 |
 |
|
|
|
Childbirth represents a period of great vulnerability to becoming mentally unwell, with postpartum mood disorders representing the most frequent form of maternal mor- bidity following delivery (1). These affective disorders range in severity from early maternity blues to postpartum psychosis (2). Among these conditions is postpartum depression (PPD)—a condition that often exhibits the disabling symptoms of dysphoria, emotional lability, insomnia, confusion, anxiety, guilt, and suicidal ideation. Frequently exacerbating these indicators are low self-esteem, inability to cope, feelings of incompetence, and loneliness (3–5). Unfortunately, PPD is a major health issue for many women from diverse cultures (6) and has well-documented health consequences for the mother, child, and family. Randomized controlled trials (RCTs) evaluating interpersonal psychotherapy (7), cognitive-behavioural counselling with antidepressants (ADs) (8), health visitor–led nondirective counselling (9,10), and nurse-facilitated support groups (11) have suggested that PPD is amenable to treatment. However, in 2001, a US National Institute of Mental Health expert panel concluded that “preventing postpartum depression is an important public health approach . . . that holds much promise”(12, p 81). This paper critically reviews the literature to determine the current state of scientific knowledge related to the prevention of PPD from a biological perspective. MethodSearch Strategy Inclusion and Exclusion Criteria Methodology for Synthesis After the quality-of-evidence assessment was complete, each strategy was further classified to determine clinical practice recommendations, according to the grading scheme shown in Table 3 (see footnote c). ResultsFor this critical review, 7 preventive studies that met inclusion criteria were examined. Study summaries and limitations are presented in Tables 1 and 2, and the clinical practice recommendations drawn from the Canadian Task Force methodology are outlined in Table 3. Pharmacologic Interventions (Table 1)
Advancing their initial work, Wisner and colleagues conducted a double-blind RCT to evaluate the efficacy of nortriptyline in the prevention of recurrent PPD (16). A total of 51 women without depression and with at least 1 previous episode of PPD meeting research diagnostic criteria were recruited antenatally and were randomly assigned to receive either nortriptyline or placebo in the immediate postpartum period. They assessed each mother for 20 sequential weeks, using the Hamilton Depression Rating Scale (HDRS). No significant group difference was found: 6 (23.1%) mothers who took nortriptyline prophylactically and 6 (24%) mothers who received placebo suffered a recurrence (P = 1.00). Consistent with previous research, the rate of recurrence was approximately 1 in 4. The results from this study suggest that nortriptyline does not confer additional preventive efficacy beyond that of placebo. Hormonal Interventions (Table 1) One of the hormonal hypotheses that have been put forward relates to the rapidly decreasing levels of sex hormones, particularly estrogen and progesterone. However, despite the fall in circulating progesterone and estrogen in the immediate postpartum period, researchers have failed to consistently demonstrate a link between hormone levels and PPD (18,19). For example, O’Hara and colleagues compared hormone concentrations in childbearing women who suffered from depression with concentrations in those who did not. Frequent assays of prolactin, progesterone, estradiol, free and total estriol, and cortisol and urinary free cortisol during pregnancy and immediately postpartum revealed few differences (20). However, failure to demonstrate endocrinological evidence of hormone deficiencies does not exclude them as etiologic factors, because both estrogen and progesterone have psychoactive properties. Thus, several researchers have evaluated diverse hormonal prophylaxis. Estrogen Therapy. In an open-label US study, 7 women with a history of postpartum psychosis and 4 with a history of PPD were consecutively treated with high-dosage oral estrogen immediately following delivery (21). None of the women had a history of nonpuerperal affective disorder, and all were affectively well throughout the current pregnancy. The intervention consisted of oral premarin daily in decreasing dosages over 4 weeks. A high dosage was chosen in the first few days postpartum to approximate term pregnancy estradiol levels before a gradual taper, which was designed to cushion the usual fall to follicular-phase estradiol levels. During the first 5 days postpartum, DSM-III-R checklist was used to evaluate women daily for mood and neurovegetative symptoms. Follow-up was conducted via clinical interview at 1, 3, 6, and 12 months postpartum. All but 1 participant remained without depression and required no treatment with psychotropic medications during the 1-year follow-up period. The low rate of relapse in this small study suggests that further research is warranted to assess the prophylactic ability of oral estrogen in the immediate postpartum period among mothers at risk for a reoccurrence of postpartum affective disorders. However, research has failed to demonstrate a consistent relation between PPD and breast-feeding (which induces lower estrogen levels), which clearly challenges the claim that estrogen therapy will be a useful preventive approach (22). Progesterone Therapy. Dalton popularized the prophylactic use of progesterone for PPD (23,24). For example, in an open-label study wherein women who had previously experienced PPD voluntarily took prophylactic progesterone treatment, a reduction from 10% to 68% was demonstrated in the recurrence rate (25). In contrast, 2 double-blind RCTs of progesterone for premenstrual syndrome, which is thought by some researchers to have a hormonal etiology similar to PPD, found no