BIPOLAR DISORDER

TREATMENT IN PREGNANCY AND BREASTFEEDING

Bipolar Disorder - Treatment

Mood Stabilizers
Lithium Antiepileptics Atypical antipsychotics

Antidepressants Electroconvulsive therapy

Lithium
severity and frequency manic and depressive episodes in 70% of patients Commonly used in combo with other meds1 FDA Pregnancy Category: D2

1. Eisendrath SJ, Lichtmacher JE. Chapter 25. Psychiatric Disorders. In: Papadakis MA, McPhee SJ, Rabow MW, eds. CURRENT Medical Diagnosis & Treatment 2013. New York: McGraw-Hill; 2013. http://www.accessmedicine.com/content.aspx?aID=13381. Accessed September 11, 2012. 2. Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Lithium Pregnancy
Side effects in pregnant women
Endocrine and GI problems Fine tremor, sedation, ataxia, metallic taste, weight gain, benign leukocytosis. Toxic levels of lithium: Confusion, coarse tremors, seizures, death. Monitor lithium levels, thyroid and kidney functions weekly. GFR in 3rd trimester dose by 30-50%
Eisendrath SJ, Lichtmacher JE. Chapter 25. Psychiatric Disorders. In: Papadakis MA, McPhee SJ, Rabow MW, eds. CURRENT Medical Diagnosis & Treatment 2013. New York: McGraw-Hill; 2013. http://www.accessmedicine.com/content.aspx?aID=13381. Accessed September 11, 2012.

Lithium Pregnancy
Side effects in infants
risk of Ebsteins anomaly 1:20,000 (general population) vs 1:1,500 (exposed during 1st trimester) birth weight, poor respiratory effort, cyanosis Neonatal hypotonicity, bradycardia, cyanosis, hypoglycemia preventable if d/ced prior to delivery

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Image from: http://www.umm.edu/graphics/images/en/22703.jpg. Accessed September 13, 2012.

Lithium Breastfeeding
Infant serum levels are - maternal levels Cyanosis, hypotonia, heart murmur, EKG changes, lethargy, hypothermia BUN, creatinine, TSH Infants more susceptible to lithium toxicity due to immature kidney function and potential for rapid dehydration2

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Antiepileptics

Valproic acid Carbazepine Oxcarbamazapine Lamotrigine

Antiepileptic drug syndrome- IUGR, thin long upper lip, shallow philtrum, prominent epicanthal folds, mid-facial hypoplasia with flat nasal bridge, small upturned nose, downturned mouth angle
Image from: http://www.womenshealthsection.com/content/art_images/obsm007a.jpg. Accessed September 13, 2012. Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Valproic Acid Pregnancy

FDA Pregnancy Category: D Risk for major congenital anomalies (6.2-13.3%) NTDs (1-2%, 10-20x general population, mostly
lumboscacral meningomyelocele) Cardiovascular anomalies, limb defects, and hypospadias. Developmental problems. Folate metabolism interference. ?Supplement? Dose dependent (>800-1000mg), combo with other antiepileptics. Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence
Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Valproic Acid Breastfeeding

Low levels in breast milk Compatible with breastfeeding

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Carbamazepine - Pregnancy
Malformation rates: 2.2-5.4%
NTDs risk: 0.5-1%

Vitamin K defeciency
Neonatal bleeding, mid-facial abnormalities ? Supplement

FDA Pregnancy Category: D

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Carbamazepine - Breastfeeding
Variable levels in infant Insignificant amount in breast milk Compatible with breastfeeding

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Oxcarbazepine Pregnancy & Breastfeeding

Limited data No toxic epoxide metabolite Plasma levels may decrease during pregnancy.

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Lamotrigine - Pregnancy
Lamotrigine

Relative risk of cleft lip +/- cleft palate: 10.4x Absolute risk: 7.3:1,000 Risk , dose >200mg/day Clearance during pregnancy, returns to baseline after delivery.

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Lamotrigine - Breastfeeding

High levels in breast milk Unknown effects Infant serum levels are maternal levels Mild thrombocytosis, concern for StevensJohnson Syndrom

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Atypical Antipsychotics
Olanzapine, risperidone, clozapine, quetiapine, aripiprazole, ziprasidone Limited data Weight gain, diabetes, LGA infants FDA Pregnancy Category: All are C, except for clozapine which is B

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Antidepressants - Pregnancy
FDA Pregnancy Category: All are C, except for paroxetine which is D SSRI - Treatment resistance or more mood episodes in "rapid-cyclers" TCAs - Mania TCAs & SSRIs - LBW and SGA infants, preterm delivery

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Antidepressants - Pregnancy
SSRIs Small risk - Omphalocele, anencephaly, craniosynostosis Persistent pulmonary hypertension of the newborn (PPHN) - 0.5-2/1000 vs 3-6/1000 exposed Paroxetine - 1.5-2x risk for cardiac malformation in 1st trimester
Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Antidepressants - Pregnancy
TCAs
Relatively safe Tachycardia, irritability, jitteriness, hypertonia, seizures, antocholinergic symptoms

MAOIs Limited data

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Antidepressants - Breastfeeding
SSRIs Low to undetectable levels in breast milk TCAs - Infant plasma levels <1% of maternal dose, no known adverse effects MAOIs - Limited data

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.

Electroconvulsive Therapy

Common side effects: Transient memory loss, muscle soreness, headache Common complications: Fetal bradyarrhythmias (2.5%, due to hypoxia), premature labor (3.5%, due to postictal of oxytocin) Fetal monitoring for fetal sedation during general anesthesia Anesthetics (methohexital sodium, propofol) and muscle relaxant (succinylcholine) - no known teratogenic effects. ECT current does not travel through uterus.

Becker MA, Weinberger TE, Denysenko L, Kunkel EJS. Chapter 21. Mood Disorders. In: Berghella V. Maternal-Fetal Evidence Based Guidelines. 2nd ed. London, New York: Informa Healthcare; 2012: 138-149.