Comment: paroxetine use during pregnancy: is it safe?
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Depressive Disorder↗
Biomedical subjects
Adrienne Einarson
Publications and source records attributed to Adrienne Einarson.
The effectiveness of Teratology Information Services (TIS).
BACKGROUND: Women and their health care providers have few reliable sources of information regarding the safety of exposures in pregnancy and lactation. Evidence-based information on these topics is provided by Teratology Information Services (TIS). Access to TIS, however, is limited in many regions, and many services have difficulty maintaining ongoing funding. The objective of this review is to highlight published reports of the effectiveness of TIS in improving maternal and neonatal health. METHODS: A search of the Pub Med and Econ Lit databases was performed with no date restriction, using the search terms teratology, information, counseling, pregnancy, effectiveness, birth defects. RESULTS: Information disseminated from TIS has been shown to prevent congenital malformations, unnecessary pregnancy terminations, and occupational risks. TIS support optimal nutritional supplementation in pregnancy and optimal drug therapy in pregnancy and breast-feeding. In addition, they correct misperceptions of risk and facilitate knowledge transfer and translation. TIS have the potential to provide health care cost savings. CONCLUSIONS: TIS are vital services in supporting optimal maternal and neonatal health. A formal economic evaluation of TIS is required in order to inform resource allocation decision-making and continued funding of these services.
Abnormalities, Drug-Induced↗
Do we have a knowledge transfer and translation plan at Teratogen Information Services?
Recently, a new field in science is emerging, which addresses the issue of ensuring that information that is generated from research, reaches the right people in the right format. This has been coined as knowledge transfer and translation and public health leaders worldwide are finding out ways to carry this out effectively. Ultimately, this should ensure greater investment in knowledge syntheses and transfer initiatives, that involve potential users of research to improve the quality of health for everyone. In this brief review/comment, an attempt will be made to help the readers understand the meaning of this new terminology and how it impacts Teratogen Information Services.
Canada↗
Quality and content of abstracts in papers reporting about drug exposures during pregnancy.
BACKGROUND: Most clinicians read only the abstract of papers in scientific journals. Therefore, it is very important that abstracts contain as much information as possible, to summarize the data succinctly. Our objectives were to evaluate the quality of information in abstracts reporting human fetal outcomes following drug exposure during pregnancy. METHODS: We developed quality criteria based on previous work, modifying them for use with pregnancy outcomes. Quality scores were calculated as present/absent for all of the equally weighted criteria, then expressed as percentages (present/[present + absent]). We examined a random sample of 100 abstracts obtained through searches of MEDLINE, EMBASE, and the Web of Science databases from 1990 to 2005. Average quality scores were compared across designs (cohort, case-control, meta-analysis, and mixed design) Using Kruskal-Wallis ANOVA and structured/unstructured formats using Student's t test. RESULTS: The overall average quality was 59.2% +/- 14% (median, 61.5%; range, 15.4-83.3%). Quality was not significantly different across designs (P = .16) or between structured and unstructured abstracts (P = .44). Quality scores increased over time (Rho = 0.23, P = .02). Most frequently absent were baseline risk (94%), drug dose (91%), nonsignificant P values (72%), confounders (69%), significant P values (57%), and risk difference (48%). CONCLUSIONS: Abstracts provide insufficient information, particularly baseline risk values, for readers to make evidence-based decisions regarding drug use during pregnancy. Efforts need to be made to improve the quality of abstracts and include critical information such as baseline risk.
Abstracting and Indexing↗
Ruminative worrying during pregnancy: a case series.
BACKGROUND: Most women worry to some extent during pregnancy about exposure to agents that might harm their babies. CASES: We describe three women who worried excessively throughout pregnancy about harming their babies because of exposure to agents including, but not limited to, psychotropic drugs. These women were extremely resistant to reassurances that their babies would not be adversely affected, and it is likely there are more women in the community who fit this profile. We have described a number of management strategies that we found effective in caring for these women during pregnancy. CONCLUSION: A collaborative effort between caregivers in psychiatry and obstetrics, as well as other health professionals, is required to provide management for these women during pregnancy.
Abnormalities, Drug-Induced↗
Smoking habits, nicotine use, and congenital malformations.
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Congenital Abnormalities↗
Defective alleles may not have contributed to adverse effects.