significant differences between treatment and placebo groups (26,27). However, synthetic progestogens have been implicated in depression among women who use them for contraception (28,29). Thus, there is evidence to support the possibility that progesterone may either reduce or increase the risk of PPD. To address this question, Lawrie and colleagues conducted a double-blind RCT to determine the effect of a long-acting progestogen contraceptive, norethisterone enanthate, administered postnatally upon development of PPD (30). A total of 180 postpartum women using a nonhormonal method of contraception were recruited from a tertiary hospital in Johannesburg, South Africa. Women were randomly allocated within 48 hours of delivery to either a progestogen group (receiving a single dose of norethisterone enanthate 200 mg by intramuscular injection; n = 90) or a placebo group (receiving 200 mg of normal saline placebo by intramuscular injection; n = 90). Mothers completed the Edinburgh Postnatal Depression Scale (EPDS) and the Montgomery–Asberg Depression Rating Scale (MADRS) as part of a clinical interview at 1, 6, and 12 weeks postpartum. Compared with the placebo group, women receiving the progestogen injection were at significantly greater risk of developing depressive symptomatology by 6 weeks postpartum. For women in the intervention group, the relative risk of scoring above 9 on the MADRS and above 11 on the EPDS was 2.56 (95% CI, 1.26 to 5.18) and 3.04 (95%CI, 1.52 to 6.08), respectively. No significant group differences were found at 12 weeks; researchers hypothesized this was related to the fact that only a single dose was administered. The results from this well-conducted trial incorporating good randomization and blinding methods a power analysis, intent-to-treat data analysis, and valid measures, indicate that progestogen contraceptives should be used with caution in the postpartum period. Thyroid Function (Table 2)
Other Interventions (Table 2) To determine the effect of DHA supplementation on plasma phospholipid DHA content and indices of depression, 138 pregnant US women who planned to breast-feed their infants were randomly assigned in double-blind fashion to receive either DHA (approximately 200 mg daily) or placebo for the first 4 months postpartum (39). Major outcome variables included plasma phospholipid fatty acid patterns and scores on the Beck Depression Inventory (BDI). Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version (SCID-CV) scores and EPDS scores were obtained from subgroups of the total population. Plasma phospholipid contents of DHA at baseline were 3.15 (SD 0.78) and 3.31 (SD 0.70) (mg/dL of total fatty acids) in the DHA and placebo groups, respectively. After 4 months, the plasma phospholipid DHA content of the DHA group was 8% higher (3.40 mg/dL [SD 0.97]), whereas that of the placebo group was 31% lower (2.27 mg/dL [SD 0.87]). Despite the higher plasma phospholipid DHA content of the supplemented group, there was no difference between groups in either self-rating or diagnostic measures of depression. The results suggest that, while DHA supplementation after delivery prevents the usual decline in plasma phospholipid DHA content among women who breast-feed, it does not influence self-ratings or diagnostic measures of depression. Calcium Supplementation. Evidence that calcium supplementation may play a beneficial role in affective disorders comes from studies evaluating the effects of dietary calcium on premenstrual syndrome (PMS) (40–42). For example, Thys-Jacobs and Alvir (43) reported a significant drop in total and ionized calcium at the midpoint of the menstrual cycle that coincided with an increase in estradiol. They also found that women with PMS and control subjects showed differences in total serum calcium across the menstrual cycle. These data suggest that calcium metabolism is influenced by the menstrual cycle and indicate that women with PMS may have an underlying deficit in calcium metabolism that is exacerbated by fluctuations in gonadal hormones. While this research links disturbance in calcium metabolism and PMS, it does not explain how calcium influences negative affect. To determine the effect of calcium carbonate on the prevention of PPD, women from Portland, Oregon, and Albuquerque, New Mexico, participated in a randomized, double-blind, placebo-controlled trial for the prevention of preeclampsia and completed the EPDS at 6 and 12 weeks postpartum (44). At 6 weeks, the proportion of EPDS scores > 14 was 11% (16/150) for the calcium group from Portland and 18% (26/143) for the placebo group. The proportions from Albuquerque were 24% (10/42) vs 21% (8/39) (P > 0.05). At 12 weeks, only 5.7% (7/123) of the calcium group had an EPDS score >14, compared with 15.3% (19/124) of the placebo recipients (P = 0.01). The results demonstrate that oral calcium supplementation reduced the point prevalence of PPD significantly at 12 weeks and marginally at 6 weeks. DiscussionThe long-term consequences of PPD suggest that preventive approaches are warranted. The manipulation of a given risk factor may decrease the associated likelihood of developing PPD. The most obvious is to decrease the amount of exposure to a given risk factor or, alternatively, to reduce the strength or mechanism of the relation between the risk factor and PPD (45). However, translating risk factor research into predictive screening protocols and preventive interventions has met with limited success, as complex interactions of biopsychosocial risk factors with individual variations need to be contemplated. The 7 studies examined in this review reflect a broad range of biological approaches. Although theoretical justifications for many of these approaches have been presented, methodological limitations render intervention efficacy equivocal; scant evidence is available to guide practice or policy recommendations (Table 3).
