Evidence-Based Reviews

Postpartum depression: What to tell patients who breast-feed

Current Psychiatry. 2008 May;7(5):87-95

Evidence suggests most—but not all—SSRIs, tricyclics are reasonable choices.

References

1. Munk-Olsen T, Laursen TM, Pedersen CB, et al. New parents and mental disorders: a population-based register study. JAMA 2006;296:2592-9.

2. Gaynes BN, Gavin N, Meltzer-Brody S, et al. Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess (Summ) 2005;(119):1-8.

3. Cox JL, Holden JM, Sagovsk R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry 1987;150:782-6.

4. Beck CT, Gable RK. Comparative analysis of the performance of the Postpartum Depression Screening Scale with two other depression instruments. Nurs Res 2001;50:242-50.

5. Bloch M, Schmidt PJ, Danaceau M, et al. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry 2000;157(6):924-30.

6. Mastorakos G, Ilias I. Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum. Ann N Y Acad Sci 2003;997:136-49.

7. Noltern WE, Lindheimer MD, Rueckert PA, et al. Diurnal patterns and regulation of cortisol secretion in pregnancy. J Clin Endocrinology Metab 1980;51:466-72.

8. Bloch M, Daly RC, Rubinow DR. Endocrine factors in the etiology of postpartum depression. Compr Psychiatry 2003;44(3):234-46.

9. Magiakou MA, Mastorakos G, Rabin D. Hypothalamic-cortico-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time. J Clin Endocrinol Metab 1996;81:1912-7.

10. Jolley SN, Elmore S, Barnard KE, Carr D. Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum depression. Biol Res Nurs 2007;8:210-22.

11. Gold PW, Gabry KE, Yasuda MR, Chrousos GP. Divergent endocrine abnormalities in melancholic and atypical depression: clinical and pathophysiologic implications. Endocrinol Metab Clin North Am 2002;31:37-62.

12. Bloch M, Rubinow DR, Schmidt PJ. Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab 2005;90(2):695-9.

13. Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry 2003;160:1554-65.

14. Pedersen CA, Johnson JL, Silva S, et al. Antenatal thyroid correlates of postpartum depression. Psychoneuroendocrinology 2007;32(3):235-45.

15. Yonkers KA. The treatment of women suffering from depression who are either pregnant or breastfeeding. Am J Psychiatry 2007;164(10):1457-9.

16. Ryan AS, Wenjun Z, Acosta A. Breastfeeding continues to increase into the new millennium. Pediatrics 2002;110:1103-9.

17. Payne J. Antidepressant use in the postpartum period: practical considerations. Am J Psychiatry 2007;164:1329-32.

18. Murray L, Sinclair D, Cooper PJ, et al. The socioemotional development of 5-year old children of postnatally depressed mothers. J Child Psychol Psychiatry 1999;40:1259-71.

19. Weissman AM, Levt BT, Hartz AJ, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 2004;161(6):1066-78.

20. Eberhard-Gran M, Eskild A, Opjordsmoen S. Use of psychotropic medications in treating mood disorders during lactation: practical recommendations. CNS Drugs 2006;20:187-98.

21. Rampono J, Hackett LP, Kristensen JH, et al. Transfer of escitalopram and its metabolite demethylescitalopram into breastmilk. Br J Clin Pharmacol 2006;62(3):316-22.

22. Wisner KL, Perel JM, Findling RL. Antidepressant treatment during breast-feeding. Am J Psychiatry 1996;153(9):1132-7.

23. Kristensen JH, Ilett KF, Rampono J, et al. Transfer of the antidepressant mirtazapine into breast milk. Br J Clin Pharmacol 2007;63(3):322-7.

24. Chaudron LH, Schoenecker CJ. Bupropion and breastfeeding: a case of a possible infant seizure. J Clin Psychiatry 2004;65(6):881-2.

25. Misri S, Kostaras X. Postpartum depression: is there an Andrea Yates in your practice? Current Psychiatry 2002;1(5):22-9.

26. Louik C, Lin AE, Werler MM, et al. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007;356(26):2675-83.

27. Dennis CL, Hodnett E. Psychosocial and psychological interventions for treating postpartum depression. Cochrane Database Syst Rev 2007;(4):CD006116.-

Whether you encounter postpartum depression (PPD) in a patient you have been treating or in one referred by her obstetrician, early, aggressive treatment is essential. Although PPD shares some symptoms with major depressive disorder (MDD)—and may be a subtype of that disorder—it also has distinguishing characteristics, such as timing of symptom onset (Box 1).^1,2 Two screening tools facilitate diagnosis (Box 2).^2-4

Women with PPD usually respond to pharmacotherapy, but antidepressants’ potential effects on a nursing mother’s newborn are important to consider.

