Psychiatric Problems During and After Pregnancy
Nicole Leistikow
Patricia F. Widra
Rebecca Sokal
Alison D. Hermann
Introduction
Although pregnancy was once thought to be protective in terms of psychiatric illness, recent data have demonstrated that prevalence rates for most psychiatric illnesses are similar in pregnant women as in the general population and that the postpartum period may be a time of particular risk, especially for mood and anxiety disorders.1,2,3,4 Perinatal depression affects nearly 20% of women throughout the peripartum,5 making it the most common obstetric (OB) complication overall, and suicide has been identified as a leading cause of maternal mortality in industrialized nations, including the United Kingdom and the United States.6,7
In addition, use of psychotropic medication during pregnancy has increased significantly in the last 20 years with prevalence rates as high as 16% in some areas of the United States.8,9,10 Multiple major professional organizations including the American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), and the United States Preventive Services Task Force (USPSTF) have recommended universal depression screening procedures for pregnant and postpartum women, recognizing the essential role that obstetricians and gynecologists play as front-line clinicians in women’s health care throughout the peripartum period.11,12,13
Unfortunately, major gaps in access to general psychiatrists exist and access to reproductive psychiatrists is even more limited. In recognition of this, ACOG has further asserted in its guidelines that OB clinicians need to be prepared to both initiate pharmacotherapy and refer patients to psychiatric treatment, if needed, as well as to put in place effective systems to prevent patients with psychiatric needs being lost to follow-up.14 It is, therefore, essential that obstetricians and gynecologists have a basic understanding of common psychiatric illnesses and their treatments.
The purpose of this chapter is to provide a foundational background to OB clinicians developing experience in identifying and treating perinatal mental illness. The first part will introduce recent changes in approach to maternal mental illness including the replacement of the US Food and Drug Administration (FDA) drug risk categories; newer understandings of the risks of psychiatric illnesses themselves for both mother and fetus; and challenges in observational research design that have led clinicians to misinterpret data related to perinatal psychopharmacology. The second part of this chapter will review the epidemiology, clinical presentation, and treatment of the major psychiatric disorders that are comorbid with and can complicate obstetrical care in the perinatal period.
Changes in Approaches to Maternal Mental Illness
Replacement of the FDA Categories
The FDA drug risk categories A, B, C, D, and X were established in 1979, after an epidemic of fetal malformations caused by thalidomide, to provide an easy-to-use standardized system that might prevent such harms in the future. Due to a lack of human studies in pregnant populations, newer drugs were typically assigned category B designation, while older drugs, about which more risks were known and more evidence had time to accumulate, were assigned C designation. This led many clinicians to assume erroneously that the absence of adverse data implied safety.15,16 Additionally, these categorical designations did not provide appropriate context as
to the potential harms of withholding or avoiding the considered medication and led to a period of undertreatment and, therefore, unnecessarily high morbidity and mortality of women with moderate-to-severe psychiatric illness.17,18
to the potential harms of withholding or avoiding the considered medication and led to a period of undertreatment and, therefore, unnecessarily high morbidity and mortality of women with moderate-to-severe psychiatric illness.17,18
Over the years, consensus developed that the categories were prone to such misinterpretations, and it was announced in 2008 that they would be phased out by 2015 and replaced by narrative descriptions to better guide clinicians.19 Although this change is considered a significant improvement, it nonetheless has its own limitations in that it relies on drug manufacturers to write summaries which may not be available immediately for many medications and requires greater effort by clinicians to access and weigh the information. Nevertheless, it is hoped that narrative summaries will better reflect and guide the real-life complexity of such medication decisions during pregnancy and lactation.
The Risks of Psychiatric Illness for the Mother and Fetus
One reason it has been challenging to determine the risk psychiatric medications may pose to developing fetuses is that psychiatric illnesses itself, the indication for which these medications are prescribed, pose independent OB risks and risks to fetal and child development. Psychiatric illnesses have been linked to increased rates of congenital anomalies; OB outcomes, such as preeclampsia, preterm birth, cesarean delivery, neonatal intensive care unit (NICU) admissions, low birth weight, and small-for-gestational age fetuses; impaired mother-infant bonding; increased rates of infant neglect or abuse; and suicide and infanticide (Table 43.1). 11,20,21,22,23,24,25,26,28,29,30,31,37,38,39,40 Potential reasons for these associations include genetic loading, disrupted maternal physiology conferred by psychiatric illness including epigenetic changes and dysregulated hypothalamic-pituitary-adrenal axis functioning, comorbid substance use, poor adherence to prenatal care and prenatal vitamins, and poor self-care and high-risk behaviors. Population groups with mental illness are less healthy than cohorts without mental illness and have increased rates of medical morbidity, including obesity, diabetes, and cardiovascular disease, which may also confer risk for some of the outcomes listed above.41 Thus, in attempting to research the effects of medications intended to treat mental illness on fetal outcomes, the possibility of confounding by indication, or the possibility that the illness itself may be causing the outcome of interest, must be rigorously explored and addressed.
