RxCe - Lithium: Bipolar in Childbearing Women Materials

LITHIUM: MANAGING BIPOLAR DISORDER IN CHILDBEARING WOMEN

DOUGLAS EVANS, APRN, PMHNP-BC

Douglas Evans is a board-certified Psychiatric Mental Health Nurse Practitioner. Douglas has over a decade of experience working with adult and adolescent mental health populations in Texas and Montana, respectively. He completed his Master of Science in Nursing (PMHNP) at Midwestern State University. Prior to his graduate degree, he earned an Associate of Applied Science in Nursing degree and a Bachelor of Science in Nursing from Angelo State University.

Topic Overview:

Bipolar disorder is a common and serious psychiatric condition with disabling consequences. Women have the highest risk of being diagnosed with bipolar or having a recurring episode during pregnancy or within one year of giving birth. In pregnant and postpartum women who are diagnosed with bipolar disorder, lithium can be used as an effective treatment to control symptoms. However, fluctuations in serum lithium levels can lead to subtherapeutic levels during the first and second trimesters and supratherapeutic or even toxic levels in the third trimester and postpartum period. In addition, lithium use during pregnancy carries risks. The American College of Obstetricians and Gynecologists issued new guidelines for lithium use during pregnancy and postpartum to address these risks.

Accreditation Statement:

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is

Pharmacist 0669-0000-23-111-H01-P

Pharmacy Technician 0669-0000-23-112-H01-T

Credits: 2 hours of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 hours, including Course Test and course evaluation

Release Date: August 2, 2023 Expiration Date: August 2, 2026

Target Audience: This educational activity is for pharmacists.

How to Earn Credit: From August 2, 2023, through August 2, 2026, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Describe the potential risks of lithium use during pregnancy

Describe the fluctuations in serum lithium levels during pregnancy and the postpartum period, leading to subtherapeutic or supratherapeutic lithium levels.

Review the 2023 American College of Obstetricians and Gynecologists guidelines for lithium use during pregnancy and postpartum.

Describe the lithium laboratory test monitoring in pregnant and postpartum women who are prescribed lithium

Disclosures

The following individuals were involved in developing this activity: Douglas Evans, APRN, PMHNP-BC, Anna S. Smith, MPH, BSN-RN, and Pamela Sardo, PharmD, BS. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

Introduction

Bipolar disorder is a common and serious psychiatric condition, which often has disabling consequences for those afflicted by it. Women have the highest risk of being diagnosed with bipolar or having a recurring episode during pregnancy or within one year of giving birth. During pregnancy and the postpartum period, lithium has been identified as an effective treatment to control symptoms of bipolar disorder and as a prevention of a relapse of symptoms. Fluctuations in serum lithium levels may occur during pregnancy and the postpartum period that can lead to subtherapeutic or supratherapeutic lithium levels. In addition, there are risks with lithium use during pregnancy for the mother and fetus. During the first trimester of pregnancy, there is a potential for congenital malformations due to lithium exposure in utero. There may also be an increased risk of miscarriage from lithium use. The decision to prescribe lithium during pregnancy should be determined by considering the risk factors of using lithium and balancing them with the mother’s risk of mood dysregulation and psychosis. Continuing lithium use during pregnancy requires close monitoring during the perinatal period, including frequent testing of lithium serum levels. Consideration must also be made for mothers who intend to breastfeed.

Bipolar Disorder and Suicidal Ideation in Pregnant Women

Bipolar disorder is a common and serious psychiatric condition, which often has disabling consequences for those afflicted by it.1 There is a high risk that a woman will experience her first episode of bipolar disorder during pregnancy or postpartum.1 Women who are diagnosed with bipolar disorder have a 52% rate of relapse of depression or manic episodes during the postpartum period.2 Additionally, suicidal ideation and suicide attempts are much higher in those with bipolar disorder.2 Suicide is a leading cause of maternal mortality in postpartum in the United States of America.3,4 One study concluded that suicide accounts for about 20% of maternal deaths in the postpartum period.5 In pregnant women with mental health conditions, 63% of the maternal deaths were by suicide.4

Providing lithium to pregnant patients diagnosed with bipolar disorder has been found to be effective in preventing postpartum mood disorders.6 Among mood-stabilizing medications, lithium has been associated with lower risks of suicide and all-cause mortality.7

To Treat or Not to Treat? A Clinical Conundrum

With the high risk of women experiencing their first episode of bipolar disorder during pregnancy or postpartum, screening is an important part of this process. The most common misdiagnosis for bipolar disorder is depression.8 Psychiatrists and researchers have found that using the Mood Disorder Questionnaire is a quick (less than 5 minutes) and accurate way to screen patients for potential bipolar disorder.9 If a patient shows a positive screening, the patients need to undergo comprehensive evaluation for diagnosis.8

Bipolar disorder is an affective (mood) disorder characterized by discrete episodes of mania, hypomania, and major depression. Some persons with bipolar disorder experience psychosis during these mood episodes. Two subtypes exist, namely, bipolar I disorder and bipolar II disorder.10 The problematic symptoms of bipolar disorder often impair a person's ability to function in society and maintain employment and interpersonal relationships. Bipolar disorder is associated with an increased incidence of suicide, violent behaviors, legal problems, comorbid psychiatric conditions, and substance use disorders.10,11 In the United States, bipolar disorder continues to be a common disabling psychiatric condition that is extremely likely to be accompanied by other disorders.11

In 1949, Australian psychiatrist John Cade established lithium as an effective treatment for bipolar disorder.12 Some 70 years later, it remains a mainstay treatment and is considered by many to be the “gold standard” treatment of bipolar disorder in the general population.4 Not only does lithium possess antimanic properties, but it also has well-established anti-suicidal and neuroprotective qualities.10,11

Childbearing women with bipolar disorder have a high risk of recurrent episodes in the perinatal period.13 Treatment with mood-stabilizing medication during pregnancy might be necessary to reduce this risk.13 Lithium is one of the medications available to childbearing women with bipolar disorder.13 Poels, et al. (2020) report that lithium is less likely to have adverse effects on the fetus than other drugs used to treat bipolar disorder, such as carbamazepine or valproate.13

Efficacy of Prescribing Lithium in Childbearing Women

Lithium is approved by the Food and Drug Administration (FDA) as monotherapy for the treatment of bipolar 1 disorder.14 It is approved for treating acute manic and mixed episodes in individuals aged 7 and older.14 It is also approved for maintenance treatment in patients aged 7 and older. It is available in 150 mg, 300 mg, and 600 mg capsules or tablets, and in liquid form.14

