Bipolar Disorder in the Perinatal Period: No Consensus on Treatment

Given the frequency with which bipolar disorder relapses occur, the perinatal period may be a precarious time for mother and baby.¹ In an effort to reconcile differences among different bipolar disorder guidelines, Graham and colleagues sought to decipher the recommendations on bipolar disorder in the perinatal period by reviewing 11 international guidelines published from 2005 to 2015.¹  

Most concerning to women and their clinicians are matters of drug teratogenicity, adverse effects during pregnancy and lactation, and subsequent behavioral disorders in offspring.¹ To improve future guidelines, Graham and colleagues recommend greater consistency, transparency, and interdisciplinary collaboration among mental health professionals, obstetricians, and gynecologists.  

No guideline collaborations between psychiatrists and obstetrician-gynecologists are forthcoming, however, acknowledged co-author psychiatrist Gordon Parker, AO, Scientia Professor in the School of Psychiatry at the University of New South Wales, Sydney, Australia, in an interview with Psychiatry Advisor. He underscored the importance “for clinicians to recognize that there is little agreement across guidelines.”

Where the Guidelines Converge and Diverge

Most of the guidelines agreed that lithium, valproate, and carbamazepine are not safe during pregnancy.¹ They warn that the first trimester is especially important for fetal development and advise discontinuing mood stabilizers during the preconception phase and first trimester.¹ Because the guidelines are all evidence based, there was surprising disagreement in determining which of these drugs would pose the least risk to pregnant women and their babies.

The guidelines were inconsistent in their recommendations about antipsychotic medications during pregnancy. Some regarded safety differences among the first- and second-generation antipsychotic medications, and other guidelines grouped them into one category.¹ 

Antidepressant medication recommendations during pregnancy were also divergent.¹ For example, 3 of the guidelines claimed that tricyclic antidepressants were safe, whereas 2 deemed them unsafe.¹ A similar pattern was observed for selective serotonin reuptake inhibitors.

What Graham and colleagues found most troubling was that the guidelines could not provide adequate evidence nor consensus about the safest or least dangerous antidepressant medication during pregnancy or breastfeeding.¹ The researchers drew a conclusion similar to the one the National Academy of Medicine deduced in 2011: the objectivity of guidelines can be compromised when more credence is given to expert opinion rather than to the evidence. Additionally, the National Academy of Medicine recommends more transparency in the guideline process, including the disclosure of conflicts of interest.^1,2

Managing the Individual Patient

Before the next set of guidelines are updated and harmonized, individual studies may provide direction for clinicians. In a 64-study analysis of aripiprazole use in women who were pregnant, postpartum, or breastfeeding, the second-generation antipsychotic was deemed safe relative to the risks of bipolar disorder or schizophrenia.³ Although the review did not include prospective, randomized trials, the case reports and databases yielded adequate data for Cuomo and colleagues to conclude that the second-generation antipsychotic aripiprazole offered more benefit than risk to most women.³

“General guidelines cannot provide extensive and updated details about each single medication,” explained lead author psychiatry professor Alessandro Cuomo, MD, from the department of molecular medicine at the University of Siena School of Medicine in Italy, in an interview with Psychiatry Advisor.

“Hence, we decided to focus on a single medication, aripiprazole, and to summarize all the information that we were able to retrieve about the studies that were published between 1995 and 2017, with the goal to provide a quick and updated reference. I hope that our paper is helpful to those clinicians who are considering prescribing aripiprazole during pregnancy or lactation and who are interested in a summary of what is currently known on the topic as an aid to evaluate whether the potential benefits of this medication outweigh its potential risks in the specific case that they are treating.”

Implementing Conception Planning With Micronutrient Supplementation

Freedman and colleagues sought to determine the effects diet and micronutrient supplements might have on preventing mental illness in developing fetuses.⁴ The 45-study systematic review examined the efficacy of prenatal folic acid, phosphatidylcholine, vitamins A and D, and omega-3 fatty acid supplements in thwarting later schizophrenia, bipolar disorder, and autism in offspring born to women who took the supplements.⁴

The analysis produced mixed results. Whereas vitamins A and D decreased the risk for schizophrenia in adulthood, omega-3 fatty acids increased the risk for the illness.⁴ Phosphatidylcholine decreased social and inattention problems in children and folic acid decreased emotional problems.⁴

Although clinicians now know how important it is to treat mothers with serious mental illness during pregnancy to protect the baby from later psychiatric disorders, they also need to recognize that preconception dietary interventions were also effective at preventing later psychiatric disorders.⁴

“We wanted to inform clinicians of the latest evidence on effects of micronutrients during pregnancy, because this intervention can be offered only at this unique time during the life of the child. More evidence may come, but the opportunity will be past for that child,” said Robert Freedman, MD, scientific director of the Institute for Children’s Mental Disorders at the University of Colorado School of Medicine, Aurora, in an interview with Psychiatry Advisor.

“There are organizations of either mental health professionals or obstetricians currently examining specific guidelines. In the meantime, the American Medical Association has recommended that all women receive choline-containing supplements in evidence-based amounts.”

Summary & Clinical Applicability

Managing bipolar disorder in pregnant and lactating patients is challenging enough, but the lack of consistent guidelines worldwide makes the task more daunting. Clinicians need to weigh the risks and benefits for individual patients while acknowledging that bipolar disorder relapses occur frequently in the perinatal period.

References

1. Graham RK, Tavella G, Parker GB. Is there consensus across international evidence-based guidelines for the psychotropic drug management of bipolar disorder during the perinatal period?J Affect Disord. 2018;228:216-221.
2. Institute of Medicine. Clinical Practice Guidelines We Can Trust. http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2011/Clinical-Practice-Guidelines-We-Can-Trust/Clinical%20Practice%20Guidelines%202011%20Report%20Brief.pdf. March 2011. Accessed May 20, 2018.
3. Cuomo A, Goracci A, Fagiolini A. Aripiprazole use during pregnancy, peripartum and lactation. A systematic literature search and review to inform clinical practice. J Affect Disord. 2018;228:229-237.
4. Freedman R, Hunter SK, Hoffman MC. Prenatal primary prevention of mental illness by micronutrient supplements in pregnancy [published online March 21, 2018]. Am J Psychiatry. doi: 10.1176/appi.ajp.2018.17070836