Charlene Laino

June 08, 2010

June 8, 2010 (New Orleans, Louisiana) — Women who decline to take antidepressants during pregnancy are often fearful of the potential adverse effects these medications may have on their unborn child.

A small, prospective cohort study presented here at the American Psychiatric Association 2010 Annual Meeting examined factors that influence antidepressant adherence or the decline of antidepressant treatment and showed that 23% of women discontinued therapy during pregnancy.

Qualitative analysis indicated that fear of exposing their fetus to potentially teratogenic drugs and denial of diagnosis were the major reasons for pregnant women declining medication.

"We found that women were very afraid to expose their fetus to medication, [and thus] frequently denied they were depressed," study investigator Shaila Misri, MD, said. Interestingly, women with a higher yearly household income were more likely to decline medication, "which seems counterintuitive," she added.

According to investigators, approximately 12% of all women in the general population suffer from depression in pregnancy, and women who are genetically predisposed to depression may relapse during pregnancy.

Untreated Depression Substantial Health Risk

In 2004, the US Food and Drug Administration (FDA) issued a warning that the use of certain antidepressants in the late third trimester may increase risk for neonatal complications, including respiratory distress, sleep and feeding disorder, and hypoglycemia, among others. The warning said that clinicians may want to gradually taper pregnant women off antidepressants in the third trimester so that the baby is not affected.

The prevalence of nonadherence to antidepressants during pregnancy ranges from 18% to 52%, according to the researchers. This is alarming, as untreated or poorly managed maternal depression during pregnancy poses a substantial health risk for mothers and their infants, Dr. Misri said.

"Despite the FDA warning, the risk of untreated or undertreated perinatal depression must be given substantial weight to maximize mother and infant well-being," agreed Shari I. Lusskin, MD, director of reproductive psychiatry at the New York University School of Medicine.

"The FDA warning is based on very limited data. Large prospective studies are needed to characterize the rate and prevalence of neonatal complications relative to neonatal [antidepressant] use," said Dr. Lusskin, who was not involved with the research.

The study included 59 pregnant women aged 18 to 45 years who met criteria for major depression, with or without a comorbid anxiety disorder.

Patients were divided into 3 groups: adhering to medications, declining medications, and declining medications antenatally but starting postpartum.

Symptoms were monitored by a psychiatrist every 4 weeks from initial enrollment at 18 to 34 weeks' gestation until 1 month postpartum, using the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A). Medication usage and smoking were also recorded at each visit.

Of the 59 participants, 39 (77%) adhered to antidepressants. Of the 20 (23%) who declined antidepressant usage, 7 (35%) resumed medication use in the postpartum period.

Adherence Linked to Better Outcomes

According to investigators, the majority of the women stayed on their antidepressant medication throughout pregnancy because the fear of the illness coming back was stronger than the fear of exposure to medications.

"These women wanted to remain mentally well and stable as they were fearful of the chronicity of their illness and the impact it could have on their baby," the researchers report.

A relapse of symptoms at 30 weeks was observed in women who stayed on medication and those who declined medication during pregnancy. However, in the women who stayed on medication, HAM-A scores improved after that time.

"Whether on or off medication, women did worse [by the third trimester]. But those who stayed on the drugs and received a dose adjustment did well by the postpartum period," said Dr. Misri, who is medical director of the Reproductive Mental Health Program at BC Women's Hospital in Vancouver, Canada.

Specifically, HAM-A scores dropped from a mean of 19.8 at study entry to 14.7 at week 22 and then shot back up to 18.5 at week 30. By week 34 and the postpartum period, however, scores decreased to a mean of 16.2 and 13.9 points, respectively.

In the group that declined medication, HAM-A scores got worse over time, from a mean of 16.0 at study entry to 18.1 at week 30, 19.4 by week 34, and 21.1 in the postpartum period.

In the postpartum period, there was a statistically significant difference in HAM-A scores between women who adhered and women who declined medication (P < .05). There was no statistically significant difference between HAM-A scores among women who adhered to and women who declined medication at any other point in the study.

There was no statistically significant difference in HAM-D scores between women who adhered to and those who declined medication at any point of their participation (P > .05).

In general, said Dr. Misri, patients who stopped taking antidepressants suffered mood fluctuations throughout the pregnancy that worsened in the postpartum period, at which point many went back on medication.

"Symptomatic worsening of symptoms in the postpartum period changed some women's perception despite potential exposure of their fetus to their drugs through breastfeeding," she said.

The major factor associated with medication adherence was acceptance that medication was needed or functionality would be impaired, the study showed.

"It is important to counsel women on the consequences of leaving depression untreated, in terms of their and fetal health and bonding," Dr. Misri told Medscape Psychiatry.

"At this point, antidepressant medication is the only proven treatment for moderate to severe depression. Staying on the drugs throughout pregnancy is key," she said.

Snapshot of Real-Life Choices

"This is a very useful study that examines real-life choices that women make during pregnancy," Dr. Lusskin said.

The findings extend previous work by Lee S. Cohen, MD (JAMA. 2006;295:499-507), showing a significantly increased risk for relapse in women who went off antidepressants in pregnancy vs those who stayed on antidepressants, Dr. Lusskin said.

"Consistent with that study, staying on medication didn't provide complete prophylaxis from relapse; however, in this study, remaining on medication provided some protection.

"Women very frequently require an increase in [antidepressant] dose in the latter half of pregnancy to maintain euthymic mood and prevent relapse," Dr. Lusskin said.

The study was funded by the Vancouver Foundation. Dr. Misri reports she has received grant/research support from AstraZeneca Canada and Forest Research Institute. She is also on the speaker bureaus for AstraZeneca Canada and Wyeth Ayerst. Dr. Lusskin reports she is on the Wyeth Ayerst's speaker bureau.

American Psychiatric Association 2010 Annual Meeting: Poster Abstract NR5-63. Presented May 25, 2010.


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