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Midwifery Cohort study
Late pregnancy use of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors is associated with increased risk of postpartum haemorrhage 10.1136/eb-2013-101595
Cande V Ananth, Alexander M Friedman Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, New York, USA Correspondence to: Professor Cande V Ananth, Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY 10032, USA; [email protected]
Commentary on: Palmsten K, Hernández-Díaz S, Huybrechts KF, et al. Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the USA. BMJ 2013;347:f4877.
Implications for research and practice ▪ Use of antidepressant medication is associated with increased risk for postpartum haemorrhage (PPH). ▪ Further research is needed to establish a causal role between antidepressant medication use and PPH. ▪ Clinicians should be aware of possible increased risk of postpartum haemorrhage when treating depression during pregnancy.
Context Antidepressant medications are commonly used to manage psychiatric conditions in pregnancy. While extensive research related to teratogenesis and neonatal outcomes has been undertaken,1 there is relatively few data related to maternal obstetrical outcomes. Research from other specialties suggests that serotonin reuptake inhibitors (SSRIs) may be associated with increased risk of hospitalisation for bleeding and acute upper gastrointestinal bleeding.2 3 Prior research on antidepressants and obstetric haemorrhage is limited.4 5 Palmsten and colleagues set out to determine whether antidepressant medication use is associated with increased risk for PPH.
Methods This retrospective cohort evaluated 106 000 pregnant women from 2000 to 2007 with a diagnosis of mood or anxiety disorder. Using pharmacy dispensing data, women were classified based on whether they were prescribed antidepressant medications currently or had used them recently or in the past. Antidepressants were classified based on serotonin reuptake inhibition. Covariates included risk factors for PPH (the primary outcome, classified based on International Classification of Diseases (ICD)-9 coding), demographic factors and psychiatric diagnoses, among other factors. A number of sensitivity analyses were performed to assess the robustness of their conclusions.
76
Evid Based Nurs July 2014 | volume 17 | number 3 |
Findings In this cohort, the use of SSRIs or non-SSRIs was associated with an approximate 40% increased risk of PPH in an analysis adjusted for risk factors. Risk for PPH was 2.8% for women with mood and/or anxiety diagnoses on no medications compared to 4% for women currently using SSRIs and 3.8% for women currently using non-SSRIs. The risk for recent users (up to 30 days before delivery date) was 3.2% for SSRIs and 3.1% for non-SSRIs.
Commentary Obstetric haemorrhage is a leading cause of maternal mortality and severe morbidity in the USA.6 Identification of further clinical risk factors for PPH could lead to novel clinical interventions and research initiatives to reduce adverse outcomes from this complication. This study demonstrates an association between PPH and medication that is relatively commonly prescribed in pregnancy. Several aspects of the methodology in this study enhance the validity of the findings: first, the control population is composed of women with similar psychiatric diagnoses not on antidepressant medications, minimising the potential for selection bias. Second, a temporal relationship between the exposure ( pharmacy dispensing the medication) and the outcome (PPH status) was established. Third, the authors incorporated adjustment for obesity (data unavailable in the nationwide Medicaid Analytic eXtract database) as an ecological construct in their regression models. This counteracted the role unobserved confounding and selection bias can play in the exposure–outcome relationship of observational epidemiology. Fourth, the authors confirm their associations through a high-dimensional propensity score method. This latter analysis is particularly well-suited when both (unobserved) confounders and selection bias are suspected to distort the associations. The findings from this study add considerably to limited prior research on this subject, which has found similar associations despite methodological shortcomings.4 5 The magnitude of increased haemorrhage risk in relation to serotonin exposure demonstrated in this study is clinically relevant. Further research both from an epidemiological and basic science standpoint is needed to more fully support a causal relationship between SSRIs, SNRIs and haemorrhage. Similarly rigorous methodology in other populations would validate the associations found in this well-designed study. While the benefits of antidepressants may outweigh the relatively small attributable maternal and neonatal risks for many women, clinicians should be aware of a modestly increased risk for this serious adverse obstetric outcome. Competing interests None.
