Psychopharmacology

, Volume 231, Issue 5, pp 939–948 | Cite as

A randomized, placebo-controlled, double-blind trial of sertraline for postpartum depression

  • Liisa Hantsoo
  • Deborah Ward-O’Brien
  • Kathryn A. Czarkowski
  • Ralitza Gueorguieva
  • Lawrence H. Price
  • C. Neill Epperson
Original Investigation

Abstract

Rationale

Postpartum depression (PMD) occurs in roughly 10 % of postpartum women and negatively impacts the mother and her offspring, but there are few placebo-controlled studies of antidepressant treatment in this population.

Objective

The objective was this study is to compare the selective serotonin reuptake inhibitor (SSRI) sertraline to placebo for treating PMD.

Methods

This was a single-center, 6-week, randomized double-blind placebo-controlled trial of sertraline with a 1-week placebo lead-in. The participants (n = 38) were women with depression onset within 3 months of delivery; a subset (n = 27) met strict DSM-IV criteria for PMD (onset within 4 weeks of delivery). The participants were prescribed sertraline 50 mg or placebo daily to a maximum of 200 mg/day. Primary outcome variables were the Hamilton Depression Rating Scale (HAM-D) and Clinical Global Impressions (CGI) scores, which were used to determine the rates of response and remission.

Results

Sertraline produced a significantly greater response rate (59 %) than placebo (26 %) and a more than twofold increased remission rate (53 % vs. 21 %). Mixed models did not reveal significant group by time effects, although in the subset of women who met the DSM-IV criteria, there was a statistically significant group by time effect for the HAM-D, Hamilton Anxiety Rating Scale (HAM-A), and CGI.

Conclusions

Women with PMD are more likely to have a remission of their depression with sertraline treatment, a finding that is more pronounced in women who have onset of depression within 4 weeks of childbirth. These data support the continued use of 4 weeks for the DSM-5 postpartum onset specifier for major depressive disorder.

