Does Antidepressant Use Attenuate the Risk of a Major Depressive Episode in Pregnancy?

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA.
Epidemiology (Cambridge, Mass.) (Impact Factor: 6.2). 09/2011; 22(6):848-54. DOI: 10.1097/EDE.0b013e3182306847
Source: PubMed


Many women become pregnant while undergoing antidepressant treatment and are concerned about continuing antidepressant medication. However, antidepressant discontinuation may increase the risk of a new episode of major depressive disorder. We sought to estimate differences in the risk of developing a new major depressive episode among pregnant and postpartum women with recurrent illness who either did or did not use antidepressants.
Participants were recruited from obstetrical settings; we analyzed a subgroup of 778 women with a history of a depressive disorder. Diagnoses were determined by the Composite International Diagnostic Interview administered twice in pregnancy and once after delivery. We used Cox Regression to model onset of a major depressive episode with a time-dependent predictor of antidepressant use.
There was no clear difference in risk of a major depressive episode between women who took antidepressants and women who did not (hazard ratio [HR] = 0.88; 95% CI = 0.51-1.50). After accounting for antidepressant use, clearly hazardous factors included 4 or more depressive episodes before pregnancy (HR = 1.97; 95% CI = 1.09-3.57), black race (HR = 3.69; 95% CI = 2.16-6.30), and Hispanic ethnicity (HR = 2.33; 95% CI = 1.47-3.69).
Failure to use or discontinuation of antidepressants in pregnancy did not have a strong effect on the development of a major depressive episode. Women with 4 or more episodes before pregnancy were at high risk of a major depressive episode, independent of antidepressant use. Black and Hispanic women also were at high risk of a major depressive episode, but it is possible that this effect is attributable to unmeasured factors.

