Bipolar disorder (BPD) is, “characterized by frequent relapses, symptoms recurrences, and persisting residual symptomatology.”1 Its key features are the presence of mood episodes — depression and mania or hypomania.
The incidence of BPD in women “peaks” between the ages of 12 and 36 years, which are the primary reproductive years.1 Episodes of mania are estimated to occur in approximately 25% to 30% of women with BPD who are pregnant.2 Women with BPD may have as much as a 1 in 5 risk for having a postpartum psychosis and an even higher risk (up to 40%-50%) for experiencing a mood episode in the postpartum period, including nonpsychotic major depression.3,4
Helping patients with BPD navigate pregnancy involves balancing the risk for recurrence of a manic or depressive episode if medications are discontinued against the risk for potential teratogenic effects from the medications. To shed light on this clinical conundrum, Psychiatry Advisor interviewed Leena Mittal, MD, instructor at Harvard Medical School and Director of the Reproductive Psychiatry Consultation Service at Brigham and Women’s Hospital in Boston, Massachusetts. Dr Mittal is also Associate Medical Director at the Massachusetts Child Psychiatry Advocacy Program (MCPAP) for Moms.
Psychiatry Advisor: Decades ago, women with BPD were often counseled to avoid pregnancy because of the risks to mother and baby. For example, Kay Redfield Jamison describes being advised by a physician not to become pregnant because of her bipolar illness.5 How has that changed?
Dr Mittal: We regard the decision to become pregnant as a woman’s choice. Women with BPD have the same choices that all women have. With planning and management of medications and other treatment, women with BPD are able to have a safe and healthy pregnancy.
There are aspects of BPD that can have an impact on risk for unplanned pregnancy. For example, the impulsivity that often accompanies mania can lead to hypersexuality, risk-taking behaviors, concurrent substance abuse, and unprotected intercourse, which lead to a higher incidence of unplanned pregnancy in women with BPD than in the general population.2 The goal is to help women make the choice in a planned, thoughtful way.6-9
Psychiatry Advisor: What is the role of psychiatrists treating women with BPD with regard to pregnancy planning?
Dr Mittal: Psychiatrists should talk to female patients with BPD about their reproductive goals. The Oregon Foundation for Reproductive Health campaign called “One Key Question”10 recommends that all medical providers ask all female patients of reproductive age whether they plan to become pregnant in the next year. If the answer is no, the next question is what the patient is doing to prevent pregnancy. If the answer is yes, the next question is what the patient is doing to prepare for pregnancy.
This approach is particularly important for psychiatrists treating women with BPD. It captures the notion that within the provision of mental health services, we should not shy away from discussions of reproductive health and should not wait until our patient becomes pregnant. Many psychiatrists avoid these discussions, however, because they do not feel it is their role or that they are not sufficiently educated to broach these subjects.
Psychiatry Advisor: What resources might psychiatrists have to help them step into this role?
Dr Mittal: Psychiatrists and obstetricians can consult with perinatal psychiatrists who specialize in the care of pregnant and postpartum women. However, accessing this kind of specialized care may be difficult.
I am the Associate Director at MCPAP for Moms (https://www.mcpapformoms.org/About/About.aspx), which helps providers identify and address the mental health and substance use concerns of pregnant and postpartum patients. We founded it as a capacity-building resource for prescribers, mostly obstetricians/gynecologists and psychiatrists, who treat women during preconception, pregnancy, postpartum, or post-loss periods.
Many women with BPD tend to fall between the 2 disciplines of psychiatry and obstetrics. Many psychiatrists are not sure what to tell women who are pregnant and refer them to the obstetrician/gynecologist. However, many obstetricians/gynecologists are not conversant in psychotropic drugs. We provide education and resources to help these practitioners.
Our program offers several components. Providers can consult us by telephone or in person about issues related to reproductive health in women with psychiatric disorders. We offer linkage to resources and also include links to studies, articles, assessment tools, and forms (https://www.mcpapformoms.org/About/ReportsandPublications.aspx).
Psychiatry Advisor: In the past, psychiatric medications were withheld from women with BPD during pregnancy because of fear of teratogenic and other effects.11 What is the current approach?
Dr Mittal: Approaching this issue involves balancing the relative risks for potential teratogenicity against the risks of treatment discontinuation, which is a highly individualized decision. No 2 patients are alike. A woman with excellent mood stabilization, medication adherence, and a less severe history will require a different approach than a woman with a more severe illness course, frequent episodes, or nonadherence.
Current research suggests1,2,11 that pregnant women with BPD should not stop medications, and that if they need to stop a particular one, they should not stop abruptly. There is a high risk for relapse in the setting of medication discontinuation during pregnancy, especially if the discontinuation is abrupt.12,13 Providers should be proactive in discussing this with patients because many women unilaterally discontinue their medications when they realize they are pregnant.
It is also not wise to discontinue one medication and substitute another with a “safer reproductive profile” because the woman is now receiving a new agent with a different molecular structure, different pharmacokinetics, different profile of passing through the placenta, and the fetus accumulates new risks with every new exposure. It is better to optimize the dose of current medications and minimize the number of agents that the woman is taking. Some medications may be safely removed. For example, if a woman takes one agent as needed for anxiety and another for sleep, it may be possible to use only one instead of both.
Psychiatry Advisor: Which medications or medication classes are most favorable for a woman to use during pregnancy?
Dr Mittal: One of the biggest changes in recent years is in the attitude toward lithium. Although it was regarded as increasing the risk for Ebstein’s anomaly, the effect size is now understood to be much smaller than previously thought.2,14,15 This shift of understanding has made lithium a more viable option as a mood stabilizer, especially because it is important in preventing postpartum psychosis.
Lamotrigine is a mainstay. It has a good safety profile in pregnancy and has been associated with lower malformation rates than other anticonvulsants.2 However, it must be managed carefully because its metabolism is influenced by the endogenous hormones of pregnancy. Moreover, immediately postpartum, dosage should be reduced to prepregnancy levels.2 The increased data supporting the use of these agents is very reassuring. Valproate has a higher risk for teratogenicity than other mood stabilizers.14,16 Atypical antipsychotics are another mainstay. Although these are new medications, there is a growing body of research regarding their use in pregnancy.2
The volume of data supporting the use of selective serotonin reuptake inhibitors has accumulated in recent decades and is also reassuring.17,18 While they are not clearly associated with structural abnormalities in babies, there is a small association with pulmonary hypertension in newborns as well as with neonatal adaptation syndrome, which usually has no long-lasting consequences.18
A recent study found no significant psychomotor, cognitive, or behavioral impact of prenatal psychotropic drug exposure in children of women with bipolar disorder at 12, 26, or 52 weeks, with most scores remaining within normal limits.19