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Breastfeeding with Postpartum Depression

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Vol. 15 •Issue 3 • Page 33
Breastfeeding with Postpartum Depression

New mothers who develop postpartum depression and who want to breastfeed their infants present a treatment challenge. SSRIs may be a safe and effective option for mother and child alike.

About 10% of women who have recently given birth experience postpartum depression (PPD),1-11 making this disorder the most common complication of childbearing.1-2 The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) does not recognize PPD as distinct from major depression, but it does provide the addition of a postpartum-onset specifier for women with an onset of depression within four weeks of delivery.9 Correctly diagnosing and treating PPD is critical—especially considering treatments that are conducive for breastfeeding mothers.

PPD Differential Diagnosis

Postpartum mood disorders are differentiated into three categories divided by severity: postpartum blues, postpartum depression, and postpartum psychosis.12 Postpartum blues, also known as "baby blues," affects 50% to 80% of new mothers and is the most common postnatal mood disturbance.12 Postpartum blues typically peaks four days after delivery and lasts from hours to days, but symptoms resolve by the 10th day postpartum.9 Symptoms include weeping, irritability, anxiety, confusion, increased sensitivity, fatigue and headache, all of which do not consistently affect the mother's ability to function.1,9,12 Women who experience baby blues have an increased risk of developing PPD later in the postpartum period.9

Postpartum psychosis occurs in 0.2% of women and is an emergency because of the risk of infanticide, suicide or both.12 The onset is most commonly within a few days of delivery but can occur within the first three weeks.12 Symptoms include delusions, hallucinations, rapid mood swings from depression to euphoria, sleep disturbances and obsessive ruminations about the baby.1,9,12

Clinical evaluation of postpartum symptoms must also include screening for thyroid disease, anemia and diabetes, since these disorders can mimic symptoms of mood disorders.10

PPD Symptoms and Risk Factors

PPD is characterized as a subtype of major depression and contains variable symptomatology (Table 1). These symptoms may be normal postpartum reactions and not signs of depression. Keeping this in mind, consider circumstances such as an infant's age, sleeping patterns and behavior and determine whether the mother's symptoms are results of daily stressors and not signs of depression.9

Studies have explored the factors that are likely to increase a woman's chance of developing PPD. Although results have been contradictory, a few variables have been constant: Women with a history of major depression, anxiety disorders or both are at risk for depression following delivery.1,10,13,14 Depressive symptoms with a previous pregnancy also are a major risk factor for PPD. At least one third of women who have had PPD have a recurrence of symptoms after a subsequent delivery.9

Other consistent risk factors for developing PPD include prenatal depression or anxiety, inadequate social support, poor quality of the relationship with a partner and child care stress.10,12 The likelihood of PPD does not appear to be related to maternal age, parity, ethnicity and race, a woman's educational level, sex of the infant, mode of delivery or whether or not the pregnancy was planned.1,10

Breastfeeding

The American Academy of Pediatrics recommends infants be breastfed exclusively during the first six months of life.5,9 Table 2 illustrates the lifelong health benefits acquired through breast milk. Although breastfeeding provides proven benefits to infants, women with postpartum depression often are reluctant to use medication,12 or they choose to discontinue breastfeeding in order to undergo medical therapy.3 At any time within the first year of delivery, depressed women have a greater tendency to discontinue breastfeeding than do women who have not developed depression.

In order to educate mothers with PPD, it is important to understand drugs' transmissions and effects on breastfed infants.

Importance of Treatment

PPD is associated with disruptive effects on the maternal-infant relationship. Depressed mothers tend to perceive their infants negatively and tend to regard the care for their infants as more than difficult.12 Several studies have connected PPD with maternal behavior that is less affectionate and infant behavior that is avoidant and/or discontent later in infancy and early childhood,10 particularly if the child is a boy.11

PPD has been associated with deficiencies in infants' cognitive performances.11,12,14 Studies have found that children of mothers with untreated PPD are delayed in motor development, have lower intelligence quotients and have slower rates of growth compared with children of successfully treated depressed mothers.14

Choosing a Treatment

Selective serotonin-reuptake inhibitors (SSRIs) are the first medication treatment choice for PPD due to their ease of administration, low toxicity and greater tolerability.1,2,10 This class of antidepressant is the most studied in mother-infant pairs.10