Lithium can be an effective treatment for mothers with bipolar disorder during pregnancy and the postpartum period. Lithium may control symptoms of bipolar disorder and may prevent a relapse of symptoms.15-17 After conducting a systematic review and meta-analysis of 29 studies, Fornaro, et al. (2020) concluded that lithium effectively prevented relapse during pregnancy.15 Rosso, et al. (2016) found the relapse rate was only 17.7% for those who continued lithium during their pregnancy.16 Uguz (2020) similarly found lithium nearly twice as effective in preventing new mood episodes in pregnant patients than lamotrigine.18

Potential Risks from Lithium Use During Pregnancy

Despite lithium’s clinical efficacy and overall safety, its medicinal use during pregnancy and the perinatal timeline presents serious challenges to clinicians, pharmacists, and patients. Continuing the use of lithium during pregnancy and the perinatal timeline may carry teratogenic risks for the fetus.17,19-21 This means that a woman who is prescribed lithium to treat a

psychiatric disorder needs to consider the teratogenic risks lithium may pose to the fetus.17,19-21

Women with bipolar disorder should coordinate with their healthcare providers prior to conception to weigh the risks, benefits, and evidenced-based recommendations for treatment with lithium during pregnancy; however, this is not always feasible because of unplanned pregnancies.19 Researchers have found a significantly higher rate of unplanned pregnancies among women with bipolar disorder.22 Zengin and Lus (2020) found that the rate of unplanned pregnancy was nearly 50% in women with bipolar disorder, compared to roughly 15% in the control group.23

The risks of continuation of lithium during pregnancy should be weighed carefully against the risks associated with discontinuation. The risk of relapse into a new mood episode is the most concerning potential risk associated with discontinuation of mood-stabilizing medicines.24 Viguera, et al. (2007) found that women who discontinued lithium proximal to pregnancy had an 85% relapse rate of at least one new mood episode.25 Furthermore, the authors found that women who abruptly stopped lithium after learning that they were pregnant had a greater than 50% rate of relapse into a mood episode within

2 weeks.25 Wesseloo, et al. (2016) conducted a meta-analysis of 5,700 deliveries from 4,023 women with bipolar disorder.26 The study found a relapse rate of 65% for those who discontinued prophylactic medications, while the rate of relapse was 23% for those who maintained prophylactic medications.26

Pharmacy technicians, as part of the healthcare team, can support patient care of women with bipolar disorder by asking the patient whether they are taking any over-the-counter products. This is important to minimize risks because lithium may interact with over-the-counter tryptophan, nonsteroidal anti-inflammatory agents, or St. John’s Wort.14 The pharmacy technician’s role in taking a medication history is helpful to support patient care. Lithium is prescribed less often than some other medications, so it is important for pharmacy technicians to manage inventory and keep lithium in stock for patients who have a prescription. Pharmacy technicians accurately process

prescriptions and inform the pharmacist of any drug interactions that appear on the computer profile while processing.

If a patient decides to continue lithium use, the clinician and pharmacist, if there is a collaborative agreement or associated scope of practice, must monitor the potential fluctuations in serum lithium levels. The variations that may occur during pregnancy can lead to subtherapeutic or supratherapeutic lithium levels.27 A patient should receive the lowest therapeutic dose based on the patient’s personal history.27

Teratogenic Risks

For decades, much research has been done on the potentially harmful effects of lithium exposure on fetuses and neonates.17 The results have varied, but overall, the consensus has been that lithium exposure does increase the risk of cardiac malformations, neurodevelopmental effects, and adverse outcomes;15,17,28 however, as will be discussed below, there may not be a significant difference in neurodevelopmental functioning for children who were exposed to lithium in utero.

Cardiac Malformations

In utero exposure to lithium is associated with cardiac malformations. In particular, lithium has been strongly associated with Ebstein’s anomaly, a defect of the tricuspid valve (that separates the right atrium from the right ventricle).17 In the 1970s, the correlation between cardiac defects and lithium was established.17 Early initial estimates found a 5-fold increase in cardiac defects and a 400-fold increased risk of an Ebstein’s anomaly.17

In a cohort study of more than 1.3 million pregnancies, Patorno, et al. (2017) found that among 663 infants exposed to lithium, the adjusted risk ratio was 1.65 for cardiac malformations.19 In daily doses greater than 900 mg, the risk increased to 3.22.19 In daily dosing between 601 to 900 mg, the risk was 1.60.19 In daily doses less than 600 mg, the risk decreased to 1.11.19

Boyle, et al. (2017) reviewed 5.6 million births in 12 countries from 1982 to 2011.20 They concluded that “the risk of Ebstein’s anomaly rises nearly threefold when the mother is reported to have mental health conditions with medications” but that the “data suggest that it is not lithium...specifically.”20

However, other studies have found the risk of cardiac malformations to be significantly less. After reviewing case studies and retrospective studies, Yacobi and Ornoy (2008) found that the literature was inconclusive and concluded that lithium was not a significant teratogen.29 However, the authors recommend that a fetal echocardiogram be utilized to check for cardiac malformations.29

A 2018 study found that cardiac malformation was not statistically significant for the fetuses of pregnant women exposed to lithium.30 Munk- Olsen, et al. (2018) reviewed 727 lithium-exposed pregnancies and 21,397 pregnancies with maternal bipolar or major depression.30 The authors concluded that lithium exposure was not associated with any predefined pregnancy complication or delivery outcome. They did find an increased risk of readmission in neonates exposed to lithium (27.5% who were exposed compared to 14.3% in unexposed).30 Lithium exposure in the first trimester was associated with an increased risk of malformations (7.4% compared to 4.3%), but cardiac malformation was not statistically significant (2.1% compared to 1.6%).30

Neurodevelopmental Risks

Poels, Schrijver, et al. (2018) reviewed case reports of eight children with lithium exposure that displayed neurodevelopmental delays. However, the authors noted that “most children were reported to have typical neurodevelopmental trajectories.”31 The authors concluded that “there is a paucity of clinical data on the neurodevelopment of children with in utero exposure to lithium. The three clinical studies published in the literature report normal neurodevelopment.”31

