Prenatal Antidepressant Exposure Research Articles

Association between maternal antidepressant use during pregnancy and the risk of autism spectrum disorder and attention deficit hyperactivity disorder in offspring.

Prenatal antidepressant exposure has been reported to be associated with adverse neurodevelopmental outcomes, yet studies considering confounding factors in Asian populations are lacking. This study utilized a nationwide data base in Taiwan, enrolling all liveborn children registered in the National Health Insurance system between 2004 and 2016. Subjects were divided into two groups: antidepressant-exposed (n = 55,707)) and antidepressant-unexposed group (n = 2,245,689). The effect of antidepressant exposure during different trimesters on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) was examined. Sibling controls and parallel comparisons by paternal exposure status were treated as negative controls. Additional sensitivity analyses were conducted to examine the effects of antidepressant exposure before and after pregnancy. Prenatal antidepressant exposure was associated with increased risks of ASD and ADHD in population-wide and adjusted analysis. However when comparing antidepressant-exposed children with their unexposed siblings, no differences were found for ASD (Hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.76-1.42 in first trimester; HR: 0.96, 95% CI 0.62-1.50 in second trimester; HR: 0.69, 95% CI 0.32-1.48 in third trimester) and ADHD (HR: 0.98, 95%CI 0.84-1.15 in first trimester; HR: 0.91, 95% CI 0.73-1.14 in second trimester; HR: 0.79, 95% CI 0.54-1.16 in third trimester). Increased risks for ASD and ADHD were also noted in paternal control, before and after pregnancy analyses. These results imply that the association between prenatal antidepressant exposure and ASD and ADHD is not contributed to by an intrauterine medication effect but more likely to be accounted for by maternal depression, genetic, and potential environmental factors.

Discussion around SSRIs and pregnancy still leans toward treatment

Last year a seminal study, “Prenatal antidepressant exposure and offspring brain morphologic trajectory” by Dojukan Koc, M.D., and colleagues was published in JAMA Psychiatry. The cohort study results suggested that there may be an association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and changed brain regions involved in emotional regulation in offspring; however, in some brain regions such as the amygdala, the changes disappeared by age 15. The Koc study included a total of 2,198 mother‐child dyads; compared to nonexposed controls, children prenatally exposed to SSRIs had less cerebral gray matter, and a steeper increase in amygdala volume and gyrus from 7 to 15 years of age. Changes in the amygdala and fusiform gyrus did not persist until early adolescence. Postnatal depression in the mother was associated with a reduced fusiform gyrus in the offspring; prenatal depression was aassociated with a smaller volume of the rostral anterior cingulate gyrus in the child. There was no association of SSRI use before pregnancy with brain outcomes in offspring. The Koc study was notable for its long follow‐up of brain growth, allowing for a focus on trajectory and not just a single image.

Prenatal antidepressant exposure and the risk of decreased gestational age and lower birthweight: A polygenic score approach to investigate confounding by indication.

Prenatal antidepressant exposure has been associated with lower gestational age and birthweight. Yet, unmeasured residual confounding may inflate this association. We explored if maternal genetic liability for major depression explains part of the association of antidepressant use in pregnancy with lower gestational age and birthweight. We employed the maternal polygenic score (PGS) for major depression as a measure of genetic liability. We used generalised linear models to estimate the differences in gestational age and birthweight at each PGS quintile between children whose mothers continued antidepressant use during pregnancy (continuation group), children whose mothers discontinued antidepressant use during pregnancy (discontinuation group) and unexposed children. After adjusting for confounders, we found significant differences in birthweight between PGS quintiles in the continuation and unexposed group. Yet, this relationship was not linear. Furthermore, at the lowest and highest PGS quintiles, the continuation group had significantly reduced mean gestational ages (adjusted β ranges: 1.7-4.5 days, p < 0.001-0.008) and lower mean birthweights (adjusted β ranges: 58.6-165.4 g, p = 0.001-0.008) than the discontinuation and unexposed groups. We confirmed that antidepressant use in pregnancy was associated with small reductions in gestational age and birthweight but found that genetic liability for depression was not linearly associated with this risk. The causality of the observed associations could not be established due to the observational nature of the study. Residual confounding linked to the underlying disease was likely still present.

