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Maines E, Cardellini MC, Stringari G, Leonardi L, Piccoli G, Urru SAM, Maiorana A, Soffiati M, Franceschi R. Drug-Induced Hypoglycemia in Neonates Born to Nondiabetic Women Treated with Medications during the Pregnancy or the Labor: A Systematic Review of the Literature. Am J Perinatol 2024; 41:e2850-e2861. [PMID: 37848046 DOI: 10.1055/s-0043-1776061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2023]
Abstract
The prompt identification of at-risk newborns for drug-induced hypoglycemia can minimize the risk for adverse side effects, inappropriate investigations, and considerable unnecessary costs. Existing literature discusses drug-induced hypoglycemia, but a systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing. We reviewed the association between neonatal hypoglycemia and maternal medications. We systematically searched the literature according to the PICOS model on drug-induced hypoglycemia in neonates born to nondiabetic women treated with medications during the pregnancy or the labor. The main outcomes of the review were: (1) prevalence of hypoglycemia, (2) risk factors and potential confounders, (3) time at onset and severity of hypoglycemia, (4) dose-response gradient, (5) metabolic features of hypoglycemia, (6) modalities to treat hypoglycemia, and (7) quality of the studies. We included 69 studies in this review and we identified 11 groups of maternal drugs related to neonatal hypoglycemia. Results were classified for each outcome. Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia and in the differential diagnosis of neonatal hypoglycemia. Further studies are necessary to assess the risk of neonatal hypoglycemia associated with common maternal medications. KEY POINTS: · A systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing.. · In our review we identified 11 groups of maternal drugs related to neonatal hypoglycemia.. · Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia..
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Affiliation(s)
- Evelina Maines
- Division of Pediatrics, S. Chiara General Hospital, APSS, Trento, Italy
| | | | - Giovanna Stringari
- Division of Neonatology, S. Chiara General Hospital, APSS, Trento, Italy
| | - Letizia Leonardi
- Division of Pediatrics, S. Chiara General Hospital, APSS, Trento, Italy
| | - Giovanni Piccoli
- CIBIO - Department of Cellular, Computational and Integrative Biology, Università degli Studi di Trento, Trento, Italy
| | | | - Arianna Maiorana
- Division of Metabolism and Research Unit of Metabolic Biochemistry, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Massimo Soffiati
- Division of Pediatrics, S. Chiara General Hospital, APSS, Trento, Italy
- Division of Neonatology, S. Chiara General Hospital, APSS, Trento, Italy
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Eleftheriou G, Zandonella Callegher R, Butera R, De Santis M, Cavaliere AF, Vecchio S, Pistelli A, Mangili G, Bondi E, Somaini L, Gallo M, Balestrieri M, Albert U. Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:6565. [PMID: 37623151 PMCID: PMC10454549 DOI: 10.3390/ijerph20166565] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/01/2023] [Accepted: 08/07/2023] [Indexed: 08/26/2023]
Abstract
INTRODUCTION The initiative of a consensus on the topic of antidepressant and anxiolytic drug use in pregnancy is developing in an area of clinical uncertainty. Although many studies have been published in recent years, there is still a paucity of authoritative evidence-based indications useful for guiding the prescription of these drugs during pregnancy, and the data from the literature are complex and require expert judgment to draw clear conclusions. METHODS For the elaboration of the consensus, we have involved the scientific societies of the sector, namely, the Italian Society of Toxicology, the Italian Society of Neuropsychopharmacology, the Italian Society of Psychiatry, the Italian Society of Obstetrics and Gynecology, the Italian Society of Drug Addiction and the Italian Society of Addiction Pathology. An interdisciplinary team of experts from different medical specialties (toxicologists, pharmacologists, psychiatrists, gynecologists, neonatologists) was first established to identify the needs underlying the consensus. The team, in its definitive structure, includes all the representatives of the aforementioned scientific societies; the task of the team was the evaluation of the most accredited international literature as well as using the methodology of the "Nominal Group Technique" with the help of a systematic review of the literature and with various discussion meetings, to arrive at the drafting and final approval of the document. RESULTS The following five areas of investigation were identified: (1) The importance of management of anxiety and depressive disorders in pregnancy, identifying the risks associated with untreated maternal depression in pregnancy. (2) The assessment of the overall risk of malformations with the antidepressant and anxiolytic drugs used in pregnancy. (3) The evaluation of neonatal adaptation disorders in the offspring of pregnant antidepressant/anxiolytic-treated women. (4) The long-term outcome of infants' cognitive development or behavior after in utero exposure to antidepressant/anxiolytic medicines. (5) The evaluation of pharmacological treatment of opioid-abusing pregnant women with depressive disorders. CONCLUSIONS Considering the state of the art, it is therefore necessary in the first instance to frame the issue of pharmacological choices in pregnant women who need treatment with antidepressant and anxiolytic drugs on the basis of data currently available in the literature. Particular attention must be paid to the evaluation of the risk/benefit ratio, understood both in terms of therapeutic benefit with respect to the potential risks of the treatment on the pregnancy and on the fetal outcome, and of the comparative risk between the treatment and the absence of treatment; in the choice prescription, the specialist needs to be aware of both the potential risks of pharmacological treatment and the equally important risks of an untreated or undertreated disorder.
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Affiliation(s)
- Georgios Eleftheriou
- Italian Society of Toxicology (SITOX), via Giovanni Pascoli 3, 20129 Milan, Italy
- Poison Control Center, Hospital Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Riccardo Zandonella Callegher
- Italian Society of Psychiatry (SIP), piazza Santa Maria della Pietà 5, 00135 Rome, Italy
- Psychiatry Unit, Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
| | - Raffaella Butera
- Italian Society of Toxicology (SITOX), via Giovanni Pascoli 3, 20129 Milan, Italy
- Poison Control Center, Hospital Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Marco De Santis
- Italian Society of Obstetrics and Gynecology (SIGO), via di Porta Pinciana 6, 00187 Rome, Italy
- Department of Obstetrics and Gynecology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Anna Franca Cavaliere
- Italian Society of Obstetrics and Gynecology (SIGO), via di Porta Pinciana 6, 00187 Rome, Italy
- Department of Gynecology and Obstetrics, Fatebenefratelli Gemelli, Isola Tiberina, 00186 Rome, Italy
| | - Sarah Vecchio
- Italian Society of Toxicology (SITOX), via Giovanni Pascoli 3, 20129 Milan, Italy
- Ser.D Biella—Drug Addiction Service, 13875 Biella, Italy
| | - Alessandra Pistelli
- Italian Society of Toxicology (SITOX), via Giovanni Pascoli 3, 20129 Milan, Italy
- Division of Clinic Toxicology, Azienda Ospedaliera Universitaria Careggi, 50134 Florence, Italy
| | - Giovanna Mangili
- Italian Society of Neonatology (SIN), Corso Venezia 8, 20121 Milan, Italy
- Department of Neonatology, Hospital Papa Giovanni XXIII, 24127 Bergamo, Italy
| | - Emi Bondi
- Italian Society of Psychiatry (SIP), piazza Santa Maria della Pietà 5, 00135 Rome, Italy
- Department of Psychiatry, ASST Papa Giovanni XXIII, 24100 Bergamo, Italy
| | - Lorenzo Somaini
- Ser.D Biella—Drug Addiction Service, 13875 Biella, Italy
- Italian Society of Addiction Diseases (SIPAD), via Tagliamento 31, 00198 Rome, Italy
| | - Mariapina Gallo
- Poison Control Center, Hospital Papa Giovanni XXIII, 24127 Bergamo, Italy
- Italian Society for Drug Addiction (SITD), via Roma 22, 12100 Cuneo, Italy
| | - Matteo Balestrieri
- Psychiatry Unit, Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
- Italian Society of Neuropsychopharmacology (SINPF), via Cernaia 35, 00158 Rome, Italy
| | - Umberto Albert
- Italian Society of Psychiatry (SIP), piazza Santa Maria della Pietà 5, 00135 Rome, Italy
- Italian Society of Neuropsychopharmacology (SINPF), via Cernaia 35, 00158 Rome, Italy
- Department of Medicine, Surgery and Health Sciences, University of Trieste, 34128 Trieste, Italy
- Division of Clinic Psychiatry, Azienda Sanitaria Universitaria Giuliano-Isontina, 34148 Trieste, Italy
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Hussain-Shamsy N, Somerton S, Stewart DE, Grigoriadis S, Metcalfe K, Oberlander TF, Schram C, Taylor VH, Dennis CL, Vigod SN. The development of a patient decision aid to reduce decisional conflict about antidepressant use in pregnancy. BMC Med Inform Decis Mak 2022; 22:130. [PMID: 35562801 PMCID: PMC9099318 DOI: 10.1186/s12911-022-01870-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/09/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND People with moderate to severe depression in pregnancy must weigh potential risks of untreated or incompletely treated depression against the small, but uncertain risks of fetal antidepressant drug exposure. Clinical support alone appears insufficient for helping individuals with this complex decision. A patient decision aid (PDA) has the potential to be a useful tool for this population. The objective of our work was to use internationally recognized guidelines from the International Patient Decision Aids Standards Collaboration to develop an evidence-based PDA for antidepressant use in pregnancy. METHODS A three-phased development process was used whereby, informed by patient and physician perspectives and evidence synthesis, a steering committee commissioned a web-based PDA for those deciding whether or not to start or continue antidepressant treatment for depression in pregnancy (Phase 1). A prototype was developed (Phase 2) and iteratively revised based on feedback during field testing based on a user-centred process (Phase 3). RESULTS We developed a web-based PDA for people deciding whether to start or continue antidepressant use for depression in pregnancy. It has five interactive sections: (1) information on depression and treatment; (2) reasons to start/continue an antidepressant and to start/stop antidepressant medication; (3) user assessment of values regarding each issue; (4) opportunity to reflect on factors that contribute to decision making; and (5) a printable PDF that summarizes the user's journey through the PDA. CONCLUSIONS This tool, which exclusively focuses on depression treatment with Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors, can be used by individuals making decisions about antidepressant use to treat depression during pregnancy. Limitations of the PDA are that it is not for other conditions, nor other medications that can be used for depression, and in its pilot form cannot be used by women who do not speak English or who have a visual impairment. Pending further study, it has the potential to enhance quality of care and patient experience.
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Affiliation(s)
- Neesha Hussain-Shamsy
- Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, 4th Floor, Toronto, ON, Canada
| | - Sarah Somerton
- Garry Hurvitz Centre for Brain and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada
| | - Donna E Stewart
- Centre for Mental Health, University Health Network, Toronto General Hospital Research Institute, 200 Elizabeth Street, Toronto, ON, Canada
- Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, Canada
| | - Sophie Grigoriadis
- Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, Canada
- Sunnybrook Health Sciences Centre and Research Institute, 2075 Bayview Avenue, Toronto, ON, Canada
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada
| | - Kelly Metcalfe
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada
- Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, 155 College Street, Toronto, ON, Canada
| | - Tim F Oberlander
- BC Children's Hospital, 4500 Oak Street, Vancouver, BC, Canada
- Department of Pediatrics, Faculty of Medicine, University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC, Canada
| | - Carrie Schram
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada
| | - Valerie H Taylor
- Department of Psychiatry, University of Calgary, 2500 University Dr NW, Calgary, AB, Canada
| | - Cindy-Lee Dennis
- Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, 155 College Street, Toronto, ON, Canada
| | - Simone N Vigod
- Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, 4th Floor, Toronto, ON, Canada.
- Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada.
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Zyoud SH, Al-Jabi SW, Shahwan MJ, Jairoun AA. Global research production in neonatal abstinence syndrome: A bibliometric analysis. World J Clin Pediatr 2022; 11:307-320. [PMID: 35663005 PMCID: PMC9134155 DOI: 10.5409/wjcp.v11.i3.307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/21/2021] [Accepted: 03/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recently, neonatal abstinence syndrome (NAS) emerged as a significant global concern with a dramatic increase in healthcare expenditures. The incidence of the NAS has increased notably in the past decade and emergence as a global public health problem. AIM To evaluate the development and trend of global NAS research from 1958 to 2019 by bibliometric analysis. METHODS Analyzed aspects included publication output per year, language, document types, journals, countries/territories, h-index, authors, and top research priorities. The VOSviewer was used to determine the top research priorities, and trends, and to present bibliometric networks concerning various dimensions, such as co-authorship, authors, and countries. RESULTS A total of 1738 articles were retrieved in the Scopus database from 1958 to 2019. It was found that the great majority of the total NAS documents (n = 1295) were original articles followed by reviews (n = 268) and letters (n = 48). The most productive countries in the NAS field were the United States (n = 833), Canada (n = 112), the United Kingdom (n = 111), and Germany (n = 77). Treatment and hospital outcomes in NAS, evidence-based nurse-driven interventions for the care of newborns with NAS, and a systematic reviews and network meta-analysis for therapeutic approaches of NAS were found in recent years (after 2010), compared with terms such as pathophysiology, mechanisms of NAS, and signs and symptoms in the early years. CONCLUSION Treatment and pediatric outcomes and the effectiveness of pharmacological treatment may be frontiers in the NAS field, and continued efforts from researchers are needed in those topics.
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Affiliation(s)
- Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Samah W Al-Jabi
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
| | - Moyad Jamal Shahwan
- Clinical Sciences, Ajman University, Ajman 2758, United Arab Emirates
- Centre of Medical and Bio‑allied Health Sciences Research, Ajman University, Ajman 2758, United Arab Emirates
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Zyoud SH, Al-Jabi SW, Shahwan MJ, Jairoun AA. Global research production in neonatal abstinence syndrome: A bibliometric analysis. World J Clin Pediatr 2022; 11:308-321. [DOI: 10.5409/wjcp.v11.i3.308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recently, neonatal abstinence syndrome (NAS) emerged as a significant global concern with a dramatic increase in healthcare expenditures. The incidence of the NAS has increased notably in the past decade and emergence as a global public health problem.
AIM To evaluate the development and trend of global NAS research from 1958 to 2019 by bibliometric analysis.
METHODS Analyzed aspects included publication output per year, language, document types, journals, countries/territories, h-index, authors, and top research priorities. The VOSviewer was used to determine the top research priorities, and trends, and to present bibliometric networks concerning various dimensions, such as co-authorship, authors, and countries.
RESULTS A total of 1738 articles were retrieved in the Scopus database from 1958 to 2019. It was found that the great majority of the total NAS documents (n = 1295) were original articles followed by reviews (n = 268) and letters (n = 48). The most productive countries in the NAS field were the United States (n = 833), Canada (n = 112), the United Kingdom (n = 111), and Germany (n = 77). Treatment and hospital outcomes in NAS, evidence-based nurse-driven interventions for the care of newborns with NAS, and a systematic reviews and network meta-analysis for therapeutic approaches of NAS were found in recent years (after 2010), compared with terms such as pathophysiology, mechanisms of NAS, and signs and symptoms in the early years.
CONCLUSION Treatment and pediatric outcomes and the effectiveness of pharmacological treatment may be frontiers in the NAS field, and continued efforts from researchers are needed in those topics.
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Affiliation(s)
- Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine,Poison Control and Drug Information Center, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine,Clinical Research Centre, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Samah W Al-Jabi
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
| | - Moyad Jamal Shahwan
- Clinical Sciences, Ajman University, Ajman 2758, United Arab Emirates,Centre of Medical and Bio‑allied Health Sciences Research, Ajman University, Ajman 2758, United Arab Emirates
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Wang J, Cosci F. Neonatal Withdrawal Syndrome following Late in utero Exposure to Selective Serotonin Reuptake Inhibitors: A Systematic Review and Meta-Analysis of Observational Studies. PSYCHOTHERAPY AND PSYCHOSOMATICS 2021; 90:299-307. [PMID: 33971648 DOI: 10.1159/000516031] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 03/20/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION A clear picture of neonatal withdrawal signs due to in utero selective serotonin reuptake inhibitor (SSRI) exposure and its consequences is still missing. OBJECTIVE A systematic review and a meta-analysis were performed to provide an overview of neonatal withdrawal signs following late in utero exposure to SSRIs and to quantify the corresponding risks. METHODS MEDLINE, Web of Science, and Embase were searched from inception to January 2021. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. English-language observational studies reporting on acute postpartum outcomes following late in utero exposure to SSRIs or SSRIs/venlafaxine were evaluated. RESULTS Of 2,269 citations reviewed, 79 studies were assessed for eligibility; 13 were included in the qualitative analysis of the literature, which allowed us to identify 26 signs. A meta-analysis was run separately for studies on SSRI exposure (n = 3) and those on SSRI/venlafaxine exposure (n = 6). Hypoglycemia was identified as a withdrawal sign based on the SSRI studies. Tremors, hypotonia, tachycardia, rapid breathing, respiratory distress, and hypertonia were identified as withdrawal signs based on the SSRI/venlafaxine studies. CONCLUSIONS The present work provides a framework for the identification of neonatal SSRI withdrawal syndrome. Tapering and discontinuation of antidepressant drugs before and during the early phase of pregnancy are worth attempting to prevent the occurrence of this syndrome.
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Affiliation(s)
- Jianjun Wang
- Department of Neurology and Psychology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Fiammetta Cosci
- Department of Health Sciences, University of Florence, Florence, Italy.,Clinical Pharmacopsychology Laboratory, University of Florence, Florence, Italy.,Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
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Xing D, Wu R, Chen L, Wang T. Maternal use of antidepressants during pregnancy and risks for adverse perinatal outcomes: a meta-analysis. J Psychosom Res 2020; 137:110231. [PMID: 32889478 DOI: 10.1016/j.jpsychores.2020.110231] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 07/10/2020] [Accepted: 08/25/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To perform an updated and comprehensive meta-analysis on the risks of adverse perinatal outcomes in children whose mothers received antidepressants during pregnancy. METHODS A systematic literature search of several databases was conducted through December 2018 to identify relevant studies. Risk estimates and their corresponding 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Subgroup and sensitivity analyses were performed to explore the source of heterogeneity and test the robustness. RESULTS Forty-eight cohort and 6 case-control studies were included. In cohort studies, children whose mothers received antidepressants during pregnancy had higher risks of preterm birth (RR = 1.62, 95% CI: 1.37, 1.90), low birth weight (RR = 1.37, 95% CI: 1.04, 1.80), and admissions to neonatal intensive care unit (RR = 1.60, 95% CI: 1.38, 1.85) when compared with children born by depressed but untreated pregnant women. The risks of spontaneous abortions (RR = 1.49, 95% CI: 1.29, 1.73), large for gestational age (RR = 1.11, 95% CI: 1.03, 1.20), stillbirths (RR = 1.16, 95% CI: 1.02, 1.32), low Apgar score at 5 min (RR = 1.91, 95% CI: 1.42, 2.56), and neonatal convulsions (RR = 1.97, 95% CI: 1.56, 2.48) increased in children whose mothers received antidepressants during pregnancy when compared with children born by healthy pregnant women. CONCLUSION Compared with children whose mothers did not receive antidepressants during pregnancy, children whose mothers received antidepressants during pregnancy had increased risks of adverse perinatal outcomes. Further research on the dose of antidepressants is needed.
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Affiliation(s)
- Dexiu Xing
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Rong Wu
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China
| | - Lizhang Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China; Hunan Provincial Key Laboratory of Clinical Epidemiology, Hunan, China.
| | - Tingting Wang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Hunan, China.
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Shah J, Sarmiento K, Yang J, Shah PS. Maternal antidepressant use during pregnancy and neonatal hypoglycemia: prospective cohort study. J Perinatol 2020; 40:1025-1030. [PMID: 32152495 DOI: 10.1038/s41372-020-0644-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 02/05/2020] [Accepted: 02/25/2020] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To evaluate associations between maternal antidepressant use during pregnancy and hypoglycemia in term neonates. STUDY DESIGN We conducted a prospective comparative cohort study of neonates of ≥37 weeks' gestation. Neonates whose mothers used antidepressants during pregnancy were compared with randomly selected cohort of neonates whose mothers did not use antidepressants. Blood glucose was measured at 24 ± 2 h after birth. Hypoglycemia was defined as blood glucose level <2.6 mmol/L. We needed 60 patients in each group to reject the null hypothesis. RESULTS Mean gestational ages were 39 vs. 40 weeks (p < 0.01) and birthweights were 3250 vs. 3360 g (p = 0.08) for antidepressant-exposed vs. -unexposed neonates. There were no significant differences between groups in odds of hypoglycemia (4/59: exposed vs. 2/61: unexposed; adjusted relative risk 1.73; 95% confidence interval [CI] 0.37-8.92) or mean blood glucose levels. CONCLUSIONS Maternal antidepressant use during pregnancy was not associated with neonatal hypoglycemia at 24 h of age.
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Affiliation(s)
- Jyotsna Shah
- Department of Pediatrics, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada.
| | - Karla Sarmiento
- Department of Pediatrics, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada
| | - Jie Yang
- Department of Pediatrics, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada
| | - Prakesh S Shah
- Department of Pediatrics, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada
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9
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Bandoli G, Chambers CD, Wells A, Palmsten K. Prenatal Antidepressant Use and Risk of Adverse Neonatal Outcomes. Pediatrics 2020; 146:peds.2019-2493. [PMID: 32513841 PMCID: PMC7329255 DOI: 10.1542/peds.2019-2493] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/11/2020] [Indexed: 02/01/2023] Open
Abstract
OBJECTIVES To estimate the risk of neonatal outcomes from patterns of prenatal antidepressant use. METHODS From the OptumLabs Data Warehouse, 226 932 singleton deliveries were identified. Antidepressant claims with coverage between the last menstrual period and 35 weeks' gestation were converted to fluoxetine equivalents, and a longitudinal cluster analysis was performed. Outcomes included major cardiac malformations (11.7 of 1000 births), preterm birth (75.7 of 1000 births), and newborn respiratory distress (54.2 of 1000 births). The lowest trajectory was the primary reference group, and depression and anxiety with no antidepressant claims served as secondary reference groups. RESULTS From 15 041 (6.6%) pregnancies exposed to an antidepressant, use patterns were best described as (1) low use (∼10 mg/day) with first-trimester reduction, (2) low sustained use (∼20 mg/day), (3) moderate use (∼40 mg/day) with first-trimester reduction, (4) moderate sustained use (∼40 mg/day), and (5) high sustained use (∼75 mg/day). Moderate sustained use increased the risk of major cardiac malformations, although results included the null when compared with depression or anxiety reference groups. Moderate sustained (adjusted risk ratio [RR] 1.31; 95% confidence interval [CI] 1.16-1.49) and high sustained (adjusted RR 1.78; 95% CI 1.48-2.14) trajectories were associated with an increased risk of preterm birth. All 4 trajectories increased the risk of neonatal respiratory distress in a dose-response fashion (adjusted RRs 1.36 [95% CI 1.20-1.50] to 2.23 [95% CI 1.83-2.77]). CONCLUSIONS Although findings support continuation of the lowest effective dose to treat depression or anxiety, which benefits the mother, they also highlight an increased risk for newborn respiratory distress in all groups and preterm birth at moderate to high sustained doses.