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Female↗
Exposure to mirtazapine during pregnancy: a prospective, comparative study of birth outcomes.
BACKGROUND: Mirtazapine is a novel piperazinoazepine antidepressant, unrelated to any known class of antidepressants. Currently, apart from a few case reports and case series in the literature, there are no studies evaluating the safety of this drug during pregnancy. OBJECTIVE: To determine whether mirtazapine increases the risk for major malformations in newborns when used by pregnant women. METHOD: The study design was prospective, with 2 comparison groups: disease-matched pregnant women diagnosed with depression taking other antidepressants and pregnant women exposed to nonteratogens. The primary outcome was major malformations in neonates; secondary endpoints included spontaneous abortions, therapeutic abortions, gestational age at birth, and mean birth weight. Women were recruited from 5 teratogen information services in Toronto, Canada; Farmington, Conn., U.S.A.; Jerusalem, Israel; Rome, Italy; Sydney, Australia; and from the Drug Safety Research Unit in Southampton, United Kingdom. Women were recruited into the study from June 2002 to August 2005. RESULTS: We were able to follow 104 pregnancy outcomes in each drug group. There were 77 live births, 1 stillbirth, 20 spontaneous abortions, 6 therapeutic abortions, and 2 major malformations in the mirtazapine group. The mean +/- SD birth weight was 3335 +/- 654 g and the mean +/- SD gestational age at delivery was 38.9 +/- 2.5 weeks. Most (95%) of the women took mirtazapine in the first trimester, but only 25% of the women took it throughout pregnancy. The differences among the 3 groups were in the rate of spontaneous abortions, which was higher in both antidepressant groups (19% in the mirtazapine group and 17% in the other antidepressant group) than in the nonteratogen group (11%), but none of the differences were statistically significant. The rate of preterm births (prior to 37 weeks' gestation) was also higher in the mirtazapine group (10%) and in the other antidepressant group (7%) than in the nonteratogen group (2%). The difference was statistically significant between the mirtazapine group and the nonteratogen group (p = .04). CONCLUSION: Mirtazapine does not appear to increase the baseline rate of major malformations of 1% to 3%. However, the higher number of spontaneous abortions in the antidepressant groups confirms the higher rates of spontaneous abortions in pregnant women taking antidepressant medications found in previous studies.
Abnormalities, Drug-Induced↗
Counseling pregnant women treated with paroxetine. Concern about cardiac malformations.
QUESTION: I have always reassured my patients that taking selective serotonin reuptake inhibitors (SSRIs) during pregnancy would not increase their risk of having children with major malformations. A recent warning from Health Canada, based on results of a study from GlaxoSmithKline, stated that infants exposed to paroxetine might be at higher risk of congenital malformations, specifically cardiovascular defects. Some of my pregnant patients who are taking paroxetine heard the warning and asked me whether they should stop taking it. What should I tell them? ANSWER: The new warning is based on unpublished, non-peer-reviewed studies. It ignored 2 published studies that failed to show any association between exposure to paroxetine and cardiovascular malformations, and no association with cardiovascular malformations has been shown by SSRIs as a class. Even if there is risk, it is minimal, and the warning does not disclose details of the cardiovascular malformations. Many cases of ventricular septal defect, the most common cardiac malformation, resolve spontaneously. Concerned pregnant women should know that, if taken after the first trimester, drugs cannot cause cardiac malformations. Failure to treat depression during pregnancy can have severe consequences for both mothers and babies and is the strongest predictor of postpartum depression.
Canada↗
The safety of psychotropic drug use during pregnancy: a review.
A substantial number of women of childbearing age are prescribed psychotropic drugs, and because nearly 50% of pregnancies are unplanned, many women are still taking them upon becoming pregnant. This article reviews the various classes of psychotropic drugs that are commonly used to treat psychiatric disorders--antidepressants, benzodiazepines, antipsychotics, antiepileptics, lithium and monoamine oxidase (MAO) inhibitors--in terms of their safety during pregnancy. Evidence-based information from epidemiologic studies indicates that most psychotropic drugs are relatively safe for use during pregnancy. There is also an increasingly large body of evidence-based information in the literature indicating that it may be more harmful to both the mother and her baby if she is not treated appropriately when suffering from a severe psychiatric disorder. Therefore, it is important for women with psychiatric disorders and their healthcare providers to have access to evidenced-based information about the safety of these drugs when taken during pregnancy to ensure that women make an informed decision as to whether they should continue with the pharmacotherapy they have been using to treat their condition.
