RationaleKnowledge transfer and translation (KT) has become an important component in health care systems worldwide. Antidepressant use in pregnancy has become a controversial subject for a number of reasons, including differing interpretations of study results.MethodsSelected key articles were indentified and retrieved from the literature. Relevant information was extracted and synthesized into themes, addressing each of the stated objectives.Objectives(1) To determine how knowledge regarding the safety/risk of antidepressant use in pregnancy is created; (2) to describe different research models and statistical analyses that have been used, so as to critically evaluate the results; and (3) to identify how this information is currently disseminated.ResultsAll of the methods used for examining the safety of antidepressants in pregnancy have some deficiencies in study design and analysis, thus reinforcing the need for accurate interpretations when discussing results. In addition, dissemination in both the scientific and lay press has been selective and therefore potentially biased.ConclusionIt is critical, starting with the creators of knowledge, through to the recipients that discrepancies are resolved, as lack of clarity may impede the transfer of unambiguous evidence-based information from health care providers to patients, thus impacting decision making. For example, by implementing improved (KT) strategies, a pregnant, depressed woman, will be empowered to make a rational evidence-based decision regarding whether or not she should take an antidepressant during pregnancy.

OBJECTIVE:Pregnant women and their health care professionals commonly believe that use of medications during pregnancy may be harmful to the unborn fetus. The objective of this study was to evaluate the risk perception of psychotropic drug use in pregnancy among physicians in different medical specialties.METHOD:This was a convenience survey conducted at outpatient clinics in the cities of Recife, Brazil, and La Plata, Bahía Blanca, and Buenos Aires, Argentina. Physicians who agreed to participate were asked to rate their perception of teratogenic risk among different classes of drugs, which included antidepressants, antipsychotics, anticonvulsants, and benzodiazepines.RESULTS:Two hundred and thirty-eight physicians completed the survey (response rate, 98%). These included psychiatrists, obstetricians, neurologists, cardiologists, gastroenterologists, and general practitioners. Among different specialties, a minority of psychiatrists perceived psychotropic drugs to be highly teratogenic (antidepressants, 12.5%; antipsychotics, 15%; benzodiazepines, 25%) as compared with other specialties (p < 0.003 for each drug class). There was no difference in perceived risk of antiepileptic drugs among specialties, including psychiatrists.CONCLUSION:The risk associated with use of psychotropic drugs in pregnancy was overestimated by physicians of all medical specialties, except psychiatry. All physicians should be aware of the safety/risk of psychotropic agents in pregnancy, as they may be required to give advice and/or prescribe these drugs to pregnant women.

PRINCIPLE: Healthcare professionals' (HCPs') perception of risk associated with drug use in pregnancy may have an impact on the pharmacological treatment of some women. The aim of this study was to examine this risk perception in a sample of Swiss HCPs with a special focus on their knowledge and use of available specialised information sources.METHOD: An online, French and German, questionnaire was e-mailed to 7,136 members of four Swiss professional societies (gynaecologists, paediatricians, midwives and pharmacists). The questionnaire was designed (a) to collect demographic characteristics, (b) to evaluate the frequency of use of several specialised sources of information on drugs in pregnancy in their daily practice, and (c) to examine the perception of risk associated with drug use during pregnancy.RESULTS: A total of 1,310 questionnaires were collected (response rate of 18.4%). More than 80% of the respondent HCPs use the Swiss Drug Reference Book (Compendium) to assess the risk associated with drugs during pregnancy and are not aware of available specialised information sources (books, websites or information centres). Despite some disparities between HPCs, the risk related to drug intake was overall highly misperceived. Blinded reading of three product monographs in the Compendium was associated with an overestimated perception of risk (e. g., after reading the "paracetamol" monograph, 38% of the participants stated they would probably not advise the use of this drug to a pregnant patient).CONCLUSION: Overall, an overestimation of the risk associated with drug use during pregnancy has been observed in our sample of HCPs, which might be related to the underuse of specialised information source among other factors. These findings evidenced the need for increased training for HCPs in order to optimise medication use during pregnancy. Further studies are needed to confirm these results and identify causes.