Table 43.1 Risks of Untreated Psychiatric Illnesses in Pregnancy and Postpartum | ||||||||||||
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Design Challenges in Research on Maternal Mental Illness
The use of the gold standard in pharmacologic research, the randomized controlled trial, is restricted in pregnant women due to ethical concerns.42 Thus, to a greater extent than in other populations, research on the effects of medications in pregnancy has relied on observational studies, which are unable to establish causation due to the limits of their design.43,44 Historically, early observational studies of antidepressants or other psychiatric medications in pregnancy did a poor job of controlling for confounding factors, especially psychiatric illness itself, leading to erroneous associations and conclusions. For example, initial comparator groups were often healthy women versus women with mental illness taking medications,
rather than women with mental illness not taking psychiatric medications being compared to women with mental illness taking psychiatric medications. Controlling for mental illness severity also remains a challenge—women with less severe psychiatric illness tend to take less or fewer medications, especially in pregnancy; may be better equipped to engage in healthy behaviors and psychotherapy; and may be at less risk for adverse obstetrical outcomes than women with severe mental illness, whether or not the latter are taking medications. Additionally, studies finding no association between perinatal medications and negative fetal outcomes are less likely to be published due to bias in favor of positive findings.45 Meta-analyses, which are higher powered to find associations by virtue of combining multiple prior studies, have no ability to change the design flaws already present in the studies they use and, therefore, may amplify confounding,46 leading to false accuracy and certainty.47 Finally, the use of pharmacy databases and filled prescriptions to denote adherence to medications is particularly problematic given high rates of women stopping psychotropic medications suddenly in pregnancy.48 Newer statistical advances that have improved the ability to control for confounding in observational studies, such as propensity score matching, have begun to correct some of the erroneous associations found in earlier studies and should continue to advance the field.44,47,49
rather than women with mental illness not taking psychiatric medications being compared to women with mental illness taking psychiatric medications. Controlling for mental illness severity also remains a challenge—women with less severe psychiatric illness tend to take less or fewer medications, especially in pregnancy; may be better equipped to engage in healthy behaviors and psychotherapy; and may be at less risk for adverse obstetrical outcomes than women with severe mental illness, whether or not the latter are taking medications. Additionally, studies finding no association between perinatal medications and negative fetal outcomes are less likely to be published due to bias in favor of positive findings.45 Meta-analyses, which are higher powered to find associations by virtue of combining multiple prior studies, have no ability to change the design flaws already present in the studies they use and, therefore, may amplify confounding,46 leading to false accuracy and certainty.47 Finally, the use of pharmacy databases and filled prescriptions to denote adherence to medications is particularly problematic given high rates of women stopping psychotropic medications suddenly in pregnancy.48 Newer statistical advances that have improved the ability to control for confounding in observational studies, such as propensity score matching, have begun to correct some of the erroneous associations found in earlier studies and should continue to advance the field.44,47,49
Future Challenges
The treatment of maternal mental illness has been evolving as the limitations of the now-outdated FDA categories have come to light and as confounding problems, especially confounding by indication, have been better addressed in study designs. The recognition of many mental illnesses as chronic relapsing-remitting illnesses associated with a wide range of potentially negative maternal and child outcomes has changed the standard of OB care to include universal screening protocols and has tipped the balance of mental illness management in favor of continuing pharmacologic treatments throughout pregnancy and postpartum for women with moderate-to-severe illnesses and initiating treatment in symptomatic women who are newly identified.
