Antidepressant Exposure Research Articles

Are selective serotonin reuptake inhibitors associated with fractures?

Antidepressant use in North America is on the rise. From 2007 to 2011, antidepressants were the most commonly used medication class by Canadian women aged 25 to 79 years and among the top 5 classes of drugs used by men aged 25 to 64 years.1 Selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, paroxetine, sertraline) are one of the most widely used classes of antidepressants because of their efficacy, favourable side effect profile and broad indications for use.2 In the past decade, more attention has been paid to the adverse effects of medications on bone health. Glucocorticoids, aromatase inhibitors (e.g., anastrazole, letrozole, exemestane), thiazolidinediones or “glitazones” (e.g., pioglitazone) and proton pump inhibitors (e.g., pantoprazole, omeprazole), among others, are suspected contributors to fractures.3 There is evidence indicating that SSRIs may also be implicated.3 In patients aged 66 years and older, current exposure to SSRIs has been associated with hip fractures compared with no antidepressant exposure (adjusted odds ratio [aOR]; 2.4; 95% CI: 2.0-2.7).4 One-third of women and one-fifth of men in Canada will experience an osteoporotic fracture during their lifetime. In 2010, osteoporosis and fractures cost the Canadian health care system upwards of 2.3 billion dollars.5 Fractures can cause a loss of long-term mobility and increase the risk of institutionalization. A prospective observational cohort of older adults showed that 12 months after a hip fracture, only half of patients regained their prefracture mobility level and only one-third of those who were previously mobile without an aid regained full mobility.6 A Canadian cohort (2001-2006) revealed that 12 months after a hip fracture, 24% of adults aged 75 years and older who were previously living in the community required institutionalization.7 However, that risk was much lower in patients aged 60 to 74 years, in whom only 14% of men and 4% of women required a transfer to a long-term care institution.7 Fractures are also associated with mortality, with 28% of women and 37% of men who experience a hip fracture dying within a year.5 It is therefore increasingly important to quantify the association between SSRIs and bone health. This review will discuss the current evidence that explores their association with an increased fracture risk.

Non-tricyclic and Non-selective Serotonin Reuptake Inhibitor Antidepressants and Recurrent Falls in Frail Older Women

To determine the risk of recurrent falls associated with antidepressants other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) among frail older women. This is a secondary analysis of the Zoledronic acid in frail Elders to STrengthen bone, or ZEST, trial data treated as a longitudinal cohort in 181 frail, osteoporotic women aged ≥65 years in long-term care. The primary exposure was individual non-TCA/non-SSRI antidepressants (i.e., serotonin norepinephrine reuptake inhibitors, mirtazapine, trazodone, and bupropion) at baseline and 6 months. The main outcome was recurrent (at least two) falls within 6 months after antidepressant exposure. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were derived using a generalized estimating equations model. At least 15% of women experienced recurrent falls between 0-6 and 6-12 months. At baseline and 6 months, 18.2% and 6.9% had a non-TCA/non-SSRI antidepressant, respectively. Adjusting for demographics, health status, and other drugs that increase risk of falls, non-TCA/non-SSRI antidepressant exposure significantly increased the risk of recurrent falls (AOR: 2.14; 95% CI: 1.01-4.54). Fall risk further increased after removing bupropion from the non-TCA/non-SSRI antidepressant group in sensitivity analyses (AOR: 2.73; 95% CI: 1.24-6.01). Other antidepressant classes may not be safer than TCAs/SSRIs with respect to recurrent falls in frail older women.

Effectiveness of Antidepressant Medications for Symptoms of Irritability and Disruptive Behaviors in Children and Adolescents.

Chronic irritability is a common presenting symptom in children and youth in both clinical settings (25%) and in the community (6%-8%). Treatment of irritability is relatively understudied. The purpose of this article is to synthesize evidence regarding the efficacy and safety of antidepressant medications for the treatment of irritability and related symptom dimensions in children and youth. Systematic review of the literature was conducted to identify studies (including youth aged 6-18) that assessed the effectiveness of antidepressant medications for the treatment of irritability or related behavioral phenotypes, including aggression or symptoms of. Studies of youth with developmental disabilities or autism spectrum disorders were excluded. We identified 99 studies (three randomized trials) assessing the effect of antidepressants in improving irritability, aggression, or oppositional symptoms as secondary outcomes. Only two studies specifically measured the outcome of irritability. Eight of the 11 studies reported significant effects on aggression, oppositionality, or irritability with antidepressant exposure, although effect sizes in all, but two of these, studies were less than 0.25. These effects were significantly reduced, but remained significant in seven of these studies after controlling for changes in comorbid depression scores with treatment. The other three studies reported no change, an increase in frequency of self-harm or aggressive behaviors or benefit in only a subsample of youth who tolerated the antidepressants after 1 year of follow-up. Antidepressant medication exposure appears to have a small effect on irritability and related symptoms in youth. Heterogeneity in the study sample and absence of irritability being measured as a primary outcome across studies restrict the validity of the conclusions. Irritability is a debilitating outcome that needs specific attention in medication treatment studies.