Objective: Investigate the association between health literacy and perception of medication risk, beliefs about medications, use and non-adherence to prescribed pharmacotherapy during pregnancy, and whether risk perception and beliefs may mediate an association between health literacy and non-adherence.Methods: This multinational, cross-sectional, internet-based study recruited pregnant woman between 1 October 2011 and 29 February 2012. Data on maternal socio-demographics, medication use, risk perception, beliefs, and non-adherence were collected via an on-line questionnaire. Health literacy was measured via a self-assessment scale. Mann-Whitney U test, Spearman's rank correlation, Generalized Estimating Equations and mediation analysis were utilized.Results: 4999 pregnant women were included. Low-health literacy women reported higher risk perception for medications, especially penicillins (Rho: -0.216) and swine flu vaccine (Rho: -0.204) and more negative beliefs about medication. Non-adherence ranged from 19.2% (high-health literacy) to 25.0% (low-health literacy). Low-health literacy women were more likely to be non-adherent to pharmacotherapy than their high-level counterparts (adjusted OR: 1.30; 95% CI: 1.02-1.66). Risk perception and beliefs appeared to mediate the association between health literacy and non-adherence.Conclusion: Health literacy was significantly associated with maternal health behaviors regarding medication non-adherence.Practice implications: Clinicians should take time to inquire into their patients' ability to understand health information, perception and beliefs, in order to promote adherence during pregnancy. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Question In my family practice, I tell my female patients of reproductive age who have depression that untreated depression in pregnancy might be more harmful than the unproven risks of antidepressants. However, I recently read in a national news magazine that there is actually no evidence for this advice. Have I missed something? Answer You did not miss anything, so you should continue to advise your pregnant patients as before. News magazines can have substantial bias, as the reporters often only interview "experts" who support their beliefs, as was probably the case in this article. Most glaringly, in this instance, no perinatal psychiatrists were interviewed and none of the experts were clinically involved with pregnant women. We believe that media statements like the one you mentioned might lead women to abruptly discontinue their antidepressants, putting themselves at risk of relapse, hospitalization, and even suicide. Your balancing role in providing your patient with evidence-based information is critical.

Background: To date, many studies have been published regarding the safety of antidepressant use in pregnancy. However, most have been regarding a possible association with major malformations and there have been relatively few studies that have examined other infant outcomes specifically.Objective: To evaluate possible adverse effects of antidepressant use in pregnancy.Methods: We searched the literature, using Medline, PUBMED, Embase, and Reprotox, and retrieved key articles and reviews of the topic. We examined all outcomes with the exception of major/minor malformations. Results: We did not find an overall increased risk associated with lower mean birthweight, small for gestational age or long-term neurodevelopmental adverse outcomes. However, there does appear to be a significantly increased risk for spontaneous abortion, preterm birth and low birthweight less than 2,500gm. In addition, a possible increased risk for Persistent Pulmonary Hypertension of the Newborn (PPHN) and evidence of Poor Neonatal Adaptation Syndrome (PNAS) following use in late pregnancy. All of the observed risks were of a very low magnitude and the clinical significance of these results is unknown.Conclusions: This information should not preclude a pregnant women from being treated for depression if required, as untreated depression is also associated with adverse effects on the infant. However, further research needs to be conducted where it is possible to control for maternal depression, in order to evaluate whether these adverse events are due to the underlying maternal illness, the antidepressant, or possibly a combination of both.

A number of human teratogens elicit their deleterious effects through mechanisms involving the generation of reactive oxygen species (ROS) and oxidative stress. However, classic definitions of oxidative stress do not fully coincide with basic fundamental principles of teratology. Newer definitions of oxidative stress focus on the targeted redox modification of cysteine/thiol functional groups found in the regulatory domains of critical signaling pathway proteins, suggesting that the targeted disruption of signaling through specific redox couples may account for the specificity of teratogen-induced malformations which previously could not be rationalized. Here, we review examples of teratogens that induce ROS and oxidative injury, describe oxidative stress-related teratogenic mechanisms, and provide rationale for developmental periods of sensitivity and species susceptibility. Understanding how chemicals disrupt redox status, induce oxidative stress leading to dysmorphogenesis becomes important to identify potential teratogens and develop therapeutic interventions for attenuation of harmful chemical effects in utero following exposure.

