Search

Background Antidepressants are commonly prescribed during pregnancy, despite a lack of evidence from randomised trials on the benefits or risks. Some studies have reported associations of antidepressants during pregnancy with adverse offspring neurodevelopment, but whether or not such associations are causal is unclear. Objectives To study the associations of antidepressants for depression in pregnancy with outcomes using multiple methods to strengthen causal inference. Design This was an observational cohort design using multiple methods to strengthen causal inference, including multivariable regression, propensity score matching, instrumental variable analysis, negative control exposures, comparison across indications and exposure discordant pregnancies analysis. Setting This took place in UK general practice. Participants Participants were pregnant women with depression. Interventions The interventions were initiation of antidepressants in pregnancy compared with no initiation, and continuation of antidepressants in pregnancy compared with discontinuation. Main outcome measures The maternal outcome measures were the use of primary care and secondary mental health services during pregnancy, and during four 6-month follow-up periods up to 24 months after pregnancy, and antidepressant prescription status 24 months following pregnancy. The child outcome measures were diagnosis of autism, diagnosis of attention deficit hyperactivity disorder and intellectual disability. Data sources UK Clinical Practice Research Datalink. Results Data on 80,103 pregnancies were used to study maternal primary care outcomes and were linked to 34,274 children with at least 4-year follow-up for neurodevelopmental outcomes. Women who initiated or continued antidepressants during pregnancy were more likely to have contact with primary and secondary health-care services during and after pregnancy and more likely to be prescribed an antidepressant 2 years following the end of pregnancy than women who did not initiate or continue antidepressants during pregnancy (odds ratioinitiation 2.16, 95% confidence interval 1.95 to 2.39; odds ratiocontinuation 2.40, 95% confidence interval 2.27 to 2.53). There was little evidence for any substantial association with autism (odds ratiomultivariableregression 1.10, 95% confidence interval 0.90 to 1.35; odds ratiopropensityscore 1.06, 95% confidence interval 0.84 to 1.32), attention deficit hyperactivity disorder (odds ratiomultivariableregression 1.02, 95% confidence interval 0.80 to 1.29; odds ratiopropensityscore 0.97, 95% confidence interval 0.75 to 1.25) or intellectual disability (odds ratiomultivariableregression 0.81, 95% confidence interval 0.55 to 1.19; odds ratiopropensityscore 0.89, 95% confidence interval 0.61 to 1.31) in children of women who continued antidepressants compared with those who discontinued antidepressants. There was inconsistent evidence of an association between initiation of antidepressants in pregnancy and diagnosis of autism in offspring (odds ratiomultivariableregression 1.23, 95% confidence interval 0.85 to 1.78; odds ratiopropensityscore 1.64, 95% confidence interval 1.01 to 2.66) but not attention deficit hyperactivity disorder or intellectual disability; however, but results were imprecise owing to smaller numbers. Limitations Several causal-inference analyses lacked precision owing to limited numbers. In addition, adherence to the prescribed treatment was not measured. Conclusions Women prescribed antidepressants during pregnancy had greater service use during and after pregnancy than those not prescribed antidepressants. The evidence against any substantial association with autism, attention deficit hyperactivity disorder or intellectual disability in the children of women who continued compared with those who discontinued antidepressants in pregnancy is reassuring. Potential association of initiation of antidepressants during pregnancy with offspring autism needs further investigation. Future work Further research on larger samples could increase the robustness and precision of these findings. These methods applied could be a template for future pharmaco-epidemiological investigation of other pregnancy-related prescribing safety concerns. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/80/19) and will be published in full in Health Technology Assessment; Vol. 27, No. 15. See the NIHR Journals Library website for further project information. Plain language summary About one in seven women experience depression during pregnancy. Left untreated, this may harm them and their unborn babies. However, the decision to take antidepressants during pregnancy is difficult because women often worry about the risks to their unborn baby. Research findings have been inconsistent, so women often do not have clear information to enable them to make informed decisions. We studied women’s and children’s outcomes after starting (compared with not starting) or continuing (compared with stopping) antidepressants in pregnancy. We used a large UK primary care database and several novel methods of analysis. We tracked 80,103 pregnancies of women with depression for up to 2 years after pregnancy. We also tracked 34,274 children from these pregnancies for at least 4 years to check for developmental outcomes. Women prescribed antidepressants were more likely than women not prescribed antidepressants to use general practice and mental health services during and after pregnancy, and to be prescribed antidepressants 2 years after pregnancy. This suggests that antidepressants were being prescribed to women with greater clinical need. Women who continued antidepressants in pregnancy had no higher likelihood than those who discontinued antidepressants of autism, attention deficit hyperactivity disorder or intellectual disability in their children. This should reassure women making the decision to continue taking their medications in pregnancy. Women who started antidepressants in pregnancy may possibly have had a slightly higher likelihood of autism in their children than those who did not start them. These findings were not seen in all analyses and were based on smaller numbers; therefore, they should be viewed with caution. Importantly, over 98 in every 100 children of women who initiated or continued antidepressants in pregnancy did not receive an autism diagnosis. The findings may help women and clinicians make informed decisions on treatment with antidepressants in pregnancy. Scientific summary Background Depression is common in women of childbearing age and up to one in seven women experience depression during pregnancy. Untreated depression may have serious consequences, such as distress, self-neglect and suicidal behaviour, in affected