HPA axis dysregulation

Although the precise cause of PPD remains unclear, a better understanding is emerging of the complicated interplay of estrogen and progesterone with the hypothalamic-pituitary-adrenal (HPA) axis and other neuroregulatory systems associated with depressive illness. Two lines of evidence implicate hormonal dysregulation:

Despite normal reproductive hormone levels, women with PPD may have an abnormal response to changes in these levels.⁵
Abnormalities in HPA axis activity appear to be associated with reproductive endocrine-related mood disorders in vulnerable women, particularly during the transition from childbirth to the immediate postpartum period.

Box 1

Not just ‘baby blues’: Clues to postpartum depression

Most women will have mild mood and anxiety symptoms in the first few days to weeks postpartum—often referred to as the ‘baby blues’—but these symptoms usually resolve spontaneously. More severe and persistent depressed mood and anxiety should arouse suspicion of postpartum depression (PPD).

Although not categorized as a distinct disorder in the DSM-IV-TR, PPD is diagnosed using DSM-IV-TR criteria for a major depressive episode, including feelings of being overwhelmed, guilt or worthlessness, tearfulness, appetite change, difficulty sleeping (even when the baby is sleeping), difficulty concentrating, and loss of interest or pleasure in activities.²

PPD symptoms differ, however, in some important ways from those of nonpuerperal depression. Distinguishing characteristics of PPD are:

severe worry, anxiety, and/or agitation
fears of hurting the baby or oneself
not having any interest in the baby.²

PPD usually begins within the first month postpartum but may occur later; the first 3 months appear to be the most vulnerable period.¹

A radical transition. Dramatic hormonal changes occur in the transition from pregnancy to postpartum.⁶ The third trimester of pregnancy is characterized by:

high estrogen and progesterone levels
a hyperactive HPA axis (normal during pregnancy)
high plasma cortisol level, stimulated in part by high levels of estrogen and progesterone.^7,8

Estrogen and progesterone rapidly decline as a woman transitions to the postpartum period, and HPA axis activity is blunted because of suppressed hypothalamic corticotrophin-releasing hormone (CRH) secretion.⁹

Clinical Point

Understanding HPA axis reactivity in women with PPD could improve early identification and treatment

Differences in HPA reactivity. In a normal HPA axis, the delivery of CRH from the paraventricular nucleus of the hypothalamus triggers the stimulation of adrenocorticotropic hormone (ACTH) from the anterior pituitary and, consequently, cortisol from the adrenal cortex. This hormonal system is regulated by negative feedback mediated by cortisol receptors on the anterior pituitary, hypothalamus, and hippocampus, as well as ACTH receptors in the anterior pituitary and CRH autoreceptors in the hypothalamus.¹⁰

A hallmark feature of the HPA axis in depression is altered response to stress and inability to maintain regulation:

In MDD, HPA axis hyperactivity is one of the most robust biological findings.¹¹ In general, women with MDD exhibit high baseline cortisol and an exaggerated response to the dexamethasone/corticotropin releasing hormone test.
In contrast, women with PPD experience a more blunted ACTH response to CRH, which may reflect a hyporeactive HPA axis.⁹

Nonetheless, Bloch et al¹² observed an increased cortisol response to CRH in women with a history of PPD during high-dose gonadal steroid administration, which suggests either a trait vulnerability related to PPD onset or a consequence of an earlier depression.

It has been hypothesized that both increased cortisol and decreased cortisol (observed under conditions of sustained elevated gonadal steroid levels or withdrawal of gonadal steroids) may result in insufficient glucocorticoid signaling.¹³ Impaired glucocorticoid signaling may be the “final common pathway” leading to psychiatric disturbance in MDD and PPD.

Understanding the characteristics of HPA axis reactivity in women with PPD could improve early identification and, theoretically, prevention or immediate treatment for at-risk women. In addition to HPA axis dysregulation, disturbances in other endocrine systems may play a role in PPD. Women with antenatal total and free thyroxine concentrations in the lower euthyroid range may be at increased risk of developing postpartum depressive symptoms.¹⁴

Box 2

2 tools for rapid postpartum depression screening

Two well-validated, simple-to-administer postpartum depression (PPD) screening instruments are useful during the postnatal period:

the Edinburgh Postnatal Depression Scale (EPDS),³ a 10-item self-report questionnaire that asks about mood, anxiety, guilt, and suicide ideation
the Postpartum Depression Screening Scale (PDSS),⁴ a 35-item self-report questionnaire that asks about sleeping/eating disturbances, anxiety/insecurity, emotional lability, mental confusion, loss of self, guilt/shame, and suicide ideation.

If screening indicates a patient has PPD, her psychiatric history will influence your treatment selection. Pay particular attention to:

past episodes of depression, hypomania, or mania
severity and timing of those episodes
treatment history, including documentation of response to antidepressants.²