We are writing in response to a paper recently published in your journal: “Campagne DM. Fact: Antidepressants and anxiolytics are not safe during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2007 Dec;135(2):145–8” [ [1] Campagne D.M. Fact: antidepressants and anxiolytics are not safe during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2007; 135: 145-148 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar ]. We have many concerns with this piece, starting with the title, which is incorrect as this is definitely not a review, it is an editorial reflecting the author's personal views. A review is a systematic search of the literature, enabling the author to produce the best evidence-based information, to assist clinicians in treating their patients. His concern over the statement that I made, as well as other authors,“the body of evidence in the literature to date, suggests that psychotropic drugs as a group are relatively safe to take during pregnancy” (which is incorrectly cited) [ [2] Einarson A. The safety of psychtopic drugs in pregnancy. MedGenMed. 2005; 5;7 (Review): 3 Google Scholar ] is unwarranted and may cause harm to women who require these medications in pregnancy, as they may be afraid to take medications for even a severe depression, which the author does acknowledge is sometimes necessary. Author's response: Antidepressants and anxiolytics in pregnancy: The facts standEuropean Journal of Obstetrics and Gynecology and Reproductive BiologyVol. 171Issue 2PreviewThe reaction of Nurse Einarson and colleagues helps us to get the problem of antidepressants and anxiolytics use during pregnancy under closer scientific and ethical scrutiny. She apparently is a staunch defender of the use of SSRIs and similar medications and, with funds from their manufacturers, has participated in studies of the effects of possibly teratogenic antidepressants on pregnant women. None of these studies considered non-pharmacologic ways to treat depression or anxiety. Indeed, these studies found that malformations occurred twice or three times as often in the SSRI or venlafaxine groups compared to the non-teratogenic group. Full-Text PDF

To identify and describe published articles dealing with issues of mental health in pregnancy from Latin American counties Medline, Embase and LILACS databases were searched for published studies originating from Latin America regarding mental health issues in pregnancy. Search terms included the names of all countries in the United States Census Bureau International Database + mental health + pregnancy. We included all research and review articles dealing with pregnancy and/or lactation, epidemiology of mental disorders, prevention or treatment of mental disorders, outcomes assessment, and counseling/drug information dissemination. Excluded were papers dealing exlusively with postpartum depression, HIV transmission, induction of abortion, in vitro fertilization, contraception or the use of alcohol or drugs of abuse. Data were analyzed descriptively. The search identified 701 studies; 110 (16%) met the criteria. The earliest was published in 1984 and the contribution has increased exponentially [Y=-1E-125*exp(0.1452X), where X is the year; R-squared=0.97). The majority (n=80; 73%) consisted of original research and the other 27% were reviews (23 overviews, 3 systematic reviews/meta-analyses, 4 other). Most frequent topics were depression (37%) as well as mixed anxiety/depression (6%), mental health during pregnancy (32%;), psychotropic drug use in pregnancy (13%), suicidality (6%), and quality of life (1%). By country, 58 (53%) were produced by Brazil, followed by Mexico (n=18, 17%), Chile (n=10, 9%), Colombia (n=9, 8%), Peru (n=5, 5%), Argentina and Ecuador (each with 3, 3%), and one each from Costa Rica, Paraguay, and Venezuela. Contributions were positively correlated with the size of the population (Spearman’s rho=0.76, P=0.03). Latin America has begun to make a small but significant contribution to the literature, However, more than 50% were from Brazil, so other countries will benefit from further research, addressing their unique social and economic needs regarding mental health in pregnancy.

Depression is a common illness during pregnancy, yet it often goes undetected and/or untreated. Untreated depression during pregnancy has been associated with increased rates of adverse maternal, obstetrical and fetal outcomes; consequently, it is crucial to manage these women effectively and adequately during this vulnerable time of their lives. The barriers to treatment include the stigma surrounding mental health and the challenges of navigating the constantly growing, and apparently conflicting, evidence regarding the safety of antidepressant use during pregnancy, as well as other concerns unique to pregnant women. In this paper, we suggest the management of women with depression during pregnancy, using evidence-based information, taking into account all of the aspects of treatment, including screening, risks of untreated depression and evaluation of the safety data regarding pharmaceutical treatments. In addition, we have designed a treatment algorithm to assist clinicians in making evidence-based decisions in this highly sensitive and complex clinical field. Finally, it is important to evaluate each woman on an individual, case-by-base basis, in order to ensure the best outcome for both the mother and her baby.