All antidepressants are excreted into breast milk;1 however, levels of SSRIs have been reported to be low.5 Evidence suggests that breastfeeding should not be discouraged in women using SSRIs.15 In a systematic evaluation of 57 studies of maternal plasma, breast milk and infant plasma levels of antidepressants, paroxetine and sertraline were undetectable in infants, and fluoxetine and citalopram were detectable in most infants.16

In order to minimize side effects, treatment should begin at half the recommended dose for four days, and then doses should be increased as tolerated until full remission is achieved.1 In addition, if a patient has a successful response to a medication, the same dose should be continued for a minimum of six months after a full remission in order to prevent relapse.1,5

Fluoxetine

Fluoxetine (Prozac) is the most studied SSRI regarding use in pregnancy and breastfeeding.14 Compared with paroxetine and sertraline, fluoxetine produces the highest concentration of medication in breastfed infants at levels above 10% of the maternal dose,16 but fluoxetine levels in breast milk typically were low (less than 5 ng/mL) with maternal dosage of 20 mg per day or less.10,13

In a study measuring platelet 5-HT levels in 11 breastfeeding mother-infant pairs in which the mother was being treated with fluoxetine, mean maternal pre-exposure of 5-HT was 156.6 ng/mL, and postexposure was 22.9 ng/mL, while the infant pre-exposure and postexposure of 5-HT concentrations were minimally changed at 229.9 ng/mL and 217.1 ng/mL.8

Breast milk concentrations of fluoxetine vary twofold to threefold throughout a 24-hour period. Concentrations peak approximately eight hours following maternal ingestion of the medication. (This parallels the time course data for sertraline.13) This observation provides nursing women with a mechanism to decrease infant's daily exposure by discarding breast milk at times of peak concentrations.

Fluoxetine is the only SSRI to have a reported one-year follow-up study: In a study observing infants exposed to fluoxetine through breast milk, the one-year follow-up examination reported no neurological or developmental abnormalities in any of the infants.14

Sertraline

Based on multiple case series, sertraline has been recommended as the first-line treatment for breastfeeding mothers.1,17 One literature review summarized 26 cases of infants exposed to sertraline through breastfeeding and concluded that sertraline is present in breast milk at low levels (less than 5 mg/mL).14

Another study observed whether SSRI exposure during breastfeeding results in clinically significant blockade of serotonin 5-HT reuptake in infants. Although decreases in maternal 5-HT levels of up to 70% to 90% were observed in mothers after sertraline treatment of 25 mg to 200 mg per day, breastfed infants showed little or no change in platelet 5-HT levels.5

It appears that breastfeeding mothers receiving sertraline do not subject their infants to drug levels that affect infant 5-HT transport. Twenty-six nursing women with a mean sertraline dose of 123.9 mg per day were studied in an effort to minimize infant exposure. Highest concentrations of sertraline were observed in the hind milk eight to nine hours after maternal ingestion. Discarding this breast milk decreased the infant daily dose of sertraline by a mean of 17.1%.18

Study Shortcomings

The difficulty with the studies of SSRIs and breastfeeding include small sample sizes, variations in sampling and measurement methods among studies and relatively short-term follow-ups.2 Thus, it is premature to propose treatment guidelines. Notwithstanding the lack of published guidelines, weigh factors such as severity of maternal PPD, possible previous maternal response to a specific SSRI and the mother's commitment to breastfeeding. Additional research is needed to definitively establish SSRI infant exposure during breastfeeding and the behavioral consequences.8

Hormone Treatment

Women become depressed twice as often as men and are particularly vulnerable at times of hormonal fluctuation–for example pregnancy–suggesting that PPD may be hormonally driven.9,19 At the end of the pregnancy term, estradiol levels are high and mostly of placenta origin. With removal of the placenta after delivery, serum estradiol levels decline. Ovarian estradiol production may recover this deficit, but slowly, causing the postpartum estradiol deficiency to be prolonged and profound. Ovarian steroid hormones are neuroactive, cross the blood-brain barrier and appear to exert effects on serotonin, norepinephrine and dopamine, all of which are associated with regulating mood and behavior.4

Estradiol and progesterone have been evaluated as treatment for PPD. One study demonstrated that high-dose (200 mcg per day) transdermal 17 beta-estradiol has significant reductions in depression scores during the first month. The implications of this study are not clear, however, because nearly half the women were also treated with antidepressants.1,10