3.36 Prenatal Antidepressant Exposure and the Risk of Decreased Gestational Age and Lower Birthweight: A Polygenic Score Approach to Investigate Confounding By Indication

3.36 Prenatal Antidepressant Exposure and the Risk of Decreased Gestational Age and Lower Birthweight: A Polygenic Score Approach to Investigate Confounding By Indication

Prenatal antidepressant exposure and emotional disorders until age 22: a danish register study

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants in pregnancy. Animal and some clinical studies have suggested potential increases in depression and anxiety following prenatal SSRI exposure, but the extent to which these are driven by the medication remains unclear. We used Danish population data to test associations between maternal SSRI use during pregnancy and children outcomes up to age 22.MethodsWe prospectively followed 1,094,202 single-birth Danish children born 1997–2015. The primary exposure was ≥ 1 SSRI prescription filled during pregnancy; the primary outcome, first diagnosis of a depressive, anxiety, or adjustment disorder, or redeemed prescription for an antidepressant medication. We used propensity score weights to adjust potential confounders, and incorporated data from the Danish National Birth Cohort (1997–2003) to further quantify potential residual confounding by subclinical factors.ResultsThe final dataset included 15,651 exposed and 896,818 unexposed, children. After adjustments, SSRI-exposed had higher rates of the primary outcome than those of mothers who either did not use an SSRI (HR = 1.55 [95%CI:1.44,1.67] or discontinued the SSRI use ≥ 3 months prior to conception (HR = 1.23 [1.13,1.34]). Age of onset was earlier among exposed (9 [IQR:7–13] years) versus unexposed (12 [IQR:12–17] years) children (p < 0.01). Paternal SSRI use in the absence of maternal use during the index pregnancy (HR = 1.46 [1.35,1.58]) and maternal SSRI use only after pregnancy (HR = 1.42 [1.35,1.49]) were each also associated with these outcomes.ConclusionsWhile SSRI exposure was associated with increased risk in the children, this risk may be driven at least partly by underlying severity of maternal illness or other confounding factors.

Prenatal antidepressant exposure and the risk of attention-deficit/hyperactivity disorder in childhood: Accounting for misclassification of exposure.

Many studies of prenatal antidepressant exposure and the risk of attention-deficit/hyperactivity disorder (ADHD) have done little to reduce bias from exposure misclassification. We assessed the prenatal antidepressant-ADHD effect by incorporating information on repeatedly redeemed prescriptions and redemptions of drug classes commonly used in pregnancy in the analyses to reduce bias from exposure misclassification. Using population-based registries, we conducted a nationwide cohort study of all children born in Denmark from 1997 through 2017. In a former-user analysis, we compared children prenatally exposed, defined by a redeemed prescription by the mother during pregnancy, to a comparison cohort consisting of prenatally unexposed children whose mother had redeemed a prescription before pregnancy. We incorporated information on repeatedly redeemed prescriptions and redemptions of drug classes commonly used in pregnancy in the analyses to reduce bias from exposure misclassification. We used incidence rate ratios (IRRs) and incidence rate differences (IRDs) as effect measures. The cohort included 1,253,362 children, among whom 24,937 were prenatally exposed to antidepressants. The comparison cohort consisted of 25,698 children. During follow-up, 1,183 exposed children and 1,291 children in the comparison cohort developed ADHD yielding an IRR of 1.05 (95% confidence interval [CI]: 0.96, 1.15) and an IRD of 0.28 (95% CI: -0.20, 0.80) pr. 1,000 person-years. IRRs from analyses attempting to reduce exposure misclassification varied from 1.03 to 1.07. Our results were not consistent with the hypothesized effect of prenatal antidepressant exposure on the risk of ADHD. Attempts to reduce exposure misclassification did not alter this finding.

Prenatal Antidepressant Exposures and Autism Spectrum Disorder or Traits: A Retrospective, Multi-Cohort Study.

Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.

Prenatal Antidepressant Exposure and the Risk of Attention-deficit/Hyperactivity Disorder in Childhood: A Cohort Study With Triangulation.