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Affiliation(s)
- Gretchen Bandoli
- Department of Pediatrics, University of California, San Diego, La Jolla, California; .,OptumLabs, Cambridge, Massachusetts; and
| | - Christina D. Chambers
- Department of Pediatrics, University of California,
San Diego, La Jolla, California;,OptumLabs, Cambridge, Massachusetts; and
| | - Alan Wells
- Department of Pediatrics, University of California,
San Diego, La Jolla, California
| | - Kristin Palmsten
- OptumLabs, Cambridge, Massachusetts; and,HealthPartners, Minneapolis, Minnesota
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Zhong X, Harris G, Smirnova L, Zufferey V, Sá RDCDSE, Baldino Russo F, Baleeiro Beltrao Braga PC, Chesnut M, Zurich MG, Hogberg HT, Hartung T, Pamies D. Antidepressant Paroxetine Exerts Developmental Neurotoxicity in an iPSC-Derived 3D Human Brain Model. Front Cell Neurosci 2020; 14:25. [PMID: 32153365 PMCID: PMC7047331 DOI: 10.3389/fncel.2020.00025] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 01/28/2020] [Indexed: 02/04/2023] Open
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy. Various concerns have been raised about the possible effects of these drugs on fetal development. Current developmental neurotoxicity (DNT) testing conducted in rodents is expensive, time-consuming, and does not necessarily represent human pathophysiology. A human, in vitro testing battery to cover key events of brain development, could potentially overcome these challenges. In this study, we assess the DNT of paroxetine—a widely used SSRI which has shown contradictory evidence regarding effects on human brain development using a versatile, organotypic human induced pluripotent stem cell (iPSC)-derived brain model (BrainSpheres). At therapeutic blood concentrations, which lie between 20 and 60 ng/ml, Paroxetine led to an 80% decrease in the expression of synaptic markers, a 60% decrease in neurite outgrowth and a 40–75% decrease in the overall oligodendrocyte cell population, compared to controls. These results were consistently shown in two different iPSC lines and indicate that relevant therapeutic concentrations of Paroxetine induce brain cell development abnormalities which could lead to adverse effects.
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Affiliation(s)
- Xiali Zhong
- Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.,Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Georgina Harris
- Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Lena Smirnova
- Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Valentin Zufferey
- Department of Physiology, Lausanne and Swiss Centre for Applied Human Toxicology (SCAHT), University of Lausanne, Lausanne, Switzerland
| | | | - Fabiele Baldino Russo
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Patricia Cristina Baleeiro Beltrao Braga
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.,Department of Obstetrics, School of Arts Sciences and Humanities, São Paulo, Brazil
| | - Megan Chesnut
- Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Marie-Gabrielle Zurich
- Department of Physiology, Lausanne and Swiss Centre for Applied Human Toxicology (SCAHT), University of Lausanne, Lausanne, Switzerland
| | - Helena T Hogberg
- Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Thomas Hartung
- Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.,CAAT-Europe, University of Konstanz, Konstanz, Germany
| | - David Pamies
- Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.,Department of Physiology, Lausanne and Swiss Centre for Applied Human Toxicology (SCAHT), University of Lausanne, Lausanne, Switzerland
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11
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Treating Obsessive-Compulsive Disorder in the Postpartum Period: Diagnostic and Cultural Considerations. Harv Rev Psychiatry 2019; 26:82-89. [PMID: 28795979 DOI: 10.1097/hrp.0000000000000146] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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12
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Developmental outcomes after gestational antidepressant treatment with sertraline and its discontinuation in an animal model of maternal depression. Behav Brain Res 2019; 366:1-12. [PMID: 30836156 DOI: 10.1016/j.bbr.2019.03.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 02/04/2019] [Accepted: 03/01/2019] [Indexed: 01/21/2023]
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to women before or during pregnancy to manage their depressive symptoms. However, there is still little knowledge regarding the long-term development effects of SSRI exposure for the fetus or the effects of discontinuing SSRI treatment during pregnancy. This study utilized a translational animal model of maternal depression (based on giving high levels of corticosterone (CORT, 40 mg/kg, s.c.) or vehicle (Oil) for 21 days prior to conception) to investigate the effects of sertraline (a frequently prescribed SSRI; 20 mg/kg p.o., treatment started ∼7 days prior to conception) and its discontinuation during pregnancy (on gestational day 16) compared to vehicle (water) treatment on the development of the offspring. Our results revealed that both corticosterone exposure prior to pregnancy and sertraline administration and its discontinuation during gestation had sex-specific effects on behavior in the adult offspring. In particular, pre-conceptional maternal corticosterone treatment impacted the stress response, anxiety-like behavior and cognitive performance in adult female offspring, while gestational SSRI exposure and its discontinuation compared to full-term exposure affected impulsivity in females, and exploratory behavior in males. More research is needed on the effects of exposure to antidepressant medication and its discontinuation compared to depression during pregnancy and how each impacts development to better help women make informed decisions about their medication use during pregnancy.
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Hsu MC, Tung CY, Chen HE. Omega-3 polyunsaturated fatty acid supplementation in prevention and treatment of maternal depression: Putative mechanism and recommendation. J Affect Disord 2018; 238:47-61. [PMID: 29860183 DOI: 10.1016/j.jad.2018.05.018] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 04/03/2018] [Accepted: 05/15/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Women are vulnerable to depression during their childbearing years, and giving birth to a child precipitates postpartum depression (PPD) in some women. This review focuses on comparing the effectiveness of omega-3 polyunsaturated fatty acid supplementation on depression during pregnancy or PPD after childbirth. METHODS MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials etc. through July 2017 were searched. Studies of dietary intake and plasma and/or milk levels of omega-3 fatty acids and trials of benefits and effects of omega-3 fatty acids supplements on pregnant or postpartum women with depression were specifically selected. RESULTS Omega-3 fatty acid deficiency, due to inadequate intake, fast depletion during pregnancy and lactation, is one of the risk factors of PPD. Associations between neuroinflammation (elevated pro-inflammatory cytokines) and aberrant neurotransmission (low serotonergic transmission activity) and risk of PPD have also been reported by numerous studies. Supplementation with eicosapentaenoic acid (EPA)-rich oil can effectively reduce depression during pregnancy and PPD after childbirth. Long term treatment with docosahexaenoic acid (DHA)-rich oil can be effective in reducing the risk of PPD in healthy women, but not in lactating women. Supplementation of DHA-rich oil to women begun at pregnancy and continued after childbirth exerts no beneficial effect on depression. CONCLUSIONS Dietary supplementation with omega-3 fatty acids rich in EPA during pregnancy or postpartum reduces some symptoms associated with depression. DHA supplementation to healthy pregnant women can also reduce the risk of PPD.
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Affiliation(s)
- Mei-Chi Hsu
- Department of Nursing, I-Shou University, No. 8, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan, ROC.
| | - Chia-Yi Tung
- Nursing Department, E-Da Hospital, No.1, Yida Road, Jiaosu Village Yanchao District, Kaohsiung City 82445, Taiwan, ROC
| | - Hsing-E Chen
- Nursing Department, E-Da Hospital, No.1, Yida Road, Jiaosu Village Yanchao District, Kaohsiung City 82445, Taiwan, ROC
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14
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Thorsness KR, Watson C, LaRusso EM. Perinatal anxiety: approach to diagnosis and management in the obstetric setting. Am J Obstet Gynecol 2018; 219:326-345. [PMID: 29803818 DOI: 10.1016/j.ajog.2018.05.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 05/09/2018] [Accepted: 05/16/2018] [Indexed: 11/16/2022]
Abstract
Anxiety is common in women during the perinatal period, manifests with various symptoms and severity, and is associated with significant maternal morbidity and adverse obstetric and neonatal outcomes. Given the intimate relationship and frequency of contact, the obstetric provider is positioned optimally to create a therapeutic alliance and to treat perinatal anxiety. Time constraints, absence of randomized controlled trials, mixed quality of data, and concern for potential adverse reproductive outcomes all limit the clinician's ability to initiate informed risk-benefit discussions. Clear understanding of the role of the obstetric provider in the identification, stabilization, and initiation of medication and/or referral to psychotherapy for women with perinatal anxiety disorders is critical to maternal and neonatal wellbeing. Informed by our clinical practice as perinatal psychiatric providers, we have provided a concise summary of current research on the approach to the treatment of perinatal anxiety disorders in the obstetric setting that includes psychotherapy and supportive interventions, primary and adjuvant psychiatric medication, and general prescribing pearls. Medications that we examined include antidepressants, benzodiazepines, sedative-hypnotics, antihistamines, quetiapine, buspirone, propranolol, and melatonin. Further research into management of perinatal anxiety, particularly psychopharmacologic management, is warranted.
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Grove K, Lewis AJ, Galbally M. Prenatal Antidepressant Exposure and Child Motor Development: A Meta-analysis. Pediatrics 2018; 142:peds.2018-0356. [PMID: 29929995 DOI: 10.1542/peds.2018-0356] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/03/2018] [Indexed: 11/24/2022] Open
Abstract
CONTEXT There is increasing use of antidepressants in pregnancy and hence children exposed in utero. Contradictory studies exist in the literature in which researchers report on the potential impact of antenatal antidepressant exposure on subsequent child motor development. OBJECTIVE Our objective in this systematic review and meta-analysis was to determine whether antenatal antidepressant exposure increases the risk of impaired motor development in children. DATA SOURCES We searched PsychINFO, Embase, Medline, PubMed, and Scopus up to July 24, 2017. STUDY SELECTION English-language cohort and case control studies in which researchers report primary data from a motor assessment of infants or children after any antidepressant exposure in pregnancy were included. DATA EXTRACTION Of the 329 studies identified, there were 160 articles screened, 24 were included in the systematic review, and 18 met inclusion criteria for the meta-analysis. RESULTS The total pooled results were based on random effects models and revealed a significant association between exposure to antidepressants during pregnancy and overall occurrence of poorer motor outcomes in children (effect size = 0.22; 95% confidence interval = 0.07 to 0.37) with a moderate degree of heterogeneity (I2 = 56.6%). LIMITATIONS There was variation in the measurement both of exposure and motor development across the identified study, and few followed up to later childhood or beyond. CONCLUSIONS A small increased risk of poorer motor development may exist for children who are exposed to antidepressant medications during pregnancy. However, the marked methodological variation among studies and the limited control for possible confounds warrants cautious interpretation of these findings.
