I want to get pregnant but take medication for bipolar disorder. What can I do?
Because bipolar disorder has its average onset in late adolescence and early adulthood, many women with bipolar disorder are faced with decisions about their treatment in the midst of their reproductive years. The best first step is to plan the steps to take before becoming pregnant. You need to familiarize yourself with the data that are available regarding medication use and its potential effect on a fetus. You also need to be aware of the risks associated with stopping medication treatment. First off, know that there is controversy in the literature as to whether or not bipolar disorder improves during pregnancy, but that even if it does for some, it does not for others. Also, it is important to know that there is a high risk for symptom recurrence in the immediate postpartum period.
The risk of use of mood-stabilizing agents during pregnancy appears to be greatest in the first trimester, although there are teratogenic effects that can occur later as well. A review of the literature on various medications was done by Yonkers et al. and noted the following:
Lithium
There is an association with cardiovascular malformations.
Ebstein’s anomaly occurs in 0.1% to 0.2% of the offspring of lithium users in contrast to 0.005% in the general population. While the risk is increased several fold, the absolute risk remains small. Lithium-exposed infants have been found to weigh more than nonexposed infants. In two studies of behavior and development, there were no differences in milestone development or behavior. Exposure to lithium during labor has been associated with “floppy baby syndrome,” so close monitoring of levels is part of routine obstetrical care.
Depakote (valproate)
Use during the first trimester is associated with high rates of neural tube defects of 5% to 9% with the risk being dose related. Craniofacial abnormalities, growth retardation, small head circumference, and heart defects are at a twofold increased risk from the use of anticonvulsants. Depakote (valproate) has neonatal complications associated with it as well such as heart rate decelerations, irritability, jitteriness, feeding problems, and abnormal tone. Some experts recommend Depakote (valproate) be switched to another mood stabilizer before pregnancy. Teratogenic risk is also higher with the use of more than one anticonvulsant agent.
Equetro (carbamazepine)
Craniofacial defects, fingernail hypoplasia, and developmental delay have been found at high rates. Neural tube defects range between 0.5% and 1%. Reduced birth weight and head circumference are associated with Equetro (carbamazepine) use. Equetro (carbamazepine) is not recommended by most experts for use during pregnancy unless there are no other options.
Lamictal (lamotrigine)
In 2004, rates of major malformations appeared to be similar to those in the general population, but new information suggests an increased risk for cleft lip and palate with first trimester exposure.
Typical Antipsychotics
There have been mixed findings on whether there is an increased rate of malformations, with many studies conducted on chlorpromazine. One study on rates between those on chlorpromazine for psychosis and those who were psychotic but not on chlorpromazine showed similar rates of malformations that were higher than in the general population, suggesting that something else about the illness was contributory. Case reports have suggested a link between Haldol (haloperidol) and limb reductions, but larger case series have not supported this. The risk from typical antipsychotics is considered by many experts to be less than the risk from some mood stabilizers, and thus during pregnancy, a switch from a mood stabilizer to an antipsychotic is often made.
Atypical Antipsychotics
There are limited data on the use of atypical antipsychotics in pregnancy. Keeping the data in mind, it is possible to manage both pregnancy and bipolar disorder safely, but again the planning should ideally occur before getting pregnant. With careful planning and monitoring, outcomes can be improved for both mother and offspring. Communication with both psychiatrist and obstetrician are critical.
I found out I am three months pregnant and have been on a mood stabilizer. Is my baby at risk?
It is ideal that planning for conception occur first, for many women pregnancy is not anticipated. Unfortunately, many of the fetal malformations do occur in the first days to weeks after conception and thus by the time pregnancy is discovered, the exposure has often already occurred. Depending upon the medication being taken, once that time period of higher risk has passed, it may no longer be prudent to go off a specific medication. Keep in mind as well that although rates are higher than the general population for various malformations, in some cases the rates with medication exposure are still low. Meetings with both your psychiatrist and obstetrician to go over your options are needed as soon as possible. Prenatal testing for some conditions may be desired to check for abnormalities. Your psychiatrist can work with you to minimize additional risk for the duration of the pregnancy and to determine the best course of treatment postpartum.
Can I take a mood stabilizer or antidepressant while I am nursing?
