine, and topiramate. Atypical antipsychotics may be considered as alternative treatment for acute mania or maintenance treatment (see below).

Schizophrenia

Women with schizophrenia are at extremely high risk for complications during the perinatal period-nearly double that in the general population, including operative deliveries, neonatal intensive care unit admissions, and neonatal morbidity.⁴

While first-generation antipsychotics have a fairly well described history in pregnancy, with high potency agents being preferred to low potency, less has been published about second-generation antipsychotics. Overall, no increased risk of congenital anomalies has emerged to date. However, metabolic effects, blood dyscrasias, and movement disorders in the mother, fetus, and newborn must be taken in to account with the use of these agents. 5

In summary, in most cases of moderate to severe psychiatric illness, the benefits of medication used to remit symptoms in the perinatal period outweigh the putative risk of exposure. Other recommendations include:

► Consider psychotherapy as an initial treatment approach for patients with mild-to-moderate depression or anxiety, and for augmentation as indicated.

► Avoid discontinuing medications that provide psychiatric stability.

► Maintain patients on previously effective medications at the minimal effective dose with symptom remission as the goal.

► Carefully substitute less teratogenic agents if necessary.

► Dose requirements may be higher in the second half of pregnancy, and should be adjusted accordingly.

► Integrating mental health care into perinatal care settings helps increase detection of perinatal psychiatric problems and can lead to early intervention.

Resources

MGH Center for Womens Mental Healthwww.womensmentalhealth.org

Postpartum Support International www.postpartum.net

Reprotoxwww.reprotox.org

References:

•  Dresner N, Byatt N, Gopalan P, et al. Psychiatric care of peritpartum women. Psychiatric Times.2015; 32:12:8-12.
• Cohen LS, Altschuler LL, Harlow BL et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA.  2006;295:499-507
• Grigoriadis S, VonderPorten EH and Mamisashvili L et al. Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence. J Clin Psych. 2013;74:e293-e308.
• Vigod SN, Kurdyak PA and Dennis CL, et al. Maternal and newborn outcomes among women with schizophrenia: a retrospective population-based newborn study. BJOG. 2014; 121:566-574.
• Cohen LS, Viguera AC, McInerney KA, et al. Reproductive safety of second-geneation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Am J Psychiatry. 2015;173:263-270.