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Affiliation(s)
- Katherine Grove
- Department of Psychiatry, Graylands Hospital, Mount Claremont, Australia
| | - Andrew J Lewis
- School of Psychology and Exercise Science, Murdoch University, Perth, Australia
| | - Megan Galbally
- School of Psychology and Exercise Science, Murdoch University, Perth, Australia; .,School of Medicine, The University of Notre Dame Australia, Fremantle, Australia; and.,King Edward Memorial Hospital, Subiaco, Australia
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16
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Ornoy A, Koren G. Selective serotonin reuptake inhibitor use in pregnant women; pharmacogenetics, drug-drug interactions and adverse effects. Expert Opin Drug Metab Toxicol 2018; 14:247-259. [PMID: 29345153 DOI: 10.1080/17425255.2018.1430139] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Possible negative effects of selective serotonin reuptake inhibitors (SSRIs) in pregnancy relate to congenital anomalies, negative perinatal events and neurodevelopmental outcome. Many studies are confounded by the underlying maternal disease and by pharmacogenetic and pharmacokinetic differences of these drugs. Areas covered: The possible interactions of SSRIs and serotonin and norepinephrine reuptake inhibitors with other drugs and the known effects of SSRIs on congenital anomalies, perinatal and neurodevelopmental outcome. Expert opinion: SSRIs should be given with caution when combined with other drugs that are metabolized by cytochrome P450 enzymes. SSRIs apparently increase the rate of severe cardiac malformations, induce neonatal adaptation problems in up to 30% of the offspring, increase the rate of persistent pulmonary hypertension of the newborn and possibly slightly increase the rate of prematurity and low birth weight. Most neurodevelopmental follow up studies did not find significant cognitive impairments except some transient gross motor delay, slight impairment of language abilities and possibly behavioral changes. The literature on the possible association of SSRIs with autism spectrum disorder is inconsistent; if an association exists, it is apparently throughout pregnancy. The risk associated with treatment discontinuation seems to outweigh the risk of treatment, as severe maternal depression may negatively affect the child's development. If needed, treatment should continue in pregnancy with the minimal effective dose.
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Affiliation(s)
- Asher Ornoy
- a Laboratory of Teratology, Department of Medical Neurobiology , Hebrew University Hadassah Medical School , Jerusalem , Israel
| | - Gideon Koren
- b Morris Kahn- Maccabi Institute of Research and Innovation, and Tel Aviv University , TEl - AVIV , Israel
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17
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Galbally M, Spigset O, Johnson AR, Kohan R, Lappas M, Lewis AJ. Neonatal adaptation following intrauterine antidepressant exposure: assessment, drug assay levels, and infant development outcomes. Pediatr Res 2017; 82:806-813. [PMID: 28665925 DOI: 10.1038/pr.2017.156] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 06/20/2017] [Indexed: 01/22/2023]
Abstract
BackgroundAlthough a meta-analysis has confirmed the association between antidepressant exposure in utero and subsequent poor neonatal adaptation, few identified studies included drug levels or standardized measures and only two studies followed up children who developed symptoms beyond infancy.MethodsThe study draws on the Mercy Pregnancy and Emotional Wellbeing Study and reports on 42 women/infant pairs at delivery. In all, 31 women continued to take antidepressants until delivery and 11 ceased earlier in pregnancy. Poor neonatal adaptation was assessed twice daily for up to 6 days by using the Neonatal Abstinence Scoring System (NASS). Drug levels were analyzed in umbilical cord blood and maternal blood obtained at delivery.ResultsIn total, 76% (32 of 42) of neonates exposed to antidepressants had symptoms observed on the NASS. These symptoms occurred up to 5 days postpartum with 25% having symptoms that persisted for more than 3 days. The most frequent symptoms were correlated most closely to antidepressant drug levels. Elevated NASS scores were found to be associated with poorer fine motor development at 6 months of age.ConclusionsPoor neonatal adaptation may be more common than previously recognized. The NASS was observed to be an effective assessment and monitoring measure. Research following symptomatic infants beyond the neonatal period is required.
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Affiliation(s)
- Megan Galbally
- School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia, Australia
| | - Olav Spigset
- Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway
| | - Andrew R Johnson
- School of Psychology and Speech Pathology, Curtin University, Perth, Western Australia, Australia
| | - Rolland Kohan
- School of Women and Infant Health, School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia
| | - Martha Lappas
- Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
| | - Andrew J Lewis
- School of Psychology and Exercise Science, Murdoch University, Perth, Western Australia, Australia
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18
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Matsuoka S, Hori S, Satoh H, Nagamatsu T, Fujii T, Sawada Y. Quantitative prediction of fetal plasma concentration of fluvoxamine during dosage-tapering to the mother. Placenta 2017; 58:74-81. [DOI: 10.1016/j.placenta.2017.08.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 08/04/2017] [Accepted: 08/21/2017] [Indexed: 01/13/2023]
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Ornoy A, Koren G. Selective Serotonin Reuptake Inhibitors during Pregnancy: Do We Have Now More Definite Answers Related to Prenatal Exposure? Birth Defects Res 2017; 109:898-908. [DOI: 10.1002/bdr2.1078] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 05/17/2017] [Accepted: 06/06/2017] [Indexed: 01/10/2023]
Affiliation(s)
- Asher Ornoy
- Laboratory of Teratology, Department of Medical Neurobiology; Hebrew University Hadassah Medical School Jerusalem and Maccabi Research Institute and Tel Aviv University; Tel Aviv Israel
| | - Gideon Koren
- Laboratory of Teratology, Department of Medical Neurobiology; Hebrew University Hadassah Medical School Jerusalem and Maccabi Research Institute and Tel Aviv University; Tel Aviv Israel
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20
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Wen X, Hartzema A, Delaney JA, Brumback B, Liu X, Egerman R, Roth J, Segal R, Meador KJ. Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model. BMC Pregnancy Childbirth 2017; 17:10. [PMID: 28061833 PMCID: PMC5219655 DOI: 10.1186/s12884-016-1190-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Accepted: 12/09/2016] [Indexed: 11/10/2022] Open
Abstract
Background Application of latent variable models in medical research are becoming increasingly popular. A latent trait model is developed to combine rare birth defect outcomes in an index of infant morbidity. Methods This study employed four statewide, retrospective 10-year data sources (1999 to 2009). The study cohort consisted of all female Florida Medicaid enrollees who delivered a live singleton infant during study period. Drug exposure was defined as any exposure to Antiepileptic drugs (AEDs) during pregnancy. Mothers with no AED exposure served as the AED unexposed group for comparison. Four adverse outcomes, birth defect (BD), abnormal condition of new born (ACNB), low birth weight (LBW), and pregnancy and obstetrical complication (PCOC), were examined and combined using a latent trait model to generate an overall severity index. Unidimentionality, local independence, internal homogeneity, and construct validity were evaluated for the combined outcome. Results The study cohort consisted of 3183 mother-infant pairs in total AED group, 226 in the valproate only subgroup, and 43,956 in the AED unexposed group. Compared to AED unexposed group, the rate of BD was higher in both the total AED group (12.8% vs. 10.5%, P < .0001), and the valproate only subgroup (19.6% vs. 10.5%, P < .0001). The combined outcome was significantly correlated with the length of hospital stay during delivery in both the total AED group (Rho = 0.24, P < .0001) and the valproate only subgroup (Rho = 0.16, P = .01). The mean score for the combined outcome in the total AED group was significantly higher (2.04 ± 0.02 vs. 1.88 ± 0.01, P < .0001) than AED unexposed group, whereas the valproate only subgroup was not. Conclusions Latent trait modeling can be an effective tool for combining adverse pregnancy and perinatal outcomes to assess prenatal exposure to AED, but evaluation of the selected components is essential to ensure the validity of the combined outcome. Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-1190-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xuerong Wen
- Health Outcomes, College of Pharmacy, University of Rhode Island, 7 Greenhouse Rd., Kingston, RI, 02881, USA.
| | - Abraham Hartzema
- Department of Pharmaceutical Outcome and Policy, University of Florida, Gainesville, FL, USA
| | - Joseph A Delaney
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Babette Brumback
- Department of Biostatistics, University of Florida, Gainesville, FL, USA
| | - Xuefeng Liu
- Department of Biostatistics & Epidemiology, Systems, Population and Leadership, University of Michigan, Ann Arbor, MI, 48109, USA
| | - Robert Egerman
- Department of Obstetrics & Gynecology, University of Florida, Gainesville, FL, USA
| | - Jeffrey Roth
- Department of Pediatrics, University of Florida, Gainesville, FL, USA
| | - Rich Segal
- Department of Pharmaceutical Outcome and Policy, University of Florida, Gainesville, FL, USA
| | - Kimford J Meador
- Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA
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Hogue AN, Temple-Cooper ME, Lagzdins M, Worley S, Scwersenski J, Floyd R, Saker F. Effects of in-utero exposure to selective serotonin reuptake inhibitors and venlafaxine on term and preterm infants. J Neonatal Perinatal Med 2017; 10:371-380. [PMID: 29286926 DOI: 10.3233/npm-16133] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
OBJECTIVE We hypothesized that in-utero SSRI exposure affects Apgar scores and immediate post-delivery oxygen requirements. STUDY DESIGN SSRI in-utero exposure was assessed retrospectively in preterm neonates ≥ 28 weeks gestation and term neonates. Primary outcome was Apgar <7 at five minutes and delivery room oxygen requirements. Secondary endpoints included one-minute Apgar, length of stay, birth weight, and NICU admission. RESULTS Fifty-one preterm and 117 term neonates were exposed to a SSRI; mostly to sertraline. Pre-term SSRI-exposed neonates had 4.1 times higher delivery room oxygen requirements. One minute Apgar <7 was 3.5 times higher and NICU admission 5 times higher 95% CI (1.3-19) in SSRI-exposed term neonates. Higher doses of sertraline had associated adverse outcomes. CONCLUSION In-utero SSRI exposure was associated with increased neonatal care at birth, differences in Apgar scores compared with controls, and increased NICU admissions. Higher sertraline doses were associated with poorer outcomes.
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Affiliation(s)
- A N Hogue
- Department of Pharmacy Services, Hillcrest - Cleveland Clinic, Mayfield Heights, OH, USA
| | - M E Temple-Cooper
- Department of Pharmacy Services, Hillcrest - Cleveland Clinic, Mayfield Heights, OH, USA
| | - M Lagzdins
- Department of Pharmacy Services, Hillcrest - Cleveland Clinic, Mayfield Heights, OH, USA
| | - S Worley
- Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - J Scwersenski
- Department of Neonatology, Cleveland Clinic Children's Hospital, Cleveland, OH, USA
| | - R Floyd
- Department of Pharmacy Services, Hillcrest - Cleveland Clinic, Mayfield Heights, OH, USA
| | - F Saker
- Department of Neonatology, Cleveland Clinic Children's Hospital, Cleveland, OH, USA
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Abstract
Objective: To evaluate the literature assessing the neonatal risks of antepartum paroxetine use. Data Sources: MEDLINE (1966–August 2006) and International Pharmaceutical Abstracts (1970–August 2006) searches were performed. Key search terms included paroxetine, SSRI, pregnancy, malformations, neonate, and fetus. Data Synthesis: Selective serotonin-reuptake inhibitors (SSRIs) are associated with neonatal withdrawal symptoms such as respiratory distress, irritability, lethargy, and tremors. In a cohort study, 30% of infants exposed to SSRIs had poor neonatal adaptation, compared with 9% of controls (p = 0.018). Some reports indicate that paroxetine is more commonly associated with neonatal withdrawal than other SSRIs. Recently, paroxetine was associated with a 1.82-fold (95% CI 1.17 to 2.82) increased risk of congenital malformations compared with other antidepressants. Other SSRIs were also associated with an increased risk of congenital malformations; however, the results were not statistically significant. Literature supporting these findings includes case reports and case–control or cohort studies. The Food and Drug Administration recommendations regarding paroxetine use during pregnancy have been added to the labeling information. Conclusions: Paroxetine may cause adverse outcomes in the neonate when used during pregnancy and should be discontinued in women who are pregnant or trying to become pregnant. The risks and benefits of other antidepressant use should be analyzed on an individual basis.