Clinical Trials as Topic↗
Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy harmful to neonates?
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Adult↗
Antidepressant use during pregnancy and the rates of spontaneous abortions: a meta-analysis.
BACKGROUND: Due to the high prevalence of depression in women of childbearing age and coupled with the fact that approximately 50% of the pregnancies are unplanned, there is a high chance that these women have been exposed to antidepressants in early pregnancy. OBJECTIVE: To determine baseline rates of spontaneous abortions (SAs) and whether antidepressants increase those rates. METHODS: Rates of SAs in women taking antidepressants compared with non-depressed women were combined into a relative risk using a random effects model. MEDLINE, EMBASE, Healthstar, Toxline, Psychlit, Cochrane database, and Reprotox were searched for studies published in any language from 1966 to 2003. Key words used to identify articles included pregnancy outcome, abortion, miscarriage, spontaneous, antidepressant, depression, and the generic names of each antidepressant and class. Bibliographies, review articles, and reference lists from studies were also used to identify potential articles expected to provide evidence of safety of antidepressants in pregnancy. RESULTS: Of 15 potential articles, 6 cohort studies of 3567 women (1534 exposed, 2033 nonexposed) provided extractable data. All matched on important confounders. Tests found no heterogeneity (chi2 3.13; p = 0.98), and all quality scores were adequate (>50%). The baseline SA rate (95% CI) was 8.7% (7.5% to 9.9%; n = 2033). For antidepressants, the rate was 12.4% (10.8% to 14.1%; n = 1534), significantly increased by 3.9% (1.9% to 6.0%); RR was 1.45 (1.19 to 1.77; n = 3567). No differences were found among antidepressant classes. CONCLUSIONS: Maternal exposure to antidepressants may be associated with increased risk for SA; however, depression itself cannot be ruled out.
Abortion, Spontaneous↗
Newer antidepressants in pregnancy and rates of major malformations: a meta-analysis of prospective comparative studies.
BACKGROUND: A substantial number of women of childbearing age suffer from depression. Despite this, relatively little is known about the safety of antidepressant use during pregnancy. PURPOSE: We conducted a meta-analysis of prospective comparative cohort studies to quantify the relationship between maternal exposure to the newer antidepressants and major malformations. METHODS: We searched Medline, Embase and Reprotox from 1996 to the present for studies comparing outcomes in first trimester exposures to citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, reboxetine, venlafaxine, nefazodone, trazodone, mirtazapine and bupropion to those of non-exposed mothers. Data were combined using a random effects model; heterogeneity was tested with chi2, and publication bias with a funnel plot and the Begg-Mazumdar statistic. RESULTS: Twenty-two studies were identified, 15 were rejected (4 reviews, 4 without comparison groups, 2 third trimester exposures, 2 retrospective database studies, 2 case reports and 1 duplicate); 7 studies (n = 1774) met inclusion criteria. Effects were not heterogeneous (chi2 = 2.04, p = 0.92); funnel plot and test (tau = -0.24, p = 0.45) indicated no publication bias. The summary relative risk was 1.01 (95%CI: 0.57-1.80). CONCLUSIONS: As a group, the newer antidepressants are not associated with an increased risk of major malformations above the baseline of 1-3% in the population.
Abnormalities, Drug-Induced↗
Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study.
OBJECTIVE: Bupropion was developed for the treatment of depression, but subsequently was found to be effective for smoking cessation. To date, there are no prospective comparative studies examining its safety in pregnancy. The primary objective was to determine whether bupropion increases the risks for major malformations above baseline. The secondary objective was to examine the rates of live births, stillbirths, spontaneous and therapeutic abortions, mean birth weight, and gestational age at birth. STUDY DESIGN: Women who were pregnant or planning a pregnancy and taking bupropion were enrolled in the study. Follow-up of pregnancy outcome was carried out between 4 months and 1 year after delivery. Three comparisons were carried out: 1) women exposed to bupropion vs a nonteratogen group; 2) those taking for depression vs other antidepressants, vs a nonteratogen group; 3) spontaneous abortions were compared between those taking for depression, vs another antidepressant group vs a nonteratogen group. RESULTS: We completed follow-up on 136 women exposed to bupropion during the first trimester of pregnancy. There were (105) live births, no major malformations, the mean birth weight was (3450g), the mean gestational age at delivery was (40 weeks), the number of spontaneous abortions was 20, there were 10 therapeutic abortions, there was 1 stillbirth, and 1 neonatal death. There were no statistically significant differences between any of the end points we examined between the exposed and comparison groups, with the exception of significantly more spontaneous abortions in the bupropion group (P = .009). CONCLUSION: These results suggest that bupropion does not increase the rates of major malformation above baseline. The higher rates of spontaneous abortions are similar to other studies examining the safety of antidepressants during pregnancy.
