Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr 18;4(4):CD004363.
doi: 10.1002/14651858.CD004363.pub3.

Antidepressants for preventing postnatal depression

Emma Molyneaux  1 , Laurence A Telesia, Carol Henshaw, Elizabeth Boath, Eleanor Bradley, Louise M Howard
Affiliations

Antidepressants for preventing postnatal depression

Emma Molyneaux et al. Cochrane Database Syst Rev. .

Abstract

Background: Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear whether antidepressants are effective for the prevention of postnatal depression and little is known about possible adverse effects for the mother and infant, particularly during breastfeeding. This is an update of a Cochrane Review last published in 2005.

Objectives: To assess the effectiveness of antidepressant medication for the prevention of postnatal depression, in comparison with any other treatment, placebo or standard care.

Search methods: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR ‒ both Studies and References), CENTRAL (Wiley), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), on 13 February 2018. We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov on 13 February 2018 to identify any additional unpublished or ongoing studies.

Selection criteria: Randomised controlled trials (RCTs) of initiation of antidepressants (alone or in combination with another treatment), compared with any other treatment, placebo or standard care for the prevention of postnatal depression among women who were either pregnant or had given birth in the previous six weeks and were not currently depressed at baseline.

Data collection and analysis: We used standard methodological procedures expected by Cochrane. We requested missing information from investigators wherever possible and sought data to allow intention-to-treat analyses.

Main results: Two trials including a total of 81 participants fulfilled the inclusion criteria for this review. All participants in both studies had a history of postnatal depression and were not taking antidepressant medication at baseline. Both trials were conducted by the same research group. Risk of bias was low or unclear in most domains for both studies. We were unable to perform a meta-analysis due to the small number of studies.One study compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression. In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (RR 0.96, 95% CI 0.36 to 2.59, very low quality evidence) in the first 17 weeks postpartum. One woman taking nortriptyline developed mania; and one side effect, constipation, was more common among women taking nortriptyline than those taking placebo.The second study compared sertraline with placebo. In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (RR 0.14, 95% CI 0.02 to 1.07, very low quality evidence). One woman taking sertraline had a hypomanic episode. Two side effects (dizziness and drowsiness) were more common among women taking sertraline than women taking placebo.Conclusions are limited by the small number of studies, small sample sizes and incomplete outcome data due to study drop-out which may have led to bias in the results. We have assessed the certainty of the evidence as very low, based on the GRADE system. No data were available on secondary outcomes of interest including child development, the mother‒infant relationship, breastfeeding, maternal daily functioning, family relationships or maternal satisfaction.

Authors' conclusions: Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Nortriptyline versus placebo, outcome: 1.1 Recurrence of postpartum major depressive disorder.
5
5
Forest plot of comparison: 2 Sertraline versus placebo, outcome: 2.1 Recurrence of postpartum major depressive disorde.
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Wisner 2001 {published data only}
    1. Gracious BL, Hanusa BH, Wisner KL, Peindl KS, Perel JM. Weight changes in postpartum women with remitted depression. Journal of Clinical Psychiatry 2005;66(3):291‐3. - PubMed
    1. Peindl KS. The use of nortriptyline for prevention of postpartum depression in a high‐risk group of women. 152nd Annual Meeting of the American Psychiatric Association, 1999 May 15‐20, Washington, DC. 1999.
    1. Peindl KS, Wisner KL. Successful recruitment strategies for women in postpartum mental health trials. Journal of Psychiatric Research 2003;37(2):117‐25. - PubMed
    1. Peindl KS, Wisner KL, Hanusa BH, Peindl KS. Identifying depression in the first postpartum year: Guidelines for office‐based screening and referral. Journal of Affective Disorders 2004;80(1):37‐44. - PubMed
    1. Wisner KL. Prevention and treatment of postpartum mood disorders. 152nd Annual Meeting of the American Psychiatric Association, 1999 May 15‐20, Washington, DC. 1999.
Wisner 2004 {published data only}
    1. Gracious BL, Hanusa BH, Wisner KL, Peindl KS, Perel JM. Weight changes in postpartum women with remitted depression. Journal of Clinical Psychiatry 2005;66(3):291‐3. - PubMed
    1. Sunder KR, Wisner KL, Hanusa BH, Perel JM. Postpartum depression recurrence versus discontinuation syndrome: observations from a randomized controlled trial. Journal of Clinical Psychiatry 2004;65(9):1266‐8. - PubMed
    1. Wisner KL, Peindl KS, Perel JM, Hanusa BH, Plontek CM, Findling RL. Sertraline prevents postpartum depression. 156th Annual Meeting of the American Psychiatric Association, May 17‐22, San Francisco CA. 2003.
    1. Wisner KL, Perel JM, Peindl KS, Hanusa BH, Piontek CM, Findling RL. Prevention of postpartum depression: a pilot randomized clinical trial. American Journal of Psychiatry 2004;161(7):1290‐2. - PubMed