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Affiliation(s)
- Genine M Thormahlen
- Department of Pharmacy Practice, The University of Montana Drug Information Service, 32 Campus Dr., #1522, Missoula, MT 59812-1522, USA.
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Nörby U, Forsberg L, Wide K, Sjörs G, Winbladh B, Källén K. Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy. Pediatrics 2016; 138:peds.2016-0181. [PMID: 27940758 DOI: 10.1542/peds.2016-0181] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/19/2016] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To estimate the rate of admissions to NICUs, as well as infants' morbidity and neonatal interventions, after exposure to antidepressant drugs in utero. METHODS Data on pregnancies, deliveries, prescription drug use, and health status of the newborn infants were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We included 741 040 singletons, born between July 1, 2006, and December 31, 2012. Of the infants, 17 736 (2.4%) had mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Infants exposed to an SSRI were compared with nonexposed infants, and infants exposed during late pregnancy were compared with those exposed during early pregnancy only. The results were analyzed with logistic regression analysis. RESULTS After maternal use of an SSRI, 13.7% of the infants were admitted to the NICU compared with 8.2% in the population (adjusted odds ratio: 1.5 [95% confidence interval: 1.4-1.5]). The admission rate to the NICU after treatment during late pregnancy was 16.5% compared with 10.8% after treatment during early pregnancy only (adjusted odds ratio: 1.6 [95% confidence interval: 1.5-1.8]). Respiratory and central nervous system disorders and hypoglycemia were more common after maternal use of an SSRI. Infants exposed to SSRIs in late pregnancy compared with early pregnancy had a higher risk of persistent pulmonary hypertension (number needed to harm: 285). CONCLUSIONS Maternal use of antidepressants during pregnancy was associated with increased neonatal morbidity and a higher rate of admissions to the NICU. The absolute risk for severe disease was low, however.
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Affiliation(s)
- Ulrika Nörby
- Centre of Reproduction Epidemiology, Tornblad Institute, Institution of Clinical Science, Lund University, Lund, Sweden; .,Department of E-health and Strategic IT, Health and Medical Care Administration, Stockholm County Council, Stockholm, Sweden
| | - Lisa Forsberg
- Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.,Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Katarina Wide
- Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.,Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Gunnar Sjörs
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden; and
| | - Birger Winbladh
- Department of Clinical Sciences and Education, Karolinska Institutet, Sachs' Children's and Youth Hospital, Stockholm, Sweden
| | - Karin Källén
- Centre of Reproduction Epidemiology, Tornblad Institute, Institution of Clinical Science, Lund University, Lund, Sweden
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Eke AC, Saccone G, Berghella V. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis. BJOG 2016; 123:1900-1907. [PMID: 27239775 PMCID: PMC9987176 DOI: 10.1111/1471-0528.14144] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2016] [Indexed: 01/28/2023]
Abstract
BACKGROUND Depression is a prevalent condition in pregnancy affecting about 10% of women. Maternal depression has been associated with an increase in preterm births (PTB), low birthweight and fetal growth restriction, and postnatal complications. Available treatments for depressive disorders are psychotherapeutic interventions and antidepressant medications including selective serotonin inhibitors (SSRIs). SSRI use during pregnancy has been associated with several fetal and neonatal complications; so far, however, the risk of PTB in women using SSRIs during pregnancy is still a subject of debate. OBJECTIVE To evaluate the risk of preterm birth (PTB) in cases of exposure to SSRIs during pregnancy. SEARCH STRATEGY Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE and the Cochrane Central Register of Controlled Trials) were searched from their inception until May 2015 with the use of a combination of the following text words 'depression', 'pregnancy', 'exposure', 'antidepressant', 'SSRI', 'selective serotonin reuptake inhibitor', 'preterm birth', 'small for gestational age' and 'prematurity'. SELECTION CRITERIA We included studies evaluating the effect of SSRIs exposure in utero and pregnancy outcomes. All cohort and case-control studies were eligible to be included if they reported the incidence of PTB after any exposure to SSRIs and had a comparison group of unexposed pregnant women. Studies without a control group were excluded. DATA COLLECTION AND ANALYSIS The primary outcome was the incidence of PTB <37 weeks. Subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy were planned. MAIN RESULTS Eight studies (1 237 669 women) were included: 93 982 in the exposure group and 1 143 687 in the control group. After adjusting for confounders, the incidence of PTB was significantly higher in the group of women treated with SSRIs compared with controls (i.e. both women with depression but without SSRI exposure and women without depression) (adjusted OR (aOR) 1.24, 95% CI 1.09-1.41). In the subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy, an increased risk of PTB (6.8 versus 5.8%; OR 1.17, 95% CI 1.10-1.25) in the SSRI group was found compared with controls (i.e. depressed women treated with psychotherapy alone). CONCLUSIONS Women who received SSRIs during pregnancy had a significantly higher risk of developing PTB compared with controls. This higher risk remained significant even when comparing depressed women on SSRI with women not on SSRI. TWEETABLE ABSTRACT Selective serotonin reuptake inhibitors may be associated with preterm birth.
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Affiliation(s)
- A C Eke
- Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - G Saccone
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
| | - V Berghella
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
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Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects. Drug Saf 2016; 39:903-24. [DOI: 10.1007/s40264-016-0435-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Making Sense Out of the Controversy: Use of SSRIs in Pregnancy. CURRENT OBSTETRICS AND GYNECOLOGY REPORTS 2016. [DOI: 10.1007/s13669-016-0173-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Alwan S, Friedman JM, Chambers C. Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy: A Review of Current Evidence. CNS Drugs 2016; 30:499-515. [PMID: 27138915 DOI: 10.1007/s40263-016-0338-3] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications worldwide. However, over the past decade, their use during pregnancy, a period of extreme vulnerability to the onset of depression, has become highly concerning to patients and their healthcare providers in terms of safety to the developing fetus. Exposure to SSRIs in pregnancy has been associated with miscarriage, premature delivery, neonatal complications, birth defects-specifically cardiac defects-and, more recently, neurodevelopmental disorders in childhood, specifically autism spectrum disorders. Studies addressing the effect of individual SSRIs indicate a small but higher risk for birth defects with maternal fluoxetine and paroxetine use. Though the excess in absolute risk is small, it may still be of concern to some patients. Meanwhile, antenatal depression itself is associated with adverse perinatal outcomes, and discontinuing antidepressant treatment during pregnancy is associated with a high risk of relapse of depression. Whether the observed adverse fetal effects are related to the mother's medication use or her underlying maternal illness remains difficult to determine. It is important that every pregnant woman being treated with an SSRI (or considering such treatment) carefully weighs the risks of treatment against the risk of untreated depression for both herself and her child. The importance of recognizing a higher risk for the development of adverse outcomes lies in the potential for surveillance and possibly a timely intervention. Therefore, we recommend that pregnant women exposed to any SSRI in early pregnancy be offered options for prenatal diagnosis through ultrasound examinations and fetal echocardiography to detect the presence of birth defects. Tapering off or switching to other therapy in early pregnancy, if appropriate for the individual, may also be considered on a case-by-case basis.
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Affiliation(s)
- Sura Alwan
- Department of Medical Genetics, University of British Columbia, BC Women's Hospital and Health Centre, 4500 Oak Street (Box 153), Vancouver, BC, V6H 3N1, Canada.
| | - Jan M Friedman
- Department of Medical Genetics, University of British Columbia, BC Women's Hospital and Health Centre, 4500 Oak Street (Box 153), Vancouver, BC, V6H 3N1, Canada
| | - Christina Chambers
- Department of Pediatrics, School of Medicine, University of California, La Jolla, San Diego, CA, USA
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Alwan S, Bandoli G, Chambers CD. Maternal use of selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. Clin Pharmacol Ther 2016; 100:34-41. [PMID: 27060574 DOI: 10.1002/cpt.376] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Revised: 03/21/2016] [Accepted: 04/01/2016] [Indexed: 11/07/2022]
Abstract
Use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy has been associated with persistent pulmonary hypertension of the newborn (PPHN), a rare condition with substantial infant mortality and morbidity. Although the increase in absolute risk is small on a population level, it may be of concern to many patients. It remains unclear the extent to which the increased risks reported for PPHN are explained by the underlying maternal illness rather than the use of SSRIs.
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Affiliation(s)
- S Alwan
- Department of Medical Genetics, University of British Columbia, Vancouver, Canada
| | - G Bandoli
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - C D Chambers
- Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, USA
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Larsen ER, Damkier P, Pedersen LH, Fenger-Gron J, Mikkelsen RL, Nielsen RE, Linde VJ, Knudsen HED, Skaarup L, Videbech P. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl 2016:1-28. [PMID: 26344706 DOI: 10.1111/acps.12479] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/06/2015] [Indexed: 02/01/2023]
Abstract
OBJECTIVE To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics. METHOD As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted. RESULTS Sertraline and citalopram are first-line treatment among selective serotonin reuptake inhibitor for depression. It is recommended to use lithium for bipolar disorders if an overall assessment finds an indication for mood-stabilizing treatment during pregnancy. Lamotrigine can be used. Valproate and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. CONCLUSION It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how it has to be administered.
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Affiliation(s)
- E. R. Larsen
- Department of Affective Disorders; Aarhus University Hospital; Risskov Denmark
| | - P. Damkier
- Department of Clinical Biochemistry and Pharmacology; Odense University Hospital; Odense Denmark
| | - L. H. Pedersen
- Department of Clinical Medicine - Gynecological/Obstetric Ward Y; Aarhus University Hospital; Skejby Denmark
| | | | - R. L. Mikkelsen
- Psychiatry in the Capital Region of Denmark; Psychiatric Centre Copenhagen; Section 6211; Rigshospitalet; Copenhagen Denmark
| | - R. E. Nielsen
- Psychiatry; Aalborg University Hospital; Aalborg Denmark
| | - V. J. Linde
- Psychiatry in the Capital Region of Denmark; Psychiatric Centre Copenhagen; Affective Ward 6203; Rigshospitalet; Copenhagen Denmark
| | - H. E. D. Knudsen
- District Psychiatry Center; Psychiatric Center; Hvidovre Denmark
| | - L. Skaarup
- Department of Affective Disorders; Aarhus University Hospital; Risskov Denmark
| | - P. Videbech
- Department of Affective Disorders; Aarhus University Hospital; Risskov Denmark
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Vigod S, Hussain-Shamsy N, Grigoriadis S, Howard LM, Metcalfe K, Oberlander TF, Schram C, Stewart DE, Taylor VH, Dennis CL. A patient decision aid for antidepressant use in pregnancy: study protocol for a randomized controlled trial. Trials 2016; 17:110. [PMID: 26923796 PMCID: PMC4770694 DOI: 10.1186/s13063-016-1233-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 02/16/2016] [Indexed: 12/28/2022] Open
Abstract
Background Many women with depression experience significant difficulty making a decision about whether or not to use antidepressant medication in pregnancy. Patient decision aids (PDAs) are tools that assist patients in making complex health decisions. PDAs can reduce decision-making difficulty and lead to better treatment outcomes. We describe the methods for a pilot randomized controlled trial of an interactive web-based PDA for women who are having difficulty deciding about antidepressant drug use in pregnancy. Methods/Design This is a pilot randomized controlled trial that aims to assess the feasibility of a larger, multi-center efficacy study. The PDA aims to help a woman: (1) understand why an antidepressant is being recommended, (2) be knowledgeable about potential benefits and risks of treatment and non-treatment with antidepressants, and (3) be clear about which benefits and risks are most important to her, with the goal of improving confidence in her decision-making. We include women aged 18 years or older who are: (1) planning a pregnancy or are pregnant (gestational age less than 30 weeks), (2) diagnosed with major depressive disorder, (3) deciding whether or not to use a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) antidepressant in pregnancy, and (4) having at least moderate decision-making difficulty as per a Decisional Conflict Scale (DCS) Score ≥25. Participants are randomized to receive the PDA or an informational resource sheet via a secure website, and have access to the stated allocation until their final study follow-up. The primary outcomes of the pilot study are feasibility of recruitment and retention, acceptability of the intervention, and adherence to the trial protocol. The primary efficacy outcome is DCS score at 4 weeks post randomization, with secondary outcomes including depressive and anxiety symptoms. Discussion Our PDA represents a key opportunity to optimize the decision-making process for women around antidepressants in pregnancy, leading to effective decision-making and optimizing improved maternal and child outcomes related to depression in pregnancy. The electronic nature of the PDA will facilitate keeping it up-to-date, and allow for widespread dissemination after efficacy is demonstrated. Trial registration This trial is registered on ClinicalTrials.Gov under the identifier NCT02308592 (first registered: 2 December 2014). Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1233-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Simone Vigod
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada. .,University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
| | - Neesha Hussain-Shamsy
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada.
