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Comparative effects of antidepressant medications and untreated major depression on pregnancy outcomes: a systematic review

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Abstract

Psychopharmacological treatment of pregnant women is an area of continued controversy; extensive observational research on the use of antidepressant medications in pregnancy has found these medications to be associated with increased risk of spontaneous abortion, preterm delivery, and low birth weight. However, depression itself has also been associated with increased risk of those same outcomes, and only recently have researchers begun trying to compare treated with untreated depression. The purpose of this study was to conduct a systematic review of the literature to integrate those comparative studies and compare risks and benefits. PubMed, PsycInfo, and CINAHL searches; study selection; and data extraction were carried out using PRISMA guidelines. Eleven prospective observational and case-control studies were selected for final inclusion. Risk of low birth weight and related outcomes do not differ between antidepressant-treated pregnant women and untreated depressed women. Average gestational lengths tend to be slightly shorter with antidepressant use but it is unclear whether these differences are clinically meaningful or extend to preterm delivery. Very limited research on spontaneous abortion did not allow conclusions to be drawn regarding that outcome. The low number of studies meeting criteria highlights the need for further research to aid in risk-benefit analysis for women considering antidepressant use in pregnancy. While further research is necessary, discontinuing antidepressant treatment of major depression in pregnancy due to concerns about length of gestation, birth weight, or spontaneous abortion is not supported by the evidence available at this time.

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Acknowledgements

The authors thank Jessica Bell MS (MGH Institute of Health Professions) for assistance with database search strategy and Brendon Stubbs PhD (Kings College London) for advice on feasibility of meta-analysis.

Funding

None.

Author information

Authors and Affiliations

  1. MGH Institute of Health Professions, School of Nursing, 36 1st Ave, Boston, MA, 02129, USA

    Jentina Mitchell & Janice Goodman

Authors
  1. Jentina Mitchell
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  2. Janice Goodman
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Corresponding author

Correspondence to Jentina Mitchell.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Appendix 1: Modified Newcastle-Ottawa Scale for Cohort Studies

Appendix 1: Modified Newcastle-Ottawa Scale for Cohort Studies

Selection (total points possible = 5)

  1. 1)

    Representativeness of the exposed cohort

    1. a)

      Truly representative of the average pregnant woman with depression in the community*

    2. b)

      Somewhat representative of the average pregnant woman with depression in the community*

    3. c)

      Selected group of users, e.g. nurses, volunteers

    4. d)

      No description of the derivation of the cohort

  2. 2)

    Selection of the non exposed cohort

    1. a)

      Drawn from the same community as the exposed cohort*

    2. b)

      Drawn from a different source

    3. c)

      No description of the derivation of the non exposed cohort

  1. 3a)

    Ascertainment of exposure to medication

    1. a)

      Secure record of medication dispensed (NOT just of prescriptions written)*

    2. b)

      Pill counts*

    3. c)

      Self-report

    4. d)

      No description

  2. 3b)

    Ascertainment of exposure to depression

    1. a)

      Secure record (e.g., ICD codes)*

    2. b)

      Structured diagnostic interview*

    3. c)

      Standardized screening instrument (CES-D, PRIME-MD, EPDS, etc.)*

    4. c)

      Written self-report

    5. d)

      No description

  1. 4)

    Demonstration that outcome of interest was not present at start of study (no history of PTB, LBW, etc. in previous pregnancies)

    1. a)

      Yes*

    2. b)

      No

Comparability (total points possible = 2)

  1. 1.

    The following are several factors known to affect birth weight and length of gestation outcomes which can be assessed early in pregnancy (March of Dimes 2014; Robinson and Norwitz 2016; National Institutes of Health n.d.). Of the following 11 factors, a study will receive 1 point if at least 3 of these factors are either exclusion criteria or explicitly controlled for, and 2 points if at least 7 of these factors are either exclusion criteria or explicitly controlled for.

    1. (a)

      Multiple gestation

    2. (b)

      Abnormalities of the reproductive organs

    3. (c)

      Underweight prepregnancy

    4. (d)

      Prepregnancy diabetes

    5. (e)

      Prepregnancy hypertension

    6. (f)

      African-American ethnicity

    7. (g)

      Maternal age < 18 or > 35

    8. (h)

      Tobacco use

    9. (i)

      Alcohol use

    10. (j)

      Substance abuse

    11. (k)

      Low socioeconomic status (SES)

Outcome (Total points possible = 3)

  1. 1)

    Assessment of birth outcome

    1. a)

      Independent blind assessment*

    2. b)

      Record linkage*

    3. c)

      Self-report

    4. d)

      No description

  2. 2)

    Was follow-up long enough for outcomes to occur

    1. a)

      Yes (all followed until birth)*

    2. b)

      No

  3. 3)

    Adequacy of follow-up of cohorts

    1. a)

      Complete follow-up—all subjects accounted for*

    2. b)

      Subjects lost to follow-up unlikely to introduce bias: small number lost (less than 2%), or description provided of those lost)*

    3. c)

      More than 2% lost to follow-up and no description of those lost

    4. d)

      No statement

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Mitchell, J., Goodman, J. Comparative effects of antidepressant medications and untreated major depression on pregnancy outcomes: a systematic review. Arch Womens Ment Health 21, 505–516 (2018). https://doi.org/10.1007/s00737-018-0844-z

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