When working with pregnant women affected by bipolar disorder, doctors inevitably face some stark choices.…
Bipolar 2 & Pregnancy: What Medications Are Safe?
Bipolar 2 involves a pattern of one or more major depressive episodes and at least one hypomanic episode. Although individuals do not experience the same degree of manic symptoms as in bipolar 1, depressive episodes can be severe. As a result, bipolar 2 may be misdiagnosed as major depression because manic episodes are unrecognized or unreported. Bipolar has negative clinical, social and economic repercussions on the individual, which can interfere with the ability to work and function normally.
The incidence of bipolar disorders in women peaks from ages 12 to 30, raising the possibility of significant bipolar illness during pregnancy and postpartum. Pregnancy in women with bipolar disorder poses concerns due to the high risk of relapse and the possible repercussions of medications on the fetus. One study found the risk of recurrence during pregnancy was 85.5% for women who discontinued mood stabilizers and 37% for those who continued. Postpartum, 40% to 70% of women with untreated bipolar may experience an episode. A planned pregnancy has obvious benefits including a multidisciplinary team assessing the severity of the disorder, treatment compliance and important factors influencing the ability to care for a baby. If the pregnancy is unplanned, an urgent clinical and medication review is necessitated. Medication should not be abruptly stopped due to the high risk of relapse.
Medications Used to Treat Bipolar 2
Traditional antidepressants can trigger manic episodes in some people with bipolar 2, so mood stabilizers are the preferred medication. Treating clinicians need to look at the client’s current mental state, longitudinal history, past history of relapse while off medication, response to medication and stage of pregnancy on first visit, among other factors. Mood stabilizers are effective at treating acute episodes (manic or depressive) and preventing relapse or recurrence of symptoms. The U.S. Food and Drug Administration (FDA) uses a risk stratification system with drugs classified as A, B, C, D or X. A is considered safe during pregnancy, but no psychotropic drugs are in this class.
Drugs in categories B to D are considered to have intermediate risks. Most antipsychotics are classified as category C agents, which means insufficient human and animal studies on fetal side effects are available, making it difficult to rule out risks. Mood stabilizers such as lithium, valproate and carbamazepine are classified as category D drugs. The FDA classification alone is inadequate for decision-making. Psychiatrists typically rely on other sources of information when recommending the use of psychotropic medications during pregnancy.
Lithium: Considered the safest mood stabilizer in pregnancy, lithium can be used with caution. This drug does not impede conception, however, some recent studies have suggested a higher risk of miscarriage. The risk of a rare heart defect called Ebstein anomaly is 10-20 times higher than in the general population, but the absolute risk is small (0.05% to 0.1%). Fetal echocardiography, regular monitoring and dose adjustment during pregnancy are necessary to maintain a safe therapeutic level. Some experts suggest withholding lithium therapy for 24 to 48 hour before delivery, which results in a reduction in lithium concentration in the mother and may improve obstetrical outcomes.
Sodium valproate: An estimated 10% to 11% of infants exposed in utero have major congenital malformations and are at risk of significant intellectual impairment. Prenatal exposure to valproate is linked to cardiovascular malformations, intrauterine growth retardation, genital anomalies, hydrocephalus and limb and pulmonary defects. For this reason, valproate should be avoided as a first-line mood stabilizer in women of childbearing age.
Carbamazepine: The use of this drug is associated with an increased risk of fetal abnormalities including neural tube defects (e.g., spina bifida), craniofacial and cardiac abnormalities, developmental delay, growth retardation and microcephaly. Therefore, it is not recommended during pregnancy.
Typical and atypical antipsychotics: Perinatal risks are well-documented including respiratory distress, seizures, feeding difficulties, tachycardia, low blood pressure, transient neurodevelopmental delay and weight gain. Few investigations have been conducted on possible adverse outcomes in infants exposed in utero to antipsychotic drugs. In one study, infants exposed to antipsychotics scored lower on neuromotor performance (posture, muscle tone, reflexes and motor skills).
Additional research is needed regarding best practices for optimizing treatment of women with bipolar 2 during pregnancy. Until more outcome studies are available, clinicians need to assess the risks to both mother and baby of untreated or undertreated bipolar illness versus the risks and benefits of pharmacotherapy.