Antidepressant Use and Subclinical Measures of Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.

Antidepressants are commonly prescribed medications used in primary care. The cardiovascular safety profile of antidepressant medications, in terms of subclinical atherosclerosis, is underexamined. A total of 6814 participants in the Multi-Ethnic Study of Atherosclerosis were examined. At baseline, the mean age was 62 years with 4 race/ethnic groups represented: European Americans (38%), Hispanic Americans (23%), African Americans (28%), and Chinese Americans (11%). Antidepressants were subgrouped as serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and "other" (bupropion, nefazodone, trazodone, mirtazapine). After adjusting for potential confounders, we estimated the association between antidepressant use and the following measures of subclinical atherosclerosis: coronary artery calcium (CAC), the ankle-brachial index, and carotid intima-media thickness, both cross-sectionally and prospectively. A total of 324 participants were exposed to SSRIs, 88 to TCAs, 41 to SNRIs, and 123 to other antidepressants. For CAC incidence, the fully adjusted longitudinal analyses revealed no consistent associations with SSRIs (relative risk [RR], 0.99; 95% confidence interval [CI], 0.71-1.37), SNRIs (RR, 0.49; 95% CI, 0.13-1.86), TCAs (RR, 0.94; 95% CI, 0.50-1.77), other antidepressant (RR, 0.87; 95% CI, 0.73-1.03) exposure, and subclinical disease. Similar null results were obtained in the cross-sectional and longitudinal exposure to antidepressants with changes in baseline CAC greater than 0, ankle-brachial index, and carotid intima-media thickness. The results of the current study do not support an association between antidepressants and subclinical atherosclerosis.

Endometrial cancer and antidepressants

To our knowledge, the association between antidepressant exposure and endometrial cancer has not been previously explored. Herein, we aim to investigate the association between antidepressant prescription, including novel antidepressants, and the risk for endometrial cancer in a population-based study.Data for the analysis were derived from National Health Insurance Research Database. We identified 8392 cases with a diagnosis of endometrial cancer and 82,432 matched controls. A conditional logistic regression model was used, with adjusting for potentially confounding variables (e.g., comorbid psychiatric diseases, comorbid physical diseases, and other medications). Risk for endometrial cancer in the population-based study sample was categorized by, and assessed as a function of, antidepressant prescription and cumulative dosage.We report no association between endometrial cancer incidence and antidepressant prescription, including those prescribed either selective serotonin reuptake inhibitors (adjusted odds ratio [OR] = 0.98; 95% confidence interval [CI], 0.84-1.15) or serotonin norepinephrine reuptake inhibitors (adjusted OR = 1.14; 95% CI, 0.76-1.71). We also did not identify an association between higher cumulative doses of antidepressant prescription and endometrial cancer.There was no association between antidepressant prescription and endometrial cancer.

Recent Advances and Controversies in Peripartum Depression.

The purpose of this review is to update readers on recent controversies and findings on the underlying biology and clinical management of peripartum depression. Topics discussed include the discovery and replication of two epigenetic biomarkers of peripartum depression, two well controlled studies that do NOT find associations between in utero antidepressant exposure and cardiac defects and persistent pulmonary hypertension of the newborn and ongoing controversy on whether antidepressant use during pregnancy prevents peripartum depression and whether or not hormonal treatments have a place in the management of postpartum depression. Peripartum depression, or depression during and/or immediately following pregnancy is a unique psychiatric illness that not only may have unique biological underpinnings but demands unique and thoughtful approaches to management due to the developing neonate. A number of controversies exist in this area ranging from the recent terminology change in psychiatry's Diagnostic and Statistical Manual from "postpartum" to "peripartum" depression, to the safety of antidepressant use during pregnancy, to whether or not antidepressants prevent or decrease peripartum depression. Research in this area is growing and a number of exciting developments have occurred including the identification of two epigenetic biomarkers of peripartum depression that may eventually lead to early identification and intervention, the potential for hormonal treatments and the recommendation for and early institution of universal screening for peripartum depression. These topics are explored and put into context from a clinical management perspective.

