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
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 spontane-
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Letters
ous abortion associated with use of antidepressant medication during pregnancy? In conclusion, the reported lack of association between spontaneous abortion and antidepressant use is not supported by the Ross et al data and pregnant women should be educated about the risk of spontaneous abortion associated with use of antidepressant medication during pregnancy. Catalin Tufanaru, MD, MPH Jon Jureidini, MBBS, PhD Author Affiliations: The Joanna Briggs Institute, School of Translational Health Science, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia (Tufanaru); Department of Psychological Medicine, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia (Jureidini). Corresponding Author: Catalin Tufanaru, MD, MPH, The Joanna Briggs Institute, School of Translational Health Science, Faculty of Health Sciences, The University of Adelaide, 5005 Adelaide, South Australia, Australia (
[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. Cumming G. Understanding the New Statistics: Effect Sizes, Confidence Intervals, and Meta-Analysis. New York, NY: Routledge; 2012. 3. Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 3rd ed. Philadelphia, PA: Wolters Kluwer Lippincott Williams & Wilkins; 2008. 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. 5. Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update. 2011;17(5):589-604.
Developmental Mismatch: Why Some Immigrants Seem Protected From Affective, Personality, and Substance Use Disorders To the Editor In a recently published article about risks of mental disorders associated with various types of foreign migration, Cantor-Graae and Pedersen 1 reported higher risks for schizophrenia-related disorders in all types of migrants, except in children born to expatriates. In addition, which I found particularly interesting, they found lower risks for affective, personality, and substance use disorders in first- and second-generation migrants with 2 foreign-born parents but higher risks in foreign-born adoptees, secondgeneration immigrants with 1 foreign-born parent, and native Danes who resided abroad. The question is, what is the difference between these 2 types of migrants compared with the other types? It is broadly assumed that high psychosocial stress makes immigrants vulnerable to mental disorders.2 Possible causes for psychosocial stress in migrants include discrimination related to different skin color and low socioeconomic 1374
status (SES) due to unemployment or low-paid jobs. Let’s compare the different types of immigrants on these characteristics with native Danes: • Foreign-born adoptees: different skin color, same SES. • First-generation immigrants: different skin color, lower SES. • Second-generation immigrants with 1 foreign-born parent: intermediate skin color, somewhat lower SES. • Second-generation immigrants with 2 foreign-born parents: different skin color, lower SES. • Native Danes who resided abroad: same skin color, same SES. Using this simple comparison, the Cantor-Graae and Pedersen1 results suggest that large differences are protective against affective, personality, and substance use disorders, whereas intermediate and small differences form a risk factor. This seemingly counterintuitive finding might be explained using evolutionary theories. The prenatal and early childhood periods are generally recognized as important programming phases. Environments that signal unpredictability steer individuals in the direction of faster life history strategies.3 Life history strategy should be seen as a coherent pattern of behaviors,4 with insecure attachment, externalizing behavior, earlier maturation, and opportunistic sexual behavior as typical fast life history strategy behaviors, which are adaptive in matched but maladaptive in mismatched situations. 5 It is not unlikely that the early environment contained more cues of unpredictability (eg, prenatal stress, house moves, and parental job changes) in all types of immigrants than in native Danes, predisposing immigrants to faster life history strategies. The Cantor-Graae and Pedersen 1 results suggest that immigrants, who have a relatively fast life history strategy, are at lower risk for affective, personality, and substance use disorders when they experience high psychosocial stress due to different skin color and low SES later in life but at higher risk when these stressors are less prominent. Thus, a match might be protective, whereas a mismatch might be a risk factor.5 Esther Nederhof, PhD
Author Affiliation: Interdisciplinary Center for Psychopathology and Emotion Regulation, University Center for Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Corresponding Author: Esther Nederhof, PhD, Interdisciplinary Center for Psychopathology and Emotion Regulation, University Center for Psychiatry, University Medical Center Groningen, University of Groningen, PO Box 30001, CC72, 9700 RB Groningen, the Netherlands (
[email protected]). Conflict of Interest Disclosures: None reported. 1. Cantor-Graae E, Pedersen CB. Full spectrum of psychiatric disorders related to foreign migration: a Danish population-based cohort study. JAMA Psychiatry. 2013;70(4):427-435. 2. Cantor-Graae E, Selten JP. Schizophrenia and migration: a meta-analysis and review. Am J Psychiatry. 2005;162(1):12-24. 3. Simpson JA, Griskevicius V, Kuo SI, Sung S, Collins WA. Evolution, stress, and sensitive periods: the influence of unpredictability in early versus late childhood on sex and risky behavior. Dev Psychol. 2012;48(3):674-686.
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