Bipolar Disorder in Women of Childbearing Age: Proper Treatment Before Pregnancy

General psychiatrists often diagnose young women with bipolar disorder, then start medication treatment. However, women of childbearing age with mania are more likely to have unprotected sex and are at higher risk of unplanned pregnancies. Those unplanned pregnancies are often exposed to potentially dangerous medications in combination, as well as the risks of comorbid substance use disorder. As reproductive psychiatrists, we are often asked to evaluate these young women after they are already pregnant, with the pregnancy exposed to various medications. However, taking a proactive approach as a general psychiatrist allows for the prevention of avoidable fetal exposures and more appropriate treatment.

The trajectory of medication decision-making is different for young men than for young women who could be pregnant before their next appointment. Women of reproductive potential are not generally appropriate for initiation of newly approved medications due to insufficient reproductive safety data, a concern that does not apply equivalently to their male counterparts. Rather, starting treatment with an agent with an appropriate reproductive safety profile, even if it is an older agent, is best.

Within our field of reproductive psychiatry, there are multiple ethical principles to consider, including errors of omission vs errors of commission; relational ethics; autonomy; and preventive ethics.^1,2 Physicians are often more concerned about acts of commission, in which treatment contributes to an adverse outcome, than acts of omission, which may bias decision-making toward undertreatment of bipolar disorder.^1,2 Relational ethics reminds us that it is important to be aware that the mother’s and the baby’s well-being are intertwined, rather than being at odds. A healthy mom makes for a healthy baby. Respecting patient autonomy includes ensuring that patients are empowered to make informed decisions through appropriate physician guidance and psychoeducation. Finally, preventative ethics is “anticipating and preventing ethical dilemmas in clinical practice.”² Anticipating potential risks should a patient with bipolar disorder unexpectedly become pregnant falls squarely in preventative ethics.

Unplanned Pregnancy in Bipolar Disorder: Why Diagnosis and Medication History Matter

Most females of reproductive potential in the United States will experience pregnancy by age 40, and nearly half of these pregnancies are unintended.³ People with bipolar disorder are at increased risk of unintended pregnancy compared with the general population.⁴ Symptoms of hypomania and mania—impulsivity, hypersexuality, and decreased risk perception—are associated with risky sexual behaviors.⁵ Additionally, both manic and depressive symptoms (including apathy and amotivation) may contribute to inconsistent or absent contraceptive use, further elevating risk.⁴ Certain mood stabilizers, including enzyme-inducing agents such as carbamazepine, may reduce the efficacy of hormonal contraception, compounding this risk.⁶ Importantly, available evidence supports the safety and effectiveness of hormonal contraception and intrauterine devices in individuals with bipolar disorder.⁴

Unintended pregnancies are frequently recognized later than planned pregnancies, often around 6 to 8 weeks’ gestation, after critical aspects of organogenesis have already occurred.⁷ Consequently, medication exposure often precedes pregnancy recognition. Changing medications after pregnancy is identified may both introduce additional fetal exposures and carry the risk of psychiatric destabilization.

Before pregnancy is the most important time to carefully consider diagnosis, past medication history, and to use a single agent for treatment where possible. Pregnancy is a difficult time to disentangle inaccurate diagnoses and poor medication choices. Does she truly merit a diagnosis of bipolar disorder, or were some symptoms of affective instability due to a personality disorder in addition to depression? As for her medications, what has she truly had a proper therapeutic trial of, vs what did she not pick up from the pharmacy or only take for a week? Psychiatric clinicians should consider her full medication history and response. Thoughtful medication choices and planning should begin long before a woman becomes pregnant.

Psychoeducation and Preconception Counseling

Treatment discussions with women of reproductive potential should include counseling on the risk of unintended pregnancy, discussion of contraception, informed consent regarding potential fetal risks associated with psychotropic medications, and discussion of the increased risk of mood episode recurrence during the perinatal period. These discussions should also, when appropriate and with the patient’s consent, include the patient’s partner and family to support shared understanding and treatment planning. Additionally, clinicians should emphasize that pregnancy should ideally be planned during a period of sustained psychiatric stability. Access to effective contraception should be facilitated until planned conception is desired.