In a subsequent study, Poels, et al. (2022) found “no evidence for significantly altered neuropsychological functioning for children exposed to lithium in utero.”32 The study participants were aged 6–14 and were born between 2003 and 2011. These children were the offspring of women diagnosed with bipolar disorder. The study compared children exposed to lithium during the prenatal period to children who had not been exposed. Poels, et al. (2022) did observe minor differences in neuropsychological functioning, but overall, the study found the clinical evaluation of the participants’ neurodevelopment to be within the normal range for lithium‐ exposed offspring. These findings are consistent with prior studies on this topic.32 This information is important for pharmacists who may be counseling women with bipolar disorder on the use of lithium during the perinatal period.32

Large for Gestational Age

In a retrospective observational cohort study spanning from 1994 to 2018, Poels, et al. (2021) concluded that lithium use during pregnancy was associated with increased fetal growth parameters at 18–22 weeks gestational age and increased birth weight.33 In a Swedish population-based cohort study looking at 434 lithium-exposed pregnancies within 854,017 total pregnancies, the authors found that lithium was associated with large for gestational age infants.28 Although the Swedish study did not explore alterations in neonatal blood glucose levels, other researchers have found an association between large gestational-aged infants and neonatal hypoglycemia.34

Adverse Neonatal Events

Epstein, Moore, and Bobo (2015) report that exposure to lithium late in pregnancy has been associated with neonatal adaptation syndrome.21 This syndrome includes hypotonicity (decreased muscle tone), respiratory and feeding difficulties, cardiac arrhythmias, muscle fasciculations (involuntary muscle twitches), lethargy, cyanosis (deoxygenated hemoglobin), and reduced reflexes. The syndrome resolves in 1 to 2 weeks and rarely leads to lasting complications.21 Low Apgar scores, longer hospitalizations, and neurological

complications are associated with lithium concentrations greater than 0.64 mEq/L at delivery. A low Apgar score means the baby needs medical help to adjust outside the womb. Other neonate complications include nontoxic goiter (enlarged thyroid with normal thyroid levels), hypoglycemia, nephrogenic diabetes insipidus (when the kidneys cannot balance body fluids or concentrate urine), and hypothyroidism.21

Risk of Spontaneous Preterm Birth

Preterm birth is defined as delivery at less than 37 weeks of completed pregnancy and is associated with negative fetal outcomes.35 Hastie, et al. (2021) found a two-fold increase in spontaneous preterm birth in women using lithium during pregnancy, with 35.2 weeks being the median gestational age at birth.28

Risk of Miscarriage

The general rate of miscarriages during pregnancies in the population at large is around 10–15%.13 For women with bipolar I disorder who have not been exposed to lithium, the rate is the same. The rate of miscarriage in women exposed to lithium during pregnancy is reportedly twice as high.13 The increased risk associated with lithium use does not appear to change when “adjusting for the age at conception, the clustering of pregnancies per woman, and their lifetime use of valproate and carbamazepine.”13

Another factor reviewed in this study was the age of onset of bipolar disorder.13 Generally, the age of onset indicates how severe the psychiatric condition will be in a patient, but the age of onset was similar for participants regardless of their exposure to lithium. This suggested that illness severity did not play a role in the increase in miscarriages and that lithium use was the cause of the effect.13

Poels, et al. (2020) hypothesized that overt and subclinical hypothyroidism was connected with pregnancy loss.13 Hypothyroidism could develop during lithium treatment, which may be the mechanism for a miscarriage.13,36

Poels, et al. (2020) did report limitations with their study. Because it was conducted by questionnaire, they did not have information on each participant’s lithium doses or levels during their pregnancy, so they could not consider dose–response relationships. Other factors, such as the mother’s physical condition, weight, and substance use (e.g., alcohol and tobacco), were unavailable.13 These limitations did not dissuade the authors from concluding that lithium may increase the risk of miscarriage.13

Managing Lithium’s Teratogenic, Miscarriage, and Suicide Risks

There is a potential teratogenic risk associated with lithium use and a higher risk for a miscarriage. These risks must be balanced against discontinuing lithium during this time because it can lead to complications in maternal treatment for maternal psychiatric disorders.13 In addition, fluctuations in serum lithium levels may occur during pregnancy that can lead to subtherapeutic or supratherapeutic lithium levels. As a consequence, lithium treatment should be carefully managed in childbearing women.19,27

Managing Teratogenic Risks

Due to concerns about teratogenic effects, women and clinicians may opt to discontinue medications during the perinatal period. If a woman does choose to discontinue lithium during the perinatal period, monitor for the potential risk of a relapse of bipolar disorder symptoms. As integral members of the healthcare team, pharmacists are adept at identifying opportunities for deprescribing with shared decision-making. Although this strategy avoids teratogenic risks, it is not without other significant risks, in particular, relapse into an affective episode.

Some experts recommend the use of up to 4mg of folic acid daily in lithium-treated pregnancies to reduce the risk of cardiac malformation.37,38

Research suggests that some teratogenic risks may be dose- dependent. One study found lithium doses greater than 900 mg daily led to a 3-fold risk of cardiac malformations.19 Similarly, rodent studies of lithium’s teratogenic effects suggest that teratogenicity may be dose related.39,40

Lithium exposure during the first trimester has long been established as an increased risk factor for teratogenic effects. Patorno, et al. (2017) found that the risk of cardiac malformation following lithium exposure in the first trimester was four times greater than previously thought.19 Although not always feasible, reducing or eliminating fetal exposure to lithium during the first trimester could be efficacious in preventing teratogenic effects.

Managing the Risk of Miscarriage

Women of child-bearing age taking lithium should be monitored and counseled on potential daily folic acid supplementation.41,42

Pre-Pregnancy Therapy Clinical Pearl

Although the correlation between increased rates of miscarriage and lithium exposure during pregnancy is well-founded, there are no clear recommendations to mitigate the risk aside from the widely established recommendation to limit lithium exposure during the first trimester.13

Managing Suicide Risks

Acute lithium overdose can occur with suicide attempts. Regular suicide screenings are important for prevention.43

Lithium Pharmacokinetics in the Perinatal Period

The perinatal period is marked by profound physiological changes that influence lithium clearance. Lithium is renally excreted, and serum lithium levels depend on intravascular volume and glomerular filtration rate (GFR).14 During pregnancy, plasma volume, total body water volume, and GFR increase by as much as 50%, which results in a significant decrease in serum lithium levels.17 Poels, Bijma, et al. (2018) report that serum levels decrease by an average of 24% during the first trimester, 36% during the second trimester, and 21% in the third trimester, respectively.17 This notable decrease in serum lithium levels can lead to subtherapeutic levels and the possible relapse into a mood episode.

