Risk of Major Malformations Following First-Trimester Exposure to Olanzapine: Preliminary Data From the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

PURPOSE/BACKGROUND: Since its US Food and Drug Administration approval in 1996, olanzapine has been one of the most commonly prescribed atypical antipsychotics, making a better understanding of its reproductive safety profile critical. The goal of the current analysis was to determine the risk of major malformations among infants exposed to olanzapine during pregnancy compared with a group of nonexposed infants. METHODS/PROCEDURES: The National Pregnancy Registry for Psychiatric Medications is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Labor and delivery and pediatric medical records were screened for evidence of major malformations followed by adjudication by a dysmorphologist blinded to medication exposure. Infants with first-trimester exposure to olanzapine were compared with controls without second-generation antipsychotic exposure. FINDINGS/RESULTS: As of April 18, 2022, 2619 women have enrolled in the study. At the time of data extraction, 49 olanzapine-exposed infants and 1156 infants in the comparison group were eligible for these analyses. There were no major malformations associated with olanzapine exposure in the first trimester. The absolute risk for major malformations in the exposure group was 0.00% (95% confidence interval, 0.00-7.25) for olanzapine compared with 1.64% (95% confidence interval, 0.99-2.55) in the control group. IMPLICATIONS/CONCLUSIONS: In this prospective cohort, no major malformations were associated with olanzapine exposure during the first trimester. Although these data are preliminary and cannot rule out more modest effects, they are nonetheless important, adding to the growing reproductive safety data for olanzapine.

Risk of Major Malformations in Infants After First-Trimester Exposure to Stimulants: Results From the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

PURPOSE/BACKGROUND: The prevalence of attention-deficit/hyperactivity disorder in adult females is 3% to 4%. Attention-deficit/hyperactivity disorder is highly comorbid with other psychiatric disorders such as mood, anxiety, and substance use disorders. For reproductive-aged women, the treatment of attention-deficit/hyperactivity disorder with stimulant medications may be considered during pregnancy or breastfeeding, although historically, data are lacking to inform these decisions. The aim of this investigation was to determine the risk of major malformations in infants after first-trimester prescription stimulant exposure in a small but rigorously characterized sample. METHODS/PROCEDURES: The Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications systematically ascertains information from pregnant females including demographic information, medical and psychiatric history, use of prescription medications, and other information relevant to fetal outcomes. Participants provide verbal informed consent and are interviewed twice during gestation and again at approximately 3 months postpartum. The primary outcome of interest is the presence of a major malformation identified within 6 months after birth. Redacted cases of major malformations are reviewed by a dysmorphologist blinded to medication exposure. FINDINGS/RESULTS: A total of N = 1988 women were eligible for this analysis, including the following exposures: n = 173 to mixed amphetamine salts; n = 40 to lisdexamfetamine; n = 45 to methylphenidate; n = 3 to dexmethylphenidate; and n = 1755 controls. The odds ratio of a major malformation among infants after first-trimester exposure to any stimulant was 0.39 (95% confidence interval, 0.09-1.61) compared with controls. There were no major malformations observed in infants exposed to lisdexamfetamine, methylphenidate, or dexmethylphenidate. IMPLICATIONS/CONCLUSIONS: Although preliminary, this analysis from an ongoing pregnancy registry provides reassurance that these stimulants do not appear to have major teratogenic effects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01246765 .

Stressors and coping mechanisms among pregnant women with psychiatric disorders during the COVID-19 pandemic.

BACKGROUND: Women with psychiatric disorders are vulnerable to relapse in pregnancy, and the COVID-19 pandemic has presented an additional stressor. METHODS: Data came from a supplemental study offered to women enrolled in the Massachusetts General Hospital Center for Women's Mental Health National Pregnancy Registry for Psychiatric Medications. Registry participants were also invited to complete an email questionnaire relating to their experiences of pregnancy during the pandemic. Prepartum experiences of 230 respondents were analyzed. RESULTS: The most common diagnoses in this group were depression (30%), anxiety disorders (29%), and bipolar affective disorder (17%). Common stressors included changes in employment, greater childcare and/or schooling responsibilities, more conflict in the household, and increased isolation. Participants reported negative impacts and/or coping mechanisms associated with the pandemic, such as sleep problems, reduced physical activity, changes in eating, and greater amounts of screen time. Positive impacts and/or coping mechanisms were also reported, including more quality time with family, more time in nature, and being more appreciative of aspects of life previously taken for granted. CONCLUSIONS: Our findings suggest that the COVID-19 pandemic has had an overall negative psychosocial impact on many pregnant women with preexisting psychiatric disorders. We also observed positive coping mechanisms, which could be drawn on as sources of resilience.

