
- Psychiatric Times Vol 30 No 4
- Volume 30
- Issue 4
Antidepressants and Pregnancy
The extent to which antidepressant use during pregnancy is associated with increased risks of postnatal adaptation syndrome, persistent pulmonary hypertension in the newborn, first-trimester teratogenicity, stillbirth, and infant mortality is explored in 2 recent studies. A close up look here. . .
The extent to which antidepressant use
In a recent interview, lead author Nancy Byatt, DO, MBA, a perinatal psychiatrist and Assistant Professor of Psychiatry and OB-GYN at the
In economically developed countries, the prevalence for depression during pregnancy ranges between 7% and 19%, according to obstetrician and epidemiologist Olof Stephansson, MD, PhD, of the
Byatt told Psychiatric Times that conflicting data have led to major controversies regarding antidepressant use during pregnancy. To help providers “understand the risks and benefits of using antidepressants during pregnancy and apply that knowledge to enhance clinical care,” she and colleagues conducted an extensive review of the literature between 1966 and 2012.
Antidepressants considered in the review included SSRIs, SNRIs, and norepinephrine reuptake inhibitors. According to Byatt, the review focused on outcomes that “have the most controversy surrounding them.” These are congenital malformations, PNAS, and PPHN.
Results
“The current evidence for malformations is limited because of inconsistent findings and limited methodology of the published studies,” the review authors wrote. “Few studies have controlled for maternal illness, and therefore do not take into account whether reproductive outcomes are due to maternal illness or antidepressant exposure.”
“There are some individual studies that show a risk between specific
“The PPHN literature is limited by small and/or uncontrolled studies,” according to Byatt and her group. In addition, “there are other reported risk factors, including race, method of delivery, obesity, asthma, and diabetes that many studies do not take into account.” The evidence regarding the risk of PPHN because of in utero antidepressant exposure remains inconclusive. Some studies suggest a small association, and other studies suggest no association.
Byatt pointed to changes in drug safety advisories on SSRIs and PPHN over the years. In 2006, the FDA issued a Public Health Advisory warning of a possible link between SSRI antidepressant use during pregnancy and reports of PPHN. However, in 2011, the FDA, in a Drug Safety Communications, said that given conflicting results from different studies, it is “premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN.”
“Overall, we do not recommend discontinuing
Risks of untreated depression/anxiety
Understandably, providers may worry about the medication risks for the pregnant woman and her fetus/child, Byatt said, but equally important are the risks of untreated depression and anxiety. “Prenatal depression and anxiety can lead to missed obstetrical appointments, poor nutrition, poor sleep, and
To assist clinicians in working with their pregnant patients, Byatt and colleagues included a Table of treatment recommendations in their article. These include using the lowest medication dose possible while avoiding undertreatment; avoiding polypharmacy; and maximizing nonmedication, evidence-based treatments.
At about the same time their literature review on antidepressant use in pregnancy was published, an article by
“You can extrapolate from the study that if you can help mom go into the
Byatt was somewhat critical of a review that discussed the impact of SSRIs on fertility, pregnancy, and neonatal health.4
SSRIs and infant death
Byatt described the recent population-based cohort study by
For the study funded by the Swedish Pharmacy Company and the authors’ affiliations, the researchers obtained information on maternal use of SSRIs from prescription registries. Exposure was defined as 1 or more filled prescriptions for an SSRI from 3 months before the start of pregnancy until birth. The researchers also gathered information on maternal characteristics, pregnancy, and neonatal outcomes from patient and medical birth registries. They then estimated relative risks of still-birth, neonatal death, and postneonatal death associated with SSRI use during pregnancy, taking into account maternal characteristics and previous psychiatric hospitalizations.
Among 1,633,877 singleton births in the study from 1996 to 2007, there were 6054 stillbirths, 3609 neonatal deaths, and 1578 postneonatal deaths. A total of 29,228 mothers (1.79%) had filled a prescription for an SSRI during pregnancy.
“Women taking SSRIs had slightly increased rates of stillbirth and postneonatal death,” said Stephansson, Associate Professor at Karolinska University’s Clinical Epidemiology Unit. Women exposed to an SSRI had higher rates of stillbirth (4.62 vs 3.69 per 1000) and postneonatal death (1.38 vs 0.96 per 1000) than those who did not. The rate of neonatal death was similar between groups (2.54 vs 2.21 per 1000).
However, when the researchers considered maternal factors, there was no association with SSRIs and stillbirth or infant death rates, Stephansson said. Such factors included a history of the severity of the psychiatric disorder among women taking SSRI drugs during pregnancy, their older age, the tendency for them to be smokers, and the greater incidence of diabetes and high blood pressure.
The researchers acknowledged that they might have overestimated the actual use of antidepressants, because having a drug prescribed doesn’t always equate with using it. Stephansson noted that the study findings need confirmation by other studies in different settings. He added that the Nordic team of researchers has been looking at various issues involving SSRI use and pregnancy. Last year, in a large, multinational cohort study,
The results indicate that out of 11,014 mothers who used antidepressants in late pregnancy (later than gestational week 20), 33 babies (0.2%) were born with PPHN (absolute risk, 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000). With regard to SSRI use in early pregnancy, the results indicated that risk for PPHN was “slightly increased.” Specific SSRIs had sim ilar increased risks of PPHN, suggesting a class effect.
Currently, the Nordic collaboration team, according to Stephansson, is investigating spontaneous abortions and congenital malformations and their possible association with antidepressant exposure.
References:
References
1. Byatt N, Deligiannidis KM, Freeman MP. Antidepressant use in pregnancy: a critical review focused on risks and controversies. Acta Psychiatr Scand. 2013;127:94-114.
2. Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA. 2013;309:48-54.
3. Nulman I, Koren G, Rovet J, et al. Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression. Am J Psychiatry. 2012;169:1165-1174.
4. Domar AD, Moragianni VA, Ryley DA, Urato AC. The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health and beyond. Hum Reprod. 2013;28:160-171.
5. Kieler H, Artama M, Engeland A, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population-based cohort study from the five Nordic countries. BMJ. 2012;344:d8012.
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