Letters COMMENT & RESPONSE
American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31(5):403-413.
A Leap of Faith in Antidepressant Treatment?
4. Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJA. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010;67(10):1012-1024.
To the Editor The Ross et al systematic review1 of pregnancy and delivery outcomes following exposure to antidepressants in pregnancy found only harm, not benefit, associated with antidepressant exposure. Some effects were attenuated after controlling for depression in pregnancy; in other cases, the association with a negative health outcome remained as strong. Ross et al describe this harm as being of small magnitude and highlight the need to weigh these adverse events against the harm from untreated depression. This recommendation is puzzling, given that their systematic review fails to demonstrate that antidepressant treatment mitigates any harm associated with depression. Of the 3 references cited to support the harmful effects of untreated depression, 2 are clinical guidelines that fail to provide original data.2,3 A third is a systematic review of selected birth outcomes among women with depression in pregnancy.4 Five of the 29 included studies controlled for antidepressant treatment, representing 9.8% of included patients. Three more studies (3% of patients) were of lowincome women in developing countries, where antidepressant treatment is less likely but poverty and lack of access to adequate health care would be expected to strongly affect health outcomes. Thus to characterize these results as indicating that untreated depression leads to worse outcomes than antidepressant treatment in pregnancy requires a leap of faith. Additionally, magnitude of effect and clinical significance were not considered. Solutions do exist that address both harm from antidepressant use and the need to provide effective care to pregnant women: nondrug depression treatments such as psychotherapy, cognitive behavioral therapy, or exercise. Barbara Mintzes, PhD Author Affiliation: School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. Corresponding Author: Barbara Mintzes, PhD, School of Population and Public Health, University of British Columbia, 2176 Health Sciences Mall, Ste 307, Vancouver, BC V6T 1Z3, Canada ([email protected]). Conflict of Interest Disclosures: None reported. 1. Ross LE, Grigoriadis S, Mamisashvili L, et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry. 2013;70(4):436-443. 2. ACOG Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020. 3. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the jamapsychiatry.com
Antidepressant Medication and Spontaneous Abortion: “No Significant Association”? Clinically Significant Association! To the Editor Ross et al reported “no significant association b e t we e n a nt i d e p r e s s a nt m e d i c at i o n ex p o s u r e a n d spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055)” (italics, our emphasis). 1(p436) Confidence intervals provide inferential evidence about the range of plausible values for the population parameter of interest.2,3 A simple examination of the values covered by the reported 95% CI from 0.99 to 2.17 suffices to show that an association between the exposure to antidepressant medic ation and spontaneous abortion is likely and that results are nonnegligible from a clinical perspective. Results are not statistically significant but the differences are of clinical interest. Elsewhere Ross et al were careful enough to nuance their other statements regarding significance (“…were statistically significantly associated with”). Their claim regarding spontaneous abortion is even more puzzling given that they acknowledged the “importance of considering clinical significance” of the results. Note for example that one of the reviews cited by Ross et al reported point estimates and 95% CI for summary relative risks for association between depression and preterm birth (PTB) of 1.39 (1.19-1.61) and for low birth weight (LBW), 1.49 (1.25-1.77) for studies using a categorical depression measure and 1.03 (1.00-1.06) for PTB and 1.04 (0.99-1.09) for LBW for studies using a continuous depression measure. These outcomes led Grote et al4 to conclude that women with depression during pregnancy are at increased risk for PTB and LBW. It is hard to understand why these results were interpreted as providing evidence of association between depression and PTB and LBW but quantitative results reported by Ross et al were interpreted as providing evidence of no association between use of antidepressant medication and spontaneous abortion. In a recent review, Hackshaw et al5 reported odds ratios and 95% CI for association between maternal smoking and birth defects (including cardiovascular defects [OR, 1.09; 95% CI, 1.02-1.17] and missing/extra digits [OR, 1.18, 95% CI, 0.99-1.41]) and suggested that information about birth defects that are associated with maternal smoking should be included in public health educational materials. What, then, about public education regarding the risk of spontaneJAMA Psychiatry December 2013 Volume 70, Number 12
Copyright 2013 American Medical Association. All rights reserved.
Downloaded From: http://archpsyc.jamanetwork.com/ by a Monash University Library User on 11/24/2015
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American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31(5):403-413.