Only 2 small US studies have evaluated the efficacy of prophylactic AD medication (nortriptyline), and it is unknown whether the conflicting results are related to methodological limitations, inadequate drug mechanism, or intervention or approach ineffectiveness. Because of the poor quality of the evidence, the effect of pharmacologic interventions in the prevention of PPD is unclear, and this approach cannot be recommended for clinical practice. Well-conducted RCTs are needed and should include interventions that evaluate commercially available ADs from diverse drug categories. Similarly, the effectiveness of hormonal interventions also needs to be rigorously examined. While the low rate of relapse in Sichel’s study (21) suggests further research in the prophylactic ability of oral estrogen is warranted, safety issues associated with administering such a high dosage need to be examined, particularly for breast-feeding women. To delineate the potential effects of hormonal changes on depression and relapse risk, research efforts should expand to include investigations that examine women’s hormonal levels across the perinatal period from pregnancy until the resumption of normal menstrual cycles. Currently, the neurochemical mechanism preventing affective relapse in high-risk women is only hypothesized, and future research is needed to clarify the role of prophylactic agents. Notably, one well-designed trial suggested that synthetic progestogens increased the risk of developing depressive symptomatology (30). There is fair evidence to support the recommendation that long-acting progestogen contraceptives should not be given in the postpartum period (46). Further, it is conceivable that natural progesterone has an AD effect, while synthetic progestogens, which also have strong androgenic activity, are depressogenic. Research to distinguish such differences is warranted. One study was found evaluating the effect of DHA supplementation on maternal mood. While the plasma phospholipid DHA content of the placebo group decreased by 31% and that of the DHA supplementation group increased by 8%, resulting in a 50% higher DHA content in the supplemented group, no significant group differences in PPD rates were found. Perhaps a higher dosage of DHA supplemen- tation may create brain membrane alterations that are capable of enhancing mood. Alternatively, DHA supplementation during pregnancy may reduce the gradual decline in plasma phospholipid DHA content, thereby reducing its impact on mood during the postpartum period. Harrison-Hohner and colleagues (44) found that, while women who supplemented with calcium during pregnancy showed a significantly lower incidence of PPD at 12 weeks, serious methodological limitations existed, including a response rate as low as 28.7% and important sample differences between the 2 sites. Further, the study was a secondary analysis of an RCT that examined the effect of calcium supplementation on preeclampsia. As such, the prophylactic effect of calcium remains unknown. It is hypothesized that the link between calcium and negative affect may be related to calcium as an intracellular messenger. For example, cytosolic calcium concentration plays a critical role in stimulus-response coupling in various tissues, including the nervous system, where the influx of calcium into the cell is proportional to the release of neurotransmitters (47). Thus, disturbances of intracellular calcium regulation could have extensive consequences for cellular function, which may modify mood. Further research is needed to examine whether calcium-mediated modification of neurohormonal activity during pregnancy and the postpartum period alters the trajectory of prenatal and postnatal neurohormonal changes and decreases the vulnerability to PPD. While this review demonstrates that no specific biological approach can be strongly recommended for clinical practice, many explicit research implications have been highlighted. To most efficiently conduct this research, there continues to be a need for further interdisciplinary networking among