Keywords

Postpartum Puerperal Depression Sertraline SSRI Pregnancy Women 

Abbreviations

5α-DHP

5α-dihydroprogesterone

ALLO

allopregnanolone

CBT

cognitive behavioral therapy

CGI

Clinical Global Impressions

CNS

central nervous system

DSM

Diagnostic and Statistical Manual of Mental Disorders

FET

Fisher exact tests

HAM-A

Hamilton Anxiety Rating Scale

HAM-D

Hamilton Depression Rating Scale

IPT

interpersonal therapy

ITT

intent-to-treat

H-MRS

proton magnetic resonance spectroscopy

EPDS

Edinburgh Postnatal Depression Scale

MDD

major depressive disorder

PMD

postpartum major depression

RCT

randomized clinical trial

SCID

Structured Clinical Interview for DSM

SERT

serotonin transporter

SSRI

selective serotonin reuptake inhibitor

References

  1. Amin Z, Canli T, Epperson CN (2005) Effect of estrogen-serotonin interactions on mood and cognition. Behav Cogn Neurosci Rev 4:43–58. doi:10.1177/1534582305277152 PubMedCrossRefGoogle Scholar
  2. APA (2000) Diagnostic and statistical manual of mental disorders (4th ed., text revision). American Psychological Association, Washington, DCGoogle Scholar
  3. Appleby L, Warner R, Whitton A, Faragher B (1997) A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression. BMJ 314:932–936PubMedCrossRefGoogle Scholar
  4. Bloch M, Meiboom H, Lorberblatt M et al (2012) The effect of sertraline add-on to brief dynamic psychotherapy for the treatment of postpartum depression: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 73:235–241. doi:10.4088/JCP.11m07117 PubMedCrossRefGoogle Scholar
  5. Cooper PJ, Murray L (1995) Course and recurrence of postnatal depression. Evidence for the specificity of the diagnostic concept. Br J Psychiatry 166:191–195PubMedCrossRefGoogle Scholar
  6. Cox JL, Holden JM, Sagovsky R (1987) Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry 150:782–786PubMedCrossRefGoogle Scholar
  7. Davanzo R, Copertino M, De Cunto A et al (2011) Antidepressant drugs and breastfeeding: a review of the literature. Breastfeed Med 6:89–98. doi:10.1089/bfm.2010.0019 PubMedCrossRefGoogle Scholar
  8. DeVane CL, Liston HL, Markowitz JS (2002) Clinical pharmacokinetics of sertraline. Clin Pharmacokinet 41:1247–1266PubMedCrossRefGoogle Scholar
  9. Epperson C, Anderson GM, McDougle CJ (1997) Sertraline and breast-feeding. N Engl J Med 336:1189–1190. doi:10.1056/NEJM199704173361615 PubMedCrossRefGoogle Scholar
  10. Epperson C, Czarkowski KA, Ward-O’Brien D et al (2001) Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. Am J Psychiatry 158:1631–1637PubMedCrossRefGoogle Scholar
  11. Epperson C, Jatlow PI, Czarkowski K, Anderson GM (2003) Maternal fluoxetine treatment in the postpartum period: effects on platelet serotonin and plasma drug levels in breastfeeding mother-infant pairs. Pediatrics 112:e425–e425. doi:10.1542/peds.112.5.e425 PubMedCrossRefGoogle Scholar
  12. First MB, Spitzer RL, Gibbon M, Williams JBW (1995) Structured clinical interview for DSM-IV Axis I Disorders, patient edition (SCID-I/P v 2.0). Biometrics Research, New York State Psychiatric Institute, New YorkGoogle Scholar
  13. Gavin NI, Gaynes BN, Lohr KN et al (2005) Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol 106:1071–1083. doi:10.1097/01.AOG.0000183597.31630.db PubMedCrossRefGoogle Scholar
  14. Griffin LD, Mellon SH (1999) Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci U S A 96:13512–13517PubMedCentralPubMedCrossRefGoogle Scholar
  15. Guy W (1976) ECDEU assessment manual for psychopharmacology. US Department of Health, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and Mental Health Administration, Rockville, MDGoogle Scholar
  16. Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32(1):50–55PubMedCrossRefGoogle Scholar
  17. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatr 23:56–62PubMedCrossRefGoogle Scholar
  18. Hübner-Liebermann B, Hausner H, Wittmann M (2012) Recognizing and treating peripartum depression. Dtsch Arztebl Int 109:419–424. doi:10.3238/arztebl.2012.0419 PubMedCentralPubMedGoogle Scholar
  19. Kaplan PS, Danko CM, Kalinka CJ, Cejka AM (2012) A developmental decline in the learning-promoting effects of infant-directed speech for infants of mothers with chronically elevated symptoms of depression. Infant Behav Dev 35:369–379. doi:10.1016/j.infbeh.2012.02.009 PubMedCentralPubMedCrossRefGoogle Scholar
  20. Kennedy SH, Andersen HF, Thase ME (2009) Escitalopram in the treatment of major depressive disorder: a meta-analysis. Curr Med Res Opin 25:161–175. doi:10.1185/03007990802622726 PubMedCrossRefGoogle Scholar
  21. Logsdon MC, Wisner K, Hanusa BH, Phillips A (2003) Role functioning and symptom remission in women with postpartum depression after antidepressant treatment. Arch Psychiatr Nurs 17:276–283PubMedCrossRefGoogle Scholar
  22. Luisi S, Petraglia F, Benedetto C et al (2000) Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients. J Clin Endocrinol Metab 85:2429–2433PubMedCrossRefGoogle Scholar
  23. Misri S, Abizadeh J, Albert G et al (2012) Restoration of functionality in postpartum depressed mothers: an open-label study with escitalopram. J Clin Psychopharmacol 32:729–732. doi:10.1097/JCP.0b013e31826867c9 PubMedCrossRefGoogle Scholar
