Depression and Breast-Feeding: Medication Use

Knowledgeable pharmacists can positively influence not only mothers who are depressed, but also women who want to breast-feed but do not because of medication use.

Major depression is considered a common and treatable mental disorder. Nine percent of the US population is affected by depression, with 6.7% being adults. Women are significantly more likely than men to be depressed (4% versus 2.7%).¹ At least 10% of women report postpartum depression.² In 2006, approximately 1 million mothers stated that “[they] had to take medicine and didn’t want [their] baby to get it” as the reason for discontinuing breast-feeding.³ Therefore, approximately 100,000 women every year apparently do not breast-feed if they have to take a medication to treat their depression. The implications for positive interventions by knowledgeable pharmacists are immense, not only for mothers who are depressed, but for all women who want to breast-feed but do not because of medication use. The potential positive benefits of breast-feeding for the mother and her baby are lost entirely.

In any breast-feeding situation, the pharmacist and mother need to weigh the benefits of medication use and breast-feeding against the risks of medication use and formula use (not breast-feeding). The benefits and risks of medication use can be readily determined from drug labeling and available literature. Pharmacists may not be knowledgeable about the benefits of breast-feeding and may be even less knowledgeable about the risks of not breast-feeding.^4-6 Table 1 lists the benefits of breast-feeding and the risks of not breast-feeding.

Prescription Antidepressant Medication

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for mothers experiencing postpartum depression or experiencing depression before giving birth. When counseling breast-feeding mothers experiencing and/or being treated for depression, pharmacists should recognize the following:

• The risk associated with not treating depression in breast-feeding mothers is much higher than the risk associated with a usually small concentration of antidepressant in human milk.
• All studies to date suggest that neurobehavioral outcomes are normal in breast-fed infants.
• Most SSRIs (and other antidepressants) are compatible with breast-feeding.
• There is potential for neonatal pulmonary hypertension when mothers take SSRIs during pregnancy; however, breast-feeding and continuing to take SSRIs should prevent this occurrence.
• Discontinuation syndrome (poor adaptation, jitteriness, irritability, and poor gaze) occurs in a small percentage of newborns for the first 24 to 48 hours when mothers take SSRIs during pregnancy.
• Breast-feeding mothers should be advised to watch for possible infant adverse reactions (eg, drowsiness, irritability, poor feeding, major changes in sleep patterns) that occur in approximately 0.3% of breast-fed infants.7,8
• Breast-feeding mothers should understand that knowledge about the long-term effects of antidepressant drugs (as with most medications) is still evolving.^9-11

High protein binding, high volumes of distribution (Vd), and high molecular weights/mass (MW) limit the passage of drugs into human milk. Low milk concentrations usually result in a low relative infant dose (RID), which is the ratio of the weight-adjusted dose in mg/ kg/d of drug that the infant receives divided by the weight-adjusted dose in mg/kg/d of drug that the mother receives. If this ratio is 10% or less, the drug is considered usually compatible with breast-feeding. The following SSRIs are commonly used antidepressants that are preferred during breast-feeding¹²:

Sertraline: High protein binding (98%), high Vd (20), and high MW (306) result in very low milk concentrations. One study assessed the effect on an infant’s own serotonin reuptake and found that the infant blood serum level did not change significantly. The RID is 0.4% to 2.2%.

Paroxetine: High protein binding (95%), high Vd (3-28), and high MW (329) result in very low concentrations with minimal amounts in milk. No or minimal infant adverse effects have been shown in numerous studies. The drug is contraindicated in the first trimester of pregnancy (to prevent cardiac defects), but this is not related to compatibility during breast-feeding. The RID is 1.2% to 2.8%.Fluoxetine: High protein binding (95%), high Vd (2.6), and high MW (309) probably result in very low concentrations in milk. A case of severe colic, fussiness, and crying has been reported. Among all SSRIs, the drug has the most extensive use in breast-feeding women. The drug is contraindicated in the first trimester of pregnancy (to prevent cardiac defects), but this is not related to compatibility during breast-feeding. The RID is 7.7%.

Fluoxetine: High protein binding (95%), high Vd (2.6), and high MW (309) probably result in very low concentrations in milk. A case of severe colic, fussiness, and crying has been reported. Among all SSRIs, the drug has the most extensive use in breast-feeding women. The drug is contraindicated in the first trimester of pregnancy (to prevent cardiac defects), but this is not related to compatibility during breast-feeding. The RID is 7.7%.

Escitalopram: High Vd (12) and high MW (414) lead to very low concentrations in milk. Breast-fed infants have very low levels in their blood. Infants should be observed for possible drowsiness. The RID is 5.2% to 7.9%.

Venlafaxine: High Vd (4—12) and high MW (313) probably result in very low concentrations in milk. Although studies are limited, no adverse effects have been reported during breast-feeding. The RID is 6.8% to 8.1%.

Fluvoxamine: Moderately high protein binding (80%) and high MW (318) result in very low concentrations in milk. There is low drug exposure to infants; no infant adverse effects have been reported in several studies. The RID is 0.3% to 1.4%.