investigators with complementary research interests. In addition, to further address PPD as a public health problem, it is critical to include ethnically and socioeconomically diverse women in research efforts examining the differences among depression symptoms and response rates to interventions. Funding and SupportI would like to thank Toronto Public Health for their financial contribution. AcknowledgementsI would also like to thank Karen Wade, RN, MScN, for her editorial suggestions. References1. Stocky A, Lynch J. Acute psychiatric disturbance in pregnancy and the puerperium. Baillieres Best Pract Res Clin Obstet Gynaecol 2000;14(1):73–87. 2. Evins GG, Theofrastous JP. Postpartum depression: a review of postpartum screening. Prim Care Update Ob Gyns 1997;4:241–6. 3. Beck CT. The lived experience of postpartum depression: a phenomenological study. Nurs Res 1992;41:166–70. 4. Mills EP, Finchilescu G, Lea SJ. Postnatal depression an examination of psychosocial factors. S Afr Med J 1995;85(2):99–105. 5. Ritter C, Hobfoll SE, Lavin J, Cameron RP, Hulsizer MR. Stress, psychosocial resources, and depressive symptomatology during pregnancy in low-income, inner-city women. J Health Psychol 2000;19:576–85. 6. Affonso DD, De AK, Horowitz JA, Mayberry LJ. An international study exploring levels of postpartum depressive symptomatology. J Psychosom Res 2000;49:207–16. 7. O’Hara MW, Stuart S, Gorman LL, Wenzel A. Efficacy of interpersonal psychotherapy for postpartum depression. Arch Gen Psychiatry 2000;57:1039–45. 8. Appleby L, Warner R, Whitton A, Faragher B. A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression. BMJ 1997;314:932–6. 9. Holden JM, Sagovsky R, Cox JL. Counselling in a general practice setting: controlled study of health visitor intervention in treatment of postnatal depression. BMJ 1989;298:223–6. 10. Wickberg B, Hwang CP. Counselling of postnatal depression: a controlled study on a population based Swedish sample. J Affect Disord 1996;39:209–16. 11. Chen CH, Tseng YF, Chou FH, Wang SY. Effects of support group intervention in postnatally distressed women. A controlled study in Taiwan. J Psychosom Res 2000;49:395–9. 12. Boyd RC, Pearson JL, Blehar MC. Prevention and treatment of depression in pregnancy and the postpartum period–summary of a maternal depression roundtable: a US perspective. Archives of Women’s Mental Health 2002;4(3):79–82. 13. CTFPHC. The Canadian Guide to Clinical Preventive Health Care. Ottawa: Canadian Task Force on Preventive Health Care; 2003. 14. Davidson J, Robertson E. A follow-up study of post partum illness, 1946–1978. Acta Psychiatr Scand 1985;71:451–7. 15. Wisner KL, Wheeler SB. Prevention of recurrent postpartum major depression. Hospital and Community Psychiatry 1994;45:1191–6. 16. Wisner KL, Perel JM, Peindl KS, Hanusa BH, Findling RL, Rapport D. Prevention of recurrent postpartum depression: a randomized clinical trial. J Clin Psychiatry 2001;62(2):82–6. 17. Karuppaswamy J, Vlies R. The benefit of oestrogens and progestogens in postnatal depression. J Obstet Gynaecol.2003;23:341–6. 18. Harris B, Johns S, Fung H, Thomas R, Walker R, Read G, and others. The hormonal environment of post-natal depression. Br J Psychiatry 1989;154:660–7. 19. Harris B, Lovett L, Smith J, Read G, Walker R, Newcombe R. Cardiff puerperal mood and hormone study: III. Postnatal depression at 5 to 6 weeks postpartum, and its hormonal correlates across the peripartum period. Br J Psychiatry 1996;168:739–44. 20. O’Hara MW, Schlechte JA, Lewis DA, Varner MW. Controlled prospective study of postpartum mood disorders: psychological, environmental, and hormonal variables. J Abnorm Psychol 1991;100(1):63–73. 21. Sichel DA, Cohen LS, Robertson LM, Ruttenberg A, Rosenbaum JF. Prophylactic estrogen in recurrent postpartum affective disorder. Biol Psychiatry 1995;38:814–8. 22. Wisner KL, Stowe ZN. Psychobiology of postpartum mood disorders. Semin Reprod Endocrinol 1997;15(1):77–89. 23. Dalton K. Postnatal depression and prophylactic progesterone. Br J Fam Plann 1994;19(Suppl):10–2. 