References to studies excluded from this review

Appleby 1997 {published data only}
    1. Appleby L. A controlled study of fluoxetine and cognitive ‐behavioural counselling in the treatment of postnatal depression. European Psychiatry 1998;13 Suppl 4:178s. - PMC - PubMed
    1. 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(7085):932‐6. - PMC - PubMed
Epperson 1996 {published data only}
    1. Epperson CN, McDougle CJ, Ward‐O'Brien D, Price LH. A controlled study of antidepressant treatment of postpartum depression. 149th Annual Meeting of the American Psychiatric Association; 1996 May 4‐9; New York, NY. 1996.
Heath 2000 {published data only}
    1. Heath AC, Yonkers KA, Rush AJ. Paroxetine in the treatment of postpartum depression. 153rd Annual Meeting of the American Psychiatric Association, 2000 May 13‐18, Chicago, (IL). 2000.
NCT02235064 {published data only}
    1. Fischer RL, Simpkins GK. Prophylactic Use of Postpartum Sertraline to Prevent Postpartum Depression. clinicaltrials.gov/ct2/show/NCT02235064 (accessed 30 October 2017). [NCT02235064]
Sharp 2004 {published data only}
    1. Sharp D. Antidepressant drug therapy vs a community‐based psychosocial intervention for the treatment of moderate postnatal depression: a pragmatic randomised controlled trial. National Research Register 2004. - PubMed

References to ongoing studies

NCT00276900 {unpublished data only}
    1. Wisner K. Sertraline for the Prevention of Recurrent Postpartum Depression [Prevention of Recurrent Postpartum Depression]. clinicaltrials.gov/ct2/show/NCT00276900 2006.