Citalopram: Moderately high protein binding (80%), high Vd (12), and high MW (405) probably result in very low concentrations in milk. In 2 cases, breast-fed infants experienced excessive sleepiness, decreased feeding, and weight loss. Most studies have shown no or limited infant adverse effects. The RID is 3.6%.

Herbal Antidepressants

Breast-feeding mothers also try herbal treatment for depression. The herbal most often used is St. John’s Wort. A study conducted by the National Institutes of Health showed that St. John’s Wort was not effective for the treatment of moderate to severe depression but probably effective for minor to moderate depression.^13,14 Herbalists, scientists, and trade organizations have criticized the study because it looked mainly at moderate to severe depression, only 1 dose range was used, and study sensitivity and accuracy were lacking. In addition, European data suggest that the herbal is a safe and effective remedy for mild to moderate depression.¹⁵ In response to these criticisms, a new study is now being conducted.

Summary

Much supporting documentation and studies show that antidepressants are appropriate and reasonable treatment for breast-feeding women and are compatible with breast-fed infants. Two resources that provide supportive information are Tom Hale’s Medications and Mother’s Milk, 14th edition,¹² and my Nonprescription Drugs for the Breastfeeding Mother, 2nd edition.¹⁶ A depressed mother who is being treated with medication can successfully bond with her baby and lower her risk for suicide.

The lack of provision of human milk to infants costs the health care system over $13 billion each year and results in over 900 unnecessary infant deaths annually.¹⁷ One of the major medical obstacles to breast-feeding is the lack of encouragement for it by health care professionals who fear potential infant toxicosis due to maternal medication. Alternative approaches and tools and techniques for counseling not only depressed but all breast-feeding women can be found in a comprehensive article covering current concepts on the use of medications while breast-feeding.¹⁸ Use of this type of objective information enables health care providers and mothers to make the most educated choices regarding drug therapy and breast-feeding.

Dr. Nice is a pharmacist project manager for the FDA in Rockville, Maryland, and is the author of Nonprescription Drugs for the Breastfeeding Mother, which was published in 2011.

References

• CDC. Current depression among adults: United States, 2006 and 2008. MMWR Morb Mortal Wkly Rep. 2010;59;1229-1235.
• CDC. Prevalence of self-reported postpartum depressive symptoms: 17 states, 2004-2005. MMWR Morb Mortal Wkly Rep. 2008;57;361-366.
• Declercq ER, Salaka C, Corry MP, Applebaum S. New mothers speak out: national survey results highlight women’s postpartum experiences. J Perinat Educ. 2007;16(4):15-17.
• Jukelevics N, Wiff R. Breastfeeding is priceless: there is no substitute for human milk. Coalition for Improving Maternity Services. http://motherfriendly.org/Resources/Documents/BreastfeedingisPricelessMarch2009.pdf. Accessed August 26, 2013.
• Ryan CA. Protection against chronic disease for the breastfed infant. In: Mannell R, Martens PJ, Walker M, eds. Core Curriculum for Lactation Consultant Practice. 2nd ed. Sudbury, MA: Jones & Bartlett; 2008:323-332.
• World Health Organization. Acceptable medical reasons for use of breast-milk substitutes. http://whqlibdoc.who.int/hq/2009/WHO_FCH_CAH_09.01_eng.pdf. Accessed August 26, 2013.
• Anderson PO, Bishop SL, Manoguerra AS. Adverse drug reactions in breastfed infants: less than imagined. Clin Ped. 2003;42:325-340.
• Ito S, Blajchman A, Stephenson M, et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168:1393-1399.
• Yonkers KA, Wisner KKL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psych. 2009;31:403-413.
• Kendall-Tackett K, Hale TW. The use of antidepressants in pregnant and breastfeeding women: a review of recent studies. J Hum Lact. 2010;26:187-195.
• Hale TW, Kendall-Tackett K, Cong Z, et al. Discontinuation syndrome in newborns whose mothers took antidepressants while pregnant or breastfeeding. Breastfeeding Med. 2010;5:283-288.
• Hale TW. Medications and Mother’s Milk. 14th ed. Amarillo, TX: Hale; 2010.
• Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John’s wort in major depression: a randomized controlled study. JAMA. 2001;285:1978-1986.
• Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John’s wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002;287:1807-1814.
• Herbalists, scientists and trade organizations criticize JAMA report of NIH study of St. John’s Wort. Supplementquality.com website. www.supplementquality.com/efficacy/JAMA_StJ_0204.html. Accessed August 26, 2013.
• Nice FJ. Nonprescription Drugs for the Breastfeeding Mother. 2nd ed. Amarillo, TX: Hale; 2011.
• Bartick M, Reinhold A. The burden of suboptimal breastfeeding in the United States: a pediatric cost analysis. Pediatrics. 2010;125:e1048-e1056.
• Nice FJ, Luo A. Medications and breast-feeding: current concepts. J Am Pharm Assoc. 2012;52:86-94.