In a prospective longitudinal study of only 3 pregnant women treated with lithium, Clark, et al. (2022) found that, compared to the nonpregnant state, lithium clearance increased on average by 63.5% by the third trimester in the population studied.44 Clark, et al., found that an increased lithium clearance continued through the second and third trimesters.44

During pregnancy, lithium clearance increases in response to profound physiological changes and increased renal excretion, and the glomerular filtration rate (GFR) rapidly returns to baseline.44 Clark, et al., found that lithium clearance had returned to baseline by 4 to 9 weeks postpartum.44

Serum levels can become supratherapeutic or even toxic in the third trimester and postpartum period due to medical conditions that may arise at this time.17,44 Medical conditions common in pregnancy, including morning sickness, hyperemesis gravidarum (severe nausea and vomiting), dehydration, impaired renal function, and preeclampsia, can increase the likelihood of developing toxic lithium levels.17

Lithium potentiates succinylcholine, pancuronium bromide, and other muscle relaxants; therefore, care should be taken during the delivery process.45 Regional anesthesia is considered safe with concurrent lithium use.17,45

Laboratory Testing and Monitoring

Due to the pharmacokinetic changes associated with pregnancy, serum lithium levels should be checked more frequently during the perinatal period. Drawing trough-lithium levels as close as possible to 12 hours after dosing is the established means to measure serum lithium concentrations.46

Most experts recommend close monitoring of lithium levels and renal function labs – every 3 weeks was suggested – until 34 weeks of pregnancy and then weekly until delivery.17 Wesseloo, Wierdsma, et al. (2017) note that more frequent monitoring may be necessary if dehydration, pre-eclampsia, or other illnesses that affect renal function develop.27 Additionally, if lithium dosage adjustments are made, another serum lithium level should be obtained in 1 week.27 Lithium levels should be checked within 24 hours after delivery and up to twice weekly for the first 2 weeks postpartum.17,27,44

Poels, et al. (2018) recommend that a lithium level, thyroid stimulating hormone (TSH), and free thyroxine (T4) level be obtained from the umbilical cord blood sample.17

Although the decline in serum levels is expected during pregnancy, Clark, et al. (2022) found that symptoms worsened in patients with lithium levels that decrease >0.2 mEq/L below their baseline concentration and/or below the minimal therapeutic level of 0.4 mEq/L; therefore, dose adjustments should be made to maintain a therapeutic serum level.44 Wesseloo, et al. (2016) recommended a target therapeutic level postpartum of >0.8 mEq/L for optimal relapse prevention.26 Poels, et al. (2018) similarly recommend a target of 0.8-1.0 mEq/L for relapse prevention postpartum.17

Lithium Dosing Adjustments During Pregnancy

Most experts agree that maintaining a therapeutic serum lithium level and symptomological management should dictate the dosing of lithium during the perinatal period while carefully weighing the associated maternal and fetal risks.

The American College of Obstetricians and Gynecologists and other experts recommend that lithium be dosed twice daily during pregnancy to avoid high peak concentrations.38 Clark, et al. (2022) suggest that sustain- release formulations of lithium could be utilized as alternatives to twice daily dosing of immediate-release lithium.44

The American College of Obstetricians and Gynecologists noted that holding lithium doses at the onset of labor or 24-48 hours before a scheduled birth may reduce the risk of adverse neonatal events.38 Poels, et al. (2018) suggest that lithium be resumed on the first evening after delivery if clinically indicated.17 This is important since the first month postpartum represents a high-risk time for maternal relapse of bipolar disorder symptoms.2

Lithium Adverse Events and Poisoning

Lithium has a relatively narrow therapeutic window, such that a small change in serum lithium concentration can result in subtherapeutic effects, intoxication, or poisoning.14,49,50 As such, the prescribing information contains a warning for lithium toxicity: “Lithium toxicity is closely related to serum lithium concentrations and can occur at doses close to therapeutic

Lithium requires a trough-level lab draw right BEFORE the next dose, which is typically 12 hours after the last dose.47,48

Therapeutic plasma concentration levels for postpartum women are 0.8-

1.0 mEq/L48

Lithium Clinical Pearl

concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating treatment.”14

Lithium use at therapeutic levels can lead to adverse events.51,52 For example, serum lithium levels >0.8 mEq/l are associated with higher rates of diarrhea.51 Lithium use at therapeutic levels can also cause T-wave depressions and sinus node dysfunction, which is often tied to the duration of lithium treatment; however, these medical events are usually benign and asymptomatic.47 Symptoms from mild to moderate toxic lithium effects may appear at levels as low as 1.5 mEq/L.53

At toxic levels, >1.5 mEq/L, lithium “can cause sinoatrial block, intraventricular conduction delay, ST depressions/elevations, the Brugada pattern, atrioventricular conduction delays, QTc prolongation, and changes in the QTdR,” which may cause ventricular instability, cardiac arrhythmias, and sudden cardiac death.47

Unintentional chronic lithium overdose is the most common cause of lithium toxicity.49 It is typically due to impaired kidney function from lithium- induced nephrogenic diabetes insipidus or intercurrent illnesses. Additionally, lithium itself can cause damage to the kidneys.49,54

Lithium can rarely precipitate serotonin syndrome, a potentially life- threatening condition.14 The risk is increased with the concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors, serotonin, and norepinephrine reuptake inhibitors.14 The risk is also increased with triptans, tricyclic antidepressants, fentanyl, tramadol, buspirone, and with drugs that impair the metabolism of serotonin, i.e., MAO Inhibitors.14 Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), or autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia).14 Neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) may also result from serotonin syndrome.14

In the context of a pregnant patient, shifts in fluid balance can lead to increased risks for maternal and infant lithium toxicity.41 For pharmacy staff in a hospital setting, laboratory monitoring can reveal these issues. It is essential that kidney and heart functions be monitored to detect and avoid chronic lithium overdose.

In the event of lithium poisoning, the Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup has developed evidence-based recommendations for the use of extracorporeal treatments for lithium poisoning.54 Extracorporeal treatments should be used in patients with severe lithium toxicity.54 A further discussion of these treatments is beyond the scope of this course, but Decker, et al. (2015) describe extracorporeal treatments and their recommended uses.54

If poisoning, teratogenicity, or other serious adverse events are identified, confirm that the institutional or practice setting leadership is aware, and consider reporting to MedWatch at this link:55 https://www.fda.gov/safety/medwatch-fda-safety-information-and- adverse-event-reporting-program

Lithium and Breastfeeding

Breastfeeding while on lithium is generally not advisable. Lithium is excreted into breast milk.13,39,40 Up to one-half of a mother’s lithium levels will be present in breast milk. A breastfeeding infant can ingest approximately one- half of that, which means an infant will take in about one-fourth of the mother’s lithium levels.39 Infants have lower GFR than adults, which increases the risk of infant lithium toxicity.13

A mother may decide to stop taking lithium if she wants to breastfeed. This may be an instance where the mother may want to look at alternative medications that can treat her mental health condition and allow her to breastfeed her infant.39

However, not all researchers agree on the topic.48,56,57 Some researchers have concluded that there is a lack of evidence finding severe negative effects on breastfed infants exposed to lithium.48 This suggests lithium could be a viable option for a breastfeeding mother being treated for bipolar disorder.48 A Swedish study that monitored the outcomes of 30 infants exposed to lithium through breastmilk concluded that it can be considered safe under strict monitoring.56 The authors found that serum lithium levels in the infants were higher than expected during the first few weeks but then stabilized to barely detectable levels.56 Poor weight gain was the only adverse effect noted in the study.56

Hermann, et al. (2019) suggest that if the mother breastfeeds while taking lithium, it should be done in close collaboration with the infant’s pediatrician.57 The authors recommend that the infant’s serum lithium level, renal function, and thyroid function be monitored during the exposure.57

The American College of Obstetricians and Gynecologists (ACOG) Guidelines

In 2023, the American College of Obstetricians and Gynecologists (ACOG) provided updated guidelines for the treatment and management of mental health during pregnancy and postpartum. The guideline included the following recommendations:38

ACOG recommends against discontinuing mood stabilizers, except for valproate, during pregnancy due to the risk of recurrence or exacerbation of mood symptoms.

ACOG recommends that pregnant patients taking lithium in the first trimester receive a detailed ultrasound examination in the second trimester.

It is imperative that lithium dosing be monitored during pregnancy and postpartum.

Alternative Drugs During Pregnancy

Lamotrigine is widely considered non-teratogenic and is often a safe alternative to lithium in pregnancy.58 Wesseloo, Liu, et al. (2017) conducted a cohort study that did not find lamotrigine inferior to lithium in preventing severe postpartum episodes.58 In addition, second-generation antipsychotics (SGAs) may have a favorable safety profile and efficacy in treating pregnant women with bipolar disorder.16 Nevertheless, lamotrigine and SGAs are not universal treatments for all pregnant women with bipolar disorder.58,59 Second-generation antipsychotics are used to treat affective disorders during pregnancy. They are mostly used as an adjuvant medication to enhance the effectiveness of a primary drug; however, the use of SGAs is controversial in this population group, and more research is needed.56 With lamotrigine, pharmacokinetic changes may alter its efficacy, which may require modifying dosing in pregnant patients.58,59

Valproate is not recommended during any trimester of pregnancy due to the well-established risk of teratogenicity and neurodevelopmental adverse effects. Similarly, carbamazepine and oxcarbazepine should be avoided, especially during the first trimester.38

Clinicians and patients should carefully make informed decisions after weighing the risks and benefits. For some women, initiation or continuation of lithium is clinically indicated.10 For example, if a woman with bipolar disorder has good, stable outcomes with lithium, she should continue on lithium.10

Lithium Use During Pregnancy Case Reports Case Report I

A 25-year-old pregnant woman was hospitalized due to suspicion of lithium toxicity at 28 weeks gestation.60 Serum lithium was 2.1 mEq/L and increased to 5.0 mEq/L over the next 6 hours despite intravenous fluid administration. As the mother underwent hemodialysis, the gynecologist

determined that a cesarean section was necessary. The baby had an Apgar score of 2 and died. The autopsy found that the cord blood lithium level was

4.8 mEq/L in an otherwise normally developed baby.60 In this case report, we see the potentially devastating consequences of lithium exposure in the perinatal period.60

Case Report II

A case report from the Journal of Brazilian Psychiatry demonstrates the importance of considering the risks and benefits of lithium use during pregnancy.61 In this report, a 32-year-old female of Hispanic ethnicity had an established diagnosis of bipolar I disorder. Reportedly, she had a 9-year history of illness with 4 severe manic episodes, which had led to lengthy hospitalizations. She had been stabilized on 1500 mg daily of lithium.61

The patient desired to become pregnant. With her psychiatrist, the patient considered the risks and benefits of lithium continuation during pregnancy. Utilizing a decision tree, she and the psychiatrist agreed to continue the lithium throughout the pregnancy. The case concludes with the successful delivery of a healthy baby and the continued psychiatric stability of the patient.61 This case study highlights the safe and effective use of lithium during pregnancy after careful consideration between a patient and her psychiatrist.61

Case Report III

A 40-year-old woman with a history of bipolar disorder sought clinical consultation as she was planning a pregnancy.62 She had been stabilized on olanzapine and lithium 1200 mg daily for 10 years. After consultation with her psychiatrist, family doctor, and gynecologist, the olanzapine was stopped, and lithium was tapered.62 A few months after the lithium taper began, while still on 300 mg daily, she developed a manic episode. Lithium was titrated, and olanzapine was re-started, effectively treating the mania.62 In this case report,

we see despite a lengthy period of stabilization, an attempt to discontinue lithium as part of reproductive planning led to a relapse into mania.62

Key Points

There are key points that pharmacists and other clinicians need to consider in women with a diagnosis of bipolar disorder before and during pregnancy, at the time of childbirth, and after the delivery of their newborn child.

