Lifeline for Pregnant and Postpartum Women Who Are Drowning in Plain Sight

Nancy Byatt, DO, MS, MBA

Premiere Date: April 20, 2018
Expiration Date: July 20, 2019

This activity offers CE credits for:

1. Physicians (CME)
2. Other

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

ACTIVITY GOAL

To understand the risk differential of pharmacotherapy compared with no treatment during pregnancy and help women make treatment decisions before, during, and after pregnancy.

LEARNING OBJECTIVES

At the end of this CE activity, participants should be able to:

• Rationalize the need for continued treatment for psychiatric illness during pregnancy

• Explain the risks involved when switching medications during pregnancy and how it affects the fetus

• Discuss the best options for treating psychiatric illness in pregnant women

TARGET AUDIENCE

This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

CREDIT INFORMATION

CME Credit (Physicians): This activity has been planned and implemented in accordance with the Essential Areas and policies of the
Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of CME Outfitters, LLC, and Psychiatric Times. CME Outfitters, LLC, is accredited by the ACCME to provide continuing medical education for physicians.

CME Outfitters designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credit ™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note to Nurse Practitioners and Physician Assistants: AANPCP and AAPA accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit ™.

DISCLOSURE DECLARATION

It is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, and scientific rigor and integrity in all of their CME/CE activities. Faculty must disclose to the participants any relationships with commercial companies whose products or devices may be mentioned in faculty presentations, or with the commercial supporter of this CME/CE activity. CME Outfitters, LLC, has evaluated, identified, and attempted to resolve any potential conflicts of interest through a rigorous content validation procedure, use of evidence-based data/research, and a multidisciplinary peer-review process.

The following information is for participant information only. It is not assumed that these relationships will have a negative impact on the presentations.

Nancy Byatt, DO, MS, MBA, reports that she has received a salary and/or funding support from the Massachusetts Department of Mental Health via the Massachusetts Child Psychiatry Access Program for Moms (MCPAP for Moms). She is also the statewide Medical Director of MCPAP for Moms. Dr. Byatt has served on the Perinatal Depression Advisory Board for the Janssen Disease Interception Accelerator Program, the Perinatal Depression Advisory Board for the Janssen Disease Interception Accelerator Program, the Physician Advisory Board for Sage Therapeutics, and is a Council Member of the Gerson Lehrman Group. She also serves as a speaker for Sage Therapeutics.

Mary C. Kimmel, MD (peer/content reviewer), reports that she has received study support from Sage Therapeutics and that her husband owns stock in Abbvie

Applicable Psychiatric Times staff and CME Outfitters staff have no disclosures to report.

UNLABELED USE DISCLOSURE

Faculty of this CME/CE activity may include discussion of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational uses (any uses not approved by the FDA) of products or devices. CME Outfitters, LLC, and the faculty do not endorse the use of any product outside of the FDA-labeled indications. Medical professionals should not utilize the procedures, products, or diagnosis techniques discussed during this activity without evaluation of their patient for contraindications or dangers of use.

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One in 7 women suffers from a mood disorder during pregnancy or in the first year postpartum.¹ It is imperative that we, as psychiatric providers, guide each woman to make thoughtful decisions that take into account the effects of the illness and the treatment on her and her baby. Depression, anxiety, and other psychiatric illnesses that occur during pregnancy and the postpartum period have deleterious effects on mom, her child, and her family.

Case Vignette #1

"Sonja," a 26-year-old with a history of postpartum depression and panic disorder reports that she experienced severe postpartum depression and panic disorder within a month of giving birth to her 2-year-old son. The symptoms resolved shortly after she began taking 20-mg escitalopram daily. Three months ago, Sonja and her husband decided that they wanted to have another baby. Her psychiatrist told her that she had to discontinue the escitalopram before attempting to conceive. She followed his recommendations and the depression symptoms and daily panic attacks soon returned. Without the escitalopram, she is completely immobilized and unable to function. She recently saw her psychiatrist, reported the symptoms and her inability to function and requested that he restart the escitalopram. He responded, "You will not take the escitalopram if you care about your baby." She left the psychiatrist's office feeling guilty and inadequate, and that she had no choice but to suffer for the sake of the baby she hoped to conceive.

