Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment [corrected] [published erratum appears in JAMA296(2): 170]

Harvard University, Cambridge, Massachusetts, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 02/2006; 295(5):499-507. DOI: 10.1001/jama.295.5.499
Source: PubMed


Pregnancy has historically been described as a time of emotional well-being, providing "protection" against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary.
To describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications.
A prospective naturalistic investigation using longitudinal psychiatric assessments on a monthly basis across pregnancy; a survival analysis was conducted to determine time to relapse of depression during pregnancy. A total of 201 pregnant women were enrolled between March 1999 and April 2003 from 3 centers with specific expertise in the treatment of psychiatric illness during pregnancy. The cohort of women was recruited from (1) within the hospital clinics, (2) self-referral via advertisements and community outreach detailing the study, and (3) direct referrals from the community. Participants were considered eligible if they (1) had a history of major depression prior to pregnancy, (2) were less than 16 weeks' gestation, (3) were euthymic for at least 3 months prior to their last menstrual period, and (4) were currently or recently (<12 weeks prior to last menstrual period) receiving antidepressant treatment. Of the 201 participants, 13 miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up prior to completion of pregnancy, and 8 chose to discontinue participation in the study.
Relapse of major depression defined as fulfilling Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID) criteria.
Among the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Among the 82 women who maintained their medication throughout their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P<.001).
Pregnancy is not "protective" with respect to risk of relapse of major depression. Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation.

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    • "Additionally, as multiple studies were conducted in regard to other reproductive events of women and depression, the results are still conflicting. Contrary to the evidence of pregnancy being harmful to major depression (Cohen et al., 2006), many studies have reported no associations between these two factors, including the result from Korea (Jung et al., 2015). Similarly, a metaanalysis of 26 studies suggested that there is a protective effect of hormone replacement therapy (HRT) against depression (Zweifel and O&apos;Brien, 1997). "
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    ABSTRACT: Background: Although there are plausible mechanisms of female hormones in depression, epidemiological evidence has shown conflicting results. Objective: This study aimed to evaluate the associations between female hormonal events and post- menopausal depression and further investigate the relative association between the age of menarche, the age of menopause and depression. Methods: Among 111,589 women who took part in the Health Examinees (HEXA) Study, a total of 60,114 postmenopausal participants were included in the final analysis. Each participant provided information on depression and questions related to reproductive history. The outcome variable was self-reported by the history of depression diagnosed by physicians and the Center for Epidemiologic Studies Depression Scale (CES-D) score. With the multivariate logistic regression, odds ratios were calculated. Possible interactions between depression prevalence and the ages of menarche and menopause were assessed. Results: A total of 2.2% (1342/60,114) women were diagnosed with depression after menopause, and 5.9% (500/8472) showed depressive symptoms. As the age of menopause and duration of reproductive years increased, the odds ratio of depression decreased (P-trend o0.001). As the age of menarche increased, the likelihood of physician-diagnosed depression also increased (P-trend 0.048). As the number of both spontaneous and induced abortions increased, the odds ratio of depression increased (P-trend <0.001). Limitation: it is possible that women show inaccuracies in recalling their hormonal events and re- porting other past mental disorders as depression. Conclusion: Both the ages of the initiation and the termination of menstruation were associated with the increased odds ratio of post-menopausal depression. However, the age of menopause seems to be more important.
    Full-text · Article · Aug 2015 · Journal of Affective Disorders
    • "Investigators have noted that the high prevalence of postpartum depression is driven by the high rates of relapse of prenatal depression after delivery (Cohen et al. 2006). Notably, investigators have reported rates of relapse in pregnant women with a history of recurrent mood disorder to be as high as 43 % (Cohen et al. 2006). "
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    ABSTRACT: The objective of this review is to summarize the literature (and to the extent possible, report the magnitude and direction of the association) concerning history of childhood sexual abuse (CSA) and depression or depressive symptoms among pregnant and postpartum women. Publications were identified through literature searches of seven databases (PubMed, EMBASE, PyscINFO, CINAHL, Web of Science, BIOSIS, and Science Direct) using keywords including "child abuse," "depression," "pregnancy," "prenatal," "pregnancy," and "postpartum." The literature search yielded seven eligible studies on the prenatal period and another seven studies on the postpartum period. All but one prenatal study observed statistically significant positive associations of CSA with depression or depressive symptoms during pregnancy. Findings on the association of CSA with postpartum depression or depressive symptoms were inconsistent; pooled unadjusted and adjusted odds ratios were 1.82 (95 % confidence interval (CI) 0.92, 3.60) and 1.20 (95 % CI 0.81, 1.76). In sum, findings suggest a positive association of history of CSA with depression and depressive symptoms in the prenatal period. Findings on the postpartum period were inconsistent. Clinical and public health implications of evidence from the available literature are discussed, as are desirable study design characteristics of future research.
    No preview · Article · May 2015 · Archives of Women s Mental Health
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    • "A French study showed that early menopause was associated with a higher risk of late-life depression (Ryan et al., 2008), and a study from the U.S. demonstrated that women with more children had a lower risk of depression (Harlow et al., 1999). Furthermore, although pregnancy is believed to be protective against psychiatric disorders, there is accumulating evidence that supports the opposite conclusion (Cohen et al., 2006a). However, there is not enough evidence to prove the effects of natural reproductive hormones on developing depression, and few epidemiological studies have been conducted on this issue, especially in Asian women. "
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    ABSTRACT: Background: Although hypotheses have been proposed regarding the biological mechanisms of hormonal fluctuations in mood disorders, few epidemiological studies have addressed this issue. The aim of this study was to examine the association between hormone-related life events and postmenopausal depression. Methods: Of 13,918 women who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) V, a total of 4869 post-menopausal women who had completed information on depression onset age and additional reproductive factors were included in the analysis. A multivariate logistic regression was applied to calculate the odds ratios between reproductive factors and post-menopausal onset depression. Results: A total of 276 women (5.7%) were diagnosed with depression after menopause. Longer reproductive years were associated with a reduced risk of depression (for more than 35 reproductive years: OR=0.41, 95% CI: 0.27-0.62, P-trend<0.001). Similarly, a later age of menopause (52 years and older) corresponded to a decreased risk of depression (OR=0.35, 95% CI: 0.22-0.55) compared to the women with a menopausal age younger than 46 years. Greater numbers of pregnancies and exogenous hormone use were also associated with increased risk of depression. Limitations: All data were collected from interviews using questionnaires. There may be some inaccuracies in recall of lifetime reproductive events, but women generally recalled their hormonal events correctly. Conclusion: Early menopause and the use of exogenous hormones were associated with the risk of post-menopausal depression. Clinicians should closely monitor and consider further screening for depressed women who undergo early menopause or those with exogenous hormone use.
    Full-text · Article · Jan 2015 · Journal of Affective Disorders
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