Another study observed a dose as high as 100 mcg per day of estradiol could be transdermally administered without appearing in breast milk.20 An additional study studied synthetic progesterone, resulting in less convincing evidence. From this double-blind randomized clinical trial, it was concluded that synthetic progesterone was not effective in preventing or treating PPD, and indeed increased depression in the postpartum period.1,10

Associated risks with estradiol administration in postpartum mothers include deep vein thrombosis, endometrial hyperplasia and inhibition of lactation. These risks prevent the recommendation of estrogen therapy for PPD until further research is conducted on efficacy and safety.10 As one study succinctly puts it, "This treatment modality should not be a first-line recommendation due to the limited benefit and lack of safety data regarding the postnatal use of estrogen supplementation in women of reproductive years."12

SSRIs, Breastfeeding and PPD

PPD is a disorder that affects a large number of women and their infants. If it is not recognized and properly treated, it can have detrimental effects on the mother-infant relationship. By recognizing the common symptoms and risk factors, mothers suffering from PPD can be properly screened and assessed for the necessity of treatment.

The importance of breastfeeding should not be compromised in infants of mothers diagnosed with PPD. The use of SSRIs is not contraindicated during breastfeeding, and these medications should be considered in women who have moderate to severe PPD. While hormonal supplements have been explored as possible PPD treatments, they should not be first-line options because of limited studies and the lack of safety data.12

Adam Slevin is a physician assistant at Philadelphia Urology Associates in Philadelphia.

References

1. Wisner KL, Parry BL, Piontek CM. Clinical practice. Postpartum depression. N Engl J Med. 2002;347:194-199.

2. Gjerdingen D. The effectiveness of various postpartum depression treatments and the impact of antidepressant drugs on nursing infants. J Am Board Fam Pract. 2003;16:372-382.

3. Henderson JJ, Evans SF, Straton JA, Priest SR, Hagan R. Impact of postnatal depression on breastfeeding duration. Birth. 2003;30:175-180.

4. Ahokas A, Kaukoranta J, Wahlbeck K, Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study. J Clin Psychiatry. 2001;62:332-336.

5. Epperson N, Czarkowski KA, Ward-O'Brien D, et al. Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. Am J Psychiatry. 2001;158:1631-1637.

6. Perfetti J, Clark R, Fillmore CM. Postpartum depression: identification, screening, and treatment. WMJ. 2004;103:56-63.

7. Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K. Citalopram in pregnancy and lactation. Clin Pharmacol Ther. 2002;72:184-191.

8. Epperson CN, Jatlow PI, Czarkowski K, Anderson GM. Maternal fluoxetine treatment in the postpartum period: effects on platelet serotonin and plasma drug levels in breastfeeding mother-infant pairs. Pediatrics. 2003;112:e425.

9. Epperson CN. Postpartum major depression: detection and treatment. Am Fam Physician. 1999;59:2247-2258.

10. Horowitz JA, Goodman JH. Identifying and treating postpartum depression. J Obstet Gynecol Neonatal Nurs. 2005;34:264-273.

11. Martins C, Gaffan EA. Effects of early maternal depression on patterns of infant-mother attachment: a meta-analytic investigation. J Child Psychol Psychiatry. 2000;41:737-746.

12. Newport DJ, Hostetter A, Arnold A, Stowe ZN. The treatment of postpartum depression: minimizing infant exposures. J Clin Psychiatry. 2002;63:31-44.

13. Hendrick V, Stowe ZN, Altshuler LL, et al. Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk. Biological Psychiatry. 2001;50:775-782.

14. Misri S, Burgmann A, Kostaras D. Are SSRIs safe for pregnant and breastfeeding women? Can Fam Physician. 2000;46:626-633.

15. Berle JO, Steen VM, Aamo TO, Breilid H, Zahlsen K, Spigset O. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes. J Clin Psychiatry. 2004;65:1228-1234.

16. Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-1078.

17. Whitby DH, Smith KM. The use of tricyclic antidepressants and selective serotonin reuptake inhibitors in women who are breastfeeding. Pharmacotherapy. 2005;25:411-425.

18. Stowe ZN, Hostetter AL, Owens MJ, et al. The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations. J Clin Psychiatry. 2003;64:73-80.

19. Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000;157:924-930.

20. Perheentupa A, Ruokonen A, Tapanainen JS. Transdermal estradiol treatment suppresses serum gonadotropins during lactation without transfer into breast milk. Fertil Steril. 2004;82:903-907.




     

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