The important question about antidepressant use in pregnancy is reviewed by Byatt and colleagues in this issue of Acta Psychiatrica Scandinavica 1. The authors main conclusions following a review of the literature focusing on controversial results, including 44 studies with (n = 18) reporting on major malformations, (n = 18) on neonatal behavioral symptoms, and (n = 8) on persistent pulmonary hypertension of the newborn (PPHN), are that while some studies suggest an increased risk of specific major malformations, the findings are inconsistent, although the overall risks appear to be small. Neonatal behavioral symptoms can occur in up to 30% of neonates exposed to antidepressants, and in some studies, PPHN has been weakly associated with in utero antidepressant exposure. They also recommend taking into account untreated maternal illness, as this may also exert its own adverse effects on the infant. In addition, they offer some valuable advice in interpreting results of studies, so as to assist the clinician in the treatment of a pregnant and depressed woman. A substantial number of women will become pregnant while taking an antidepressant and may require pharmacological treatment throughout their pregnancy. As almost half of all pregnancies are unintended, this represents a large number of pregnant women taking an antidepressant. Prior to 2005, research using observational designs conducted on the use of SSRIs (Serotonin Reuptake Inhibitors) in pregnancy reported no association between SSRI use and congenital malformations 2, which was based on a meta-analysis of the current data at that time. They appeared to be relatively safe to take during pregnancy and there was no evidence of concern in both the scientific literature and the media. However, this all changed in late 2005, when GlaxoSmithKline (GSK) published on their website, pregnancy outcomes of 815 infants exposed to paroxetine during pregnancy and reported a 2% incidence of cardiovascular malformations (where 1% is expected in the general population). Subsequently, based on this report and data from two unpublished abstracts presented at scientific meetings, The Food and Drug Administration (FDA) issued a warning about the possible adverse effects associated with paroxetine in the first trimester of pregnancy. Subsequently, as Byatt et.al 1 reported, many studies and reviews have been published with 'conflicting results' reporting on thousands of pregnancy outcomes. A recent (August 2nd 2012) GOOGLE search using the keywords 'antidepressants, pregnancy, birth defects' revealed 1 550 000 results, many describing how 'dangerous/harmful' antidepressants are to take in pregnancy and warning women 'not to take them if they are pregnant.' In addition, there are many websites encouraging women who had a baby who had PPHN or a birth defect and took an antidepressant during pregnancy, to seek the advice of a lawyer to sue the drug company. Even 'experts' disagree regarding the teratogenicity of antidepressants, most notably paroxetine as illustrated by 2 commentaries in a prominent teratology journal, which were published along with a meta-analysis and presented opposing opinions. Scialli concluded that 'the scientific evidence does not support the conclusion that paroxetine causes cardiovascular defects,' while Bérard stated that 'evidence-based literature shows consistent epidemiologic evidence that paroxetine use during pregnancy increases the risk of cardiac malformations in newborns.'3 From these statements, one is prompted to question how it is that two experts in the same field have offered such opposing conclusions based on their evaluation of the same data. Understandably, this mixed information has caused anxiety for pregnant women, who may require pharmacological treatment for the depression and for their healthcare providers from whom they seek advice. Due to the ethical restrictions of randomized controlled trials (RCTs) in pregnant women, studying the safety of drugs in pregnancy is a complex process. Consequently, observational study designs (i.e., case reports, case series, cohort studies, case–control and nested case–control studies and administrative database studies) are currently used, which have many limitations. Recent years have seen an increase in the number of computerized databases, which were not designed for scientific studies, especially prescription data bases, where it is only known if the woman redeemed the prescription, not if she actually took the drug. Nevertheless, researchers have used these databases to conduct complex analyses of data, resulting in a substantial increase in such studies. Together with other observational studies using different methodologies, seemingly conflicting results have been published in the peer-reviewed literature and subsequently in the media regarding the safety of antidepressant use in pregnancy. This brings up a very important question of how are these results disseminated to the scientific community and subsequently to their patients. Most clinicians have a very rudimentary knowledge of epidemiology and statistics, so do not have the skills to carefully examine the often complex methodology of these studies, so rely on the conclusions of the authors, which do not always match their results, most often just from reading the abstract in the journal. When individual studies regarding the safety of antidepressants in pregnancy are published, much is made of very small increased odds ratios (OR), usually <2 (which most epidemiologists consider relatively unimportant) and are explained in a way that it appears much more significant than it really is. Small but statistically significant risks are the key at the population level, but most often are not clinically important, which is the information that a clinician requires to inform the patient of their individual risk. In addition, studies that did not find an increased risk are frequently ignored by both the scientific literature and in the media. It is rare to see in the media that a new study reporting on the safety/risk of an antidepressant did not find an increased risk for birth defects or other adverse outcomes. Consequently, studies with marginally significant results can have a far reaching impact on events such as precedent setting lawsuits. In the case of GlaxoSmithKline, the company was ordered to pay $1.5 million to a couple whose baby was born with a heart defect following exposure to Paxil® in pregnancy. By July 2010, the company reportedly settled about 800 Paxil® birth defects lawsuits for approximately $1 billion 4. In addition, widely disseminated frightening headlines in the media can also cause women to stop taking a needed antidepressant during pregnancy, sometimes with serious consequences, such as contemplating suicide 5. In summary, this is observational research, and consequently, there are some deficiencies in study design and analysis among all of the studies. However, this does not mean that the information provided from the results of these studies is not valuable, as long as the methodology and analysis are critically evaluated. It is unlikely that in the near future, pregnant women will be included in randomized controlled trials, so this reinforces the need to improve the rigor of the available study methods. However, the bottom line is that current differing research designs regarding the safety of antidepressants in pregnancy did not produce conflicting results per se. Apparent small differences appear to have been likely because of the way selected results were disseminated. Finally and of great importance, improved knowledge transfer and translation will ensure that pregnant women and their healthcare providers receive the most accurate evidence-based information, for decision-making regarding the use of antidepressants during pregnancy. Adrienne Einarson for The Motherisk Program received an unrestricted educational grant to study the safety of Cymbalta®(duloxetine) in pregnancy from Eli Lilly Inc. Canada.