  24. Misri S, Kendrick K, Oberlander TF et al (2010) Antenatal depression and anxiety affect postpartum parenting stress: a longitudinal, prospective study. Can J Psychiatry 55:222–228PubMedGoogle Scholar
  25. Misri S, Reebye P, Corral M, Milis L (2004) The use of paroxetine and cognitive-behavioral therapy in postpartum depression and anxiety: a randomized controlled trial. J Clin Psychiatry 65:1236–1241PubMedCrossRefGoogle Scholar
  26. Murray L, Hipwell A, Hooper R et al (1996) The cognitive development of 5-year-old children of postnatally depressed mothers. J Child Psychol Psychiatry 37:927–935PubMedCrossRefGoogle Scholar
  27. Nonacs RM, Soares CN, Viguera AC et al (2005) Bupropion SR for the treatment of postpartum depression: a pilot study. Int J Neuropsychopharmacol 8:445–449. doi:10.1017/S1461145705005079 PubMedCrossRefGoogle Scholar
  28. Paul IM, Downs DS, Schaefer EW et al (2013) Postpartum anxiety and maternal-infant health outcomes. Pediatrics 131:e1218–1224. doi:10.1542/peds.2012-2147 PubMedCrossRefGoogle Scholar
  29. Philipps LH, O'Hara MW (1991) Prospective study of postpartum depression: 4 1/2-year 0follow-up of women and children. J Abnorm Psychol 100:151–155PubMedCrossRefGoogle Scholar
  30. Reck C, Hunt A, Fuchs T et al (2004) Interactive regulation of affect in postpartum depressed mothers and their infants: an overview. Psychopathology 37:272–280. doi:10.1159/000081983 PubMedCrossRefGoogle Scholar
  31. Reck C, Noe D, Gerstenlauer J, Stehle E (2012) Effects of postpartum anxiety disorders and depression on maternal self-confidence. Infant Behav Dev 35:264–272. doi:10.1016/j.infbeh.2011.12.005 PubMedCrossRefGoogle Scholar
  32. Shanmugan S, Epperson CN (2012) Estrogen and the prefrontal cortex: towards a new understanding of estrogen's effects on executive functions in the menopause transition. Hum Brain Mapp. doi:10.1002/hbm.22218 PubMedGoogle Scholar
  33. Sharp DJ, Chew-Graham C, Tylee A, et al. (2010) A pragmatic randomised controlled trial to compare antidepressants with a community-based psychosocial intervention for the treatment of women with postnatal depression: the RESPOND trial. Health Technol Assess 14:iii–iv, ix–xi, 1–153. doi:10.3310/hta14430
  34. Sockol LE, Epperson CN, Barber JP (2011) A meta-analysis of treatments for perinatal depression. Clin Psychol Rev 31:839–849. doi:10.1016/j.cpr.2011.03.009 PubMedCrossRefGoogle Scholar
  35. Stowe ZN, Hostetter AL, Owens MJ et al (2003) The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations. J Clin Psychiatry 64:73–80PubMedCrossRefGoogle Scholar
  36. Stuart S, Couser G, Schilder K et al (1998) Postpartum anxiety and depression: onset and comorbidity in a community sample. J Nerv Ment Dis 186:420–424PubMedCrossRefGoogle Scholar
  37. Thase ME, Nierenberg AA, Vrijland P et al (2010) Remission with mirtazapine and selective serotonin reuptake inhibitors: a meta-analysis of individual patient data from 15 controlled trials of acute phase treatment of major depression. Int Clin Psychopharmacol 25:189–198. doi:10.1097/YIC.0b013e328330adb2 PubMedCrossRefGoogle Scholar
  38. Turkmen S, Backstrom T, Wahlstrom G et al (2011) Tolerance to allopregnanolone with focus on the GABA-A receptor. Br J Pharmacol 162:311–327. doi:10.1111/j.1476-5381.2010.01059.x PubMedCrossRefGoogle Scholar
  39. Wisner KL, Hanusa BH, Perel JM et al (2006) Postpartum depression: a randomized trial of sertraline versus nortriptyline. J Clin Psychopharmacol 26:353–360. doi:10.1097/01.jcp.0000227706.56870.dd PubMedCrossRefGoogle Scholar
  40. Wisner KL, Perel JM, Peindl KS et al (2001) Prevention of recurrent postpartum depression: a randomized clinical trial. J Clin Psychiatry 62:82–86PubMedCrossRefGoogle Scholar
  41. Yonkers KA, Lin H, Howell HB et al (2008) Pharmacologic treatment of postpartum women with new-onset major depressive disorder: a randomized controlled trial with paroxetine. J Clin Psychiatry 69:659–665PubMedCentralPubMedCrossRefGoogle Scholar
  42. Yonkers KA, Vigod S, Ross LE (2011) Diagnosis, pathophysiology, and management of mood disorders in pregnant and postpartum women. Obstet Gynecol 117:961–977. doi:10.1097/AOG.0b013e31821187a7 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Liisa Hantsoo
    • 1
    • 2
    • 3
  • Deborah Ward-O’Brien
    • 4
  • Kathryn A. Czarkowski
    • 1
    • 2
    • 3
  • Ralitza Gueorguieva
    • 5
    • 6
  • Lawrence H. Price
    • 7
    • 8
  • C. Neill Epperson
    • 1
    • 2
    • 3
    • 9
  1. 1.Department of Psychiatry, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Penn Center for Women’s Behavioral WellnessPhiladelphiaUSA
  3. 3.Penn Center for the Study of Sex and Gender in Behavioral HealthPhiladelphiaUSA
  4. 4.Department of Psychiatry, School of MedicineYale UniversityNew HavenUSA
  5. 5.Department of Biostatistics, School of Public HealthYale UniversityNew HavenUSA
  6. 6.School of MedicineYale UniversityNew HavenUSA
  7. 7.Butler Hospital, Alpert Medical SchoolBrown UniversityProvidenceUSA
  8. 8.Department of Psychiatry and Human Behavior, Alpert Medical SchoolBrown UniversityProvidenceUSA
  9. 9.Department of Obstetrics and Gynecology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations