Benefits and Risks of Antidepressant Drugs During Pregnancy: A Systematic Review of Meta-analyses.
Journal
Paediatric drugs
ISSN: 1179-2019
Titre abrégé: Paediatr Drugs
Pays: Switzerland
ID NLM: 100883685
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
accepted:
06
02
2023
medline:
14
4
2023
pubmed:
1
3
2023
entrez:
28
2
2023
Statut:
ppublish
Résumé
The prescription of antidepressant drugs during pregnancy has been steadily increasing for several decades. Meta-analyses (MAs), which increase the statistical power and precision of results, have gained interest for assessing the safety of antidepressant drugs during pregnancy. We aimed to provide a meta-review of MAs assessing the benefits and risks of antidepressant drug use during pregnancy. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search on PubMed and Web of Science databases was conducted on 25 October, 2021, on MAs assessing the association between antidepressant drug use during pregnancy and health outcomes for the pregnant women, embryo, fetus, newborn, and developing child. Study selection and data extraction were carried out independently and in duplicate by two authors. The methodological quality of included studies was evaluated with the AMSTAR-2 tool. Overlap among MAs was assessed by calculating the corrected covered area. Data were presented in a narrative synthesis, using four levels of evidence. Fifty-one MAs were included, all but one assessing risks. These provided evidence for a significant increase in the risks for major congenital malformations (selective serotonin reuptake inhibitors, paroxetine, fluoxetine, no evidence for sertraline; eight MAs), congenital heart defects (paroxetine, fluoxetine, sertraline; 11 MAs), preterm birth (eight MAs), neonatal adaptation symptoms (eight MAs), and persistent pulmonary hypertension of the newborn (three MAs). There was limited evidence (only one MA for each outcome) for a significant increase in the risks for postpartum hemorrhage, and with a high risk of bias, for stillbirth, impaired motor development, and intellectual disability. There was inconclusive evidence, i.e., discrepant results, for an increase in the risks for spontaneous abortion, small for gestational age and low birthweight, respiratory distress, convulsions, feeding problems, and for a subsequent risk for autism with an early antidepressant drug exposure. Finally, MAs provided no evidence for an increase in the risks for gestational hypertension, preeclampsia, and for a subsequent risk for attention-deficit/hyperactivity disorder. Only one MA assessed benefits, providing limited evidence for preventing relapse in severe or recurrent depression. Effect sizes were small, except for neonatal symptoms (small to large). Results were based on MAs in which overall methodological quality was low (AMSTAR-2 score = 54.8% ± 12.9%, [19-81%]), with a high risk of bias, notably indication bias. The corrected covered area was 3.27%, which corresponds to a slight overlap. This meta-review has implications for clinical practice and future research. First, these results suggest that antidepressant drugs should be used as a second-line treatment during pregnancy (after first-line psychotherapy, according to the guidelines). The risk of major congenital malformations could be prevented by observing guidelines that discourage the use of paroxetine and fluoxetine. Second, to decrease heterogeneity and bias, future MAs should adjust for maternal psychiatric disorders and antidepressant drug dosage, and perform analyses by timing of exposure.
Sections du résumé
BACKGROUND
BACKGROUND
The prescription of antidepressant drugs during pregnancy has been steadily increasing for several decades. Meta-analyses (MAs), which increase the statistical power and precision of results, have gained interest for assessing the safety of antidepressant drugs during pregnancy.
OBJECTIVE
OBJECTIVE
We aimed to provide a meta-review of MAs assessing the benefits and risks of antidepressant drug use during pregnancy.
METHODS
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search on PubMed and Web of Science databases was conducted on 25 October, 2021, on MAs assessing the association between antidepressant drug use during pregnancy and health outcomes for the pregnant women, embryo, fetus, newborn, and developing child. Study selection and data extraction were carried out independently and in duplicate by two authors. The methodological quality of included studies was evaluated with the AMSTAR-2 tool. Overlap among MAs was assessed by calculating the corrected covered area. Data were presented in a narrative synthesis, using four levels of evidence.
RESULTS
RESULTS
Fifty-one MAs were included, all but one assessing risks. These provided evidence for a significant increase in the risks for major congenital malformations (selective serotonin reuptake inhibitors, paroxetine, fluoxetine, no evidence for sertraline; eight MAs), congenital heart defects (paroxetine, fluoxetine, sertraline; 11 MAs), preterm birth (eight MAs), neonatal adaptation symptoms (eight MAs), and persistent pulmonary hypertension of the newborn (three MAs). There was limited evidence (only one MA for each outcome) for a significant increase in the risks for postpartum hemorrhage, and with a high risk of bias, for stillbirth, impaired motor development, and intellectual disability. There was inconclusive evidence, i.e., discrepant results, for an increase in the risks for spontaneous abortion, small for gestational age and low birthweight, respiratory distress, convulsions, feeding problems, and for a subsequent risk for autism with an early antidepressant drug exposure. Finally, MAs provided no evidence for an increase in the risks for gestational hypertension, preeclampsia, and for a subsequent risk for attention-deficit/hyperactivity disorder. Only one MA assessed benefits, providing limited evidence for preventing relapse in severe or recurrent depression. Effect sizes were small, except for neonatal symptoms (small to large). Results were based on MAs in which overall methodological quality was low (AMSTAR-2 score = 54.8% ± 12.9%, [19-81%]), with a high risk of bias, notably indication bias. The corrected covered area was 3.27%, which corresponds to a slight overlap.
CONCLUSIONS
CONCLUSIONS
This meta-review has implications for clinical practice and future research. First, these results suggest that antidepressant drugs should be used as a second-line treatment during pregnancy (after first-line psychotherapy, according to the guidelines). The risk of major congenital malformations could be prevented by observing guidelines that discourage the use of paroxetine and fluoxetine. Second, to decrease heterogeneity and bias, future MAs should adjust for maternal psychiatric disorders and antidepressant drug dosage, and perform analyses by timing of exposure.
Identifiants
pubmed: 36853497
doi: 10.1007/s40272-023-00561-2
pii: 10.1007/s40272-023-00561-2
doi:
Substances chimiques
Paroxetine
41VRH5220H
Sertraline
QUC7NX6WMB
Fluoxetine
01K63SUP8D
Antidepressive Agents
0
Types de publication
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
247-265Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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