A Leap of Faith in Antidepressant Treatment?
4. Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJA. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010;67(10):1012-1024.
To the Editor The Ross et al systematic review1 of pregnancy and delivery outcomes following exposure to antidepressants in pregnancy found only harm, not benefit, associated with antidepressant exposure. Some effects were attenuated after controlling for depression in pregnancy; in other cases, the association with a negative health outcome remained as strong. Ross et al describe this harm as being of small magnitude and highlight the need to weigh these adverse events against the harm from untreated depression. This recommendation is puzzling, given that their systematic review fails to demonstrate that antidepressant treatment mitigates any harm associated with depression. Of the 3 references cited to support the harmful effects of untreated depression, 2 are clinical guidelines that fail to provide original data.2,3 A third is a systematic review of selected birth outcomes among women with depression in pregnancy.4 Five of the 29 included studies controlled for antidepressant treatment, representing 9.8% of included patients. Three more studies (3% of patients) were of lowincome women in developing countries, where antidepressant treatment is less likely but poverty and lack of access to adequate health care would be expected to strongly affect health outcomes. Thus to characterize these results as indicating that untreated depression leads to worse outcomes than antidepressant treatment in pregnancy requires a leap of faith. Additionally, magnitude of effect and clinical significance were not considered. Solutions do exist that address both harm from antidepressant use and the need to provide effective care to pregnant women: nondrug depression treatments such as psychotherapy, cognitive behavioral therapy, or exercise. Barbara Mintzes, PhD Author Affiliation: School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. Corresponding Author: Barbara Mintzes, PhD, School of Population and Public Health, University of British Columbia, 2176 Health Sciences Mall, Ste 307, Vancouver, BC V6T 1Z3, Canada ([email protected]). Conflict of Interest Disclosures: None reported. 1. Ross LE, Grigoriadis S, Mamisashvili L, et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry. 2013;70(4):436-443. 2. ACOG Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020. 3. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the jamapsychiatry.com
Antidepressant Medication and Spontaneous Abortion: “No Significant Association”? Clinically Significant Association! To the Editor Ross et al reported “no significant association b e t we e n a nt i d e p r e s s a nt m e d i c at i o n ex p o s u r e a n d spontaneous abortion (odds ratio [OR], 1.47; 95% CI, 0.99 to 2.17; P = .055)” (italics, our emphasis). 1(p436) Confidence intervals provide inferential evidence about the range of plausible values for the population parameter of interest.2,3 A simple examination of the values covered by the reported 95% CI from 0.99 to 2.17 suffices to show that an association between the exposure to antidepressant medic ation and spontaneous abortion is likely and that results are nonnegligible from a clinical perspective. Results are not statistically significant but the differences are of clinical interest. Elsewhere Ross et al were careful enough to nuance their other statements regarding significance (“…were statistically significantly associated with”). Their claim regarding spontaneous abortion is even more puzzling given that they acknowledged the “importance of considering clinical significance” of the results. Note for example that one of the reviews cited by Ross et al reported point estimates and 95% CI for summary relative risks for association between depression and preterm birth (PTB) of 1.39 (1.19-1.61) and for low birth weight (LBW), 1.49 (1.25-1.77) for studies using a categorical depression measure and 1.03 (1.00-1.06) for PTB and 1.04 (0.99-1.09) for LBW for studies using a continuous depression measure. These outcomes led Grote et al4 to conclude that women with depression during pregnancy are at increased risk for PTB and LBW. It is hard to understand why these results were interpreted as providing evidence of association between depression and PTB and LBW but quantitative results reported by Ross et al were interpreted as providing evidence of no association between use of antidepressant medication and spontaneous abortion. In a recent review, Hackshaw et al5 reported odds ratios and 95% CI for association between maternal smoking and birth defects (including cardiovascular defects [OR, 1.09; 95% CI, 1.02-1.17] and missing/extra digits [OR, 1.18, 95% CI, 0.99-1.41]) and suggested that information about birth defects that are associated with maternal smoking should be included in public health educational materials. What, then, about public education regarding the risk of spontaneJAMA Psychiatry December 2013 Volume 70, Number 12
Copyright 2013 American Medical Association. All rights reserved.
Downloaded From: http://archpsyc.jamanetwork.com/ by a Monash University Library User on 11/24/2015
1373