Antidepressant Exposure and Risk of Fracture Among Medicaid-Covered Youth.

This study examines the association between antidepressant use and risk of fracture in depressed youth and assesses whether fracture incidence varies over the course of antidepressant treatment. A retrospective cohort analysis of Ohio Medicaid claims data was conducted for youth ages 6-17 years with a new episode of ICD-9-diagnosed depression from 2001-2009. The primary outcome variable was time to fracture. Fracture rates were compared between depressed youth treated with antidepressant medication and untreated depressed youth. Time categories of no use, past use, and current use were compared. Of 50,673 depressed youths, 5,872 (11.6%) experienced a fracture. Of those who had a fracture, 2,228 (37.9%) were exposed to antidepressants, 80% of which were selective serotonin reuptake inhibitors. The adjusted hazard ratio (HR) was 3% higher in those currently prescribed antidepressants (HR = 1.03; 95% CI, 1.00-1.06; P = .03). The risk ratio (RR) for adjusted fracture rates per 10,000 persons was twice as high during the first 30 days of antidepressant use compared to the other time periods (RR = 2.0; 95% CI, 1.2-3.3; P = .007). The number of fractures for those with past antidepressant use did not differ from those with no history of antidepressant use. Antidepressant use may be associated with a small but significant increase in fracture risk, particularly within the first 30 days of treatment. Findings underscore a need for additional prospective and mechanistic research. Prescribers should consider other risks for fracture in antidepressant-treated youth, particularly disability and the concomitant use of other medications that increase fracture risk.

Co-exposure to fish oil or folic acid does not reverse effects in the progeny induced by maternal exposure to fluoxetine

The serotonin reuptake inhibitor antidepressant fluoxetine (FLX) has been widely prescribed for the treatment of some diseases during pregnancy and/or lactation. Despite possible adverse effects observed in the progeny after maternal exposure to FLX, it is recognized that not treating a mother who has clinical indication for antidepressants may also impact negatively her well being and the fetal/newborn development. The present study investigated if two supplements already used by pregnant women, i.e., folic acid (FA) and fish oil (FO) could minimize effects in pubertal rats induced by maternal exposure to FLX during pregnancy and lactation. Evaluations included two behavioral tests (elevated plus maze and novelty-induced suppressed feeding) and quantification of brain derived neurotrophic factor (BDNF) in the hippocampus. Wistar rats were gavaged with FLX (5mg/kg) or tap water associated or not with FA (3mg/kg) or FO (1.3mg/kg) during pregnancy and lactation. Pups exposed to FLX presented anxiety-like behavior and decreased hippocampal BDNF levels that were not influenced by co-exposure with FA or FO. FO exposure resulted in anxiety-like behavior, decreased BDNF levels and eating behavior whereas FA exposure increased BDNF and induced hyperactivity in the elevated plus maze. In conclusion, this study suggests that reduced hippocampal BDNF may play a role in the developmental neurotoxicity of FLX. FA and FO were not effective as employed in the present study but the search for alternatives to manage the risk of antidepressant exposure during pregnancy and/or lactation is likely to continue.

Treatment Emergent Suicidal Ideation in depressed older adults.

Treatment-Emergent Suicidal Ideation (TESI) in older adults is poorly understood. We characterized TESI in older depressed adults during treatment with venlafaxine and explored whether TESI is related to antidepressant exposure versus dimensions of the psychiatric illness. We examined the relationship among medication exposure, onset of TESI, and clinical characteristics. We analyzed data on 233 clinical trial participants with major depression and no baseline suicidal ideation who were treated for up to 12 weeks with venlafaxine XR (target dose: 150-300 mg/day). Suicidal ideation was assessed weekly with the Scale for Suicide Ideation. A Kaplan-Meier curve displayed the time course of TESI. Differences in baseline demographic and clinical variables between the TESI and Non-TESI groups were assessed with analyses of covariance or logistic regression. A final multivariate logistic regression model indicated baseline predictors of TESI. Depression treatment outcomes in subjects developing TESI versus those who did not were examined with a mixed effects model. TESI occurred in 10% of participants, typically with onset within 4 weeks of the start of treatment. Anxiety, and depression severity at baseline were predictors of TESI. Most TESI was mild and transient, with 6/233 participants having TESI considered clinically meaningful. TESI was not associated with venlafaxine blood levels or side effects. In older depressed adults, TESI is relatively uncommon and it is likely related to the underlying illness rather than to a medication adverse effect. This suggests that TESI requires continuing rather than discontinuing antidepressant treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Association of Antenatal Depression Symptoms and Antidepressant Treatment With Preterm Birth.