Despite these advances, significant challenges for OB clinicians remain. At this point, clinicians are not only expected to implement universal depression screening but also to accurately diagnose depression and initiate treatment. Meeting this new standard of care requires further clinical evaluation (discussed below), consideration of comorbid conditions, and a ruling out of important conditions based upon the differential diagnosis, such as bipolar disorders or substance use disorders, that may masquerade as depression. The clinician must additionally determine severity and consider when to initiate treatment and when to refer. While problems with access to psychiatric care necessitate that OB clinicians treat common psychiatric illnesses such as anxiety and mild-to-moderate unipolar depression, more severe or complicated illnesses are best managed by a psychiatrist. The illness-specific sections below are meant to assist OB clinicians in navigating these challenges.
Psychiatric Illness in the Perinatal Period
Mood Disorders
Depression
Epidemiology and Risk Factors
Pregnancy does not protect against depression. A woman’s risk of depression in pregnancy is about the same as it is in the nonpregnant state, and the prevalence of depression in pregnancy is estimated to be 6% to 17% in the United States.50,51 Women with anxiety, stress, a prior history of depression, low social support, unintended pregnancy, lower income, a history of domestic violence, and less education are at greater risk.52 Postpartum, the risk of depression goes up, with as many as one in five women developing depression following childbirth.53 The primary risk factor for postpartum depression is depression during pregnancy.54 Additional risk factors include anxiety, low social support, high stressors, and difficult infant temperament among others.54,55,56
Clinical Presentation
OB clinicians should suspect a diagnosis of depression in patients who have two or more weeks of sustained low or irritable mood and/or loss of interest in pleasurable activities (anhedonia). To meet full diagnostic criteria for depression, one or both of these cardinal symptoms must be accompanied by additional cognitive, emotional, and neurovegetative symptoms such as a change in perception of self-worth, excessive feelings of guilt, increased
difficulty concentrating or making decisions, unexpected alterations in sleep, appetite, energy, or activity level, or recurrent thoughts of death, for a total of at least five symptoms overall. Anxious and/or intrusive thoughts, discussed further below, are more common in perinatal depression than depression at other times of life and, for many women, may be the most prominent symptom of the syndrome, especially in the postpartum. Moderate-to-severe depression is additionally marked by significant difficulty functioning with everyday tasks, including cognitive slowing or distraction, which may interfere with work or other responsibilities, severe fatigue or other physical impairments that interfere with activities of daily living, or impaired ability to cope with problems and/or higher emotional reactivity which causes significant conflict in important relationships. Thoughts of not wanting to live, wishing to die, or having impulses to self-injure are not normal responses to stressors and are considered markers of severe depression.
difficulty concentrating or making decisions, unexpected alterations in sleep, appetite, energy, or activity level, or recurrent thoughts of death, for a total of at least five symptoms overall. Anxious and/or intrusive thoughts, discussed further below, are more common in perinatal depression than depression at other times of life and, for many women, may be the most prominent symptom of the syndrome, especially in the postpartum. Moderate-to-severe depression is additionally marked by significant difficulty functioning with everyday tasks, including cognitive slowing or distraction, which may interfere with work or other responsibilities, severe fatigue or other physical impairments that interfere with activities of daily living, or impaired ability to cope with problems and/or higher emotional reactivity which causes significant conflict in important relationships. Thoughts of not wanting to live, wishing to die, or having impulses to self-injure are not normal responses to stressors and are considered markers of severe depression.
Postpartum depression should be distinguished from “baby blues,” which are experienced by up to 85% of women. Similar to depression, postpartum blues can manifest as emotional lability and tearfulness; in contrast to depression, these symptoms typically peak at Day 5 after delivery and resolve without intervention by 2 weeks.57 Within the first 2 weeks’ postpartum, it can be difficult to parse depression and “baby blues” based on mood symptoms alone. However, if symptoms include an inability to sleep when the baby is sleeping, a desire to flee or avoid proximity to the baby, or if the emotional lability persists beyond 2 weeks’ postpartum, a diagnosis of depression should be considered. If symptoms such as confusion, disorientation, changes in personality or judgment, paranoia, or other psychotic symptoms are present, other diagnoses, such as bipolar disorder or postpartum psychosis (discussed below), should be investigated.