| | - Sophie Grigoriadis
- University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. .,Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
| | - Louise M Howard
- King's College London, Institute of Psychiatry, Box P031, De Crespigny Park, London, SE5 8AF, United Kingdom.
| | - Kelly Metcalfe
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada. .,University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
| | - Tim F Oberlander
- Department of Pediatrics, University of British Columbia, Child and Family Research Institute, 4480 Oak St., Vancouver, BC, V6H 3V4, Canada.
| | - Carrie Schram
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada. .,University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
| | - Donna E Stewart
- University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. .,University Health Network, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.
| | - Valerie H Taylor
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada. .,University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
| | - Cindy-Lee Dennis
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON, M5S 1B2, Canada. .,University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
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Hanley GE, Brain U, Oberlander TF. Prenatal exposure to serotonin reuptake inhibitor antidepressants and childhood behavior. Pediatr Res 2015; 78:174-80. [PMID: 25897539 DOI: 10.1038/pr.2015.77] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Accepted: 01/19/2015] [Indexed: 11/09/2022]
Abstract
BACKGROUND Animal research has suggested that prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure causes increased anxiety-like behaviors in adulthood. We examined whether in utero SRI exposure influenced externalizing and internalizing behaviors in children at 3 y and again at 6 y of age. METHODS We recruited women in their second trimester of pregnancy from primary maternity care providers in Vancouver British Columbia, Canada. We compared the internalizing, externalizing, and the anxious and attention subscales of the internalizing behaviors scores of children exposed to SRIs and children not exposed to SRIs at age 3 and age 6. RESULTS We included 110 mother-child pairs (44 exposed to SRI and 66 not exposed). Higher levels of internalizing and anxious behaviors were reported in SRI exposed children at both 3 and 6 y of age compared with children who were not exposed (F = 7.52, P = 0.0072 and F = 7.91, P = 0.0058, respectively). The fully adjusted hierarchical regression models indicated a positive and significant relationship between SRI exposure and increased internalizing and anxious behaviors even when controlling for maternal mood during pregnancy, postpartum and childhood. CONCLUSION SRI exposure was associated with sustained higher levels of internalizing behaviors in early childhood even when controlling for maternal depression.
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Affiliation(s)
- Gillian E Hanley
- Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Ursula Brain
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Tim F Oberlander
- 1] Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada [2] Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract
AIMS Untreated perinatal depression and anxiety disorders are known to have significant negative impact on both maternal and fetal health. Dilemmas still remain regarding the use and safety of psychotropics in pregnant and lactating women suffering from perinatal depression and anxiety disorders. The aim of the current paper was to review the existing evidence base on the exposure and consequences of antidepressants, anxiolytics, and hypnotics in women during pregnancy and lactation and to make recommendations for clinical decision making in management of these cases. MATERIALS AND METHODS We undertook a bibliographic search of Medline/PubMed (1972 through 2014), Science Direct (1972 through 2014), Archives of Indian Journal of Psychiatry databases was done. References of retrieved articles, reference books, and dedicated websites were also checked. RESULTS AND CONCLUSIONS The existing evidence base is extensive in studying multiple outcomes of the antidepressant or anxiolytic exposure in neonates, and some of the findings appear conflicting. Selective serotonin reuptake inhibitors are the most researched antidepressants in pregnancy and lactation. The available literature is criticized mostly on the lack of rigorous well designed controlled studies as well as lacunae in the methodologies, interpretation of statistical information, knowledge transfer, and translation of information. Research in this area in the Indian context is strikingly scarce. Appropriate risk-benefit analysis of untreated mental illness versus medication exposure, tailor-made to each patient's past response and preference within in the context of the available evidence should guide clinical decision making.
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Affiliation(s)
- Daya Ram
- Director, Central Institute of Psychiatry, Ranchi, Jharkhand, India
| | - S. Gandotra
- Department of Psychiatry, Central Institute of Psychiatry, Kanke, Ranchi, Jharkhand, India
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Wen X, Meador KJ, Hartzema A. Antiepileptic drug use by pregnant women enrolled in Florida Medicaid. Neurology 2015; 84:944-50. [PMID: 25653296 PMCID: PMC4351665 DOI: 10.1212/wnl.0000000000001304] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Accepted: 11/03/2014] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE The study aims were to investigate secular trends in antiepileptic drug (AED) use in women during pregnancy, and to compare the use of first- and second-generation AEDs. METHODS Study participants consisted of female Florida Medicaid beneficiaries, older than 15 years, and pregnant within the time period 1999 to 2009. Fifteen AEDs were categorized into first and second generation of AEDs. Continuous use of AEDs was defined as at least 2 consecutive AED prescriptions totaling more than a 30-day supply. Polytherapy was defined as 2 or more AEDs continuously used for at least 30 overlapping days. Annual prevalence was estimated and compared. RESULTS We included 2,099 pregnant women who were enrolled in Florida Medicaid from 1999 to 2009 and exposed to AEDs during pregnancy. Although there were fluctuations, overall AED use in the study cohort did not increase from 2000 to 2009 (β ± standard error [SE]: -0.07 ± 0.06, p = 0.31). The use of first-generation AEDs decreased (β ± SE: -6.21 ± 0.47, p < 0.0001), whereas the use of second-generation AEDs increased (β ± SE: 6.27 ± 0.52, p < 0.0001) from 2000 to 2009. AED use in polytherapy did not change through the study period. Valproate use reduced from 23% to 8% in the study population (β ± SE: -1.61 ± 0.36, p = 0.0019), but this decrease was only for women receiving an AED for epilepsy and was not present for other indications. CONCLUSION The second-generation AEDs are replacing first-generation AEDs in both monotherapy and polytherapy. Valproate use has declined for epilepsy but not other indications. Additional changes in AED use are expected in future years.
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Affiliation(s)
- Xuerong Wen
- From the Department of Medicine (X.W.), and Department of Pharmaceutical Outcomes and Policy, College of Pharmacy (A.H.), University of Florida, Gainesville; and Department of Neurology & Neurological Sciences (K.J.M.), Stanford University, CA.
| | - Kimford J Meador
- From the Department of Medicine (X.W.), and Department of Pharmaceutical Outcomes and Policy, College of Pharmacy (A.H.), University of Florida, Gainesville; and Department of Neurology & Neurological Sciences (K.J.M.), Stanford University, CA
| | - Abraham Hartzema
- From the Department of Medicine (X.W.), and Department of Pharmaceutical Outcomes and Policy, College of Pharmacy (A.H.), University of Florida, Gainesville; and Department of Neurology & Neurological Sciences (K.J.M.), Stanford University, CA
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The Use of Antidepressants in Pregnancy: Focus on Maternal Risks. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2015; 37:56-63. [DOI: 10.1016/s1701-2163(15)30364-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Vigod S, Dennis CL, Daskalakis Z, Murphy K, Ray J, Oberlander T, Somerton S, Hussain-Shamsy N, Blumberger D. Transcranial direct current stimulation (tDCS) for treatment of major depression during pregnancy: study protocol for a pilot randomized controlled trial. Trials 2014; 15:366. [PMID: 25234606 PMCID: PMC4177439 DOI: 10.1186/1745-6215-15-366] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Accepted: 09/10/2014] [Indexed: 11/15/2022] Open
Abstract
Background Women with depression in pregnancy are faced with difficult treatment decisions. Untreated, antenatal depression has serious negative implications for mothers and children. While antidepressant drug treatment is likely to improve depressive symptoms, it crosses the placenta and may pose risks to the unborn child. Transcranial direct current stimulation is a focal brain stimulation treatment that improves depressive symptoms within 3 weeks of treatment by inducing changes to brain areas involved in depression, without impacting any other brain areas, and without inducing changes to heart rate, blood pressure or core body temperature. The localized nature of transcranial direct current stimulation makes it an ideal therapeutic approach for treating depression during pregnancy, although it has never previously been evaluated in this population. Methods/design We describe a pilot randomized controlled trial of transcranial direct current stimulation among women with depression in pregnancy to assess the feasibility of a larger, multicentre efficacy study. Women over 18 years of age and between 14 and 32 weeks gestation can be enrolled in the study provided they meet diagnostic criteria for a major depressive episode of at least moderate severity and have been offered but refused antidepressant medication. Participants are randomized to receive active transcranial direct current stimulation or a sham condition that is administered in 15 30-minute treatments over three weeks. Women sit upright during treatment and receive obstetrical monitoring prior to, during and after each treatment session. Depressive symptoms, treatment acceptability, and pregnancy outcomes are assessed at baseline (prior to randomization), at the end of each treatment week, every four weeks post-treatment until delivery, and at 4 and 12 weeks postpartum. Discussion Transcranial direct current stimulation is a novel therapeutic option for treating depression during pregnancy. This protocol allows for assessment of the feasibility of, acceptability of and adherence with a clinical trial protocol to administer this treatment to pregnant women with moderate to severe depression. Results from this pilot study will guide the development of a larger multicentre trial to definitively test the efficacy and safety of transcranial direct current stimulation for pregnant women with depression. Trial registration Clinical Trials Gov NCT02116127.
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Affiliation(s)
- Simone Vigod
- Women's College Hospital and Research Institute, 76 Grenville Street, Toronto, ON M5S 1B1, Canada.