Risk of major malformations in infants after first-trimester exposure to benzodiazepines: Results from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

BACKGROUND: Perinatal anxiety affects 20% of women, and untreated maternal mental illness can cause deleterious effects for women and their children. Benzodiazepines are commonly used to treat anxiety disorders. The reported risk of congenital malformations after in utero benzodiazepine exposure has been inconsistent. METHODS: The Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications prospectively enrolls pregnant women with psychiatric illness who take one or more psychiatric medications. Participants are interviewed twice during pregnancy and at 12 weeks postpartum. Women taking any benzodiazepine during the first trimester of pregnancy were compared with a group of women taking psychiatric medication(s) other than benzodiazepines during pregnancy. RESULTS: A total of 1053 women were eligible for this analysis; N = 151 women who had taken a benzodiazepine during the first trimester, and the comparison group was N = 902 women. There were 5 (3.21%) major malformations in the exposure group and 32 (3.46%) in the comparison group (odds ratio 0.92; 95% confidence interval 0.35-2.41). CONCLUSION: This ongoing pregnancy registry offers reassurance that benzodiazepines do not appear to have major teratogenic effects. The precision of relative risk estimate will improve as the number of participants increases. This and other pregnancy registries will better inform the reproductive safety of benzodiazepines.

Pregnancy outcomes after first-trimester exposure to buspirone: prospective longitudinal outcomes from the MGH National Pregnancy Registry for Psychiatric Medications.

Buspirone is commonly used to treat anxiety disorders among reproductive-aged women. To date, the reproductive safety of buspirone in humans has been particularly sparse. We sought to provide preliminary data from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications (NPRPM) on the risk of major malformations after first-trimester buspirone exposure. The NPRPM enrolls pregnant women with psychiatric disorders to prospectively assess for major congenital malformations after in utero exposure to psychotropics. Women are interviewed twice during pregnancy and once at 12 weeks postpartum. Data regarding women who took buspirone during the first trimester were extracted from the NPRPM database. Data were assessed as a rigorously ascertained case series to determine the incidence of major malformations among those exposed to buspirone. The primary outcome was obtained by maternal postpartum interview and medical record review. As of January 6, 2022, N = 97 women enrolled in the registry took buspirone during their first trimester. Of these women, 68 were evaluable and eligible for this analysis. Four women had twins, resulting in 72 infants. Among this sample, there were no malformations present. These preliminary data represent the only prospectively ascertained sample of pregnancy outcomes after first-trimester buspirone exposure. Albeit a small sample, no major malformations were observed in this cohort. The rigorous prospective ascertainment of outcomes is a strength of this study. Future analyses are planned that will include larger numbers of women with exposures to buspirone and comparison with control groups matched for demographic and diagnostic variables.

Breastfeeding practices among women taking second-generation antipsychotics: findings from the National Pregnancy Registry for Atypical Antipsychotics.

The purpose of this study is to examine initiation rates of breastfeeding and other breastfeeding outcomes among women taking second generation antipsychotics (SGAs). Participants were enrolled in the National Pregnancy Registry for Atypical Antipsychotics; an ongoing prospective cohort study enrolling women age 18-45 years who are exposed and unexposed to SGAs during pregnancy. A 3-month postpartum interview collects information regarding breastfeeding behaviors. Specifically, women are asked the following questions about ever breastfeeding, still breastfeeding at 3 months postpartum, and whether women are breastfeeding exclusively, bottle-feeding exclusively, or breast and bottle feeding. Descriptive statistics were used to summarize demographic variables and breastfeeding practices. Rates of breastfeeding initiation and continuation were higher among participants who did not use SGAs. Among women not on SGAs, 88.2% of women reported "ever breastfeeding" compared to 59.3% of women on an SGA. At 3 months postpartum, 47% of women on a non-SGA were exclusively breastfeeding compared to 23% of women on an SGA. While the majority of women on an SGA initiated breastfeeding, breastfeeding rates were considerably lower than for women who were not on a SGA. More research is needed on the safety of lactation and use of combinations of psychotropics for women in pregnancy and postpartum.

Reproductive safety of aripiprazole: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

Aripiprazole has become one of the most commonly prescribed psychotropics, making a more comprehensive understanding of its reproductive safety profile a priority. The goal of the current analysis was to determine the risk of major malformations in infants exposed during the first trimester of pregnancy to aripiprazole compared to infants whose mothers had psychiatric diagnoses but did not use an atypical antipsychotic during pregnancy. The National Pregnancy Registry for Atypical Antipsychotics is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Medical records are assessed to confirm presence or absence of major malformations. Pregnant women ages 18-45 with psychiatric diagnoses are enrolled. As of April 2020, N = 848 women who had delivered infants were eligible for analyses. A total of 158 women with first trimester exposure to aripiprazole were compared to 690 controls. For 163 infants born to women in the exposed group, seven major malformations were confirmed (4.29%), compared to fourteen of the 690 unexposed infants (1.99%). The unadjusted odds ratio for major malformations between aripiprazole-exposed and unexposed infants was 2.21 (95% confidence interval [CI] = (0.88, 5.57) The adjusted odds ratio for major malformations was 1.35 (95% confidence interval [CI] = (0.43, 4.20). After adjustment for confounding variables, the risk of major malformations after first trimester exposure to aripiprazole was not significant compared to controls. While these results are reassuring, they are limited by relatively small numbers of participants. Future analyses with larger numbers are expected to provide more of a complete and precise reproductive safety profile regarding aripiprazole use during pregnancy. Trial registration: clinicaltrials.gov NCT01246765.