Sadly, this is just one example of countless similar incidents that occur daily. As this case illustrates, we miss the opportunity to have a trans-generational impact by optimizing maternal mental health, which in turn affects infant and child health. It is a complete fallacy that a woman needs to ignore her mental health or suffer for her baby. Having a baby is extraordinarily challenging. The best thing a woman can do for herself and her baby is get the treatment that she needs and deserves. There are many safe and effective treatment options for pregnant women.

Risks to mother and child

Although there can be adverse effects of psychotropics on the mother and fetus, there are inherent risks of the illness itself. If medications are discontinued in pregnancy, there is a high risk of illness relapse. The duration of and number of depressive episodes pre-pregnancy are the greatest predictors of the same for during pregnancy. Other risk factors include personal or family history of postpartum depression, history of mood changes related to hormonal contraception, and premenstrual dysphoric disorder. Medications should not be automatically discontinued due to pregnancy. It is critical to ask: "What could happen if my patient does not take her medication? How might her illness affect her ability to take of herself and her baby?"

The FDA's A, B, C, D, and X categories for medicines used in pregnancy are extremely limited and misleading. For example, the risks of untreated illness are not included. Realizing this, the FDA developed a new approach to replace the risk categories and better support evidence-based decisions.² The new system, the Pregnancy and Lactation Labeling Rule, uses a narrative model that includes 3 sections on the prescription label for pregnancy-related information: (1) Pregnancy; (2) Lactation; and, (3) Females and males of reproductive potential. Each section summarizes risks to the fetus, illness-related considerations, and available safety data.

Because approximately 50% of pregnancies are unplanned, it is imperative to consider and discuss the possibility of pregnancy with all women of reproductive age. This should include discussing and documenting birth control and the current use of all medications and their risks-especially important with highly teratogenic medications, such as valproic acid. Being aware of interactions between hormonal contraceptives and mood stabilizers is crucial and also needs to be discussed. Some hormonal contraceptives decrease levels of anti-convulsant medications, such as lamotrigine. Conversely, oxcarbazepine and topiramate can decrease the efficacy of hormonal contraceptives. Any discussions and documentation of preconception planning should also include recommendations for prenatal vitamins and folic acid.

Depression

Depression during pregnancy is associated with poor health care use, increased use of substances, and poor maternal health care. It is also associated with poor birth outcomes, including low birth weight in preterm delivery. Children of women with maternal depression have also been found to be at increased risk of cognitive delays or behavioral problems.^3,4 Moreover, maternal suicide is a leading cause of death among postpartum women.⁵ It is critical to educate women about the various options for treating depression during pregnancy. It is also essential that non-pharmacologic treatments and lifestyle changes be included in treatment planning (Table). Evidence-based psychotherapy, such as cognitive behavioral therapy and interpersonal psychotherapy, should be considered as first-line therapy when possible. However, many women will need a combination of psychotherapy and pharmacotherapy to achieve full symptom remission. Pharmacotherapy may be the only treatment option for women who do not have access to psychotherapy or who do not see the value of psychotherapy.

Case Vignette #2

"Melissa" is a 32-year-old with a history of severe depression who has 2 children. She is now 14 weeks pregnant. She is currently asymptomatic and taking 300-mg bupropion XL. She notes that she had been severely depressed to the extent that it has affected her functioning and her ability to parent. Once she started taking bupropion, the symptoms resolved. During a visit with her psychiatrist, she reported that she had Googled bupropion because she was concerned about the risks of taking it during pregnancy. As a result of her Google search, she believes that she should stop the bupropion and start sertraline. She notes that the information she found online indicated that sertraline is safer and the best option.

How should her psychiatrist counsel her? Melissa's fetus has already been exposed to bupropion. If bupropion is continued, the fetus will likely experience only a single exposure. While bupropion has less available reproductive safety data than the SSRIs and has been associated with a possible increased risk of congenital heart defects, it is important to consider the risk of switching medications during pregnancy.