References 1. Patil AS, Kuller JA, Rhee EH. Antidepressants in pregnancy: a review of commonly prescribed medications. Obstet Gynecol Surv 2011;66:777–87. 2. Meijer WE, Heerdink ER, Nolen WA, et al. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Intern Med 2004;164:2367–70. 3. Van Walraven C, Mamdani MM, Wells PS, et al. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ 2001;323:655–8. 4. Salkeld E, Ferris LE, Juurlink DN. The risk of postpartum haemmorhage with selective serotonin reuptake inhibitors and other antidepressants. J Clin Psychopharmacol 2008;28:230–4. 5. Reis M, Kallen B. Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med 2010;40:1723–33. 6. Callaghan WM. Overview of maternal mortality in the United States. Semin Perinatol 2012;36:2–6.
Downloaded from http://ebn.bmj.com/ on March 19, 2015 - Published by group.bmj.com
Late pregnancy use of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors is associated with increased risk of postpartum haemorrhage Cande V Ananth and Alexander M Friedman Evid Based Nurs 2014 17: 76 originally published online November 28, 2013
doi: 10.1136/eb-2013-101595 Updated information and services can be found at: http://ebn.bmj.com/content/17/3/76
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This article cites 6 articles, 1 of which you can access for free at: http://ebn.bmj.com/content/17/3/76#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Midwifery (38) Pregnancy (240) Drugs: CNS (not psychiatric) (83) Stroke (216) Child and adolescent psychiatry (154) Child and adolescent psychiatry (paedatrics) (154) Drugs: musculoskeletal and joint diseases (150) Reproductive medicine (321) Child health (440) Anxiety disorders (including OCD and PTSD) (11) GI bleeding (8) Health policy (184) Health service research (156) Health education (323) Obesity (nutrition) (94) Obesity (public health) (94)
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Downloaded from http://ebn.bmj.com/ on March 19, 2015 - Published by group.bmj.com
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Midwifery Cohort study
Late pregnancy use of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors is associated with increased risk of postpartum haemorrhage 10.1136/eb-2013-101595
Cande V Ananth, Alexander M Friedman Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, New York, USA Correspondence to: Professor Cande V Ananth, Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY 10032, USA; [email protected]
Commentary on: Palmsten K, Hernández-Díaz S, Huybrechts KF, et al. Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the USA. BMJ 2013;347:f4877.
Implications for research and practice ▪ Use of antidepressant medication is associated with increased risk for postpartum haemorrhage (PPH). ▪ Further research is needed to establish a causal role between antidepressant medication use and PPH. ▪ Clinicians should be aware of possible increased risk of postpartum haemorrhage when treating depression during pregnancy.
Context Antidepressant medications are commonly used to manage psychiatric conditions in pregnancy. While extensive research related to teratogenesis and neonatal outcomes has been undertaken,1 there is relatively few data related to maternal obstetrical outcomes. Research from other specialties suggests that serotonin reuptake inhibitors (SSRIs) may be associated with increased risk of hospitalisation for bleeding and acute upper gastrointestinal bleeding.2 3 Prior research on antidepressants and obstetric haemorrhage is limited.4 5 Palmsten and colleagues set out to determine whether antidepressant medication use is associated with increased risk for PPH.
Methods This retrospective cohort evaluated 106 000 pregnant women from 2000 to 2007 with a diagnosis of mood or anxiety disorder. Using pharmacy dispensing data, women were classified based on whether they were prescribed antidepressant medications currently or had used them recently or in the past. Antidepressants were classified based on serotonin reuptake inhibition. Covariates included risk factors for PPH (the primary outcome, classified based on International Classification of Diseases (ICD)-9 coding), demographic factors and psychiatric diagnoses, among other factors. A number of sensitivity analyses were performed to assess the robustness of their conclusions.