Uncontrolled confounding from maternal depression and genetic and environmental factors is expected in studies investigating the effect of prenatal antidepressant exposure on the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and may explain inconsistencies in the existing evidence. We aimed to assess this effect using triangulation. Using population-based health registries, we conducted a nationwide cohort study of all children born in Denmark between 1997 and 2017 and followed through 2018 for ADHD. We assessed the effect of prenatal antidepressant exposure on the risk of ADHD in childhood by comparing children with and without prenatal antidepressant exposure in terms of adjusted incidence rate ratios (IRRs), adjusted incidence rate differences (IRDs), and adjusted risk differences (RDs) and the associated 95% confidence intervals (CIs). We triangulated results from four different analytic approaches: an overall analysis, a negative control analysis, a sibling analysis, and a former-user analysis. The overall study cohort consisted of 1,253,362 children, among whom 28,910 (2.3%) had prenatal antidepressant exposure. ADHD during follow-up was diagnosed among 1,411 (4.9%) of the exposed and in 37,196 (3.0%) of the unexposed children. Triangulation suggested an IRR of 1.09-1.15; an IRD less than 1 case/1,000 person-years, and an RD of 0.9%-2.2% over an up to 18-year period. Based on triangulation, we estimated a modest effect of prenatal antidepressant exposure on the risk of ADHD in childhood. However, considering the limitations of our approaches, this observed association may be partially due to residual biases. See video abstract at, http://links.lww.com/EDE/B935.

Antidepressant use during pregnancy and risk of adverse neonatal outcomes: A comprehensive investigation of previously identified associations.

Prenatal antidepressant use is widespread. Observational studies have investigated the neonatal effects of prenatal antidepressant exposure with inconclusive results. We aimed to comprehensively investigate the associations between prenatal antidepressant exposure and the most commonly studied adverse neonatal outcomes: preterm birth, birthweight, poor neonatal adaptation, persistent pulmonary hypertension of the neonate (PPHN), neonatal admission and congenital malformations. We included 45,590singletons (born 1997-2015) whose mothers used antidepressants within one year before pregnancy. Children were categorised into two groups: continuation (antidepressant use before and during pregnancy) or discontinuation (antidepressant use before but not during pregnancy). We applied random-effects logistic and linear regressions, adjusting for covariates. After adjusting for confounders, prenatal antidepressant exposure was associated with a 2.3day (95% CI -2.9; -2.0) decrease in gestational age and a 51g (95% CI -62g; -41g) decrease in birthweight. The continuation group was at increased risk for moderate-to-late preterm birth (32-37weeks) (aOR=1.43; 95%CI 1.33; 1.55), moderately low birthweight (1500-2499g) (aOR=1.28; 95%CI 1.17; 1.41), postnatal adaptation syndrome (aOR=2.59; 95%CI 1.87; 3.59) and neonatal admission (aOR=1.52; 95%CI 1.44; 1.60) compared to the discontinuation group. Prenatal antidepressant exposure was associated with small decreases in gestational age and birthweight, as well as higher risk for moderate-to-late preterm birth, moderately low birthweight, neonatal admission and postnatal adaptation syndrome. No differences in risk were found for PPHN, or congenital malformations. The causality of the observed associations cannot be established due to the potential for unmeasured residual confounding linked to the underlying disease.

Gestational Exposure to Antidepressant Drugs and Neurodevelopment: An Examination of Language, Mathematics, Intelligence, and Other Cognitive Outcomes.

During the past decade, nearly a dozen small and large, prospective and retrospective observational studies examined cognitive neurodevelopmental outcomes in childhood after gestational exposure to antidepressant drugs. Many of the studies found that exposure was associated with poorer outcomes on measures of language, cognition, intellectual skills, and academic performance, but, in most instances, the association appeared to be more related to maternal depression during pregnancy and other confounds than to antidepressant use during pregnancy. A large new population-based observational study specifically examined language and mathematics performance in serial, nationally standardized tests. The study found that, in fully adjusted analyses, in children and adolescents aged 9-15 years, a history of gestational exposure to antidepressant drugs was associated with a small (by about 2 out of 100 points) but statistically significantly poorer performance in mathematics but not in language. The findings were consistent though attenuated in a large number of important and appropriate sensitivity analyses, some of which adjusted for confounding in additional ways. The body of literature reviewed suggests that prenatal antidepressant exposure is indeed associated with cognitive neurodevelopmental deficits and that the deficits are attenuated or eliminated by adjustment for maternal depression and other confounds. It is suggested that the deficits that remain despite adjustment may be due to residual confounding from unmeasured behavioral and internal environment variables associated with untreated maternal depression. Thus, prenatal antidepressant exposure may merely be a marker rather than the cause of cognitive neurodevelopmental deficits. Whereas the literature in the field does not drive a case for withholding antidepressants from depressed pregnant women, decision-making must remain a shared process.

