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Dilemma: Pregnant Women & Antidepressants



I.   PREGNANT WOMEN WHO SUSPEND ANTIDEPRESSANTS RISK RELAPSE


BOSTON, Feb. 1 - Women with major depression who decide to forgo their antidepressant medications during pregnancy are at a fivefold greater risk of relapse than if they stay on the drugs, according to investigators.


The researchers dismissed the notion that hormonal changes associated with pregnancy help protect women against depression as an old wives' tale not buttressed by evidence.


"Pregnancy has historically been described as a time of emotional well-being, providing 'protection' against psychiatric disorder," wrote Lee S. Cohen, M.D., of the Massachusetts General Hospital, and colleagues in the Feb.1 issue of the Journal of the American Medical Association. "However, systematic data to support this impression are sparse."


The authors pointed to a prospective community-based study which found that pregnant and non-pregnant women had similar rates of depression, and to a second study indicating that depressive symptoms persist into pregnancy.


To determine whether pregnant women with major depression who discontinue antidepressants are at greater risk for relapse compared with pregnant women who stay on their drugs, the authors conducted a prospective longitudinal study of 201 women who were being treated at three centers that specialize in the treatment of psychiatric illnesses during pregnancy.


They looked at data on monthly psychiatric assessments and calculated time to relapse of depression during pregnancy, using as their main outcome measure major depression as determined by criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).


Women were eligible for the study if they had a history of major depression before becoming pregnant, were at less than 16 weeks' gestation, were euthymic for at least three months prior to their last menstrual period, and were currently or had recently (less than 12 weeks prior to last menstrual period) been taking antidepressant medication.


Thirteen of the 201 women in the study had miscarriages, five elected to terminate their pregnancies, 12 were lost to follow-up and eight dropped out.


In all, 86 of the 201 women (43%) had a relapse of major depression during pregnancy. Among the 65 women who opted to stop taking antidepressants, 44 (68%) had a relapse, compared with 21 of 82 (26%) of women who stayed on their drugs.


Women who discontinued medication had significantly more frequent relapses over the course of their pregnancies compared with women who stayed on their drugs, the authors noted (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P <0.001).


"Of those who relapsed, approximately 50% did so in the first trimester of pregnancy and 90% experienced recurrence of depression by the end of the second trimester," the authors wrote.


They also found that 60% of women who discontinued antidepressant medications at the beginning of pregnancy ended up going back on the drugs during their pregnancy, they noted.


"Given the prevalence of depression in reproductive age women, the prevalence of antidepressant use in this population, and the frequency of unplanned pregnancy, the ability to inform patients about risk of depressive relapse if either discontinuation or maintenance of treatment is pursued as a clinical course has significant implications," the authors wrote.


Physicians caring for women who become pregnant while on medication for major depression should discuss with their patients the relative risks to the fetus of the medication versus the risk to the mother-to-be of relapse, the authors said.


They noted that the data from case series and prospective studies suggest that most older and new antidepressants are not associated with increased risk for congenital malformations when they are taken during the first trimester, although recent studies have suggested that there could be a link between Paxil (paroxetine) and congenital cardiovascular malformations.


"Quantification of these risks affords clinicians the opportunity to make collaborative treatment decisions consistent with individual needs and wishes," they wrote. "Such information can also help to refine treatment guidelines for women with a history of depression who are planning to conceive or who experience mood disorders during pregnancy."


II.  ANTIDEPRESSANTS IN PREGNANCY LINKED TO NEWBORN HANGOVER


PETAH TIQWA, Israel. Feb. 6 - Fetal exposure to a mother's antidepressants during pregnancy may leave her newborn in withdrawal, according to researchers here.


Of 60 full-term neonates exposed in utero to selective serotonin reuptake inhibitors (SSRIs), almost one third developed symptoms of so-called neonatal abstinence syndrome, according to a study in the February issue of the Archives of Pediatric and Adolescent Medicine.


Symptoms, which include high-pitched crying, tremors, gastrointestinal problems, hypertonicity, and disturbed sleep, were severe in eight newborns and mild in 10, reported Rachel Levinson-Castiel, M.D., of the Children's Medical Center of Israel here.


These infants and 60 controls not exposed to SSRIs were assessed two hours after birth and regularly if they showed withdrawal symptoms. In addition to standard monitoring, the protocol included a Finnegan score, an objective method of monitoring the onset and progress of symptoms.


Drug exposure occurred through the entire pregnancy or at least during the third trimester, said Dr. Levinson-Castiel. No unexposed infants developed the syndrome.


The findings leave patients and physicians on the horns of a dilemma. According to a study in the Feb.1 Journal of the American Medical Association, investigators at Massachusetts General Hospital reported a five-fold greater risk of relapse for pregnant women who suspended antidepressants compared with those who continued throughout pregnancy.


Well aware of the stress of pregnancy on the mother and the risk of relapse or termination of the pregnancy, the Israeli physicians wrote, "Because maternal depression during pregnancy also entails a risk to the newborn, the risk-benefit ratio of continuing SSRI treatment should be assessed by physicians and their patients."


In the Israeli study, 37 infants were exposed to Paxil (paroxetine), 12 to Prozac (fluoxetine), and the rest to Celexa (citalopram), Effexor (venlafaxine), or Zoloft (sertraline). Because of the small subgroup size, the relationship of SSRI dosage to neonatal abstinence syndrome could be assessed only in those taking Paxil, the researchers said. For this drug, mean dose exposure was 19 mg for infants with no symptoms, 23 mg for those with mild symptoms, and 27 mg for infants with severe symptoms.


When Dr. Levinson-Castiel's team compared infants with symptoms (Finnegan>3) with those without symptoms (Finnegan 0-3), they found a higher drug dose of Paxil correlated with neonatal abstinence syndrome (P = .01). Although the researchers were unable to find a specific cutoff point for increased risk, no infant exposed to a dose less than 20 mg developed symptoms, they said.


If SSRIs are prescribed during pregnancy, the researchers advise using the minimum dose and avoiding polytherapy. Exposed infants should be closely monitored for a minimum of 48 hours and even longer if symptoms are severe. Although breastfeeding is not contraindicated for SSRI monotherapy, infants should be checked for NAS signs after discharge, Dr. Levinson-Castiel said.

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