Prior to desired pregnancy, preconception counseling should be performed. Having such discussions allow women to have agency, and to take an active role in their own mental health decisions. Ideally, such counseling assesses illness severity and relapse risk and reviews fetal safety risk of current medication treatment. The psychiatrist should also consider other potential risk factors for negative pregnancy outcomes that a patient with bipolar disorder may have, such as comorbid substance use disorder.⁸

Individuals with a history of severe, recurrent, or psychotic episodes are at particularly high risk of relapse if medications are discontinued, and continuation of current pharmacotherapy is usually recommended (if not a known significant teratogen). Lithium is particularly efficacious in the perinatal period and may be considered based on prior treatment response, illness severity, or as an augmentation strategy. When possible, first-trimester exposure—during which dose-dependent teratogenic risk is greatest—should be minimized, with more reassuring data supporting use beginning in the second trimester.^7,9 In contrast, for individuals with milder illness or prolonged stability, cautious medication simplification and dose optimization may be considered in advance of pregnancy. Abrupt medication discontinuation should be avoided, as it is associated with significantly increased risk of recurrence.

While there is a common myth that discontinuing medications for bipolar disorder during pregnancy eliminates fetal risk, untreated bipolar disorder itself is associated with adverse pregnancy outcomes as well as an increased risk of psychiatric decompensation.¹⁰ Whenever possible, monotherapy should be preferred over polypharmacy. Although the safety profiles of individual medications during pregnancy may be known, available studies do not address the potential risks associated with their combined use. When questions arise regarding diagnosis or medication management during pregnancy, consultation with a perinatal psychiatrist should be sought as early as possible. Many clinicians also have access to free provider-to-provider case consultation through state reproductive psychiatry access programs. In the event of pregnancy, clinicians should collaborate closely with the patient’s obstetric provider to coordinate care and optimize both maternal psychiatric stability and fetal outcomes.

Recommendations for Treatment

Given the elevated risk of unintended pregnancy in this population and later recognition of pregnancy, a distinct treatment approach is warranted for females of reproductive potential (Table). For instance, the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines recommend several first-line agents for acute bipolar mania, including lithium, valproate, asenapine, and cariprazine.¹¹ However, these recommendations do not fully account for potential fetal risk should the patient become pregnant. Valproate is generally contraindicated in antepartum mood disorders due to its well-established teratogenicity, with an approximately 10% risk of major congenital malformations, including neural tube defects, as well as significant risk of adverse neurodevelopmental outcomes.^12,13 Lithium is associated with a smaller but still elevated risk of congenital malformations (approximately 4% to 7%), particularly cardiac anomalies.⁹ Atypical antipsychotic agents, such as olanzapine have reassuring safety data.¹⁴ In contrast, newer agents such as asenapine and cariprazine lack sufficient reproductive safety data.

Alternatively, for those women with reproductive potential, we recommend that clinicians preferentially prescribe medications with both established efficacy for the phase of illness (mania, depression, or maintenance) and reassuring reproductive safety data. Many popular newer first-line agents for bipolar disorder lack sufficient fetal safety data and should be used cautiously in this population. Before changing or continuing psychiatric medications, clinicians should weigh the risks of medication exposure against the risks of untreated maternal mental illness to the maternal–fetal dyad. Clinicians should also be mindful of the potential adverse effects of bipolar disorder during pregnancy, including substance use, smoking, poor sleep, impaired self-care, decreased adherence to prenatal care, suicidality, and increased risk of obstetric complications such as preterm birth, gestational hypertension, hemorrhage, cesarean delivery, and small-for-gestational-age infants.^10,15,16

Women of childbearing potential should be treated as if pregnancy during medication treatment is a possibility, because it is. For acute mania, agents with more established reproductive safety data include olanzapine, quetiapine, risperidone, haldol, and aripiprazole, with lithium as reasonable second-line option.¹⁷ For bipolar depression, quetiapine and lamotrigine are preferred, with lithium as an alternative when clinically indicated; agents such as lurasidone and cariprazine remain less well studied in pregnancy.¹¹ For maintenance treatment, quetiapine, lamotrigine, olanzapine, and aripiprazole are preferred first-line options, with lithium as a second-line agent depending on prior response and clinical severity.^7,9,14,18,19