Prenatal antidepressant exposure and neurodevelopmental problems in children: to get the right answer, we must ask the right question.

Prenatal antidepressant exposure and neurodevelopmental problems in children: to get the right answer, we must ask the right question.

Prenatal antidepressant exposure and child development at kindergarten age: a population-based study.

Though prenatal antidepressant exposure has been associated with adverse developmental outcomes, the extent to which the effects are due to prenatal drug exposure or underlying maternal mood disturbances is unclear. This was a population-based retrospective cohort study using administrative data from British Columbia, Canada (n = 94,712). Analyses were designed to remove confounding effects of prenatal antidepressant exposure from maternal mood. First, children prenatally exposed to antidepressants were matched to unexposed children using high-dimensional propensity scores (HDPS). Second, children whose mothers had used antidepressants throughout pregnancy were compared against those whose mothers discontinued treatment. In all, 3.87% (n = 3661) of children in the overall study population were prenatally exposed to antidepressants. In both analyses, we report increased odds for lower levels of physical independence (HDPS: OR, 1.14; 95% CI, 1.00-1.30; continuers/discontinuers: OR, 1.14; 95% CI, 0.99-1.32), and higher levels of anxious behaviors (HDPS: OR, 1.30; 95% CI, 1.01-1.66; continuers/discontinuers: OR, 1.32; 95% CI, 1.01-1.72) associated with antidepressant use in pregnancy. All other relationships were not significant using these methods. Prenatal antidepressant exposure was selectively associated with worse anxious behaviors and physical independence at kindergarten age, with no effects on other developmental domains. Effectsare also likelyattributable to maternal mental illness severity or other unmeasured confoundingfactors. Selective associations between prenatal antidepressant exposure and children's anxiety and physical independence at kindergarten were identified, with no impact on other developmental domains. Contradictory reports have emerged regarding the association of adverse child outcomes with prenatal antidepressant exposure. These inconsistencies may be due to differences in control for confounding. Effects of prenatal antidepressant exposure on anxious behaviors and physical independence are likely also attributable to severity of underlying maternal mood disorders, highlighting the importance of maternal mental health for developmental health.

Alternative study designs show no link between antidepressant exposure, autism

Most studies examining the association between prenatal antidepressant exposure and autism risk do not adequately control for factors such as maternal depression, and alternative study designs call into question the association, a meta‐analysis has concluded. Two less commonly used, but more rigorous, study designs do not support an association between prenatal antidepressant exposure and autism, the meta‐analysis found. Results were published in the June 2020 issue of the American Journal of Psychiatry.

Long-Term Effects of Intrauterine Exposure to Antidepressants on Physical, Neurodevelopmental, and Psychiatric Outcomes: A Systematic Review.

Reviews on child outcomes following in utero antidepressant exposure have focused on short-term outcomes. However, several recent individual studies reported on adverse physical, neurodevelopmental, and psychiatric outcomes beyond infancy and early childhood. The objective of this systematic review was to establish the long-term effects of prenatal antidepressant exposure on physical, neurodevelopmental, and psychiatric outcomes in individuals aged 4 years and older. Embase, MEDLINE Ovid, Web of Science, Cochrane Central, and Google Scholar were systematically searched for all relevant articles, written in English and published prior to November 8, 2018, using terms describing antidepressants, pregnancy, and developmental outcomes. All original research articles on long-term outcomes of prenatal antidepressant exposure were eligible for inclusion. After screening and removal of duplicates, a total of 34 studies were identified. Included articles were qualitatively analyzed to determine inconsistency, indirectness, imprecision, and study bias. The identified studies demonstrated statistically significant associations between prenatal antidepressant exposure and a range of physical, neurodevelopmental, and psychiatric outcomes. Yet, the risk of confounding by indication was high. When controlling for confounders, 5 studies investigating physical outcomes (asthma, cancer, body mass index [BMI], epilepsy) found no association except conflicting outcomes for BMI. Eighteen studies examining neurodevelopmental outcomes (cognition, behavior, IQ, motor development, speech, language, and scholastic outcomes) found no consistent associations with antidepressant exposure after taking confounders into account. Eleven studies investigated psychiatric outcomes. After adjusting for confounders, prenatal antidepressant exposure was associated with affective disorders but not with childhood psychiatric outcomes (eg, autism spectrum disorders, attention-deficit/hyperactivity disorder). Reported associations between in utero exposure to antidepressants and physical, neurodevelopmental, and psychiatric outcomes, in large part, seem to be driven by the underlying maternal disorder. When limiting confounding by indication, prenatal exposure to antidepressants was significantly associated only with offspring BMI and affective disorders.