Clinical Assessment
The most widely used screening tool for depression in adult populations is the Patient Health Questionnaire-9 (PHQ-9), although it is not as well validated in perinatal populations, particularly in the postpartum. The PHQ-9 is a nine-item scale listing depressive symptoms based on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, with a score of 10 or greater considered as a positive screen.58 However, due to the normal physiologic changes of the peripartum as well as infant care demands in the postpartum, patient-reported symptoms included in this measure, such as fatigue, poor sleep, or changes in appetite, are less reliable indicators of depression and therefore can cause confusion (Table 43.2). To address this, the Edinburgh Postnatal Depression Scale (EPDS) was developed and is the preferred screening tool for this population where feasible. It is a ten-item self-report scale that places greater emphasis on anxiety questions and less emphasis on neurovegetative symptoms. It is freely available in more than 20 languages and has been extensively validated both during pregnancy and in the postpartum; a score greater than 12 is considered a positive screen.59
Management of Depression in Pregnancy
For women with mild-to-moderate depression, first-line treatment recommendations include a trial of evidence-based psychotherapy such as cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT). For women with moderate-to-severe depression or in women for whom psychotherapy is ineffective or insufficiently effective, an antidepressant is often needed to achieve symptom relief and remission.60 When an antidepressant medication is indicated, clinicians can help women decide on a treatment strategy by providing accurate information on the risks of antidepressant exposure versus the risks of allowing depression to relapse or persist. These discussions should be standardized with reference to updated treatment guidelines and documented in the medical record. Online patient decision aids are currently being developed and can be helpful.61
Pharmacologic Treatment
Risks of Antidepressants Selective serotonin reuptake inhibitors (SSRIs) are the most studied class of antidepressants and are considered first-line treatment for use in pregnant and lactating women (Table 43.3). Recent data suggest that SSRIs are not associated with an increased risk of fetal malformations, with the possible exception of paroxetine, which has been inconsistently shown to be associated with an increased risk of cardiac malformations in small samples.60,62,63 SSRIs may have an association with persistent pulmonary hypertension of the newborn (PPHN), although this association is much weaker than initially suspected, with a small absolute risk increase of 0.619 per 1000 live
births and a number needed to harm of 1615 in a 2019 meta-analysis.66,67 Although some studies have found increased risk of preterm delivery with exposure to antidepressants, untreated depression is also associated with an increased risk of preterm delivery, and, therefore, confounding by indication must be considered.27,68,69
births and a number needed to harm of 1615 in a 2019 meta-analysis.66,67 Although some studies have found increased risk of preterm delivery with exposure to antidepressants, untreated depression is also associated with an increased risk of preterm delivery, and, therefore, confounding by indication must be considered.27,68,69
Table 43.2 Psychiatric Symptoms Versus Normal Peripartum Changes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Studies have consistently shown antidepressants to be associated with an increased risk for poor neonatal adaptation syndrome (PNAS), which is a transient syndrome experienced by up to 30% of exposed newborns compared to 9% of newborns who are not exposed and who do not require medical interventions.64,65 Infants with PNAS can experience increased fussiness, jitteriness, tremors, rapid breathing, increased muscle tone, and insomnia with symptoms lasting typically 2 days to 2 weeks postbirth. Although respiratory symptoms may be present in more severe cases of PNAS, this condition should not be confused with the previously discussed and much more severe condition, PPHN. Risk of PNAS increases with concomitant exposure to benzodiazepines in utero.37 Breastfeeding and skin-on-skin contact are thought to reduce PNAS symptoms for infants, but importantly, tapering off antidepressants in the third trimester does not and is not recommended.37,38
Risks of Untreated Depression The risks of not treating depression in pregnancy are significant and include increased morbidity and mortality for both mother and infant (Table 43.1). Risk of suicide, though rare in pregnancy, is a leading cause of postpartum maternal mortality in industrialized nations and the risk of postpartum depression increases with untreated depression in pregnancy. Other risks include poorer prenatal care, lower birth weight and earlier delivery, increased risk of preeclampsia and cesarean section, and increased NICU admission rates.20,21,22,23,25,27 Long-term adverse child outcomes, such as attachment problems, delays in language acquisition, and behavioral problems, have also been associated with maternal depression.30,32,33
Initiating Antidepressants Prior to initiating antidepressants, a brief screen for bipolar illness should be completed (see below). Alternatively, a validated screening tool, such as the Mood Disorder Questionnaire (MDQ), can also be used to rule out bipolar disorder.70 Patients strongly suspected to have bipolar disorder should not be prescribed antidepressants without an additional mood-stabilizing agent and should instead be referred to psychiatrists or specialists for management. All patients should be warned to watch for signs of mania or hypomania induced by antidepressants and to stop taking medications if symptoms seem to be worsening. Psychiatric emergencies, including acute mania or psychotic states, are addressed later in this chapter.