76
Evid Based Nurs July 2014 | volume 17 | number 3 |
Findings In this cohort, the use of SSRIs or non-SSRIs was associated with an approximate 40% increased risk of PPH in an analysis adjusted for risk factors. Risk for PPH was 2.8% for women with mood and/or anxiety diagnoses on no medications compared to 4% for women currently using SSRIs and 3.8% for women currently using non-SSRIs. The risk for recent users (up to 30 days before delivery date) was 3.2% for SSRIs and 3.1% for non-SSRIs.
Commentary Obstetric haemorrhage is a leading cause of maternal mortality and severe morbidity in the USA.6 Identification of further clinical risk factors for PPH could lead to novel clinical interventions and research initiatives to reduce adverse outcomes from this complication. This study demonstrates an association between PPH and medication that is relatively commonly prescribed in pregnancy. Several aspects of the methodology in this study enhance the validity of the findings: first, the control population is composed of women with similar psychiatric diagnoses not on antidepressant medications, minimising the potential for selection bias. Second, a temporal relationship between the exposure ( pharmacy dispensing the medication) and the outcome (PPH status) was established. Third, the authors incorporated adjustment for obesity (data unavailable in the nationwide Medicaid Analytic eXtract database) as an ecological construct in their regression models. This counteracted the role unobserved confounding and selection bias can play in the exposure–outcome relationship of observational epidemiology. Fourth, the authors confirm their associations through a high-dimensional propensity score method. This latter analysis is particularly well-suited when both (unobserved) confounders and selection bias are suspected to distort the associations. The findings from this study add considerably to limited prior research on this subject, which has found similar associations despite methodological shortcomings.4 5 The magnitude of increased haemorrhage risk in relation to serotonin exposure demonstrated in this study is clinically relevant. Further research both from an epidemiological and basic science standpoint is needed to more fully support a causal relationship between SSRIs, SNRIs and haemorrhage. Similarly rigorous methodology in other populations would validate the associations found in this well-designed study. While the benefits of antidepressants may outweigh the relatively small attributable maternal and neonatal risks for many women, clinicians should be aware of a modestly increased risk for this serious adverse obstetric outcome. Competing interests None.
References 1. Patil AS, Kuller JA, Rhee EH. Antidepressants in pregnancy: a review of commonly prescribed medications. Obstet Gynecol Surv 2011;66:777–87. 2. Meijer WE, Heerdink ER, Nolen WA, et al. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Intern Med 2004;164:2367–70. 3. Van Walraven C, Mamdani MM, Wells PS, et al. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ 2001;323:655–8. 4. Salkeld E, Ferris LE, Juurlink DN. The risk of postpartum haemmorhage with selective serotonin reuptake inhibitors and other antidepressants. J Clin Psychopharmacol 2008;28:230–4. 5. Reis M, Kallen B. Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med 2010;40:1723–33. 6. Callaghan WM. Overview of maternal mortality in the United States. Semin Perinatol 2012;36:2–6.
Downloaded from http://ebn.bmj.com/ on March 19, 2015 - Published by group.bmj.com
Late pregnancy use of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors is associated with increased risk of postpartum haemorrhage Cande V Ananth and Alexander M Friedman Evid Based Nurs 2014 17: 76 originally published online November 28, 2013
doi: 10.1136/eb-2013-101595 Updated information and services can be found at: http://ebn.bmj.com/content/17/3/76
These include:
References Email alerting service
Topic Collections
This article cites 6 articles, 1 of which you can access for free at: http://ebn.bmj.com/content/17/3/76#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Articles on similar topics can be found in the following collections Midwifery (38) Pregnancy (240) Drugs: CNS (not psychiatric) (83) Stroke (216) Child and adolescent psychiatry (154) Child and adolescent psychiatry (paedatrics) (154) Drugs: musculoskeletal and joint diseases (150) Reproductive medicine (321) Child health (440) Anxiety disorders (including OCD and PTSD) (11) GI bleeding (8) Health policy (184) Health service research (156) Health education (323) Obesity (nutrition) (94) Obesity (public health) (94)
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Downloaded from http://ebn.bmj.com/ on March 19, 2015 - Published by group.bmj.com
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