Implementation of Advanced Methods for Reproductive Pharmacovigilance in Autism: A Meta-Analysis of the Effects of Prenatal Antidepressant Exposure

Observational studies of prenatal antidepressant safety are hindered by methodological concerns, including susceptibility to surveillance bias. Some studies address potential bias by using alternative strategies to operationalize study comparison groups. In a meta-analysis of the association between prenatal antidepressant exposure and autism risk, the authors examined the utility of comparison group operationalization in reducing surveillance bias. A systematic search of multiple databases through August 2017 was conducted, selecting controlled observational studies of the association of prenatal antidepressant exposure with autism. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis produced summary effect measures with 95% confidence intervals stratified by comparator group composition, antidepressant class, and trimester of exposure. Fourteen studies were included, with 13 reporting results using a population-based comparison group, five using a psychiatric control group, and four using a discordant-sibling control group. Eight of the 14 studies were rated poor because of inadequate control for prenatal depression and maternal ethnicity. Autism risk estimates after prenatal exposure to any antidepressant were decidedly different for population-based designs (hazard ratio=1.42, 95% CI=1.18, 1.70; odds ratio=1.58, 95% CI=1.25, 1.99) compared with psychiatric control (hazard ratio=1.14, 95% CI=0.84, 1.53; odds ratio=1.24, 95% CI=0.93, 1.66) and discordant-sibling (hazard ratio=0.97, 95% CI=0.68, 1.37; odds ratio=0.85, 95% CI=0.54, 1.35) designs. Findings for prenatal exposure to selective serotonin reuptake inhibitors were similar. Meta-regression of population-based studies demonstrated that despite statistical adjustment, ethnicity differences remained a significant source of study heterogeneity. In this meta-analysis, neither psychiatric control nor discordant-sibling designs supported an association between prenatal antidepressant exposure and autism. Discordant-sibling designs effectively addressed surveillance bias in pharmacovigilance reports derived from national registries and other large databases.

Patterns of prenatal antidepressant exposure and risk of preeclampsia and postpartum haemorrhage.

Antidepressant use later in pregnancy has been associated with preeclampsia and postpartum haemorrhage (PPH) in some studies. To evaluate the association between patterns of prenatal antidepressant dose across gestationand risk of precclampsia and PPH. We utilised OptumLabs® Data Warehouse (2012-2016) administrative health care claims, identifying 226932 singleton liveborn deliveries for this retrospective cohort study. Antidepressant dispensing doses were converted to fluoxetine equivalents. Using k-means longitudinal, we identified women with similar patterns of antidepressant exposure, that is, trajectory groups, during the first 20 and 35 gestational weeks. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between trajectory groups and preeclampisa (20-week groups) and PPH (35-week groups), adjusting for demographics, co-morbidities, and other psychotropic medications. Linear trend tests assessing increasing risk of the outcomes across groups were performed. Among 15041 (6.6%) pregnancies exposed to an antidepressant, the following trajectory groups were identified: A-low exposure, starting pregnancy at ~10mg/d, with 1st trimester reduction/discontinuation, B-low sustained exposure of ~20mg/d, C-moderate exposure (~40mg/d) with 1st trimester reduction/discontinuation, D-moderate sustained exposure of ~40mg/d, and E-high sustained exposure of ~75mg/d. In the low exposure with reduction/discontinuation trajectory, risks were 8.2% for preeclampsia and 2.7% for PPH. Compared with this group, low, moderate, and high sustained trajectories were associated with preeclampsia (adjusted RR 1.17, 95% CI 1.01, 1.34; RR 1.31, 95% CI 1.12, 1.54; and RR 1.41, 95% CI 1.05, 1.90, respectively) and PPH (RR 1.32, 95% CI 1.05, 1.66; RR 1.35, 95% CI 1.03, 1.78; RR 2.51, 95% CI 1.69, 3.71, respectively); P<.01 for linear trend tests for both outcomes. There was no increased risk for either outcome for moderate exposure with reduction/discontinuation(trajectory C). Women with sustained antidepressant exposure, especially at higher doses, were at increased risk for preeclampsia and PPH, butunderlying depression and anxiety may contribute to the increased risk.