In psychotropic-naïve women of reproductive potential, clinicians should consider first-line agents with favorable tolerability and safety profiles. In those with prior treatment, previous medication response should guide selection, with preference given to agents that have demonstrated efficacy in the past for the patient. Teratogenic agents, particularly valproate and carbamazepine, should generally be avoided unless highly reliable contraception (eg, long-acting reversible contraception) is in place.²⁰

Long-acting injectable antipsychotics may be considered for women with poor medication adherence or frequent hospitalization, given their potential to improve treatment continuity and reduce relapse risk, although reproductive safety data remain limited and insufficient to draw definitive conclusions.²¹

Bipolar Disorder in the Perinatal Period: Clinical Symptoms and Risk Recognition

Pregnancy itself is a period of elevated risk for recurrence of mood episodes. Prospective data demonstrate that discontinuation of mood stabilizers during pregnancy is associated with a markedly increased risk of relapse, with rates as high as 85% among those who discontinue treatment compared to approximately 37% among those who maintain pharmacotherapy; recurrence is also more rapid among those who discontinue abruptly.²² These findings underscore the importance of careful risk of illness vs risk of treatment discussions regarding medication continuation during pregnancy.⁸ For further information about treatment in pregnancy, the reader is referred to Ross et al²³ and Hasser et al²⁴ and CANMAT-Perinatal Guideline²⁵ managing bipolar disorder in women who are pregnant. Clinicians should advise patients about the potential need for increased medication-level monitoring and anticipated dose adjustments during the perinatal period because of changes in drug levels and the potential for symptom exacerbation. Patients and their support systems should be educated about early symptoms of mood episodes, including depressed mood, anhedonia, sleep disturbance beyond expected physiologic changes, fatigue, impaired concentration, excessive guilt, anxiety, and intrusive thoughts. In bipolar disorder, early warning signs of mania or hypomania—such as decreased need for sleep, increased energy, irritability, impulsivity, and mood lability—should also be emphasized to facilitate early intervention.

In the postpartum, women with bipolar disorder are at significantly elevated risk of developing postpartum psychosis, postpartum depression, or other mental health symptoms. While the general population’s risk of postpartum psychosis is 1 to 2 per thousand new mothers, women with bipolar disorder are at significantly elevated risk.^23,26 With rapid onset of mood symptoms, psychotic symptoms, and confusion, postpartum psychosis is considered a psychiatric emergency almost always requiring urgent hospitalization.^23,26 Postpartum depression itself may present with symptoms similar to depression at other times in a woman’s life.²⁷ However, postpartum depression is critical to treat due to risks of impaired bonding and difficulty caring for the infant.

Concluding Thoughts

Women of reproductive potential with bipolar disorder require particularly thoughtful diagnostic assessment and treatment planning. The diagnosis of bipolar disorder should be established carefully, with consideration of alternative explanations for mood instability, including substance use disorders, personality disorders, and irritable depression. A thorough review of prior medication trials and treatment response is essential, as the number of evidence-based agents with reassuring reproductive safety data is relatively limited. Contraceptive counseling should be incorporated into routine care as part of a preventive ethics framework, given the increased risk of unprotected sex and unintended pregnancy associated with bipolar disorder. Treatment decisions should be made proactively, recognizing that pregnancy may occur while taking the medication. As such, medications with known reproductive safety should be first-line. Monotherapy should be used whenever possible, and medication doses should be optimized to maintain psychiatric stability while minimizing fetal exposure. Reproductive psychiatrists should be consulted as needed. By anticipating the possibility of pregnancy before conception occurs, clinicians can help optimize both maternal psychiatric outcomes and future maternal–fetal health.

Dr Mulvihill is an assistant professor of psychiatry at Case Western Reserve University in Cleveland, Ohio.

Dr Hatters Friedman is the Phillip J. Resnick Professor of Forensic Psychiatry; professor of psychiatry, reproductive biology, and pediatrics; and adjunct professor of law at Case Western Reserve University in Cleveland, Ohio. She served as editor of the Group for the Advancement of Psychiatry volume Family Murder: Pathologies of Love and Hate, which won the Manfred S. Guttmacher Award.

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