Data regarding use of many medications during breastfeeding are scarce. The FDA gives a category classification for most medications as to whether they are safe during pregnancy or nursing, but this information is not always reliably based upon available data. Some medications, like benzodiazepines, are known to be present in large quantities in breast milk and thus are presumed to be unsafe. There have been increasing amounts of data as well as interest in the risks versus the benefits of taking bipolar medications while breastfeeding. Typical medications taken for bipolar disorder may include both antidepressants and mood stabilizers, such as anticonvulsants and/or antipsychotics.
All antidepressants are excreted into breast milk. Although differences may exist between antidepressants as to quantities found in breast milk, data are insufficient to make definitive statements about these differences. Both tricyclic antidepressants (TCAs) and SSRIs are generally undetectable in nursing infant blood. Nortriptyline has been the most studied TCA in breastfeeding women. Children exposed to TCAs have been followed through preschool, and no developmental differences have been found compared to children not exposed to TCAs. TCAs, however, are not typically the first-line treatment for depression because of their side effects and are not recommended in bipolar depression. Data are available on the use of Sarafem (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Celexa (citalopram), and Luvox (fluvoxamine), with Zoloft (sertraline) being studied most over the past few years. Although SSRI medications have not usually been detectable in most studies, there have been infrequent reports of detectable serum levels of Zoloft (sertraline), Celexa (citalopram), and Sarafem (fluoxetine) in exposed infants. A case report on paroxetine found no evidence of it in breast milk, thought possibly due to its half-life, but more studies are needed. No adverse developmental or behavioral effects have been detected to date in nursing infants, but there have been no long-term studies. Zoloft (sertraline) is generally considered relatively low-risk, but Sarafem (fluoxetine) may have some level of risk associated with it, possibly due to its long half-life. Three cases of colic have been reported in babies with detectable levels of Sarafem (fluoxetine), and there is some evidence for reduced weight gain after birth. Although for the most part levels of SSRIs are not usually detectable in infant serum, this does not exclude the possibility of the drug having entered the central nervous system. In unipolar depression, the benefits of breastfeeding may outweigh the risks of SSRI exposure alone, and thus staying on medication while nursing is often warranted.
In considering use of other medications for bipolar disorder while nursing, data too are limited. Lithium levels in breast milk are close to half the levels in maternal blood. Infant kidney function is not optimal, which can result in elevated blood levels of lithium. If lithium is taken during breastfeeding, the infant’s blood levels and complete blood count should be monitored closely.
Depakote (valproate) has not been associated with adverse effects in exposed infants or mothers, and the American Academy of Neurology does advocate breastfeeding for mothers on antiseizure medication. Equetro (carbamazepine) levels in breast milk are low. The American Academy of Pediatrics lists both Depakote (valproate) and Equetro (carbamazepine) as compatible with breastfeeding. As for the antipsychotic agents, there had been twenty-eight reports on infant exposure during breastfeeding at the time of the Yonkers et al. review; no adverse events were reported in the majority of cases.
Deciding whether to breastfeed while on bipolar medications is difficult. The risk of going off medication, however, is great. There is a high rate of recurrence of illness during the postpartum period. Lithium has been found to reduce the rate of relapse from 50% to less than 10% in the postpartum period. Although it is desirous of many women to breastfeed, if you absolutely do not want the infant exposed to any medications, the more conservative approach is to remain on medication and not breastfeed, as both depression and mania can be associated with adverse outcomes in an infant. Untreated maternal depression is associated with reduced weight gain in infants. A depressed or manic mother will be less in tune with a baby’s needs, less able to monitor the environment for safety, and less apt to engage in a nonverbal dialogue with the baby. Early attachment is important in a baby’s development, as poor attachment early on confers risks later in life for emotional and behavioral problems.
Terms:
Teratogenic – that which can interfere with normal embryonic development.
Half-life – the time it takes for half of the blood concentration of a medication to be eliminated from the body. Half-life determines as well the time to equilibrium of a drug in the blood and determines the frequency of dosing to achieve that equilibrium.
Attachment – the psychological connection between a child and his or her caretaker. Infants develop attachment behaviors within the first month. Deficits in early attachments can result in problems in later relationships in life.
