Lithium May Reduce Risk of Relapse in Pregnant Women With History of Bipolar Disorder, Postpartum Psychosis

Pregnant women with a history of bipolar disorder or postpartum psychosis are at heightened risk of postpartum relapse. To reduce this risk, the authors of a study published October 30 in AJP in Advance recommend the use of prophylactic medication during pregnancy or—in the case of a history of postpartum psychosis—immediately following delivery.

“Among all mood stabilizers, lithium has the largest evidence base for efficacy in the peripartum period,” study coauthor Richard Wesseloo, M.D., of the Erasmus Medical Centre in Rotterdam, the Netherlands, told Psychiatric News. “Lithium is the first choice in the prophylactic treatment of women with bipolar disorder, both during pregnancy and the postpartum period. This prophylactic regimen is not different from maintenance treatment recommendations outside the peripartum period.”

In the AJP in Advance study, Wesseloo and colleagues conducted a systematic literature search and meta-analysis to examine the risk of postpartum relapse in women with a history of bipolar disorder, postpartum psychosis or mania, or both diagnoses, according to DSM or ICD criteria or the Research Diagnostic Criteria.

Based on their analysis of 37 articles describing 5,700 deliveries in 4,023 patients, the authors found that overall postpartum relapse risk was 35 percent. Patients with bipolar disorder were significantly less likely to experience severe episodes postpartum than patients with a history of postpartum psychosis. But in women with bipolar disorder, postpartum relapse rates were significantly higher among those who were medication free during pregnancy than those who used prophylactic medication.

Jennifer Payne, M.D.

“This is an important study that confirms what clinicians [often] experience, which is that there’s a high relapse rate among women with bipolar disorder and women with postpartum psychosis, and that medications decrease that risk,” said Jennifer Payne, M.D., an associate professor of psychiatry and director of the Johns Hopkins Women’s Mood Disorders Center, who was not involved with this study.

Wesseloo said that in the Netherlands, most women with bipolar disorder who are in their childbearing years take lithium as maintenance treatment—a practice he advises is continued throughout a pregnancy.

While the findings of the AJP study highlight the potential benefits of prophylaxis during pregnancy, the decision does come with some risks, he noted.

“We inform women about teratogenic risks of lithium during early pregnancy and the elevated rate of neonatal complications of lithium. Further, we advise against the use of valproate during the peripartum period because of high teratogenic risks during pregnancy,” Wesseloo said. “However, given the potential risks of switching medications, our treatment plan discussion always includes carbamazepine, lamotrigine, and antipsychotics as important considerations, if women are taking these medications.”

According to Wesseloo, lithium crosses the placenta and the fetal blood-brain barrier, and exposed infants may be at risk for toxicity and other lithium side effects. There have been several reports of acute side effects in infants who were exposed to lithium in utero that resolve shortly after birth, but little is known of long-term effects of the medication, he said.

Still, “the evidence that exposure to lithium is teratogenic is quite limited. Other treatment options for bipolar disorder such as anti-epileptics are more teratogenic,” Wesseloo said.

If women are clinically stable without medication prior to pregnancy, Wesseloo recommended that they start lithium prophylaxis immediately postpartum.

“I absolutely agree with treatment during pregnancy with appropriate medications,” Payne told Psychiatric News. “Most women relapse when they stop their medications for depression, and depression and/or mania are not good for babies. The women end up going back on medications—sometimes more meds at higher doses. It’s safer to keep a woman well than to chance it.”

Payne noted that in the United States there isn’t a “typical” practice regarding management of medications during and after pregnancy. “It’s an area that needs to be researched more. In general, as a women’s mood disorder specialist, I tend to use medications prophylactically in pregnancy. But certainly every case needs to be considered individually,” she said. “This is an interesting paper hopefully moving us towards coming up with some standards of care.”

In the February 2015 issue of the American Journal of Psychiatry, Veerle Bergink, M.D., Ph.D., a coauthor on the current study, and colleagues reported that a structured treatment algorithm with the sequential addition of benzodiazepines, antipsychotics, and lithium results in high rates of remission in patients with first-onset postpartum psychosis and that lithium maintenance may be most beneficial for relapse prevention. ■