Before Pregnancy:

Shared decision-making should weigh the risks and benefits of lithium continuation or discontinuation10

Begin folate supplementation37,38,41,42 During Pregnancy:

Use the lowest effective lithium dosage while maintaining therapeutic serum levels27

Dosing greater than 900 mg daily has the greatest risk of cardiac malformations19

In the 1st and 2nd trimesters, lithium levels decrease (without dose adjustments)17,44

In the 3rd trimester, lithium levels increase (without dose adjustments)17,44

Monitor serum lithium levels during pregancy17

Monitor fetal cardiac development during pregnancy using fetal echocardiography or ultrasound19,29

Dehydration secondary to morning sickness and other common conditions of pregnancy can result in rapid, severe increases in serum lithium levels27

Delivery:

Continue monitoring because shifts in fluid balance has led to increased risks for maternal and infant lithium toxicity13,52

Withholding lithium for 24-48 hours prior to delivery improves neonatal outcomes38

After Delivery:

Monitor the infant’s serum lithium level, renal function, and thyroid function be monitored during the exposure57

Resume preconception dosing if clinically indicated17

The first month postpartum represents a high-risk time for maternal relapse2

Breastfeeding while on lithium is generally not recommended13,39,40 Patient Education:14

Emphasize the importance of adherence to prescribed dosing

Emphasize avoiding dose adjustment unless directed by the prescriber

Inform the patient that regular blood draws will be needed

Tell the patients never to double the dose if they miss a dose

Tell the patient to immediately contact the prescriber if diarrhea, vomiting, tremor, lack of muscle coordination, drowsiness, abnormal heart rhythm or muscular weakness occurs

Inform the patient of the importance of maintaining a normal diet, staying hydrated, and not to change their intake of salt without telling the prescriber

Advise the patient NOT to start or stop any medicines while taking lithium without talking to the healthcare provider first

Keep a list of medicines to show the healthcare provider and pharmacist when prescribing or purchasing any new medicine

Summary

Lithium has been an effective treatment for bipolar disorder for more than 70 years. The efficacy of lithium in treating mothers during pregnancy and the postpartum period has been confirmed: Lithium has been identified as an effective treatment to control symptoms of bipolar disorder and prevent a relapse of symptoms. Childbearing women with bipolar disorder have a high risk of recurrent episodes in the perinatal period. Lithium is one of the medications available to childbearing women with bipolar disorder. Lithium is less likely to have adverse effects on the fetus than other drugs that are used to treat bipolar disorder.

Despite its clinical efficacy and overall safety, the medicinal use of lithium during pregnancy and the perinatal timeline presents serious challenges to clinicians and patients. Continuing the use of lithium during pregnancy and the perinatal timeline may carry teratogenic risks for the fetus, and it may raise the risk of a miscarriage. This means that a woman who is prescribed lithium to treat a psychiatric disorder needs to consider the teratogenic risks lithium may pose to the fetus. She must also consider the risk that continued lithium use during this time may be associated with a higher risk of a miscarriage. Nevertheless, there appears to be no need at this time to alter clinical guidelines for lithium use during pregnancy, but dosing adjustments may need to be made to address the fluctuations in serum lithium levels that can occur during pregnancy.

Women with bipolar disorder should coordinate with their healthcare providers prior to conception in order to weigh the risks, benefits, and evidenced-based recommendations for treatment with lithium during pregnancy. Breastfeeding while on lithium is generally not advisable as lithium is excreted into breast milk. However, some research suggests that breastfeeding while on lithium is safe under close monitoring.

Course Test

Lithium has been found to be an effective treatment for pregnant and postpartum women

by controlling bipolar disorder symptoms.

by reducing the risk of miscarriage.

because mothers on lithium can breastfeed since the drug is not excreted into breast milk.

by reducing teratogenic risks for the fetus.

Exposure to lithium late in pregnancy has been associated with neonatal adaptation syndrome, which may include the following symptom:

hypertonicity.

hyperactivity.

muscle fasciculations.

higher than normal oxygen saturation in the blood.

The 2023 guidelines of the American College of Obstetricians and Gynecologists for the treatment and management of mental health during pregnancy and postpartum provide that

pregnant patients NOT take lithium in the first trimester.

all mood stabilizers be discontinued during pregnancy and restarted during the postpartum period.

valproate is the first-line drug to treat mood disorders during pregnancy.

pregnant patients taking lithium in the first trimester receive a detailed ultrasound examination in the second trimester.

When women and their clinicians opt to discontinue lithium use during the perinatal period, monitor for the potential risk of

infections.

a relapse of bipolar disorder symptoms.

lithium toxicity.

gestational diabetes.

Lithium therapy should be resumed as soon as possible after delivery of the baby because

this is when Ebstein’s anomaly is most likely.

the first month postpartum is a high-risk time for maternal relapse of bipolar disorder symptoms.

the mother will likely be breastfeeding the newborn.

this is when lithium is likely to be at a supratherapeutic level.

Lithium use at therapeutic levels can cause , which are often associated with the duration of lithium therapy in patients.

dry eyes and chapped lips

T-wave depressions and sinus node dysfunction

pregnancy-induced type 1 and 2 diabetes

severe constipation and middle ear infection

Ebstein’s anomaly is a teratogenic risk associated with taking lithium during pregnancy that is categorized as

a cardiac malformation.

a neurodevelopmental risk.

an adverse event associated with breastfeeding.

a fluctuation in a mother’s serum lithium level.

Low Apgar scores, longer hospitalizations, and neurological complications are associated with lithium serum concentrations

at delivery.

of 0.2-0.4 mEq/L

< 0.4 mEq/L

> 0.64 mEq/L

< 0.2 mEq/L

Serum levels can become supratherapeutic or even toxic during the third trimester of pregnancy due to

glomerular filtration rate (GFR).

increases in total body water volume.

an increase in intravascular volume.

hyperemesis gravidarum and dehydration.

The American College of Obstetricians and Gynecologists noted that holding lithium doses at the onset of labor, or a scheduled birth, may reduce the risk of adverse neonatal events.

one hour before

for 24-48 hours before

for 8 hours

at the time of

References

Masters GA, Brenckle L, Sankaran P, et al. Positive screening rates for bipolar disorder in pregnant and postpartum women and associated risk factors. Gen Hosp Psychiatry. 2019;61:53-59. doi:10.1016/j.genhosppsych.2019.09.002

Vichi M, Berardelli I, Pompili M. Completed suicide during pregnancy and postpartum. Ann Ist Super Sanita. 2021;57(1):57-66. doi:10.4415/ANN_21_01_09

Chin K, Wendt A, Bennett IM, Bhat A. Suicide and Maternal Mortality. Curr Psychiatry Rep. 2022;24(4):239-275. doi:10.1007/s11920-022- 01334-3

Trost SL, Beauregard JL, Smoots AN, et al. Preventing Pregnancy- Related Mental Health Deaths: Insights From 14 US Maternal Mortality Review Committees, 2008-17. Health Aff (Millwood). 2021;40(10):1551-1559. doi:10.1377/hlthaff.2021.00615

Lindahl V, Pearson JL, Colpe L. Prevalence of suicidality during pregnancy and the postpartum. Arch Womens Ment Health. 2005;8(2):77-87. doi:10.1007/s00737-005-0080-1

Rybakowski J. Lithium treatment – the state of the art for 2020.

