Sophie Grigoriadis

The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE Depression often remains undertreated during pregnancy and there is growing evidence that untoward perinatal outcomes can result. Our systematic review and meta-analysis was conducted to determine whether maternal depression during pregnancy is associated with adverse perinatal and infant outcomes. DATA SOURCES MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from their start dates to June 2010. Keywords utilized included depressive/mood disorder, postpartum/postnatal, pregnancy/pregnancy trimesters, prenatal or antenatal, infant/neonatal outcomes, premature delivery, gestational age, birth weight, NICU, preeclampsia, breastfeeding, and Apgar. STUDY SELECTION English language studies reporting on perinatal or child outcomes associated with maternal depression were included, 3,074 abstracts were reviewed, 735 articles retrieved, and 30 studies included. DATA EXTRACTION Two independent reviewers extracted data and assessed article quality. All studies were included in the primary analyses, and between-group differences for subanalyses are also reported. RESULTS Thirty studies were eligible for inclusion. Premature delivery and decrease in breastfeeding initiation were significantly associated with maternal depression (odds ratio [OR] = 1.37; 95% CI, 1.04 to 1.81; P = .024; and OR = 0.68; 95% CI, 0.61 to 0.76; P < .0001, respectively). While birth weight (mean difference = -19.53 g; 95% CI, -64.27 to 25.20; P = .392), low birth weight (OR = 1.21; 95% CI, 0.91 to 1.60; P = .195), neonatal intensive care unit admissions (OR = 1.43; 95% CI, 0.83 to 2.47; P = .195), and preeclampsia (OR = 1.35; 95% CI, 0.95 to 1.92; P = .089) did not show significant associations in the main analyses, some subanalyses were significant. Gestational age (mean difference = -0.19 weeks; 95% CI, -0.53 to 0.14; P = .262) and Apgar scores at 1 (mean difference = -0.05; 95% CI, -0.28 to 0.17; P = .638) and 5 minutes (mean difference = 0.01; 95% CI, -0.08 to 0.11; P = .782) did not demonstrate any significant associations with depression. For premature delivery, a convenience sample study design was associated with higher ORs (OR = 2.43; 95% CI, 1.47 to 4.01; P = .001). CONCLUSIONS Maternal depression during pregnancy is associated with increased odds for premature delivery and decreased breastfeeding initiation; however, the effects are modest. More research of higher methodological quality is needed.

Gender issues in depression.

BACKGROUND Gender differences in depression have been documented for many years and thought to be insignificant to treatment selection until recently. METHODS This article reviews gender differences in the prevalence, presentation, etiology, and antidepressant treatment of depressive disorders. RESULTS The high female to male sex ratio in the prevalence of depression, especially during the reproductive years, is one of the most replicated findings in epidemiology. Women more often have a seasonal component, anxious and atypical depression. Explanations for the differences include psychological, neurochemical, anatomic, hormonal, genetic, and personality factors. Gender differences in antidepressant treatment response have not been found consistently. Hormonal status may be an important variable in addition to the effects of the menstrual cycle, pregnancy, perimenopause and menopause. CONCLUSIONS Women have higher rates of depression and can often present differently than do men. Further research can ascertain which combination of factors increase womens risk. The effect of pregnancy and the impact of the menstrual cycle on the course of all depressive disorders need increased attention. Large prospective randomized controlled trials with gender differences in treatment response as the primary endpoint are necessary in order to answer the now controversial question of gender differences in antidepressant treatment response.

Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis

IMPORTANCE Untreated depression during pregnancy has been associated with increased morbidity and mortality for both mother and child and, as such, optimal treatment strategies are required for this population. CONTEXT There are conflicting data regarding potential risks of prenatal antidepressant treatment. OBJECTIVE To determine whether prenatal antidepressant exposure is associated with risk for selected adverse pregnancy or delivery outcomes. DATA SOURCES MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Library were searched from their start dates to June 30, 2010. STUDY SELECTION English-language studies reporting outcomes associated with pharmacologic treatment during pregnancy were included. We reviewed 3074 abstracts, retrieved 735 articles, and included 23 studies in this meta-analysis. DATA EXTRACTION Study design, antidepressant exposure, adjustment for confounders, and study quality were extracted by 2 independent reviewers. RESULTS There was no significant association between antidepressant medication exposure and spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055). Gestational age and preterm delivery were statistically significantly associated with antidepressant exposure (mean difference [MD] [weeks], -0.45; 95% CI, -0.64 to -0.25; P < .001; and OR, 1.55; 95% CI, 1.38 to 1.74; P < .001, respectively), regardless of whether the comparison group consisted of all unexposed mothers or only depressed mothers without antidepressant exposure. Antidepressant exposure during pregnancy was significantly associated with lower birth weight (MD [grams], -74; 95% CI, -117 to -31; P = .001); when this comparison group was limited to depressed mothers without antidepressant exposure, there was no longer a significant association. Antidepressant exposure was significantly associated with lower Apgar scores at 1 and 5 minutes, regardless of whether the comparison group was all mothers or only those who were depressed during pregnancy but not exposed to antidepressants. CONCLUSIONS AND RELEVANCE Although statistically significant associations between antidepressant exposure and pregnancy and delivery outcomes were identified, group differences were small and scores in the exposed group were typically within the normal ranges, indicating the importance of considering clinical significance. Treatment decisions must weigh the effect of untreated maternal depression against the potential adverse effects of antidepressant exposure.

Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication

BACKGROUND In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. This article, one of five in the series, reviews new studies of psychotherapy in the acute and maintenance phase of MDD, including computer-based and telephone-delivered psychotherapy. METHODS The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. Evidence-based responses are based on updated systematic reviews of the literature and recommendations are graded according to the Level of Evidence, using pre-defined criteria. Lines of Treatment are identified based on criteria that included evidence and expert clinical support. RESULTS Cognitive-Behavioural Therapy (CBT) and Interpersonal Therapy (IPT) continue to have the most evidence for efficacy, both in acute and maintenance phases of MDD, and have been studied in combination with antidepressants. CBT is well studied in conjunction with computer-delivered methods and bibliotherapy. Behavioural Activation and Cognitive-Behavioural Analysis System of Psychotherapy have significant evidence, but need replication. Newer psychotherapies including Acceptance and Commitment Therapy, Motivational Interviewing, and Mindfulness-Based Cognitive Therapy do not yet have significant evidence as acute treatments; nor does psychodynamic therapy. LIMITATIONS Although many forms of psychotherapy have been studied, relatively few types have been evaluated for MDD in randomized controlled trials. Evidence about the combination of different types of psychotherapy and antidepressant medication is also limited despite widespread use of these therapies concomitantly. CONCLUSIONS CBT and IPT are the only first-line treatment recommendations for acute MDD and remain highly recommended for maintenance. Both computer-based and telephone-delivered psychotherapy--primarily studied with CBT and IPT--are useful second-line recommendations. Where feasible, combined antidepressant and CBT or IPT are recommended as first-line treatments for acute MDD.

Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis.

Objective To examine the risk for persistent pulmonary hypertension of the newborn associated with antenatal exposure to antidepressants. Design Systematic review and meta-analysis. Data sources Embase, Medline, PsycINFO, and CINAHL from inception to 30 December 2012. Eligibility English language studies reporting persistent pulmonary hypertension of the newborn associated with exposure to antidepressants. Two independent reviewers extracted data and assessed the quality of each article. Results Of the 3077 abstracts reviewed, 738 papers were retrieved and seven included. All seven studies were above our quality threshold. Quantitative analysis was only possible for selective serotonin reuptake inhibitors (SSRIs). Although exposure to SSRIs in early pregnancy was not associated with persistent pulmonary hypertension of the newborn (odds ratio 1.23, 95% confidence interval 0.58 to 2.60; P=0.58), exposure in late pregnancy was (2.50, 1.32 to 4.73; P=0.005). Effects were not significant for any of the moderator variables examined, including study design, congenital malformations, and meconium aspiration. It was not possible to assess for the effect of caesarean section, body mass index, or preterm delivery. The absolute risk difference for development of persistent pulmonary hypertension of the newborn after exposure to SSRIs in late pregnancy was 2.9 to 3.5 per 1000 infants; therefore an estimated 286 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of one additional case of persistent pulmonary hypertension of the newborn. Conclusions The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined. A significant relation for exposure to SSRIs in early pregnancy was not evident. Although the statistical association was significant, clinically the absolute risk of persistent pulmonary hypertension of the newborn remained low even in the context of late exposure to SSRIs.

Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence.

OBJECTIVE Depression is often not optimally treated during pregnancy, partially because of conflicting data regarding antidepressant medication risk. This meta-analysis was conducted to determine whether antenatal antidepressant exposure is associated with congenital malformations and to assess the effect of known methodological limitations. DATA SOURCES EMBASE, CINAHL, PsycINFO, and MEDLINE were searched from their start dates to June 2010. Keywords of various combinations were used, including, but not limited to depressive/mood disorder, pregnancy, antidepressant drug/agent, congenital malformation, and cardiac malformation. STUDY SELECTION English language studies reporting congenital malformations associated with antidepressants were included. Of 3,074 abstracts reviewed, 735 studies were retrieved and 27 studies were included. DATA EXTRACTION Two reviewers working independently assessed article quality. Data on use of any antidepressant, including fluoxetine and paroxetine specifically, were extracted. Outcomes included congenital malformations, major congenital malformations, cardiovascular defects, septal heart defects (ventral septal defects and atrial septal defects), and ventral septal defects only. RESULTS Nineteen studies were above quality threshold and make up the primary meta-analyses. Pooled relative risks (RRs) were derived by using random-effects methods. Antidepressant exposure was not associated with congenital malformations (RR = 0.93; 95% CI, 0.85-1.02; P = .113) or major malformations (RR = 1.07; 95% CI, 0.99-1.17; P = .095). However, increased risk for cardiovascular malformations (RR = 1.36; 95% CI, 1.08-1.71; P = .008) and septal heart defects (RR = 1.40; 95% CI, 1.10-1.77; P = .005) were found; the RR for ventral septal defects was similar to septal defects, although not significant (RR = 1.54; 95% CI, 0.71-3.33; P = .274). Pooled effects were significant for paroxetine and cardiovascular malformations (RR = 1.43; 95% CI, 1.08-1.88; P = .012). These results are contrasted with those addressing methodological limitations but are typically consistent. CONCLUSIONS Overall, antidepressants do not appear to be associated with an increased risk of congenital malformations, but statistical significance was found for cardiovascular malformations. Results were robust in several sensitivity analyses. Given that the RRs are marginal, they may be the result of uncontrolled confounders. Although the RRs were statistically significant, none reached clinically significant levels.

The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and meta-analysis.