To evaluate the association of antenatal depression symptoms with preterm birth and small for gestational age (SGA). This was an observational cohort study conducted among women who completed Edinburgh Postnatal Depression Scale screening and delivered at 20 weeks of gestation or greater. The primary outcomes were preterm birth and an SGA neonate at birth (less than 10th percentile for gestational age); the primary predictor was an Edinburgh Postnatal Depression Scale antepartum score of 10 or greater, indicating symptoms of depression. Logistic regression models were used with and without consideration of antidepressant exposure during pregnancy. Among 7,267 women, 831 (11%) screened positive for depression. In multivariable analyses adjusting for maternal age, race, income, body mass index, tobacco use, lifetime diagnosis of major depression and anxiety, diabetes, hypertension, and preeclampsia, women who screened positive for depression experienced an increased risk of preterm birth (less than 37 weeks of gestation) (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.04-1.55) and very preterm birth (less than 32 weeks of gestation) (adjusted OR 1.82, 95% CI 1.09-3.02) as well as of having an SGA neonate (adjusted OR 1.28, 95% CI 1.04-1.58). In secondary analyses, among women who were treated with an antidepressant during pregnancy (19% of those who screened positive and 5% of those who screened negative), depressive symptoms were not associated with a significantly increased risk of preterm and very preterm birth or an SGA neonate. In a large cohort of women screened for depression antepartum, those with depressive symptoms had an increased likelihood of preterm and very preterm delivery as well having an SGA neonate. Such risk was not apparent among women who were treated with an antidepressant medication.

Selective Serotonin Re-Uptake Inhibitors and Hyponatremia in Acutely Medically-Ill Inpatients.

Selective Serotonin Reuptake Inhibitors (SSRIs) have become the mainstay of treatment for depression, anxiety, and many other conditions. However, they have been associated with an increased risk of hyponatremia. Little is known about the risk of SSRI-associated hyponatremia in certain potentially at-risk populations, such as patients with acute medical illnesses. The main objective of this study was to examine the effect of SSRIs on serum sodium levels in medically-ill inpatients. We performed a retrospective cohort study of 239 medically-ill inpatients assessed by the psychiatric consultation-liaison team of a large Canadian academic hospital between 2008 and 2014. We grouped patients based on whether they were exposed to an SSRI, a non-SSRI antidepressant, or no antidepressant at all. Our primary outcome was the maximum decrease in serum sodium level observed within 30 days of antidepressant exposure in the inpatient setting. Our secondary outcome was the incidence of hyponatremia (serum sodium level <135 mEq/L) or severe hyponatremia (sodium level <130 mEq/L) within the same time frame. The maximum decrease in sodium serum level from baseline did not differ between the 3 groups studied (SSRIs - 3.31 mEq/L vs non-SSRI antidepressants -3.41 mEq/L vs no antidepressants -3.13 mEq/L, F (2) = 0.79, p= 0.92). The incidence of hyponatremia and severe hyponatremia did not differ between groups either. This remained the case after controlling for covariates. SSRIs do not appear to be associated with an increased risk of hyponatremia in medically-ill inpatients. Clinicians should not avoid prescribing SSRIs in this population based solely on the assumption of hyponatremia risk.

The Prevalence and Characteristics of REM Sleep without Atonia (RSWA) in Patients Taking Antidepressants.