women and birth complications in their babies. Many women with depression may, therefore, encounter a situation in which they need to decide whether to start or continue an antidepressant during their pregnancy; however, the potential for resulting harm to the neurodevelopment of their offspring is a common concern. In the absence of randomised controlled trials, the information available to guide these decisions is based on observational data, which are subject to confounding. Given that maternal depression may itself lead to adverse outcomes, isolating any effect of antidepressants from the underlying depression is particularly difficult: a problem known as confounding by indication. In the absence of randomised trials, studies designed to emulate such trials and using methods to account for confounding may help triangulate results and strengthen causal inference. Objectives This research aimed to simulate two scenarios that could be tested in pregnant women with depression in a hypothetical target randomised controlled trial asking the following research questions: Does the initiation of antidepressants for depression during pregnancy affect maternal service use outcomes and childhood neurodevelopmental outcomes? Does the continuation of antidepressant use during pregnancy for depression affect maternal service use outcomes and childhood neurodevelopmental outcomes? The data were interrogated using several methods of causal inference, and assessed in relation to dose response, timing of exposure and type of antidepressants according to class and their serotonin-receptor affinity. Methods Design: This was an observational cohort design, with use of multiple methods to strengthen causal inference. Setting and participants: This took place in UK general practice. Participants were UK primary care patients, specifically pregnant women with depression. Data sources: This study used data from the Clinical Practice Research Datalink (CPRD), a large ongoing database of anonymised primary care medical records in the UK. The CPRD’s pregnancy register was used to identify the dates and stages of pregnancy, and the CPRD mother–baby link allowed for the linkage of the records of pregnant women with their live born offspring. For consenting CPRD practices in England, the primary care records were linked to Hospital Episode Statistics, which include registers for inpatient admissions, outpatient care and accident and emergency (A&E) attendance in England, and with mortality data from the Office for National Statistics and Census small-area socioeconomic data. Eligible patients: The data extract covered dates between 1 January 1995 and 31 December 2017. Within this time frame, we identified 344,720 pregnancies in the pregnancy register for which there was evidence of depressive symptoms, or prescription of an antidepressant up to 1 year before or during pregnancy. From this sample, we constructed two cohorts: (1) the pregnant women’s cohort, which contained all pregnancies for which women could be followed up for at least 2 years beyond the pregnancy end date, regardless of the pregnancy outcome or ability to link to the child; (2) the mother and child cohort, which consisted of pregnancies followed up at least until delivery that could be linked with the patient records of the children arising from these pregnancies. The pregnant women’s cohort: The exclusion criteria were (1) records for which the general practice was not yet up to standard, as defined by CPRD (n = 61,704); (2) where the patient had not yet registered with her current general practice 1 year prior to conception (n = 93,638); (3) records suggesting that the woman had transferred out of the general practice while still pregnant (n = 15,627); (4) records with

Background Teachers are at heightened risk of poor mental health and well-being, which is likely to impact on the support they provide to students, and student outcomes. We conducted a cluster randomised controlled trial, to test whether an intervention to improve mental health support and training for high school teachers led to improved mental health and well-being for teachers and students, compared to usual practice. We also conducted a cost evaluation of the intervention. Methods and findings The intervention comprised (i) Mental Health First Aid training for teachers to support students; (ii) a mental health awareness session; and (iii) a confidential staff peer support service. In total 25 mainstream, non-fee-paying secondary schools stratified by geographical area and free school meal entitlement were randomly allocated to intervention (n = 12) or control group (n = 13) after collection of baseline measures. We analysed data using mixed-effects repeated measures models in the intention-to-treat population, adjusted for stratification variables, sex, and years of experience. The primary outcome was teacher well-being (Warwick-Edinburgh Mental Well-being Scale). Secondary outcomes were teacher depression, absence, and presenteeism, and student well-being, mental health difficulties, attendance, and attainment. Follow-up was at months 12 (T1) and 24 (T2). We collected process data to test the logic model underpinning the intervention, to aid interpretation of the findings. A total of 1,722 teachers were included in the primary analysis. Teacher well-being did not differ between groups at T2 (intervention mean well-being score 47.5, control group mean well-being score 48.4, adjusted mean difference -0.90, 95% CI -2.07 to 0.27, p = 0.130). The only effect on secondary outcomes was higher teacher-reported absence among the intervention group at T2 (intervention group median number of days absent 0, control group median number of days absent 0, ratio of geometric means 1.04, 95% CI 1.00 to 1.09, p = 0.042). Process measures indicated little change in perceived mental health support, quality of relationships, and work-related stress. The average cost of the intervention was £9,103 per school. The study's main limitations were a lack of blinding of research participants and the self-report nature of the outcome measures. Conclusions In this study, we observed no improvements to teacher or student mental health following the intervention, possibly due to a lack of impact on key drivers of poor mental health within the school environment. Future research should focus on structural and cultural changes to the school environment, which may be more effective at improving teacher and student mental health and well-being. Trial registration www.isrctn.com ISRCTN95909211., Author(s): Judi Kidger 1,*, Nicholas Turner 1, William Hollingworth 1, Rhiannon Evans 2, Sarah Bell 1, Rowan Brockman 1, Lauren Copeland 2, Harriet Fisher 1, Sarah Harding 3, Jillian Powell [...]