Exposure to prenatal antidepressant alters medial prefrontal-striatal synchronization in mice

Citalopram (CTM), a selective serotonin reuptake inhibitor (SSRI), has been widely used to treat panic disorders, such as depression which is one of the most disabling, yet common, psychiatric disorders. Although prenatal antidepressant exposure has a major impact on the neurobehavioral development of the offspring, such as anxiety, depression- and autism-like behaviors, the brain alterations of SSRI influence remained largely unknown. We show here, using electrophysiological recordings, that CTM exposure during the last 7 d of gestation can alter theta- and gamma-band oscillation and synchronization in the corticostriatal loop of 2–3 month-old mouse offspring. The dendritic length and number of dendritic branches in prefrontal neurons of these CTM-exposed mice are significantly reduced, consistent with decreased levels of N-methyl-d-aspartate receptors (NMDARs) and calcium/calmodulin-dependent protein kinase II (CaMKII) in the medial prefrontal cortex (mPFC). In addition, the level of c-Fos in both the mPFC and striatum is significantly increased. Together, these results advance our understanding of a neural network that is potentially responsible for abnormalities induced by prenatal antidepressant exposure.

0780 Longitudinal and Multimodal Sleep Assessment in Children of Mothers with Depression During Pregnancy: Prenatal Antidepressant Exposure Associated with Decreased Sleep Duration at 18-months and Earlier Sleep Schedules at 18- and 36-months

0780 Longitudinal and Multimodal Sleep Assessment in Children of Mothers with Depression During Pregnancy: Prenatal Antidepressant Exposure Associated with Decreased Sleep Duration at 18-months and Earlier Sleep Schedules at 18- and 36-months

Effects of long-term paroxetine or bupropion treatment on puberty onset, reproductive and feeding parameters in adolescent male rats.

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n=8/group) aged 21days were exposed to paroxetine (3.6mg/kg) or bupropion (17mg/kg) orally by gastric gavage every day from postnatal day 21-90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats.

Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems - a critical review and recommendations for future research.

Children of women treated with antidepressants during pregnancy are more likely to develop neurodevelopmental problems than are unexposed children. Associations between prenatal antidepressant exposure and neurodevelopmental problems could reflect a causal effect or could be partially or fully explained by other factors that differ between exposed and unexposed offspring, including having mothers with conditions requiring antidepressant treatment (e.g. depression), environmental risk factors, and/or genetic risk factors shared across disorders. This translational review aims to provide a brief overview of findings from rodent experiments and critically evaluate observational studies in humans to assess the extent to which associations between prenatal antidepressant exposure and neurodevelopmental problems are due to causal mechanisms versus other influences. We focus our review on two important neurodevelopmental outcomes - autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). In general, rodent studies have reported adverse effects of perinatal antidepressant exposure on neurodevelopment. Between-species differences raise questions about the generalizability of these findings to humans. Indeed, converging evidence from studies using multiple designs and approaches suggest that observed associations between prenatal antidepressant exposure and neurodevelopmental problems in humans are largely due to confounding factors. We also provide specific recommendations for future research. Animal research should explicitly evaluate the impact of timing of exposure and dosage of medications, as well as better map outcome measures in rodents to human neurodevelopmental problems. Observational studies should investigate specific confounding factors, specific antidepressant drugs and classes, the potential impact of timing of exposure, and a wider range of other potential offspring outcomes. The findings summarized in this review may help women and their doctors make informed decisions about antidepressant use during pregnancy by providing reassurance that use of these medications during pregnancy is unlikely to substantially increase the risk of ASD and ADHD.