Amy Cheung

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.

Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and Ongoing Management

OBJECTIVES. To develop clinical practice guidelines to assist primary care clinicians in the management of adolescent depression. This second part of the guidelines addresses treatment and ongoing management of adolescent depression in the primary care setting. METHODS. Using a combination of evidence- and consensus-based methodologies, guidelines were developed in 5 phases as informed by (1) current scientific evidence (published and unpublished), (2) a series of focus groups, (3) a formal survey, (4) an expert consensus workshop, and (5) revision and iteration among members of the steering committee. RESULTS. These guidelines are targeted for youth aged 10 to 21 years and offer recommendations for the management of adolescent depression in primary care, including (1) active monitoring of mildly depressed youth, (2) details for the specific application of evidence-based medication and psychotherapeutic approaches in cases of moderate-to-severe depression, (3) careful monitoring of adverse effects, (4) consultation and coordination of care with mental health specialists, (5) ongoing tracking of outcomes, and (6) specific steps to be taken in instances of partial or no improvement after an initial treatment has begun. The strength of each recommendation and its evidence base are summarized. CONCLUSIONS. These guidelines cannot replace clinical judgment, and they should not be the sole source of guidance for adolescent depression management. Nonetheless, the guidelines may assist primary care clinicians in the management of depressed adolescents in an era of great clinical need and a shortage of mental health specialists. Additional research concerning the management of youth with depression in primary care is needed, including the usability, feasibility, and sustainability of guidelines and determination of the extent to which the guidelines actually improve outcomes of youth with depression.

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.

Guidelines for Adolescent Depression in Primary Care (GLAD-PC): I. Identification, Assessment, and Initial Management

OBJECTIVES. To develop clinical practice guidelines to assist primary care clinicians in the management of adolescent depression. This first part of the guidelines addresses identification, assessment, and initial management of adolescent depression in primary care settings. METHODS. By using a combination of evidence- and consensus-based methodologies, guidelines were developed by an expert steering committee in 5 phases, as informed by (1) current scientific evidence (published and unpublished), (2) a series of focus groups, (3) a formal survey, (4) an expert consensus workshop, and (5) draft revision and iteration among members of the steering committee. RESULTS. Guidelines were developed for youth aged 10 to 21 years and correspond to initial phases of adolescent depression management in primary care, including identification of at-risk youth, assessment and diagnosis, and initial management. The strength of each recommendation and its evidence base are summarized. The identification, assessment, and initial management section of the guidelines includes recommendations for (1) identification of depression in youth at high risk, (2) systematic assessment procedures using reliable depression scales, patient and caregiver interviews, and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, (3) patient and family psychoeducation, (4) establishing relevant links in the community, and (5) the establishment of a safety plan. CONCLUSIONS. This part of the guidelines is intended to assist primary care clinicians in the identification and initial management of depressed adolescents in an era of great clinical need and a shortage of mental health specialists but cannot replace clinical judgment; these guidelines are not meant to be the sole source of guidance for adolescent depression management. Additional research that addresses the identification and initial management of depressed youth in primary care is needed, including empirical testing of these guidelines.

Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses.

OBJECTIVE To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. DATA SOURCES Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. STUDY SELECTION 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting response and/or remission rates in adult subjects treated with an antidepressant monotherapy for unipolar major depression were included. DATA EXTRACTION The primary investigator recorded the number of responders and/or remitters in the intent-to-treat population of each study arm or computed these numbers using the quoted rates. DATA SYNTHESIS Poisson regression analyses demonstrated that mean response rate for the active medication was higher in studies comparing 2 or more active medications without a placebo arm than in studies comparing 2 or more active medications with a placebo arm (65.4% vs 57.7%, P < .0001) or in studies comparing only 1 active medication with placebo (65.4% vs 51.7%, P = .0005). Mean response rate for placebo was significantly lower in studies comparing 1 rather than 2 or more active medications (34.3% vs 44.6%, P = .003). Mean remission rates followed a similar pattern. Meta-analysis confirmed results from the pooled analysis. CONCLUSIONS These data suggest that antidepressant response rates in randomized control trials may be influenced by the presence of a placebo arm and by the number of treatment arms and that placebo response rates may be influenced by the number of active treatment arms in a study.

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.

Community Survey of Bipolar Disorder in Canada: Lifetime Prevalence and Illness Characteristics

Objective: This study reports on the lifetime prevalence and illness characteristics of bipolar disorder (BD) in a large, representative sample of Canadians. Method: Data were obtained from the Canadian Community Health Survey: Mental Health and Well-Being. This representative, cross-sectional survey, conducted by Statistics Canada in 2002, examines the mental health of Canadians aged 15 years and over. The national response rate was 77%. We determined the prevalence rate of BD, correlates of a bipolar diagnosis, and illness characteristics. Results: The weighted lifetime prevalence rate of BD was 2.2% (95% confidence interval [CI], 1.94% to 2.37%). Younger age, low income adequacy, lifetime anxiety disorder, and presence of a substance use disorder in the past 12 months were each significantly associated with the presence of a BD diagnosis (P < 0.001 for each). The largest effect found was for the presence of an anxiety disorder (odds ratio 7.94; 95%CI, 6.35 to 9.92). A lifetime history of anxiety disorder was reported by 51.8% (95%CI, 47.1% to 56.5%) of the respondents with BD, with both panic disorder and agoraphobia each being more frequent among women, compared with men (P = 0.01 and P < 0.001, respectively). The mean age at onset of illness was 22.5 years, SD 12.0. Conclusions: According to the estimated lifetime prevalence of BD found in this study, over 500 000 Canadians likely suffer from this condition. Identifying those at highest risk for BD may assist in developing more effective community-based identification and intervention strategies.

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.

Mental Health Service Use Among Adolescents and Young Adults With Major Depressive Disorder and Suicidality

Objectives: Despite being recognized as a serious public health concern, suicidality among adolescents and young adults is frequently missed, and completed suicide remains the second leading cause of death for young Canadians. With such close links between depression, suicidality, and completed suicide, any intervention must address all 3 of these issues. However, to develop effective interventions, we must understand the types and rates of mental health service use among adolescents and young adults. This study examines service use rates in young Canadians with depression and suicidality and the influence of sex on the types of service provider chosen. Methods: We used data from the Canadian Community Health Survey: Mental Health and Well-Being. Our sample included 619 individuals, aged 15 to 24 years, who screened positive for depression and suicidality in the past 12 months. We examined mental health service use rates in general and by provider type. Results: Among adolescents aged 15 to 18 years with depression, 40% had not used any mental health services. This rate was higher for adolescents with suicidality at 50%. In young adults aged 19 to 24 with depression, 42% had not used any mental health services. Among young adults with suicidality, 48% had not accessed services. Female adolescents and young adults were more likely to receive services from nonspecialty mental health providers. Conclusions: In Canada, many adolescents and young adults with depression and suicidality do not receive mental health services. Further, there may be a preferential treatment of young men by mental health specialists. Further research is needed to understand the quality of care received by these young Canadians and the factors influencing service use.

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.