The association of REM sleep without atonia (RSWA) as well as REM sleep behavior disorder (RBD) with the intake of selective serotonin reuptake inhibitors (SSRI) and selective norepinephrine reuptake inhibitors (SNRI) is well established. Our study objective was to determine the prevalence of RSWA and RBD among a group of sleep center patients taking SSRI and SNRI. A retrospective chart review was done at our tertiary sleep center, and 10,746 consecutive records from October 1, 2007, through October 31, 2013, were searched for SSRI and SNRI names using the Sleep Cataloguer Software. The search resulted in 1,444 records, which were then reviewed for keywords of RSWA and RBD. The AASM scoring criteria were used to determine RSWA. Reports of 41 patients with known narcolepsy or α-synucleinopathies were excluded. The remaining records were mined for age, sex, presence of obstructive sleep apnea (OSA), type of antidepressant (SSRI or SNRI), and diagnosis for which antidepressant was prescribed. We used logistic regression analysis to adjust for age, OSA, and sex. Of the 1,444 participants on antidepressants, 176 (12.2%) had RSWA (all confirmed by the investigators) compared to 226 of the entire sleep lab population of 10,746 (2.1%), risk ratio (95% CI) 9.978 (8.149, 12.22). Seven of the 176 patients on antidepressants had RBD (0.48%) compared to 108 of 10,746 (1%), p = 0.005. SSRI and SNRI are associated with a higher prevalence of RSWA but not of RBD. This is independent of medication type.

Is increased antidepressant exposure a contributory factor to the obesity pandemic?

Major depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, and vice versa. Hypothalamic–pituitary–adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination of stress and antidepressants followed by long-term high-fat diet results, long after discontinuation of antidepressant treatment, in markedly increased weight, in excess of what is caused by high-fat diet alone. On the basis of existing epidemiological, clinical and preclinical data, we have generated the testable hypothesis that escalating use of antidepressants, resulting in high rates of antidepressant exposure, might be a contributory factor to the obesity epidemic.

Case‐only designs for studying the association of antidepressants and hip or femur fracture

AbstractPurposeThe purpose of this study is to evaluate the performance and validity of the case‐crossover (CCO) and self‐controlled case‐series (SCCS) designs when studying the association between hip/femur fracture (HF) and antidepressant (AD) use in general practitioner databases. In addition, comparability with cohort and case–control designs is discussed.MethodsAdult patients with HF and who received an AD prescription during 2001–2009 were identified from UK's The Health Improvement Network (THIN) and the Dutch Mondriaan databases. AD exposure was classified into current, recent and past/non‐use (reference). In the CCO, for each patient, a case moment (date of HF) and four prior control moments at −91, −182, −273 and −365 days were defined. In SCCS, incidence of HF was compared between exposure states. Conditional logistic regression was used in the CCO and Poisson regression in the SCCS to compute odds ratios and incidence rate ratios, respectively. In CCO, we adjusted for time‐varying co‐medication and in SCCS for age.ResultsAdjusted estimates for the effect of current AD exposure on HF were higher in the CCO (co‐medication‐adjusted odds ratio, THIN: 2.24, 95% confidence interval [CI]: 2.04–2.47; Mondriaan: 2.57, 95%CI [1.50, 4.43]) than in the SCCS (age‐adjusted incidence rate ratio, THIN: 1.41, 95%CI [1.32, 1.49]; Mondriaan: 2.14, 95%CI [1.51, 3.03]). The latter were comparable with the traditional designs.ConclusionCase‐only designs confirmed the association between AD and HF. The CCO design violated assumptions in this study with regard to exchangeability and length of exposure, and transient effects on outcome. The SCCS seems to be an appropriate design for assessing AD–HF association. Copyright © 2016 John Wiley &amp; Sons, Ltd.

Depression During Pregnancy and Postpartum.

Depression is a common complication of pregnancy and the postpartum period. There are multiple risk factors for peripartum mood disorders, most important of which is a prior history of depression. Both depression and antidepressant medications confer risk upon the infant. Maternal depression has been associated with preterm birth, low birth weight, fetal growth restriction, and postnatal cognitive and emotional complications. Antidepressant exposure has been associated with preterm birth, reductions in birth weight, persistent pulmonary hypertension, and postnatal adaptation syndrome (PNAS) as well as a possible connection with autism spectrum disorder. Paroxetine has been associated with cardiac malformations. Most antidepressant medications are excreted in low levels in breast milk and are generally compatible with breastfeeding. The use of antidepressants during pregnancy and postpartum must be weighed against the risk of untreated depression in the mother.

Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children.