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Epstein RA, Moore KM, Bobo WV. Treatment of nonpsychotic major depression during pregnancy: patient safety and challenges. DRUG HEALTHCARE AND PATIENT SAFETY 2014; 6:109-29. [PMID: 25258558 PMCID: PMC4173755 DOI: 10.2147/dhps.s43308] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
In pregnant women with major depression, the overarching goal of treatment is to achieve or maintain maternal euthymia, thus limiting both maternal and fetal exposure to the harmful effects of untreated or incompletely treated depression. However, the absence of uniformly effective therapies with guaranteed obstetric and fetal safety makes the treatment of major depression during pregnancy among the most formidable of clinical challenges. Clinicians and patients are still faced with conflicting data and expert opinion regarding the reproductive safety of antidepressants in pregnancy, as well as large gaps in our understanding of the effectiveness of most antidepressants and nonpharmacological alternatives for treating antenatal depression. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated maternal depression during pregnancy, the effectiveness of interventions for maternal depression during pregnancy, and potential obstetric, fetal, and neonatal risks associated with antenatal antidepressant use.
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Affiliation(s)
- Richard A Epstein
- Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Katherine M Moore
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
| | - William V Bobo
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
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Discontinuation of antidepressants during attempts to conceive: a pilot trial of cognitive behavioral therapy for the prevention of recurrent depression. J Clin Psychopharmacol 2014; 34:455-60. [PMID: 24911438 PMCID: PMC4959421 DOI: 10.1097/jcp.0000000000000158] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Many women discontinue antidepressants (ADs) when trying to conceive, although risk of depressive relapse is high. We examined the feasibility and potential clinical effect of cognitive behavioral therapy for the prevention of recurrence (CBT-PR) for women with a history of recurrent major depressive disorder (MDD) who planned to discontinue maintenance AD treatment for pregnancy. METHODS This was an open preliminary study of CBT-PR in women (N = 12) planning or early in pregnancy with remitted MDD on maintenance ADs with a plan to discontinue ADs for pregnancy. Participants received 12 sessions of CBT-PR during the acute phase and optional monthly booster sessions during follow-up. Participants were assessed monthly during the acute phase and then twice additionally during follow-up by an independent rater using mood scales (depression module of the Mini-International Neuropsychiatric Interview and Montgomery-Åsberg Depression Rating Scale); pregnancy status was also assessed. RESULTS Over the 24 weeks of the trial, 75% (n = 9) of participants did not restart ADs and did not relapse to depression. Of the 3 who reintroduced AD, 2 experienced a depressive relapse, whereas one did not meet full criteria for MDD. Adherence to the intervention was very good with all participants completing all therapy sessions and assessments. CONCLUSIONS Cognitive behavioral therapy for the prevention of recurrence seems feasible and may provide protection for women with recurrent depression on ADs who discontinue their medication while trying to conceive. The extent to which euthymia is sustainable with CBT-PR requires further study; the results of which may broaden treatment choices for women in anticipation of and during pregnancy.
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Hanley GE, Mintzes B. Patterns of psychotropic medicine use in pregnancy in the United States from 2006 to 2011 among women with private insurance. BMC Pregnancy Childbirth 2014; 14:242. [PMID: 25048574 PMCID: PMC4223368 DOI: 10.1186/1471-2393-14-242] [Citation(s) in RCA: 110] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Accepted: 07/08/2014] [Indexed: 02/01/2023] Open
Abstract
Background Psychiatric disorders are equally common during pregnancy as among non-pregnant women, and many of these conditions are treated with psychotropic medicines. Relatively little is known about patterns of use of many these agents during pregnancy, and specifically of how rates may have shifted during the last decade. We aimed to quantify the rate of pregnancy related exposures to categories of psychotropic medicines stratified according to the primary indication for use (antidepressants, antipsychotics, anxiolytics, and psychostimulants), trimester of pregnancy, trends over time and region, and indication for use. Methods We conducted a retrospective cohort study of pregnancies among women in the Truven Health MarketScan database (source population 70 million Americans), which captures person-specific clinical use and includes detailed information on filled prescriptions, hospitalizations and outpatient visits for all privately insured employees and their dependents. We classified psychotropic medicines of interest using ATC level 3 accordingly: antipsychotics (N05A); anxiolytics (N05B); antidepressants (N06A); psychostimulants, agents used for ADHD and cognitive enhancement (N06B). We also examined temporal and regional trends in use. Results We included 343,299 women who had a live birth between Jan 1, 2006 and Dec 31, 2011, of whom 10.3% were dispensed one or more psychotropic medicines during pregnancy. This rate varied from 6% to 15% between states. The rate of use of psychotropic medicines was relatively stable between 2006 and 2011. The most commonly used psychotropic medicines were selective serotonin reuptake inhibitors (5.1%) and benzodiazepine or benzodiazepine-like medicines (3.9%). Among psychotropic users, the most commonly associated psychiatric diagnosis was depression (25.0%), followed by anxiety disorders (24.4%). Approximately 1.6% of women used more than one category of psychotropic medicine in pregnancy, most commonly an antidepressant and an anxiolytic medicine (1.2%). Conclusions Given this relatively high rate of use, the lack of evidence that the most frequently used medications improve birth outcomes and the safety concerns associated with both early and late pregnancy use for many frequently-used medications, there is a need for further study of factors driving psychotropic medication use during pregnancy.
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Affiliation(s)
| | - Barbara Mintzes
- School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
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Ornoy A, Koren G. Selective serotonin reuptake inhibitors in human pregnancy: on the way to resolving the controversy. Semin Fetal Neonatal Med 2014; 19:188-94. [PMID: 24321501 DOI: 10.1016/j.siny.2013.11.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
There has been an increase in the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. However, in the last 10 years, in spite of a vast literature regarding use in pregnancy there seems to be some confusion as to the possible risk of these drugs, especially related to cardiovascular anomalies. In addition, there are data on developmental follow-up studies that raise the question of possible slight developmental and neurobehavioral problems. The purpose of the present review is therefore to critically summarize the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. Although most studies have not shown an increase in the overall risk of major malformations, several have suggested that the use of SSRIs may be associated with a small increased risk for cardiovascular malformations. However, new compelling evidence shows that this apparent increased risk occurs also in women with untreated depression, highlighting the probable ascertainment bias involved in many of these studies. Persistent pulmonary hypertension of the newborn (PPHN) has also been described with an absolute risk of <1%; however, here too, higher rates were described among offspring of women with untreated depression. Poor neonatal adaptation has been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Of the few postnatal developmental follow-up studies, there are no significant developmental problems. The literature on SSRIs in pregnancy is somewhat confusing but when analysing all prospective cohort data there seems to be no demonstrable increase in the rate of major anomalies or developmental disorders. When evaluating the risk/benefit ratio of SSRI treatment in pregnancy, the risk associated with treatment discontinuation - e.g. higher frequency of relapse, increased risk of preterm delivery and postpartum depression - appear to outweigh the potential, unproven risks of treatment. Moreover, maternal depression may negatively affect the child's development, emphasizing the importance of prevention by appropriate treatment during pregnancy with the least minimal effective dose.
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Affiliation(s)
- Asher Ornoy
- Hebrew University Hadassah Medical School, Jerusalem, Israel; Israeli Teratology Information Service, Israel Ministry of Health, Jerusalem, Israel.
| | - Gideon Koren
- Israeli Teratology Information Service, Israel Ministry of Health, Jerusalem, Israel; Motherisk Program, Division of Clinical Pharmacology/Toxicology, Department of Pediatrics, Hospital for Sick Children, Toronto, Canada
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Huybrechts KF, Sanghani RS, Avorn J, Urato AC. Preterm birth and antidepressant medication use during pregnancy: a systematic review and meta-analysis. PLoS One 2014; 9:e92778. [PMID: 24671232 PMCID: PMC3966829 DOI: 10.1371/journal.pone.0092778] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 02/25/2014] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Preterm birth is a major contributor to neonatal morbidity and mortality and its rate has been increasing over the past two decades. Antidepressant medication use during pregnancy has also been rising, with rates up to 7.5% in the US. The objective was to systematically review the literature to determine the strength of the available evidence relating to a possible association between antidepressant use during pregnancy and preterm birth. METHODS We conducted a computerized search in PUBMED, MEDLINE and PsycINFO through September 2012, supplemented with a manual search of reference lists, to identify original published research on preterm birth rates in women taking antidepressants during pregnancy. Data were independently extracted by two reviewers, and absolute and relative risks abstracted or calculated. Our a priori design was to group studies by level of confounding adjustment and by timing of antidepressant use during pregnancy; we used random-effects models to calculate summary measures of effect. RESULTS Forty-one studies met inclusion criteria. Pooled adjusted odds ratios (95% CI) were 1.53 (1.40-1.66) for antidepressant use at any time and 1.96 (1.62-2.38) for 3rd trimester use. Controlling for a diagnosis of depression did not eliminate the effect. There was no increased risk [1.16 (0.92-1.45)] in studies that identified patients based on 1st trimester exposure. Sensitivity analyses demonstrated unmeasured confounding would have to be strong to account for the observed association. DISCUSSION Published evidence is consistent with an increased risk of preterm birth in women taking antidepressants during the 2nd and 3rd trimesters, although the possibility of residual confounding cannot be completely ruled out.
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Affiliation(s)
- Krista F. Huybrechts
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail:
| | - Reesha Shah Sanghani
- Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tennessee, United States of America
| | - Jerry Avorn
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Adam C. Urato
- MetroWest Medical Center, Tufts University School of Medicine, Framingham, Massachusetts, United States of America
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Bourke CH, Stowe ZN, Owens MJ. Prenatal antidepressant exposure: clinical and preclinical findings. Pharmacol Rev 2014; 66:435-65. [PMID: 24567054 PMCID: PMC3973612 DOI: 10.1124/pr.111.005207] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Pharmacological treatment of any maternal illness during pregnancy warrants consideration of the consequences of the illness and/or medication for both the mother and unborn child. In the case of major depressive disorder, which affects up to 10-20% of pregnant women, the deleterious effects of untreated depression on the offspring can be profound and long lasting. Progress has been made in our understanding of the mechanism(s) of action of antidepressants, fetal exposure to these medications, and serotonin's role in development. New technologies and careful study designs have enabled the accurate sampling of maternal serum, breast milk, umbilical cord serum, and infant serum psychotropic medication concentrations to characterize the magnitude of placental transfer and exposure through human breast milk. Despite this progress, the extant clinical literature is largely composed of case series, population-based patient registry data that are reliant on nonobjective means and retrospective recall to determine both medication and maternal depression exposure, and limited inclusion of suitable control groups for maternal depression. Conclusions drawn from such studies often fail to incorporate embryology/neurotransmitter ontogeny, appropriate gestational windows, or a critical discussion of statistically versus clinically significant. Similarly, preclinical studies have predominantly relied on dosing models, leading to exposures that may not be clinically relevant. The elucidation of a defined teratological effect or mechanism, if any, has yet to be conclusively demonstrated. The extant literature indicates that, in many cases, the benefits of antidepressant use during pregnancy for a depressed pregnant woman may outweigh potential risks.
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Teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses. Adv Pharmacol Sci 2014; 2014:132034. [PMID: 24527029 PMCID: PMC3914285 DOI: 10.1155/2014/132034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 11/25/2013] [Accepted: 12/16/2013] [Indexed: 11/26/2022] Open
Abstract
Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses. Method. Forty-two pregnant rats were divided into seven groups, randomly. The first group received 0.5 mL of normal saline as the control. The second and third groups received fluoxetine at doses of 9 mg/kg and 18 mg/kg, respectively. Olanzapine was injected at 3 mg/kg and 6 mg/kg to the fourth and fifth groups, respectively. The sixth group received 9 mg/kg fluoxetine and 3 mg/kg olanzapine. Finally, the seventh group was administrated with fluoxetine and olanzapine at 18 mg/kg and 6 mg/kg, respectively. Drugs were injected intraperitoneally between day eight and day 15 of the pregnancy. On the 17th day of pregnancy, the fetuses were removed and micro-/macroscopically studied. Results. Fetuses of rats receiving high doses of these drugs showed a significant rate of cleft palate development, premature eyelid opening and torsion anomalies, compared to the control group (P ≤ 0.01). It is concluded that these drugs can lead to teratogenicity, so their concomitant use during pregnancy should be avoided, or if necessary their doses must be decreased.