Additional references

American Psychiatric Association 2013
    1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatry Association, 2013.
Bland 2000
    1. Bland JM, Altman DG. The odds ratio. BMJ 2000;320(7247):1468. - PMC - PubMed
Cohen 2006
    1. Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC, et al. Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment. JAMA 2006;295(5):499. - PubMed
Cox 1982
    1. Cox J, Connor Y, Kendell RE. Prospective study of the psychiatric disorders of childbirth. British Journal of Psychiatry 1982;140:111‐7. - PubMed
Cox 1987
    1. Cox JL, Holden J, Sagovsky R. Detection of postnatal depression: development of the 10‐item Edinburgh Postnatal Depression Scale (EPDS). British Journal of Psychiatry 1987;150:782‐6. - PubMed
Dennis 2007
    1. Dennis C‐L, Hodnett ED. Psychosocial and psychological interventions for treating postpartum depression. Cochrane Database of Systematic Reviews 2007, Issue 10. [DOI: 10.1002/14651858.CD006116.pub2] - DOI - PubMed
Elbourne 2002
    1. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. - PubMed
Fournier 2010
    1. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant Drug Effects and Depression Severity. A Patient‐Level Meta‐analysis. JAMA 2010;303(1):47‐53. - PMC - PubMed
Geddes 2003
    1. Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003;361(9358):653‐61. - PubMed
Higgins 2011
    1. Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Howard 2006
    1. Howard LM, Boath E, Henshaw C. Antidepressant Prevention of Postnatal Depression. PLOS Medicine 2006;3(10):e389. - PMC - PubMed
Howard 2014
    1. Howard LM, Molyneaux E, Dennis C‐L, Rochat T, Stein A, Milgrom J. Non‐psychotic mental disorders in the perinatal period. Lancet 2014;384(9956):1775–88. - PubMed
Khalifeh 2016
    1. Khalifeh H, Hunt IM, Appleby L, Howard LM. Suicide in perinatal and non‐perinatal women in contact with psychiatric services: 15 year findings from a UK national inquiry. Lancet Psychiatry 2016;3(3):233‐42. - PubMed
Molenaar 2016
    1. Molenaar NM, Brouwer ME, Bockting CL, Bonsel GJ, Veere CN, Torij HW, et al. Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non‐inferiority randomized controlled trial. BMC Psychiatry 2016;16:72. [DOI: 10.1186/s12888-016-0752-6] - DOI - PMC - PubMed
Molyneaux 2014
    1. Molyneaux E, Howard LM, McGeown HR, Karia AM, Trevillion K. Antidepressant treatment for postnatal depression. Cochrane Database of Systematic Reviews 2014, Issue 9. [DOI: 10.1002/14651858.CD002018.pub2] - DOI - PMC - PubMed
Morrell 2016
    1. Morrell CJ, Sutcliffe P, Booth A, Stevens J, Scope A, Stevenson M, et al. A systematic review, evidence synthesis and meta‐analysis of quantitative and qualitative studies evaluating the clinical effectiveness, the cost‐effectiveness, safety and acceptability of interventions to prevent postnatal depression. Health Technology Assessment (Winchester, England) 2016;20(37):1‐414. - PMC - PubMed
NICE 2009
    1. NICE. Depression: the Treatment and Management of Depression in Adults (Update). NICE clinical guideline 90, 2009.
Sharp 2010
    1. Sharp DJ, Chew‐Graham C, Tylee A, Lewis G, Howard L, Anderson I, et al. 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 Technology Assessments 2010;14(43):1‐153. - PubMed
Spitzer 1978
    1. Spitzer R, Endicott J, Robins E. Research Diagnostic Criteria; rationale and reliability. Archives of General Psychiatry 1978;35(6):773‐82. - PubMed
Stein 2014
    1. Stein A, Pearson RM, Goodman SH, Rapa E, Rahman A, McCallum M, et al. Effects of perinatal mental disorders on the fetus and child. Lancet 2014;384(9956):1800‐19. - PubMed
Tierney 2007
    1. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time‐to‐event data into meta‐analysis. Trials 2007;8:16. - PMC - PubMed
Turner 2008
    1. Turner KM, Sharp D, Folkes L, Chew‐Graham C. Women's views and experiences of antidepressants as a treatment for postnatal depression: a qualitative study. Family Practice 2008;25(6):450‐5. - PubMed
Wisner 2013
    1. Wisner KL, Sit DK, McShea MC, Rizzo DM, Zoretich RA, Hughes CL, et al. Onset timing, thoughts of self‐harm, and diagnoses in postpartum women with screen‐positive depression findings. JAMA Psychiatry 2013;70(4):490‐8. - PMC - PubMed
World Health Organization 2004
    1. World Health Organization. The ICD‐10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guideline. Geneva, World Health Organization, 2004.
Yonkers 2008
    1. Yonkers KA, Lin H, Howell HB, Heath AC, Cohen LS. Pharmacologic treatment of postpartum women with new‐onset major depressive disorder: a randomized controlled trial with paroxetine. Journal of Clinical Psychiatry 2008;69(4):659‐65. - PMC - PubMed
Yonkers 2011
    1. Yonkers KA, Gotman N, Smith MV, Forray A, Belanger K, Brunetto WL, et al. Does antidepressant use attenuate the risk of a major depressive episode in pregnancy?. Epidemiology 2011;22(6):848‐54. - PMC - PubMed

Publication types

MeSH terms