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September 2009

Prenatal Valproate Lowers IQ
Valproate may adversely affect fetal cognitive development throughout pregnancy.

Stimulant Augmentation for Treatment-Resistant OCD?
In one study, amphetamine was not superior to caffeine as an augmentation strategy for patients with obsessive compulsive disorder.

Antipsychotics in Alzheimer's Patients: New Evidence on Metabolic Effects
Second-generation antipsychotic drugs increase the risk of weight gain and metabolic effects in patients with Alzheimer’s disease.

In Brief
Contraception Use in Female Bipolar Patients Suboptimal; CBT Available over Internet for Insomnia

SSRIs and Gestational Hypertension
Use of a serotonin selective reuptake inhibitor beyond the first trimester of pregnancy is associated with an increased risk of hypertension and preeclampsia.

SSRIs and Gestational Hypertension

September 2009

Data regarding selective serotonin reuptake inhibitors (SSRIs) taken during pregnancy are inconsistent but suggest they are not "major teratogens" (BTP 2009;32:12, 2007;30:36–38, 2006;29:25–26, 2005;28:45).1,2 Maternal use of antidepressants has been associated with preterm delivery, although in one study, pregnancies were shortened by less than a week.3 Suri and colleagues found an increased risk of preterm birth when SSRIs were taken during pregnancy, as well as significantly lower gestational age at birth and greater risk of admission to a special care nursery (BTP 2007;30:45).4 Wisner et al recently reported that infants exposed to either SSRIs or maternal depression continuously throughout pregnancy were more likely to be born preterm, but SSRIs did not increase the risk of physical anomalies.5

Toh and coworkers addressed a possible risk of SSRIs to the mothers themselves.6 They observed that a leading cause of morbidity and mortality during pregnancy is preeclampsia, manifested by gestational hypertension and proteinuria. Serotonin has vascular and hemostatic effects and may play a role in the etiology of preeclampsia, and SSRIs affect circulating levels of serotonin. The authors investigated the risk of gestational hypertension and preeclampsia associated with continuation and discontinuation of antidepressant use beyond the first trimester. They analyzed data from 5731 women with nonmalformed infants and no underlying hypertension, who participated in the Slone Epidemiology Center Birth Defects Study from 1998 to 2007.

The scientists included 199 women who used SSRIs during the 2 months before pregnancy and possibly during pregnancy. Of these, 92 women continued to take the antidepressants beyond the first trimester. The comparison group comprised 5532 pregnant women who did not take SSRIs.

The onset of hypertension after 20 weeks occurred in 9% of those who did not use an SSRI, 13.1% of the 107 women who discontinued SSRI treatment before the end of the first trimester, and 26.1% of the 92 women who continued treatment beyond the first trimester. Preeclampsia occurred in 2.4% of women who did not take SSRIs, 3.7% of women who discontinued SSRIs during the first trimester, and 15.2% of women who continued SSRIs beyond the first trimester. The authors conclude that SSRI exposure late in pregnancy might identify women at increased risk for gestational hypertension and preeclampsia. The question of whether the SSRIs themselves cause this syndrome remains unresolved.

In an accompanying editorial, Yonkers points out that gestational hypertension is a relatively common and heterogeneous condition.7 By definition, gestational hypertension affects women who develop new-onset hypertension after the 20th week of pregnancy. The reason SSRI-treated mothers may be more likely to develop gestational hypertension and preeclampsia could lie in factors unrelated to the medication per se. For example, in the study by Toh et al, women who took SSRIs weighed more, were older, and were more likely to have used alcohol and drugs and to have received infertility treatment. Women who did not discontinue antidepressants once they found out they were pregnant were likely to be more severely ill and to have more comorbid conditions.

Yonkers suggests that if a women taking an SSRI medication plans to get pregnant, the medicine should not automatically be discontinued. Rather, the patient should discuss options with her physician and discontinue medication only if the risk of clinical deterioration is minimal. If a pregnant woman taking an SSRI does develop hypertension or preeclampsia during pregnancy, it is unlikely that discontinuing the antidepressant will reverse either condition. Presumably, a propensity to develop hypertension has been unmasked and will require antihypertensive therapy. If the condition is preeclampsia, the pathological insult must have occurred earlier in pregnancy, and stopping the SSRI will not affect it.

Treating any disorder in women of childbearing age is complex. Yonkers' suggestions emphasize the importance of monitoring the patient carefully and treating hypertension as needed, rather than rushing to discontinue the SSRI, which could destabilize the psychiatric condition. It is also important to bear in mind that roughly half of all pregnancies are unplanned. Therefore, clinicians should discuss treatment options with all women who could become pregnant, not just those who already are.

1Freeman MP: Antenatal depression: Navigating the treatment dilemmas. Am J Psychiatry 2007;164:1162–1165.

2Greene MF: Teratogenicity of SSRIs: Serious concern or much ado about little? N Engl J Med 2007;356:2732–2733.

3Simon GE, Cunningham ML, Davis RL: Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002;159:2055–2061.

4Suri R, Altshuler L, Hellemann G, Burt VK, Aquino A, Mintz J: Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth. Am J Psychiatry 2007;164:1206–1213.

5Wisner KL, Sit DK, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF, Perel JM, Jones-Ivy S, Bodnar LM, Singer LT: Major depression and antidepressant treatment: Impact on pregnancy and neonatal outcomes. Am J Psychiatry 2009;166:557-566.

6Toh S, Mitchell AA, Louik C, Werler MM, Chambers CD, Hernández-Díaz S: Selective serotonin reuptake inhibitor use and risk of gestational hypertension. Am J Psychiatry 2009;166:320–328.

7Yonkers KA: Parsing risk for the use of selective serotonin reuptake inhibitors in pregnancy. Am J Psychiatry 2009;166:268–270.