Antidepressant use in pregnancy: knowledge transfer and translation of research findings.

RATIONALE: Knowledge 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. METHODS: Selected 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. RESULTS: All 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. CONCLUSION: It 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.

Antidepressant use in pregnancy: an evaluation of adverse outcomes excluding malformation.

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 2,500 gm. 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.

Pregnancy outcome following in utero exposure to lithium: a prospective, comparative, observational study.

OBJECTIVE: The authors conducted a prospective, comparative observational study to evaluate the risk of major anomalies following exposure to lithium during pregnancy. METHOD: A total of 183 lithium-exposed pregnancies of women who contacted the Israeli Teratology Information Service were followed up (90.2% in the first trimester) and compared with 72 disease-matched and 748 nonteratogenic-exposed pregnancies. RESULTS: There were significantly more miscarriages (adjusted odds ratio=1.94, 95% CI=1.08-3.48) and elective terminations of pregnancy (17/183 [9.3%] compared with 15/748 [2.0%]) in the lithium-exposed group compared with the nonteratogenic exposure group. The rate of major congenital anomalies after exclusion of genetic or cytogenetic anomalies was not significantly different between the three groups (lithium-exposed in the first trimester: 8/123 [6.5%]; bipolar: 2/61 [3.3%]; nonteratogenic: 19/711 [2.7%]). Cardiovascular anomalies occurred more frequently in the lithium group exposed during the first trimester when compared with the nonteratogenic exposure group (5/123 [4.1%] compared with 4/711 [0.6%]) but not after excluding anomalies that spontaneously resolved (3/123 [2.4%] compared with 2/711 [0.3%]). Ebstein's anomaly was diagnosed in one lithium-exposed fetus and in two retrospective lithium cases that were not included because contact with the information service was made after the prenatal diagnosis by ultrasound. The rate of noncardiovascular anomalies was not significantly different between the groups. The rate of preterm deliveries was higher in the lithium group compared with the nonteratogenic exposure group (18/131 [13.7%] compared with 41/683 [6.0%]). CONCLUSIONS: Lithium treatment in pregnancy is associated with a higher rate of cardiovascular anomalies. Women who are treated with lithium during organogenesis should undergo fetal echocardiography and level-2 ultrasound.

Health literacy and its association with perception of teratogenic risks and health behavior during pregnancy.

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.

Use of psychotropic medications during pregnancy: perception of teratogenic risk among physicians in two Latin American countries

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. .

Risk perception by healthcare professionals related to drug use during pregnancy: a Swiss survey.

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.

Use of psychotropic medications during pregnancy: perception of teratogenic risk among physicians in two Latin American countries.

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.

Risks of untreated depression in pregnancy.

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.

Managing depression during 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.

Antidepressant use during pregnancy: navigating the sea of information.

QUESTION: When some of my patients who are taking antidepressants learn they are pregnant, they become anxious and confront me with the following statement: "I need this medication, but have heard so many conflicting stories from my friends and on the Internet and in the media that I am not sure if I should continue taking it." How do I advise them, as I have also seen conflicting evidence in the scientific literature? ANSWER: To date, antidepressants are the most studied drugs during pregnancy, with more than 30 000 outcomes examining increased risks of adverse effects on exposed infants. The results of the studies can appear to be conflicting owing to differing interpretation of statistical analysis and subsequent knowledge transfer and translation of the information. However, there does not appear to be a clinically significant increased risk of any of the adverse outcomes reported in peer-reviewed published studies that would preclude a woman from taking a needed antidepressant during pregnancy.

Pregnancy outcomes following gabapentin use: results of a prospective comparative cohort study.

OBJECTIVES: Our objectives were to 1) determine whether first-trimester use of gabapentin is associated with an increased risk for major malformations; 2) examine rates of spontaneous abortions, therapeutic abortions, stillbirths, mean birth weight and gestational age at delivery; and 3) examine rates of poor neonatal adaptation syndrome following late pregnancy exposure. METHODS: The study design was prospective. Women were included who initially contacted the services between 5 and 8 weeks with a comparison group of women exposed to nonteratogens, collected in a similar manner. RESULTS: We have data on 223 pregnancy outcomes exposed to gabapentin and 223 unexposed pregnancies. The rates of major malformations were similar in both groups (p = 0.845). There was a higher rate of preterm births (p = 0.019) and low birth weight <2,500 g (p = 0.033) in the gabapentin group. Among infants who were exposed to gabapentin up until delivery, 23 of 61 (38%) were admitted to either the neonatal intensive care unit or special care nursery for observation and/or treatment, vs 6 of 201 (2.9%) live births in the comparison group (p < 0.001). There were 2 cases of possible poor neonatal adaptation syndrome in neonates exposed to gabapentin close to delivery, compared with none in the comparison group, although it must be noted that these infants were concomitantly exposed to other psychotropic drugs. Among the women who took gabapentin, the major indications were pain (n = 90; 43%) and epilepsy (n = 71; 34%); the remainder were for other indications, mostly psychiatric. CONCLUSION: Our results suggest that although this sample size is not large enough to make any definitive conclusions, and there was no comparator group treated with other antiepileptic drugs, gabapentin use in pregnancy does not appear to increase the risk for major malformations. This finding and the increased risk for low birth weight and preterm birth require further investigation.