If her psychiatrist were to discontinue the bupropion and start sertraline, there is a risk of 3 exposures: her fetus is 14 weeks gestational age and has already been exposed to bupropion; switching would expose the fetus to a second medication (sertraline); and, sertraline may not be as effective as bupropion. Melissa could relapse and expose the fetus to illness. In general, pregnancy is not a good time to switch medications.

To avoid exposure to untreated or undertreated illness and more than one medication, it is best to continue medications with known efficacy. Moreover, the risks of untreated illness need to be considered because the risks of exposure to illness are often as or more important than the risks of exposure to the medication.

There may be a small risk of birth defects when taking antidepressants during pregnancy-the data for paroxetine are most concerning. These findings, however, are inconsistent and the absolute risk of birth defects is small; most meta-analyses have been reassuring.

Antidepressant use during pregnancy has been associated with transient neonatal symptoms. This is a self-limited syndrome that can occur in up to 30% of newborns exposed to antidepressants during pregnancy. It can present as irritability, tachypnea, and/or tremulousness. The syndrome is time-limited and resolves within days; in rare cases it can last 1 to 2 weeks. Discontinuing SSRIs in the third trimester has not been shown to decrease the risk of transient neonatal symptoms.⁶

Although the data are inconsistent, antidepressant use in pregnancy has also been associated with a small increase of risk (baseline rate of 1-2/1000 births) for persistent pulmonary hypertension (PPHN) in the newborn. While there may be a small increased risk (3-4/1000 with antidepressant use during pregnancy), the absolute risk of PPHN appears to be small and more modest than suggested by initial studies.⁷

Antidepressant use during pregnancy has also been associated with preterm labor and low birth weight; changes in IQ or language development have also been seen. However, depression itself has been associated with an increased risk of preterm birth and low birth weight as well as with changes in IQ or language development.⁸

Some studies suggest that the risk of autistic spectrum disorders in the offspring of women with psychiatric illness may be higher with exposure to antidepressants during pregnancy. However, other studies suggest that lack of antidepressant exposure increases the risk of autistic spectrum disorders. Overall, results from available studies do not suggest long-term neurobehavioral effects on children.

Bipolar Disorder and Psychosis

The perinatal period is the time of highest risk for first onset or recurrence of bipolar disorder episodes. Bipolar disorder among perinatal women is associated with self-injury, substance use, disruption of mother-child bonding, suicide, and infanticide. Psychotic illnesses have been associated with increased risk of pregnancy complications, including cesarean deliveries, intensive care unit admissions, and higher neonatal morbidity. Moreover, bipolar disorder is the most potent, best-established risk factor for postpartum psychosis.

Lithium is considered the treatment of choice for patients with type 1 bipolar disorder who are pregnant or are of child-bearing age. Preconception levels can be used to guide the therapeutic range of lithium during pregnancy.

Lithium use during pregnancy has been associated with preterm labor, polyhydramnios, polyuria/polydipsia, and lithium toxicity. In addition, babies of mothers who are on lithium during pregnancy may be large for gestational age at birth, have cardiac and neural tube defects, neonatal adaptation symptoms, and changes in long-term neurodevelopment. More recent studies suggest that the risk of major cardiovascular anomalies, such as Ebstein's anomaly, is less than previously thought.

Women who take lithium during pregnancy should be monitored carefully by an obstetrician who is experienced in high-risk pregnancies. A 3D echocardiogram is needed at 16 to 18 weeks gestational age. Lithium should be continued during labor and delivery. To prevent lithium toxicity, patients should be well hydrated during labor and immediately post-partum. Postpartum, infant levels of lithium, thyroid-stimulating hormone, and renal function need to be checked. Consider decreasing the dosage to that of pre-pregnancy in the postpartum period.

Lamotrigine is often considered a first-line medication for women with type 2 bipolar disorder who are pregnant or are of child bearing age. Preconception lamotrigine levels can be used to guide dosing throughout pregnancy with the goal of maintaining the therapeutic preconception level. Postpartum, lamotrigine dose should be decreased to the preconception level.