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Available from: Kimberly Ann Yonkers, Jan 10, 2014
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    • "In the Cohen et al study, women who chose to continue an effective antidepressant throughout pregnancy still had a 26% risk of relapse during follow-up.50 Moreover, in a well-controlled study of 778 women with a history of any depressive disorder (as determined by lay interviewers using the Composite International Diagnostic Interview) who were recruited from obstetric rather than specialty mental health care settings, the risk of a major depressive episode during pregnancy did not differ statistically between women who took antidepressants and those who did not (hazard ratio 0.85, 95% CI 0.52–1.40).52 The overall rate of major depressive episode onset during pregnancy was 16%, though differences by antidepressant exposure in rates of depressive episode occurrence were not reported, and the analyses were not stratified by depression severity or presence of comorbid illnesses, such as anxiety disorders. "
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    ABSTRACT: In pregnant women with major depression, the overarching goal of treatment is to achieve or maintain maternal euthymia, thus limiting both maternal and fetal exposure to the harmful effects of untreated or incompletely treated depression. However, the absence of uniformly effective therapies with guaranteed obstetric and fetal safety makes the treatment of major depression during pregnancy among the most formidable of clinical challenges. Clinicians and patients are still faced with conflicting data and expert opinion regarding the reproductive safety of antidepressants in pregnancy, as well as large gaps in our understanding of the effectiveness of most antidepressants and nonpharmacological alternatives for treating antenatal depression. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated maternal depression during pregnancy, the effectiveness of interventions for maternal depression during pregnancy, and potential obstetric, fetal, and neonatal risks associated with antenatal antidepressant use.
    Full-text · Article · Sep 2014 · Drug, Healthcare and Patient Safety
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    • "Under these circumstances, patients and prescribers may place greater focus on the potential for adverse outcomes related to pharmacotherapy (Wisner et al. 2009b), and may be more sensitive to regulatory actions that warn of potential risks to the neonate. Antidepressants are established treatment options for mood and anxiety disorders, and there is evidence that antidepressant use in pregnancy can reduce the risk of antenatal depressive relapses and post-partum depression (Cohen et al. 2006; Wisner et al. 2004), although not all studies are in agreement (Yonkers et al. 2011). It remains that case that the effectiveness of antidepressant treatment in the setting of pregnancy has received only limited investigation (Yonkers et al. 2009), and reports of adverse neonatal effects associated with fetal antidepressant exposure (Udechuku et al. 2010), including potential risk of cardiovascular malformations (Wurst et al. 2010) and persistent pulmonary hypertension ('t Jong et al. 2012), have raised increasing concerns about the reproductive safety of SSRIs and other antidepressants. "
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    ABSTRACT: The purpose of this study was to assess whether antidepressant prescribing during pregnancy decreased following release of U.S. and Canadian public health advisory warnings about the risk of perinatal complications with antidepressants. We analyzed data from 228,876 singleton pregnancies among women (aged 15-44 years) continuously enrolled in Tennessee Medicaid with full pharmacy benefits (1995-2007). Antidepressant prescribing was determined through outpatient pharmacy dispensing files. Information on sociodemographic and clinical factors was obtained from enrollment files and linked birth certificates. An interrupted time series design with segmented regression analysis was used to quantify the impact of the advisory warnings (2002-2005). Antidepressant prescribing rates increased steadily from 1995 to 2001, followed by sharper increases from 2002 to late 2004. Overall antidepressant prescribing prevalence was 34.51 prescriptions [95 % confidence interval (CI) 33.37-35.65] per 1,000 women in January 2002, and increased at a rate of 0.46 (95 % CI 0.41-0.52) prescriptions per 1,000 women per month until the end of the pre-warning period (May 2004). During the post-warning period (October 2004-June 2005), antidepressant prescribing decreased by 1.48 (95 % CI 1.62-1.35) prescriptions per 1,000 women per month. These trends were observed for both selective serotonin reuptake inhibitors (SSRI) and non-SSRI antidepressants, although SSRI prescribing decreased at a greater rate. We conclude that antidepressant prescribing to pregnant women in Tennessee Medicaid increased from 1995 to late 2004. U.S. and Canadian public health advisories about antidepressant-associated perinatal complications were associated with steady decreases in antidepressant prescribing from late 2004 until the end of the study period, suggesting that the advisory warnings were impactful on antidepressant prescribing in pregnancy.
    Full-text · Article · Oct 2013 · Archives of Women s Mental Health
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    • "Two naturalistic studies have examined the effects of discontinuation of antidepressant medication during pregnancy . While Cohen et al. (2006) reported relapse rates of 67.7 % in women who discontinued antidepressants in pregnancy , compared to 25.6 % of women who continued medication , Yonkers and colleagues failed to find a difference in relapse rates between groups (Yonkers et al. 2011). Due to ethical concerns, to date, there are no placebo-controlled studies of antenatally depressed women randomized to antidepressant medications (Coverdale et al. 2008); the rates of pharmacological treatment-resistant depression are currently unknown. "
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    ABSTRACT: This study aims to summarize the current state of knowledge regarding approaches to treatment-resistant depression in pregnancy and the postpartum period and to develop algorithms for ante- and postnatal management in cases of refractory major depression. PubMed, Scopus, Google Scholar, and the Cochrane Library databases were searched without temporal restriction. Search terms included pregnancy and depression, perinatal depression, postnatal depression, treatment resistance and depression, antipsychotics and pregnancy, antidepressants and pregnancy, and mood stabilizers and pregnancy. Abstracts were reviewed for relevance, and further articles were obtained from bibliographic citations. There is a significant subpopulation of patients in pregnancy and postpartum whose depressive symptoms do not respond to first-line treatments. No research studies have focused specifically on this population. Data extracted from studies on women with depressive symptoms in pregnancy suggest that in the absence of evidence on which to base clinical decisions, many are receiving combinations of psychotherapeutic medications that have not been specifically studied for use in pregnancy. Antidepressant use in pregnancy is well studied, but studies specifically addressing the case of the patient who does not respond to first-line treatments are absent. Research in this area is urgently needed. The authors review a number of possible therapeutic approaches to treatment-resistant depression in pregnancy and the postpartum period.
    Full-text · Article · Jul 2013 · Archives of Women s Mental Health
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