Table 43.3 First-Line Antidepressants (SSRIs) in Pregnancy and Breastfeeding | ||||||||||||||||||||||||||||||||
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In addition to fetal exposure concerns described above, informed consent should include a discussion of potential maternal side effects, such as nausea and diarrhea, which typically fade after 2 weeks; sexual side effects; weight gain; and increased anxiety which can be related to higher starting doses or faster dose increases. Women who opt for treatment with SSRIs can be given a patient handout from the free resource MotherToBaby (https://mothertobaby.org), which summarizes potential risks of medications in pregnancy and breastfeeding in an easy to understand language. See Table 43.4 for this and other resources.
Once the decision has been made to treat depression in pregnancy with medication, first-line SSRI options include sertraline, escitalopram, citalopram, fluoxetine, and fluvoxamine. These agents are preferred because they are older medications about which a substantial research base has formed. Newer agents are generally avoided unless there is clinical reason to use them such as documented prior efficacy for a particular patient and/or demonstrated failure or inability to tolerate older agents. Tricyclic antidepressants are reasonable options in pregnancy, especially if a patient has prior experience of efficacy with them, but they are not typically first-line agents due to having more side effects and more narrow therapeutic windows.71,72
Best practice guidelines recommend limiting the number of exposures for a fetus while considering untreated mental illness as an exposure.73 Some patients respond to one SSRI but not another. Following this principle, clinicians should prioritize, if known, agents with demonstrated efficacy for a particular patient over untried agents with unknown efficacy for that individual. Single agents should be titrated to their maximum dose, if needed, before adding any additional medications or embarking on a new medication trial (Table 43.3). Additionally, the physiologic changes of pregnancy typically cause antidepressant blood levels to drop over the course of gestation, often requiring active uptitration of doses to maintain symptom control.74 Dose titrations are typically based on clinical observation of worsening symptoms but can be anticipated and discussed ahead of time.
For women already taking antidepressants when they become pregnant, decision-making should include a discussion of the risks of remaining on the medications (with an acknowledgment that the baby has already been exposed) versus the risks of
relapse of illness. Rates of depression relapse are high in pregnancy in general, but typically higher when antidepressants are discontinued. One study found that 26% of pregnant women with a history of depression who continued taking antidepressants had a recurrence of depression, whereas 68% of those who stopped their antidepressants experienced a recurrence of depression.75 If a woman and her doctor decide to stop psychiatric mediations in pregnancy, tapering slowly, over the course of at least 1 to 2 months, is recommended to reduce the risk of relapse.75
relapse of illness. Rates of depression relapse are high in pregnancy in general, but typically higher when antidepressants are discontinued. One study found that 26% of pregnant women with a history of depression who continued taking antidepressants had a recurrence of depression, whereas 68% of those who stopped their antidepressants experienced a recurrence of depression.75 If a woman and her doctor decide to stop psychiatric mediations in pregnancy, tapering slowly, over the course of at least 1 to 2 months, is recommended to reduce the risk of relapse.75
Table 43.4 Resources for Information on Women’s Mental Health and Medications in Pregnancy and Breastfeeding | ||||||||||||
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Postpartum depression should be treated promptly. Antidepressants in general are expressed in low levels in breast milk and should not be considered a contraindication to breastfeeding. The same principals are followed as in pregnancy: limiting the number of exposures to the baby, including untreated maternal depression as an exposure, and using adequate doses of older agents as first-line options. LactMed is a free online database produced by the US National Library of Medicine that summarizes the available research on each medication and its risks in breastfeeding (Table 43.4). Anxiety and insomnia are frequently comorbid with postpartum depression and often resolve with antidepressant treatment (see Management of General Anxiety Disorder below). It should be noted that novel treatments for postpartum depression are currently being developed and include brexanolone, which was approved by the FDA as an intravenous infusion in 2019, but which, as of this writing, is not yet widely available.76,77
Patients with postpartum depression should be counseled to balance the value of breastfeeding through the night with the need to prioritize sleep to stabilize mood; patients should consider enlisting support persons to provide a portion of the overnight infant care, which can include bottle feeding via expressed breast milk or formula, changing, soothing the infant, and in general, relieving a new mother of a portion of nighttime responsibilities. If sleep remains substantially disrupted, the chances of successfully treating depression are low.