While early reports suggested an increased risk of cleft lip and palate with first trimester exposure, more recent data are reassuring—lamotrigine has not been associated with an increased risk of neurodevelopmental disorders. However, the following limitations need to be considered before prescribing lamotrigine:

• It can increase cycling at higher dosages

• It needs to be titrated slowly, thus is not ideal for acute treatment

• It needs to be taken consistently because of the need to re-titrate slowly if not taken consistently

Antipsychotics are often indicated for the treatment of mood disorders with or without psychotic features or primary psychotic illnesses. It is important to use antipsychotics that are currently or have previously been effective, while taking into account the relative risk of the medication.

No single malformation has been consistently reported with antipsychotics, although some data suggest a possible association with septal defects. In addition, antipsychotic use during pregnancy has been associated with preterm labor, low and high birth weight, increased risk of postnatal adaptation syndrome, and increased neonatal intensive care unit stays.

There are more data for typical than for atypical antipsychotics. Typical antipsychotics have been associated with a small increase in risk for transient abnormal muscle movement; however, limited long-term data are reassuring. Compared with high-potency agents, low-potency agents have been more strongly associated with teratogenic effects. Atypical antipsychotics have been associated with gestational diabetes and obesity; but the limited data from studies that followed women for up to 12 months are reassuring.⁹

Conclusion

Anticonvulsants such as carbamazepine and oxcarbazepine have been associated with neural tube defects and cognitive deficits among offspring and should be avoided. Valproic acid is highly teratogenic and should be avoided by pregnant women. Supplementation with folic acid is required for women taking an anticonvulsant during pregnancy.

Changes in absorption, distribution, metabolism, and elimination that occur in pregnancy can lower psychotropic drug levels and possibly treatment effects, particularly in mood stabilizers, during the perinatal period. Vigilant monitoring of clinical symptoms is needed for all classes of medications during pregnancy and the postpartum period to assess for symptom recurrence and the need for dose adjustments. Mood stabilizers also require therapeutic drug monitoring in combination with clinical monitoring.

When considering treatment options for pregnant women, there's no such thing as no exposure: there is no risk-free choice. We need to work with our patients to assess the risks of untreated psychiatric illness and the risks and benefits of medication treatment. A detailed and individualized discussion of the risks, benefits, alternatives to medication treatment, and the risks of untreated psychiatric illness is needed. Careful consideration and discussion of risks of treatment and under-treatment or no treatment can help can decrease the risk of decompensation during pregnancy or the postpartum period. And, it will mitigate negative effects on birth, infant, and child outcomes associated with untreated psychiatric illness.

CME POST-TEST

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References:

1. Vesga-Lopez O, Blanco C, Keyes K, et al. Psychiatric disorders in pregnant and postpartum women in the United States. Arch Gen Psychiatry. 2008;65:805-815.

2. Ramoz LL, Patel-Shori NM. Recent changes in pregnancy and lactation labeling: retirement of risk categories. Pharmacother. 2014;34:389-395.

3. Forman DR, O̢۪Hara MW, Stuart S, et al. Effective treatment for postpartum depression is not sufficient to improve the developing mother-child relationship. Dev Psychopathol. 2007;19:585-602.

4. Deave T, Heron J, Evans J, Emond A. The impact of maternal depression in pregnancy on early child development. BJOG. 2008;115:1043-1051.

5. Lindahl V, Pearson JL, Colpe L. Prevalence of suicidality during pregnancy and the postpartum. Arch Womens Ment Health. 2005;8:77-87.

6. Byatt N, Deligiannidis KM, Freeman MP. Antidepressant use in pregnancy: a critical review focused on risks and controversies. Acta Psychiatr Scand. 2013;127:94-114.

7. Huybrechts KF, Bateman BT, Palmsten K, et al. Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA. 2015;313:2142-51.

8. Nulman I, Koren G, Rovet J, et al. Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression. Am J Psychiatry. 2012;169:1165-1174.

9. Cohen LS, Viguera AC, McInerney KA, et al. Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Am J Psychiatry. 2016;173:263-270.