Psychiatria Polska. 2020;54(6):1047-1066. doi:10.12740/PP/128340

Chen PH, Tsai SY, Chen PY, et al. Mood stabilizers and risk of all-cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study. Acta Psychiatr Scand. 2023;147(3):234-247. doi:10.1111/acps.13519

Hirschfeld RM. The Mood Disorder Questionnaire: A Simple, Patient- Rated Screening Instrument for Bipolar Disorder. Prim Care Companion J Clin Psychiatry. 2002;4(1):9-11. doi:10.4088/pcc.v04n0104

The Mood Disorder Questionnaire (MDQ) - Overview. Undated. https://ibpf.org/wp-content/uploads/2016/11/MDQ.pdf. Accessed May 20, 2023.

Volkmann C, Bschor T, Köhler S. Lithium Treatment Over the Lifespan in Bipolar Disorders. Front Psychiatry. 2020;11:377. Published 2020 May

7. doi:10.3389/fpsyt.2020.00377

Blanco C, Compton WM, Saha TD, et al. Epidemiology of DSM-5 bipolar I disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions - III. J Psychiatr Res. 2017;84:310-317. doi:10.1016/j.jpsychires.2016.10.003

Draaisma D. Lithium: the gripping history of a psychiatric success story.

Nature. 2019;572(7771):584–585. doi: 10.1038/d41586-019-02480-0

Poels EMP, Kamperman AM, Vreeker A, et al. Lithium Use during Pregnancy and the Risk of Miscarriage. J Clin Med. 2020;9(6):1819. Published 2020 Jun 11. doi:10.3390/jcm9061819

Lithium. Prescribing information. West-Ward Pharmaceuticals. December 2018.

https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/017812s0 33,018421s032,018558s027lbl.pdf. Accessed July 26, 2023.

Fornaro M, Maritan E, Ferranti R, et al. Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta- Analysis of Safety and Efficacy Outcomes. Am J Psychiatry. 2020;177(1):76-92. doi:10.1176/appi.ajp.2019.19030228

Rosso G, Albert U, Di Salvo G, Scatà M, Todros T, Maina G. Lithium prophylaxis during pregnancy and the postpartum period in women with lithium-responsive bipolar I disorder. Arch Womens Ment Health. 2016;19(2):429-432. doi:10.1007/s00737-016-0601-0

Poels EMP, Bijma HH, Galbally M, Bergink V. Lithium during pregnancy and after delivery: a review. Int J Bipolar Disord. 2018;6(1):26. Published 2018 Dec 2. doi:10.1186/s40345-018-0135-7

Uguz F. Pharmacological prevention of mood episodes in women with bipolar disorder during the perinatal period: A systematic review of current literature. Asian J Psychiatr. 2020;52:102145. doi:10.1016/j.ajp.2020.102145

Patorno E, Huybrechts KF, Bateman BT, et al. Lithium Use in Pregnancy and the Risk of Cardiac Malformations. N Engl J Med. 2017;376(23):2245-2254. doi:10.1056/NEJMoa1612222

Boyle B, Garne E, Loane M, et al. The changing epidemiology of Ebstein's anomaly and its relationship with maternal mental health conditions: a European registry-based study. Cardiol Young. 2017;27(4):677-685. doi:10.1017/S1047951116001025

Epstein RA, Moore KM, Bobo WV. Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges. Drug Healthc Patient Saf. 2014;7:7-29. Published 2014 Dec 24. doi:10.2147/DHPS.S50556

Marengo E, Martino DJ, Igoa A, et al. Unplanned pregnancies and reproductive health among women with bipolar disorder. J Affect Disord. 2015;178:201-205. doi:10.1016/j.jad.2015.02.033

Zengin Eroglu M, Lus MG. Impulsivity, Unplanned Pregnancies, and Contraception Among Women with Bipolar Disorder. Neuropsychiatr Dis Treat. 2020; 16:407-414. Published 2020 Feb 7. doi:10.2147/NDT.S238887

Larsen ER, Saric K. Pregnancy and bipolar disorder: the risk of recurrence when discontinuing treatment with mood stabilisers: a

systematic review. Acta Neuropsychiatr. 2017;29(5):259-266. doi:10.1017/neu.2016.60

Viguera AC, Whitfield T, Baldessarini RJ, et al. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007;164(12):1817- 1923. doi:10.1176/appi.ajp.2007.06101639

Wesseloo R, Kamperman AM, Munk-Olsen T, Pop VJ, Kushner SA, Bergink V. Risk of Postpartum Relapse in Bipolar Disorder and Postpartum Psychosis: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2016;173(2):117-127. doi:10.1176/appi.ajp.2015.15010124

Wesseloo R, Wierdsma AI, van Kamp IL, Munk-Olsen T, Hoogendijk WJG, Kushner SA, Bergink V. Lithium dosing strategies during pregnancy and the postpartum period. Br J Psychiatry. 2017 Jul;211(1):31-36. doi: 10.1192/bjp.bp.116.192799

Hastie R, Tong S, Hiscock R, et al. Maternal lithium use and the risk of adverse pregnancy and neonatal outcomes: a Swedish population-based cohort study. BMC Med. 2021;19(1):291. Published 2021 Dec 2. doi:10.1186/s12916-021-02170-7

Yacobi S, Ornoy A. Is lithium a real teratogen? What can we conclude from the prospective versus retrospective studies? A review. Isr J Psychiatry Relat Sci. 2008;45(2):95-106.

Munk-Olsen T, Liu X, Viktorin A, et al. Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies. Lancet Psychiatry. 2018;5(8):644- 652. doi:10.1016/S2215-0366(18)30180-9

Poels EMP, Schrijver L, Kamperman AM, et al. Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2018;27(9):1209-1230. doi:10.1007/s00787-018- 1177-1

Poels EMP, Schrijver L, White TJH, et al. The effect of prenatal lithium exposure on the neuropsychological development of the child. Bipolar Disord. 2022;24(3):310-319. doi:10.1111/bdi.13133

Poels EM, Sterrenburg K, Wierdsma AI, et al. Lithium exposure during pregnancy increases fetal growth. J Psychopharmacol. 2021;35(2):178-

183. doi:10.1177/0269881120940914

Weissmann-Brenner A, Simchen MJ, Zilberberg E, et al. Maternal and neonatal outcomes of large for gestational age pregnancies. Acta Obstet Gynecol Scand. 2012;91(7):844-849. doi:10.1111/j.1600- 0412.2012.01412.x