OBJECTIVE Conflicting reports on potential risks of antidepressant exposure during gestation for the infant have been reported in the literature. This systematic review and meta-analysis on immediate neonatal outcomes were conducted to clarify what, if any, risks are faced by infants exposed to antidepressants in utero. Subanalyses address known methodological limitations in the field. DATA SOURCES MEDLINE, EMBASE, CINAHL, and PsycINFO were searched from their start dates to June 2010. Various combinations of keywords were utilized including, but not limited to, depressive/mood disorder, pregnancy/pregnancy trimesters, antidepressant drugs, and neonatal effects. STUDY SELECTION English language and cohort and case-control studies reporting on a cluster of signs defined as poor neonatal adaptation syndrome (PNAS) or individual clinical signs (respiratory distress and tremors) associated with pharmacologic treatment were selected. Of 3,074 abstracts reviewed, 735 articles were retrieved and 12 were included in this analysis. DATA EXTRACTION Two independent reviewers extracted data and assessed the quality of the articles. RESULTS Twelve studies were retrieved that examined PNAS or the signs of respiratory distress and tremors in the infant. There was a significant association between exposure to antidepressants during pregnancy and overall occurrence of PNAS (odds ratio [OR] = 5.07; 95% CI, 3.25-7.90; P < .0001). Respiratory distress (OR = 2.20; 95% CI, 1.81-2.66; P < .0001) and tremors (OR = 7.89; 95% CI, 3.33-18.73; P < .0001) were also significantly associated with antidepressant exposure. For the respiratory outcome, studies using convenience samples had significantly higher ORs (Q1 = 5.4, P = .020). No differences were found in any other moderator analyses. CONCLUSIONS An increased risk of PNAS exists in infants exposed to antidepressant medication during pregnancy; respiratory distress and tremors also show associations. Neonatologists need to be prepared and updated in their management, and clinicians must inform their patients of this risk.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 2. Psychological Treatments.

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) has revised its 2009 guidelines for the management of major depressive disorder (MDD) in adults by updating the evidence and recommendations. The target audiences for these 2016 guidelines are psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Psychological Treatments” is the second of six sections of the 2016 guidelines. Results: Evidence-informed responses were developed for 25 questions under 5 broad categories: 1) patient characteristics relevant to using psychological interventions; 2) therapist and health system characteristics associated with optimizing outcomes; 3) descriptions of major psychotherapies and their efficacy; 4) additional psychological interventions, such as peer interventions and computer- and technology-delivered interventions; and 5) combining and/or sequencing psychological and pharmacological interventions. Conclusions: First-line psychological treatment recommendations for acute MDD include cognitive-behavioural therapy (CBT), interpersonal therapy (IPT), and behavioural activation (BA). Second-line recommendations include computer-based and telephone-delivered psychotherapy. Where feasible, combining psychological treatment (CBT or IPT) with antidepressant treatment is recommended because combined treatment is superior to either treatment alone. First-line psychological treatments for maintenance include CBT and mindfulness-based cognitive therapy (MBCT). Patient preference, in combination with evidence-based treatments and clinician/system capacity, will yield the optimal treatment strategies for improving individual outcomes in MDD.

Traditional postpartum practices and rituals: a qualitative systematic review

Many cultures around the world observe specific postpartum rituals to avoid ill health in later years. This qualitative systematic review examined the literature describing traditional postpartum practices from 51 studies in over 20 different countries. Commonalities were identified in practices across cultures. Specifically, the themes included organized support for the mother, periods of rest, prescribed food to be eaten or prohibited, hygiene practices and those related to infant care and breastfeeding, among others. These rituals allow the mother to be ‘mothered’ for a period of time after the birth. They may have beneficial health effects as well as facilitate the transition to motherhood. In todays society, with modernization, migration and globalization, individuals may be unable to carry out the rituals or, conversely, feel pressured to carry out activities in which they no longer believe. The understanding of traditional postpartum practices can inform the provision of culturally competent perinatal services.

Role of estrogen in the treatment of depression.

The role of estrogen in the treatment of depression is reviewed. The relation is examined in studies of perimenopausal and postmenopausal women with depressed mood, in studies of depressive disorders, and in studies of estrogen as an adjunct to antidepressant medication. The literature has many methodologic shortcomings, including combining women of various ages, failure to confirm life stage, the use of different types of estrogens, the inclusion of women with a range of mood disturbances, and the enrollment of women with concurrent psychiatric illness. There are few controlled evaluations of the use of estrogen to supplement ongoing antidepressant treatment. Estrogen alone seems to be beneficial for improving mood in perimenopausal and postmenopausal women. Estrogen is superior to placebo for reproductive-related mood disorders, including postpartum depression and mild depressive disorders during perimenopause. Replication is necessary, especially in moderate to severe levels of major depression. Estrogen may augment antidepressant treatment. Assessment and treatment implications are discussed.