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Am Fam Physician. 2000;62(3):638-640

Based on limited data, it is generally thought that pregnancy may protect against recurrence of major affective disorders or suicide. The postpartum period, however, is widely considered a high-risk period for recurrence of potentially severe and life-threatening episodes of major affective disorders. Use of antimanic agents (lithium, valproate, carbamazepine) is complicated because of the balance between some fetal teratogenic risk, the risk of untreated psychiatric illness during pregnancy and the early relapse of manic-depressive illness following cessation of medication. Viguera and associates studied whether pregnancy is associated with a greater or lesser risk of recurring mania or bipolar depression, and whether pregnant and nonpregnant women respond differently to treatment cessation.

Women with bipolar illness who discontinued lithium maintenance treatment were evaluated. Forty-two pregnant women were followed throughout pregnancy and for 24 weeks postpartum and compared with 59 nongravid women followed through equivalent times. The women, aged 16 to 50 years, discontinued lithium rapidly (1 to 14 days) or gradually (15 to 30 days). The pregnant women discontinued treatment within six weeks of the date of conception. Comparison data were obtained for the same women from the year before they discontinued lithium as well as another nine women who continued lithium throughout pregnancy.

During the 40 weeks after lithium discontinuation, there was little difference in recurrence rates between the two groups. The overall recurrence rate was 55.4 percent. The rates of recurrence had been much lower for both groups in the year before treatment was discontinued. In contrast, among the women who remained euthymic for 40 weeks after discontinuation of lithium, significantly more pregnant women experienced a postpartum recurrence than nonpregnant women. Among the women who remained stable, postpartum recurrences were 2.9 times more frequent than recurrences in nonpregnant women during weeks 41 to 64 (70 versus 24 percent). None of the nine women who continued lithium throughout pregnancy relapsed during weeks 1 to 40, but three experienced a recurrence within two weeks of delivery despite maintenance therapy. Over the entire 64-week period after lithium discontinuation, recurrences were common in both groups (85.7 percent in the pregnant/postpartum group and 67.8 percent in the nonpregnant group). Depressive/mixed-dysphoric episodes were significantly more common among the pregnant/postpartum women than among the nonpregnant women.

Survival analysis was carried out among the women who remained stable throughout the first 40 weeks after discontinuation of lithium. In contrast to the similar early recurrence risk during weeks 41 to 64, recurrences of mania or depression in weeks 41 to 64 after discontinuation of lithium were much greater in postpartum women. Only 30 percent of 20 women without recurrence during pregnancy remained stable postpartum, but 76 percent of 25 nonpregnant women remained stable through the additional six months of follow-up.

During weeks 1 to 40 following discontinuation of lithium, the resulting time to 25 percent recurrence risk was 2.5 times shorter after rapid than after gradual lithium discontinuation.

Results of this study demonstrate that survival functions after lithium discontinuation were similar in pregnant and nonpregnant women. Recurrence rates were higher in patients with a history of four or more previous episodes of illness and in patients who underwent rapid discontinuation of lithium. Recurrence rates were much higher postpartum than during the equivalent period for nonpregnant women (weeks 41 to 64). This finding demonstrates that the postpartum period brings particularly great risk for women with major affective and psychotic disorders. Postpartum recurrence can be reduced by lithium maintenance during pregnancy, although the protection is not complete.

The authors conclude that gradually discontinuing lithium limits the recurrence risk of bipolar disorder during the first 40 weeks after discontinuation of the drug. Clinicians managing pregnant women receiving maintenance psychotropic medications should consider the rate of drug discontinuation as an important risk factor. Although gradual discontinuation of lithium in the first trimester increases fetal exposure, reducing the risk of potentially serious psychiatric disease following rapid discontinuation of lithium may offset this effect. Preconception counseling of patients with bipolar disorder should include a discussion of the high risk of relapse associated with lithium discontinuation in pregnancy.

editor's note:The authors point out that psychiatric disease such as mania or depression left untreated during pregnancy puts the mother and fetus at risk because of potential suicide attempts, lack of prenatal care or substance abuse. Weighing potentially serious adverse effects of discontinuation of lithium against possible fetal malformations if the drug is continued can be difficult. Counseling of women of reproductive age with bipolar disorder should include a discussion about the need for close follow-up should lithium be discontinued during pregnancy.—b.a.

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