Abnormalities, Drug-Induced↗
Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome.
OBJECTIVE: Citalopram is a selective serotonin reuptake inhibitor indicated for depression. The safety of this medication in pregnancy has not been fully established. The purpose of this study was to investigate whether citalopram is associated with an increased incidence of adverse pregnancy outcomes. STUDY DESIGN: Pregnant women who contacted the Motherisk Program, a Teratogen Information Center in Toronto, Ontario, with regard to the safety of citalopram in pregnancy were enrolled in the study. The exposed women were matched to a disease-matched group of women and a nonteratogenic group. All women were matched for age (+/- 2 years) and gestational age at time of first call to the Motherisk (+/- 2 weeks). A structured telephone follow-up interview was conducted following the expected date of confinement. RESULTS: The total number of pregnant women enrolled in this study was 396 (132 women in each group). A total of 125 women took citalopram at least in the first trimester. Seventy-one (54%) women continued to take the drug throughout pregnancy. One hundred fourteen women (86%) had live births, 14 (11%) had spontaneous abortions, 2 (1.5%) had elective terminations, and 2 (1.5%) experienced stillbirths. Fetal survival rates, mean birth weights, and duration of pregnancy were not statistically different among the 3 groups. Of 108 live-born infants whose mothers were exposed to citalopram in the first trimester, there was 1 (0.9%) male infant born with a major malformation. There was a relative risk of 4.2 (95% confidence interval 1.71-10.26) in neonates exposed to citalopram close to term to be admitted to special-care nurseries as compared with the unexposed infants. CONCLUSION: Citalopram use during the period of embryogenesis in pregnancy is not associated with an apparent major teratogenic risk. Late pregnancy use of citalopram is associated with increased risk of poor neonatal adaptation syndrome, recently described with other selective serotonin reuptake inhibitors.
Antidepressive Agents, Second-Generation↗
Abrupt discontinuation of psychotropic drugs following confirmation of pregnancy: a risky practice.
A number of pregnant women suffer from psychiatric disorders that require treatment with psychotropic drugs. A literature review suggests that these medications are relatively safe to use during pregnancy. Abrupt discontinuation of these drugs can have both physiological and psychological ramifications, which include unpleasant physical symptoms and re-emergence of the psychiatric condition. Therefore, it is not good practice to discontinue these medications abruptly upon diagnosis of pregnancy.
Adult↗
Effectiveness of bupropion for smoking cessation during pregnancy.
Gestational smoking has been established as a risk to the fetus. However, many pregnant smokers are unable to quit due to the highly addictive nature of nicotine. Nicotine replacement therapy has failed in several studies in pregnant women. In a prospective matched, controlled observational study, of 22 pregnant smokers receiving bupropion, 10 (45%) ceased smoking, as compared to 3 (14%) of 22 controls (P = 0.047). Bupropion appears to be effective for smoking cessation therapy during pregnancy.
Adult↗
The safety of antidepressant use in pregnancy.
Depression during pregnancy affects an estimated 10 - 20% of women, some of whom will require treatment with antidepressants. It is of great importance that the safety of this particular class of drugs is reviewed, to ensure the optimal treatment of the mother while protecting her unborn child. In this review, current safety data on all available antidepressants are discussed in detail, including the pharmacokinetics of the maternal-fetal unit and the epidemiological studies that have been published to date. The classes of antidepressants discussed include: tricyclics, selective serotonin re-uptake inhibitors and other antidepressants. After reviewing these studies, it is evident that these drugs appear to be relatively safe to take during pregnancy. This evidence-based information will be helpful to women and their healthcare providers, when the decision of whether or not to treat with anti-depressants during pregnancy must be made.
Abortion, Induced↗