Objective: Data from South Asia indicate that for 15%–20% of suicide attempts, pesticides are purchased from shops; otherwise, pesticides are obtained from an individual's house or nearby environment. We aimed to investigate the difference between individuals who directly purchase pesticides from shops for suicide attempts and suicide deaths versus those related to accessing the pesticides from an individual's house or nearby environment. Methods: We conducted two comparative studies in rural Sri Lanka: (1) non‐fatal shop cases (n = 50) were survivors of self‐poisoning with pesticides who ingested the pesticides after purchasing them from a shop; non‐fatal domestic cases (n = 192) were survivors who accessed pesticides from their house or nearby environment. (2) fatal shop cases (n = 50) were individuals who died after ingesting pesticides they purchased for the act; fatal domestic cases (n = 102) were patients who died after ingesting pesticides they accessed at house or nearby environment. Logistic regression analysis was used to assess the characteristics which distinguished between the shop and domestic cases. Results: Data indicate that 20.7% and 32.9% of individuals who used pesticides for suicide attempts and suicide deaths had purchased them from shops, respectively. Being a non‐farmer was the main distinguishing characteristic of shop cases: adjusted odds ratios (AOR) 8.9, 95% confidence intervals (CI) 3.2–24.4 for non‐fatal shop cases, and AOR 4.0, 95% CI 1.5–10.6 for fatal shop cases. Non‐fatal shop cases also had higher suicide intent (AOR 3.0, CI 1.0–8.9), and ingesting an insecticide (AOR 4.8, CI 1.8–1.0–8.9) than non‐fatal domestic cases. Conclusion: A high suicide intent of individuals who purchase pesticides for the event explains the high proportion of such fatal cases. Such high suicide intent makes the prevention implications difficult to spell out for those individuals who purchase pesticides for self‐poisoning. However, our findings are valuable for clinicians to assess pesticide poisoning cases in hospitals. [ABSTRACT FROM AUTHOR]

Aims. Suicidal acts may cluster in time and space and lead to community concerns about further imitative suicidal episodes. Although suicide clusters have been researched in previous studies, less is known about the clustering of non-fatal suicidal behaviour (self-harm). Furthermore, most previous studies used crude temporal and spatial information, e.g., numbers aggregated by month and residence area, for cluster detection analysis. This study aimed to (i) identify space-time clusters of self-harm and suicide using daily incidence data and exact address and (ii) investigate the characteristics of cluster-related suicidal acts. Methods. Data on emergency department presentations for self-harm and suicide deaths in Taipei City and New Taipei City, Taiwan, were used in this study. In all-age and age-specific analyses, self-harm and suicide clusters were identified using space-time permutation scan statistics. A cut-off of 0.10 for the p value was used to identify possible clusters. Logistic regression was used to investigate the characteristics associated with cluster-related episodes. Results. A total of 5,291 self-harm episodes and 1,406 suicides in Taipei City (2004-2006) and 20,531 self-harm episodes and 2,329 suicides in New Taipei City (2012-2016) were included in the analysis. In the two cities, two self-harm clusters (n [number of self-harm episodes or suicide deaths in the cluster] = 4 and 8 in Taipei City), four suicide clusters (n = 3 in Taipei City and n = 4, 11 and 4 in New Taipei City) and two self-harm and suicide combined clusters (n = 4 in Taipei City and n = 8 in New Taipei City) were identified. Space-time clusters of self-harm, suicide, and self-harm and suicide combined accounted for 0.05%, 0.59%, and 0.08% of the respective groups of suicidal acts. Cluster-related episodes of self-harm and suicide were more likely to be male (adjusted odds ratio [aOR] = 2.22, 95% confidence interval [CI] 1.26, 3.89) and young people aged 10-29 years (aOR = 2.72, 95% CI 1.43, 5.21) than their cluster-unrelated counterparts. Conclusions. Space-time clusters of self-harm, suicide, and self-harm and suicide combined accounted for a relatively small proportion of suicidal acts and were associated with some sex/age characteristics. Focusing on suicide deaths alone may underestimate the size of some clusters and/or lead to some clusters being overlooked. Future research could consider combining self-harm and suicide data and use social connection information to investigate possible clusters of suicidal acts. [ABSTRACT FROM AUTHOR]