24. Dalton K. Progesterone or progestogens? Br Med J 1976;2(6046):1257. 25. Dalton K. Progesterone prophylaxis used successfully in postnatal depression. Practitioner 1985;229:507–8. 26. Sampson GA. Premenstrual syndrome: a double-blind controlled trial of progesterone and placebo. Br J Psychiatry 1979;135:209–15. 27. Freeman EW, Rickels K, Sondheimer SJ, Polansky M. A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome. JAMA 1995;274(1):51–7. 28. Wagner KD. Major depression and anxiety disorders associated with Norplant. J Clin Psychiatry 1996;57:152–7. 29. Wagner KD, Berenson AB. Norplant-associated major depression and panic disorder. J Clin Psychiatry 1994;55:478–80. 30. Lawrie TA, Hofmeyr GJ, De Jager M, Berk M, Paiker J, Viljoen E. A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: the effect on postnatal depression and serum hormones. Br J Obstet Gynecol 1998;105:1082–90. 31. Harris B, Fung H, Johns S, Kologlu M, Bhatti R, McGregor AM, and others. Transient post-partum thyroid dysfunction and postnatal depression. J Affect Disord 1989;17:243–9. 32. Pop VJ, de Rooy HA, Vader HL, van der Heide D, van Son MM, Komproe IH. Microsomal antibodies during gestation in relation to postpartum thyroid dysfunction and depression. Acta Endocrinol (Copenh) 1993;129(1):26–30. 33. Harris B, Oretti R, Lazarus J, Parkes A, John R, Richards C, and othersRandomised trial of thyroxine to prevent postnatal depression in thyroid-antibody-positive women. Br J Psychiatry 2002;180:327–30. 34. Hibbeln JR. Fish consumption and major depression. Lancet 1998;351:1213. 35. Al MD, van Houwelingen AC, Kester AD, Hasaart TH, de Jong AE, Hornstra G. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr 1995;74(1):55–68. 36. Neuringer M, Anderson GJ, Connor WE. The essentiality of n-3 fatty acids for the development and function of the retina and brain. Annu Rev Nutr 1988;8:517–41. 37. Hibbeln JR, Salem N, Jr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr 1995;62(1):1–9. 38. Otto SJ, de Groot RH, Hornstra G. Increased risk of postpartum depressive symptoms is associated with slower normalization after pregnancy of the functional docosahexaenoic acid status. Prostaglandins Leukot Essent Fatty Acids 2003;69:237–43. 39. Llorente AM, Jensen CL, Voigt RG, Fraley JK, Berretta MC, Heird WC. Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing. Am J Obstet Gynecol 2003;188:1348–53. 40. Penland JG, Johnson PE. Dietary calcium and manganese effects on menstrual cycle symptoms. Am J Obstet Gynecol 1993;168:1417–23. 41. Thys-Jacobs S, Ceccarelli S, Bierman A, Weisman H, Cohen MA, Alvir J. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med 1989;4:183–9. 42. Thys-Jacobs S, Starkey P, Bernstein D, Tian J. Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol 1998;179:444–52. 43. Thys-Jacobs S, Alvir MJ. Calcium-regulating hormones across the menstrual cycle: evidence of a secondary hyperparathyroidism in women with PMS. J Clin Endocrinol Metab 1995;80:2227–32. 44. Harrison-Hohner J, Coste S, Dorato V, Curet LB, McCarron D, Hatton D. Prenatal calcium supplementation and postpartum depression: an ancillary study to a randomized trial of calcium for prevention of preeclampsia. Arch Women Ment Health 2001;3:141–6. 45. McLennan JD, Offord DR. Should postpartum depression be targeted to improve child mental health? J Am Acad Child Adolesc Psychiatry 2002;41(1):28–35. 46. Lawrie TA, Herxheimer A, Dalton K. Oestrogens and progestogens for preventing and treating postnatal depression (Cochrane Review). In: The Cochrane Library. Issue 2. 2004. Chichester (UK): John Wiley & Sons, Ltd. 47. Llinas RR. Depolarization-release coupling systems in neurons. Neurosci Res Program Bull 1977;15:555–687. Author(s)Manuscript received May 2003, revised, and accepted April 2004. 1. Assistant Professor, Faculty of Nursing, University of Toronto, Toronto, Ontario. Address for correspondence: Dr C-L Dennis, Assistant Professor, Faculty of Nursing, University of Toronto, 50 St George Street, Toronto, ON M5S 3H4 e-mail: cindylee.dennis@utoronto.ca
1 | 2
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||