Background: Antidepressant use during pregnancy has increased over the last decades, while safety has been under debate. Our aim was to measure the international prevalence of antidepressant use before, during, and after pregnancy and examine timing, type of prescriptions and geographic variability. Methods: We searched Embase, Medline Ovid, Web of Science, Cochrane Central and Google Scholar from their inception until February 19, 2019. We determined pooled prevalence estimates of antidepressants before, during, and after pregnancy, as well as stratified according to substantive variables. Results: We identified 40 cohorts from 15 countries, together reporting on 14,072,251 pregnancies. Included studies had a low risk of bias, often reporting on large representative cohorts. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly used antidepressants during pregnancy, with an international prevalence estimate of 3.0% (95%CI 2.3;3.7). While Europe and Australasia had pooled prevalence estimates of 1.6% and 1.3% respectively, Northern America had a prevalence estimate of 5.5% (Q-value = 126.19; df = 2; p-value<0.01). Highest SSRI prevalence rates were found for sertraline (1.10%), followed by citalopram and fluoxetine (0.77% and 0.76% respectively) (Q-value = 121.25; df = 5; p-value<0.01). Qualitative analysis indicated an increase in antidepressant use over subsequent calendar years. Limitations: Substantial heterogeneity remained unaccounted for throughout the analyses, even after accounting for hypothetical contributors. Conclusions: This meta-analysis revealed substantial regional differences in antidepressant use around pregnancy, which could be due to variability in prescription behavior, healthcare seeking behavior and organization of healthcare. There is an urgent need for evidence on effectiveness, benefit, and harm of antidepressants during pregnancy to guide clinical practice. greatly contribute to this increase (Andrade et al., 2016;Charlton et al., 2015;Cooper et al., 2007). In the general population, antidepressants are now among the top three most commonly prescribed therapeutic drug classes in the United States (Pratt et al., 2017). Antidepressants showed the largest increase in prescriptions during pregnancy over time, compared to other drugs associated with potential harmful neonatal effects (van Gelder et al., 2014).
Objective:Several countries have developed Clinical Practice Guidelines regarding treatment of perinatal depressive symptoms and perinatal use of antidepressant. We aimed to compare guidelines to guide clinicians in best clinical practice.Methods:An extensive search in guideline databases, MEDLINE and PsycINFO was performed. When no guidelines were (publicly) available online, we contacted psychiatric-, obstetric-, perinatal- and mood disorder societies of all first world countries and the five largest second world countries. Only Clinical Practice Guidelines adhering to quality criteria of the Appraisal of Guidelines for Research and Evaluation instrument and including a systematic review of evidence were included. Data extraction focussed on recommendations regarding continuation or withdrawal of antidepressants and preferred treatment in newly depressed patients.Results:Our initial search resulted in 1094 articles. After first screening, 40 full-text articles were screened. Of these, 24 were excluded for not being an official Clinical Practice Guidelines. In total, 16 Clinical Practice Guidelines were included originating from 12 countries. Eight guidelines were perinatal specific and eight were general guidelines.Conclusion:During pregnancy, four guidelines advise to continue antidepressants, while there is a lack of evidence supporting this recommendation. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioural therapy) as initial treatment for mild to moderate depression and antidepressants for severe depression, with a preference for sertraline. Paroxetine is not preferred treatment for new episodes but switching antidepressants for ongoing treatment is discouraged (three guidelines). If mothers use antidepressants, observation of the neonate is generally recommended and breastfeeding encouraged.
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