Bipolar Illness
Epidemiology and Risk Factors
Bipolar illness is rare, with a prevalence of about 3% in the United States. It is characterized by both manic/hypomanic and depressive episodes, with the latter typically outnumbering the former and delaying accurate diagnosis, often by years.78,79 Women whose first episode of depression occurs during their first year postpartum have an increased risk of later being diagnosed with bipolar disorder.80 Women with a diagnosis of bipolar illness have an increased risk of attempting suicide, above that of other psychiatric illnesses. One estimate is that as many as
50% of those with bipolar disorder attempt suicide at least once in their lifetime.81,82,83 Women with bipolar illness are also at higher risk of comorbid health conditions, such as obesity, smoking, and substance use, as well as negative obstetrical outcomes such as induction, cesarian section, late preterm birth, and use of instrumentation at delivery.84
50% of those with bipolar disorder attempt suicide at least once in their lifetime.81,82,83 Women with bipolar illness are also at higher risk of comorbid health conditions, such as obesity, smoking, and substance use, as well as negative obstetrical outcomes such as induction, cesarian section, late preterm birth, and use of instrumentation at delivery.84
Bipolar illness relapse during pregnancy is common and the risk is substantially increased by discontinuing medications.85 One small prospective study found that stopping mood stabilizers during pregnancy increased rates of recurrence from 36% to 87% and resulted in women being ill longer.86 Other predictors of illness recurrence during pregnancy include a history of prior perinatal mood disturbance, a family history of perinatal mood problems, severe illness, or recent depression or hypomania.
Postpartum women with bipolar illness remain at high risk for relapse, which can include psychotic, manic, and depressive symptoms, sometimes requiring hospitalization.87 Studies consistently show lower rates of relapse postpartum in the setting of prophylactic pharmacotherapy, initiated either during pregnancy or immediately after delivery.88
Postpartum psychosis is considered a variant of bipolar illness with approximately 20% of cases manifesting only in the postpartum period and 80% of cases having a chronic relapsing-remitting course.89,90,91,92 It is rare, with a prevalence of about 1/1000, and onsets typically within the first 2 weeks after delivery with a 50% risk of recurrence after subsequent pregnancies.91 Postpartum psychosis is addressed below under Psychiatric Emergencies.
Clinical Presentation
Hypomanic or manic episodes, which are necessary for the diagnosis of bipolar illness, are characterized by a noticeable change in functioning that occurs for a period lasting longer than 2 days with decreased need for sleep, fewer hours of sleep (typically 4 hours or less), increased energy, abnormally elevated or irritable mood, increased impulsivity, and changes in hedonic behaviors such as increased spending, risk taking, socializing, or having more sex. For an accurate diagnosis, these periods of increased energy and change in behavior should not be in the setting of drug use or other confounding factors, such as medical conditions or medications used to treat them.
Management of Bipolar Illness in Pregnancy
Given the higher health risks associated with bipolar illness and the challenges of using mood stabilizers and antipsychotics in pregnant women, patients with bipolar disorder generally should be referred to a psychiatrist, and if available, preferably a reproductive psychiatrist. In general, the standard of care is to continue an appropriate mood stabilizer in pregnancy for those women already stabilized on medications when they become pregnant and to initiate an appropriate mood stabilizer in pregnancy for those women not already on medication who are symptomatic or at high risk of relapse.
Pharmacologic Treatment
Lithium, lamotrigine, quetiapine, and olanzapine are all reasonable choices to treat bipolar illness in pregnancy, with studies generally demonstrating tolerable risk profiles (Table 43.5).96,99,102,103 Higher doses of mood stabilizers or neuroleptics may be required to maintain euthymia as pregnancy progresses due to the physiologic changes of pregnancy affecting drug blood levels. For lithium (the concentration of which is reduced by increased glomerular filtration rate and greater blood volume) and lamotrigine (the concentration of which is reduced by estrogenic induction of hepatic glucuronidation), regular blood level monitoring is recommended throughout pregnancy.103 In general, decreasing or discontinuing mood-stabilizing medications in pregnancy is not recommended as it increases the risk for symptom relapse. Once symptoms reemerge, higher doses and additional mood-stabilizing agents may be required to achieve symptom control.
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