Di Renzo GC, Roura LC; European Association of Perinatal Medicine- Study Group on Preterm Birth. Guidelines for the management of

spontaneous preterm labor. J Perinat Med. 2006;34(5):359-366. doi:10.1515/JPM.2006.073

Czarnywojtek A, Zgorzalewicz-Stachowiak M, Czarnocka B, et al. Effect of lithium carbonate on the function of the thyroid gland: mechanism of action and clinical implications. J Physiol Pharmacol. 2020;71(2):10.26402/jpp.2020.2.03. doi:10.26402/jpp.2020.2.03

Huhta JC, Linask K. When should we prescribe high-dose folic acid to prevent congenital heart defects?. Curr Opin Cardiol. 2015;30(1):125-

131. doi:10.1097/HCO.0000000000000124

Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023;141(6):1262-1288. doi:10.1097/AOG.0000000000005202

Szabo KT. Teratogenic effect of lithium carbonate in the foetal mouse.

Nature. 1970;225:73–5.

Smithberg M, Dixit PK. Teratogenic effects of lithium in mice.

Teratology. 1982;26:239–46.

Kennedy MLH. Medication management of bipolar disorder during the reproductive years. Ment Health Clin. 2018;7(6):255-261. Published 2018 Mar 23. doi:10.9740/mhc.2017.11.255

Post RM, Yatham LN, Vieta E, Berk M, Nierenberg AA. Beyond evidence- based treatment of bipolar disorder: Rational pragmatic approaches to management. Bipolar Disord. 2019;21(7):650-659. doi:10.1111/bdi.12813

Weber AN, Michail M, Thompson A, Fiedorowicz JG. Psychiatric Emergencies: Assessing and Managing Suicidal Ideation. Med Clin North Am. 2017;101(3):553-571. doi:10.1016/j.mcna.2016.12.006

Clark CT, Newmark RL, Wisner KL, Stika C, Avram MJ. Lithium Pharmacokinetics in the Perinatal Patient With Bipolar Disorder. J Clin Pharmacol. 2022;62(11):1385-1392. doi:10.1002/jcph.2089

Kishimoto N, Yoshikawa H, Seo K. Potentiation of Rocuronium Bromide by Lithium Carbonate: A Case Report. Anesth Prog. 2020;67(3):146-

150. doi:10.2344/anpr-66-04-04

Reddy DS, Reddy MS. Serum Lithium Levels: Ideal Time for Sample Collection! Are We Doing it Right?. Indian J Psychol Med. 2014;36(3):346-347. doi:10.4103/0253-7176.135399

Mehta N, Vannozzi R. Lithium-induced electrocardiographic changes: A complete review. Clin Cardiol. 2017;40(12):1363-1367. doi:10.1002/clc.22822

Pacchiarotti I., Leon-Caballero J., Murru A., Verdolini N., Furio M.A., Pancheri C., Valenti M., Samalin L., Roige E.S., Gonzalez-Pinto A., et al. Mood stabilizers and antipsychotics during breastfeeding: Focus on

bipolar disorder. Eur. Neuropsychopharmacol. 2016;26:1562–1578. doi: 10.1016/j.euroneuro.2016.08.008

Baird-Gunning J, Lea-Henry T, Hoegberg LCG, Gosselin S, Roberts DM. Lithium Poisoning. J Intensive Care Med. 2017;32(4):249-263. doi:10.1177/0885066616651582

Haussmann R, Bauer M, von Bonin S, Grof P, Lewitzka U. Treatment of lithium intoxication: facing the need for evidence. Int J Bipolar Disord. 2015;3(1):23. doi:10.1186/s40345-015-0040-2

Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 2016;4(1):27. doi:10.1186/s40345-016- 0068-y

Enderle J, Klink U, di Giuseppe R, et al. Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates. Nutrients. 2020;12(8):2489. Published 2020 Aug 18. doi:10.3390/nu12082489

Boltan DD, Fenves AZ. Effectiveness of normal saline diuresis in treating lithium overdose. Proc (Bayl Univ Med Cent). 2008;21(3):261-263. doi:10.1080/08998280.2008.11928407

Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol. 2015;10(5):875-887. doi:10.2215/CJN.10021014

U.S. Food and Drug Administration. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. FDA. 2023. https://www.fda.gov/safety/medwatch-fda-safety-information-and- adverse-event-reporting-program. Accessed August 1, 2023.

Heinonen E, Tötterman K, Bäck K, Sarman I, Svedenkrans J, Forsberg L. Lithium use during breastfeeding was safe in healthy full-term infants under strict monitoring. Acta Paediatr. 2022;111(10):1891-1898. doi:10.1111/apa.16444

Hermann A, Gorun A, Benudis A. Lithium Use and Non-use for Pregnant and Postpartum Women with Bipolar Disorder. Curr Psychiatry Rep. 2019;21(11):114. Published 2019 Nov 7. doi:10.1007/s11920-019-

1103-3

Wesseloo R, Liu X, Clark CT, Kushner SA, Munk-Olsen T, Bergink V. Risk of postpartum episodes in women with bipolar disorder after lamotrigine or lithium use during pregnancy: A population-based cohort study. J Affect Disord. 2017;218:394-397. doi:10.1016/j.jad.2017.04.070

Trifu SC, Popescu A, Marian MA. Affective disorders: A question of continuing treatment during pregnancy (Review). Exp Ther Med. 2020;20(4):3474-3482. doi:10.3892/etm.2020.8989

Pinheiro EA, Stika CS. Drugs in pregnancy: Pharmacologic and physiologic changes that affect clinical care. Semin Perinatol. 2020;44(3):151221. doi:10.1016/j.semperi.2020.151221

Restrepo CG, Pedraza RS, Camacho A. Use of lithium during pregnancy: a case report using clinical decision analysis. Braz J Psychiatry. 2010;32(1):95-98. doi:10.1590/s1516-44462010000100020

DISCLAIMER

The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization, for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses are constantly changing, and any person taking this course understands that such person must make an independent review of medication information prior to any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

Nothing contained in this course represents the opinions, views, judgments, or conclusions of RxCe.com LLC. RxCe.com LLC is not liable or responsible to any person for any inaccuracy, error, or omission with respect to this course, or course material.

Back to Lithium: Managing Bipolar Disorder in Childbearing Women (Pharmacist)
Back to Lithium: Managing Bipolar Disorder in Childbearing Women (Pharmacy Tech)