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Giudici V, Pogliani L, Cattaneo D, Dilillo D, Zuccotti GV. Serotonin reuptake inhibitors in pregnancy: can genes help us in predicting neonatal adverse outcome? BIOMED RESEARCH INTERNATIONAL 2014; 2014:276918. [PMID: 24524073 PMCID: PMC3913519 DOI: 10.1155/2014/276918] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 12/22/2013] [Accepted: 12/23/2013] [Indexed: 02/07/2023]
Abstract
Lots has been written on use of SSRI during pregnancy and possible short and long term negative outcomes on neonates. the literature so far has described a various field of peripartum illness related to SSRI exposure during foetal life, such as increased incidence of low birth weight, respiratory distress, persistent pulmonary hypertension, poor feeding, and neurobehavioural disease. We know that different degrees of outcomes are possible, and not all the newborns exposed to SSRIs during pregnancy definitely will develop a negative outcome. So far, still little is known about the possible etiologic mechanism that could not only explain the adverse neonatal effects but also the degree of clinical involvement and presentation in the early period after birth. Pharmacogenetics and moreover pharmacogenomics, the study of specific genetic variations and their effect on drug response, are not widespread. This review describes possible relationship between SSRIs pharmacogenetics and different neonatal outcomes and summarizes the current pharmacogenetic inquiries in relation to maternal-foetal environment.
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Affiliation(s)
- Valentina Giudici
- Department of Paediatrics, Hospital Luigi Sacco, Via GB Grassi 74, 20157 Milan, Italy
| | - Laura Pogliani
- Department of Paediatrics, Hospital Luigi Sacco, Via GB Grassi 74, 20157 Milan, Italy
| | - Dario Cattaneo
- Unit of Clinical Pharmacology, Hospital Luigi Sacco, Via GB Grassi 74, 20157 Milan, Italy
| | - Dario Dilillo
- Department of Paediatrics, Hospital Luigi Sacco, Via GB Grassi 74, 20157 Milan, Italy
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Ramoz LL, Patel-Shori NM. Recent changes in pregnancy and lactation labeling: retirement of risk categories. Pharmacotherapy 2014; 34:389-95. [PMID: 24390829 DOI: 10.1002/phar.1385] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The rapid development and increased availability of novel pharmacologic therapies and pharmaceutical products has amplified the potential for drug exposure during pregnancy. Many drugs are beneficial for disease state management during pregnancy and provide significant fetal and maternal health benefits. However, a paucity of safety data combined with the imprecision of the current risk category system renders risk versus benefit assessment difficult. In response to decades of criticism, the U.S. Food and Drug Administration (FDA) is implementing a new pregnancy and lactation labeling rule designed to improve risk versus benefit assessment of drugs used in pregnant and nursing mothers. These recommendations will provide clear and detailed information for both patients and health care providers, and they will include three main categories: risk summary, clinical considerations, and data. The new labeling rules remove the previous letter risk categorization system (A, B, C, D, X). In this review, we summarize the upcoming FDA labeling changes and discuss their potential consequences on clinical practice.
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Affiliation(s)
- Leda L Ramoz
- Temple University School of Pharmacy, Philadelphia, Pennsylvania
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Hanley GE, Oberlander TF. The effect of perinatal exposures on the infant: Antidepressants and depression. Best Pract Res Clin Obstet Gynaecol 2014; 28:37-48. [DOI: 10.1016/j.bpobgyn.2013.09.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Revised: 07/16/2013] [Accepted: 09/06/2013] [Indexed: 10/26/2022]
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Yonkers KA, Blackwell KA, Glover J, Forray A. Antidepressant use in pregnant and postpartum women. Annu Rev Clin Psychol 2013; 10:369-92. [PMID: 24313569 DOI: 10.1146/annurev-clinpsy-032813-153626] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Women in their reproductive years are at risk of experiencing depressive and anxiety disorders. As such, it is likely that pregnant women will undergo treatment with antidepressants. We review the risk of adverse birth outcomes and neonatal complications subsequent to antidepressant use in pregnancy. An inconsistent literature shows that antidepressant exposure is associated with shortened gestations and diminished fetal growth; these effects are small. Transitory neonatal signs are seen in some neonates after exposure to antidepressants in utero. No specific pattern of malformations has been consistently associated with antidepressants, with the possible exception of paroxetine and cardiac malformations. There is inconclusive evidence of a link between antidepressants in late pregnancy and persistent pulmonary hypertension in the newborn. Extensive study finds that antidepressants cannot be considered major teratogens. It is likely that confounding factors contribute to a number of the adverse effects found to be associated with antidepressant use in pregnancy.
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Myles N, Newall H, Ward H, Large M. Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Aust N Z J Psychiatry 2013; 47:1002-12. [PMID: 23761574 DOI: 10.1177/0004867413492219] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
CONTEXT It has been suggested that the commonly prescribed class of antidepressants selective serotonin reuptake inhibitors (SSRIs) are associated with birth defects. However, the teratogenic effect of individual SSRIs has not been previously compared using meta-analysis. OBJECTIVE To determine the strength of the association between individual SSRIs and major, minor, and cardiac malformation among infants born to women taking these medications. DATA SOURCES Electronic search of CINAHL, EMBASE, Medline, PsycINFO, and ISI Web of Science using the search terms (SSRI OR antidepressant) AND (obstetric outcome OR malformation OR birth outcome OR teratogen), supplemented by manual searching of published references and requests of primary researchers for unpublished data. STUDY SELECTION There were 115 studies identified by electronic search and reviewed in full text, which yielded 16 papers reporting 36 data samples for major malformations, nine papers reporting 26 data samples for cardiac malformations, and four papers reporting seven data samples for minor malformations. DATA SYNTHESIS Fluoxetine (OR 1.14, 95% CI 1.01-1.30) and paroxetine (OR 1.29, 95% CI 1.11-1.49) were associated with increased risk of major malformations. Paroxetine was associated with increased risk of cardiac malformations (OR 1.44, 95% CI 1.12-1.86). Sertraline and citalopram were not significantly associated with congenital malformation. Between-sample heterogeneity was low and a range of methodological considerations had no significant impact on effect size. There was little evidence of publication bias. CONCLUSIONS Fluoxetine and paroxetine should be avoided in the first trimester and among those at risk of an unplanned pregnancy.
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Affiliation(s)
- Nicholas Myles
- 1Department of Medicine, Queen Elizabeth Hospital, Woodville South, Australia
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Ray S, Stowe ZN. The use of antidepressant medication in pregnancy. Best Pract Res Clin Obstet Gynaecol 2013; 28:71-83. [PMID: 24211026 DOI: 10.1016/j.bpobgyn.2013.09.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 09/06/2013] [Accepted: 09/27/2013] [Indexed: 01/08/2023]
Abstract
The use of antidepressant medications during pregnancy has stimulated much professional and public debate. As a consequence, considerable data on the reproductive safety of antidepressants has been generated that exceeds the available information for most, if not all, other classes of medications that may be used in the perinatal period. Despite progress to date, definitive conclusions are limited by the methodological issues inherent to clinical research involving illness versus treatment effects in pregnancy. A notable shortcoming is the limited discussion of statistically significant (a mathematical determination) versus clinically significant (incorporation of incidence and effect sizes into practical relevance). Research emphasises completing an individualised 'risk-benefit' assessment, which is a laudable goal but falls short in providing succinct practical guidelines that includes the key educational points for patients. In this chapter, we focus on areas in which the preponderance of data are consistent, and there is concordance with the preclinical literature to generate a practical approach for antidepressant use in pregnancy.
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Affiliation(s)
- Shona Ray
- Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Zachary N Stowe
- Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pediatrics and Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Psychiatric Research Institute, University of Arkansas for Medical Sciences, 4301 W. Markham Street 843, Little Rock, AR 72205-7199, USA.
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Källén B, Borg N, Reis M. The use of central nervous system active drugs during pregnancy. Pharmaceuticals (Basel) 2013; 6:1221-86. [PMID: 24275849 PMCID: PMC3817603 DOI: 10.3390/ph6101221] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 09/10/2013] [Accepted: 09/25/2013] [Indexed: 12/03/2022] Open
Abstract
CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson's disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996-2011) are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found.
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Affiliation(s)
- Bengt Källén
- Tornblad Institute, Lund University, Biskopsgatan 7, Lund SE-223 62, Sweden
| | - Natalia Borg
- Department of Statistics, Monitoring and Analyses, National Board of Health and Welfare, Stockholm SE-106 30, Sweden; E-Mail:
| | - Margareta Reis
- Department of Medical and Health Sciences, Clinical Pharmacology, Linköping University, Linköping SE-581 85, Sweden; E-Mail:
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Kieviet N, Dolman KM, Honig A. The use of psychotropic medication during pregnancy: how about the newborn? Neuropsychiatr Dis Treat 2013; 9:1257-66. [PMID: 24039427 PMCID: PMC3770341 DOI: 10.2147/ndt.s36394] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Infants are at risk of developing symptoms of Poor Neonatal Adaptation (PNA) after exposure to psychotropic drugs in utero. Such symptoms are largely similar after exposure to antidepressants, antipsychotics and benzodiazepines and consist of mostly mild neurologic, autonomic, respirator and gastro-intestinal abnormalities. Most symptoms develop within 48 hours after birth and last for 2-6 days. After exposure to Selective Serotonin Reuptake Inhibitors (SSRIs), mirtazapine or venlafaxine in utero, breastfeeding is presumably protective for development of PNA. The dosage of antidepressants does not seem to be related to the risk of PNA. In order to objectify possible symptoms of PNA, observation of mother and child at the maternity ward is advisable. If PNA symptoms do not occur, an observation period of 48-72 hours is sufficient. This applies to all types of psychotropic drugs. When PNA symptoms are present it is advisable to observe the infant until the symptoms are fully resolved. Observation can be performed by trained nurses using the Finnegan scoring list. This observation list should be administered every 8 hours. Interpretation of the scores should be carried out by a paediatrician. In most cases symptoms are non-specific. Therefore other diagnoses, such as infection or neurologic problems, have to be excluded. When there is any doubt on possible intoxications during pregnancy, toxicological urine screening is indicated. Most cases of PNA are mild, of short duration and self-limiting without need for treatment. Supporting measures such as frequent small feedings, swaddling and increase of skin to skin contact with the mother is usually sufficient. In case of severe PNA it is advised to admit the infant to the Neonatal Care Unit (NCU). Phenobarbital is a safe therapeutic option. There seem to be no major long term effects; however, additional studies are necessary in order to draw definite conclusions.
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Affiliation(s)
- Noera Kieviet
- Department of Paediatrics, Amsterdam, The Netherlands
| | | | - Adriaan Honig
- Department of Psychiatry, Psychiatry Obstetrics Paediatrics Expert Center, Sint Lucas Andreas Hospital, Amsterdam, The Netherlands
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