Article AbstractBecause this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text.Many more women than men are diagnosed with depression, most often between 25 and 44 years of age when women are of childbearing age, and approximately 10% to 15% will experience depression during pregnancy. Therefore, a substantial number of women could be taking an antidepressant when they become pregnant.The use of antidepressants has increased in the past decade, as reported by a group using data from the National Birth Defects Prevention Study, an ongoing case-control study of risk factors for birth defects covering 10 US states.

BACKGROUND:Many studies examining the teratogenic potential of antidepressants have been published. A variety of observational designs have been used with apparent conflicting results, although odds ratios were rarely >2.OBJECTIVES:To examine whether these apparent differences were associated with research methods such as model, comparison groups, data source, data collection procedures, definition of malformations, outcome ascertainment or management of confounders.METHODS:Medline and Embase were searched using terms: pregnancy, antidepressants, serotonin uptake inhibitors OR SSRI, AND embryonic structures OR congenital malformations OR fetal development for observational studies with original data. Data were analyzed using a structured approach and narrative review. Designs that were compared, included prospective cohort, retrospective cohort, and case-control studies. Rates of major malformations and cardiac malformations were combined by study type using random effects meta-analytic models.RESULTS:We identified 150 papers; 127 were rejected, 23 were analyzed: 9 prospective cohort, 8 retrospective cohort, and 6 case-control studies. Sample sizes were large (1,818 exposed in case-control and 16,824 in cohort studies), providing relatively robust findings. Overall Odds Ratios for major malformations ranged from 1.03-1.24 and 0.81-1.32 for cardiac malformations. No discrepancies among research designs were identified.CONCLUSIONS:Diverse observational models with differing strengths and weaknesses produced remarkably similar non-significant results. Perceived conflicting results may be due to subsequent dissemination of results with attention given to small statistically differences with negligible clinical importance. Improved methods of knowledge transfer and translation are required to provide sound evidence-based information to assist in decision-making surrounding the use of antidepressants in pregnancy.

The two highest-ranking winners of the 2011 CIHR/CMAJ competition for Top Achievements in Health Research are Daniel Drucker, and Gideon Koren and colleagues for the Motherisk team. In the following essay, Dr. Koren and colleagues describe the work of the Motherisk team in the area of fetal-maternal toxicity. The essay by Dr. Drucker and synopses of the other four winning achievements are available at www.cmaj.ca.

Background: An association between PPHN and antidepressant use in pregnancy has been reported.Purpose: We sought to examine this relationship.Methods: A review of the literature was performed, to evaluate this association.Results: Six published studies fulfilled our criteria for inclusion, with only three studies large enough to have the power to detect an association. There appears to be a small but significantly, increased risk of late pregnancy SSRI exposure associated with PPHN in one case-control study; OR 5.1 (95% CI, 1.9-13.3) and two large cohort studies; RR 2.56; (95% CI, 1.17-4.85) and OR 2.1 (95% CI, 1.5-3.0) The other three studies did not find an association.Conclusion: the absolute risk cannot be determined, but it is very small, probably less than 1%. If a pregnant woman requires pharmacological treatment, this information does not support discontinuation or lowering the dose of the antidepressant. (c) 2012 Elsevier Inc. All rights reserved.