The association between the use of antidepressants during gestation and the risk of autism spectrum disorder (ASD) in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression. To examine the risk of ASD in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression. We conducted a register-based study of an ongoing population-based cohort, the Québec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Québec from January 1, 1998, to December 31, 2009. A total of 145,456 singleton full-term infants born alive and whose mothers were covered by the Régie de l'assurance maladie du Québec drug plan for at least 12 months before and during pregnancy were included. Data analysis was conducted from October 1, 2014, to June 30, 2015. Antidepressant exposure during pregnancy was defined according to trimester and specific antidepressant classes. Children with ASD were defined as those with at least 1 diagnosis of ASD between date of birth and last date of follow-up. Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios with 95% CIs. During 904,035.50 person-years of follow-up, 1054 children (0.7%) were diagnosed with ASD; boys with ASD outnumbered girls by a ratio of about 4:1. The mean (SD) age of children at the end of follow-up was 6.24 (3.19) years. Adjusting for potential confounders, use of antidepressants during the second and/or third trimester was associated with the risk of ASD (31 exposed infants; adjusted hazard ratio, 1.87; 95% CI, 1.15-3.04). Use of selective serotonin reuptake inhibitors during the second and/or third trimester was significantly associated with an increased risk of ASD (22 exposed infants; adjusted hazard ratio, 2.17; 95% CI, 1.20-3.93). The risk was persistent even after taking into account maternal history of depression (29 exposed infants; adjusted hazard ratio, 1.75; 95% CI, 1.03-2.97). Use of antidepressants, specifically selective serotonin reuptake inhibitors, during the second and/or third trimester increases the risk of ASD in children, even after considering maternal depression. Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy.

Antidepressant Prescription Claims Among Reproductive-Aged Women With Private Employer-Sponsored Insurance - United States 2008-2013.

Antidepressant medication use during pregnancy has been increasing in the United States (1). Many women require antidepressants on an ongoing basis, and a clear consensus on the safest medication options for both the mother and her fetus does not exist (2). Given that half of all U.S. pregnancies are unplanned (3), antidepressant use will occur during the first weeks of pregnancy, a critical period for fetal development. To understand trends among women of reproductive age, CDC used Truven Health's MarketScan Commercial Claims and Encounters data* to estimate the number of antidepressant prescriptions filled by women aged 15-44 years with private employer-sponsored insurance. During 2008-2013, an average of 15.4% of women aged 15-44 years filled at least one prescription for an antidepressant in a single year. The most frequently filled antidepressants included sertraline, bupropion, and citalopram. Prescribing of antidepressants is common, and research on antidepressant safety during pregnancy needs to be accelerated to provide evidence-based information to health care providers and women about the potential risks for antidepressant exposure before and during pregnancy and between pregnancies.

Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.

Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50−1.54 for ASD; 0.97, 95% confidence interval 0.53−1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.

Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study.

Although mortality related to psychotropic medications has received much attention in recent years, little is known about the relationship between risk of death and cumulative antipsychotic load, and even less about the relationship between mortality and cumulative exposure to antidepressants or benzodiazepines. The authors examined these relationships using nationwide databases. The authors used prospectively collected nationwide databases to identify all individuals 16-65 years of age with a schizophrenia diagnosis (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010. Compared with no exposure, both moderate (adjusted hazard ratio=0.59, 95% CI=0.49-0.70) and high (adjusted hazard ratio=0.75, 95% CI=0.63-0.89) antipsychotic exposures were associated with substantially lower overall mortality. Moderate antidepressant exposure was associated with a lower mortality (adjusted hazard ratio=0.85, 95% CI=0.73-0.98), and high exposure, even lower (adjusted hazard ratio=0.71, 95% CI=0.59-0.86). Exposure to benzodiazepines showed a dose-response relationship with mortality (hazard ratios up to 1.74 [95% CI=1.50-2.03]). Moderate and high-dose antipsychotic and antidepressant use were associated with 15%-40% lower overall mortality, whereas chronic high-dose use of benzodiazepines was associated with up to a 70% higher risk of death compared with no exposure. Since patients with anxiety and depressive symptoms may have a higher intrinsic risk of death, the finding for benzodiazepines may be attributable to some extent to residual confounding.

Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64years: cohort study using a primary care database.

BackgroundEpilepsy is a serious condition which can profoundly affect an individual’s life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years.MethodsData on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox’s proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables.ResultsIn the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166).ConclusionsRisk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0701-9) contains supplementary material, which is available to authorized users.