Mood-Stabilizing Anticonvulsants, Spina Bifida, and Folate Supplementation: Commentary.

PURPOSE/BACKGROUND: High risks of neural tube defects and other teratogenic effects are associated with exposure in early pregnancy to some anticonvulsants, including in women with bipolar disorder. METHODS/PROCEDURES: Based on a semistructured review of recent literature, we summarized findings pertaining to this topic. FINDINGS/RESULTS: Valproate and carbamazepine are commonly used empirically (off-label) for putative long-term mood-stabilizing effects. Both anticonvulsants have high risks of teratogenic effects during pregnancy. Risks of neural tube defects (especially spina bifida) and other major malformations are especially great with valproate and can arise even before pregnancy is diagnosed. Standard supplementation of folic acid during pregnancy can reduce risk of spontaneous spina bifida, but not that associated with valproate or carbamazepine. In contrast, lamotrigine has regulatory approval for long-term use in bipolar disorder and appears not to have teratogenic effects in humans. IMPLICATIONS/CONCLUSIONS: Lack of protective effects against anticonvulsant-associated neural tube defects by folic acid supplements in anticipation of and during pregnancy is not widely recognized. This limitation and high risks of neural tube and other major teratogenic effects, especially of valproate, indicate the need for great caution in the use of valproate and carbamazepine to treat bipolar disorder in women of child-bearing age.

Gestational Weight Gain and Pre-pregnancy Body Mass Index Associated With Second-Generation Antipsychotic Drug Use During Pregnancy.

BACKGROUND: Obesity during pregnancy is the most common high-risk obstetric condition, resulting in increased rates of adverse maternal and neonatal outcomes. Individuals with psychiatric disorders have a higher risk of obesity than the general population, but data regarding implications of obesity in women with psychiatric disorders are sparse. OBJECTIVE: The objective of this study was to assess pre-pregnancy weights and gestational weight gain in women who were exposed to second-generation antipsychotics (SGAs) during pregnancy compared to controls. METHODS: We assessed pre-pregnancy weights and gestational weight gain from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics for patients exposed to SGAs and controls unexposed to these medicines during pregnancy. Both groups experienced similar psychiatric morbidity. RESULTS: A total of 403 participants had evaluable data for these analyses (N = 279 exposed to SGAs; N = 124 controls). The mean pre-pregnancy weight, body mass index (BMI), and likelihood to begin pregnancy with an obese BMI were significantly higher in the exposed group compared to controls (p = 0.0003, p < 0.0001, and p < 0.0001 respectively), as were the mean weight and BMI at delivery (p < 0.0001). The mean weight gain did not differ significantly between groups. Across pre-pregnancy BMI categories, both groups gained more than the recommended amount of weight during pregnancy. CONCLUSION: We found that women exposed to SGAs began pregnancy with higher BMIs than controls. Both exposed and unexposed groups experienced similar weight gain during pregnancy. Strategies are needed to prevent excessive gestational weight gain and to reduce pre-pregnancy obesity in women with psychiatric disorders, especially those treated with SGAs.

Prevalence and Predictors of Depression Among Patients With Epilepsy, Stroke, and Multiple Sclerosis Using the Cleveland Clinic Knowledge Program Within the Neurological Institute.

BACKGROUND: Neurological conditions carry a high risk of depression. Given this risk, the Neurological Institute (NI) at Cleveland Clinic has initiated systematic screening for depression using the 9-item Patient Health Questionnaire-9 (PHQ-9) embedded within its electronic medical record and its data capture system, the Knowledge Program (KP)1. OBJECTIVE: We sought to (1) estimate the prevalence of depression among patients with epilepsy, stroke, and multiple sclerosis (MS); (2) identify risk factors for depression within each disease; and (3) determine differential risks and predictors across neurological disorders. METHODS: The KP1 database provided information on approximately 23,000 visits involving 7946 outpatients with epilepsy, stroke, or MS seen in neurology specialty clinics. The primary outcome measure was depression as defined as a PHQ-9 ≥ 10. RESULTS: Overall, the point prevalence of depression was 29.0%. For stroke, epilepsy, and MS, prevalence of depression was 23% (95% CI: 21-25%), 33% (95% CI: 31-35%), and 29% (95% CI: 28-30%), respectively. For all 3 conditions, increasing disease severity and decreased health-related quality of life were independent predictors of depression. In multivariable models, there was a significant interaction between age and condition, and condition with disease severity. In stroke and MS, increasing age was associated with reduced odds for depression, whereas in epilepsy, increasing age was associated with an increased odds for depression. CONCLUSIONS: Although depression is common among patients with neurological disorders, our data suggest that predictors of depression such as age and disease severity varied by condition, supporting important possible phenomenological and pathophysiological differences of depression across these neurological conditions.

Supplement use by women during pregnancy: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

Women of reproductive age commonly use integrative treatments. However, the reproductive safety for most complementary products lacks systematic study. We aimed to study the use of supplements by women in a prospective pregnancy registry. The Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics was established to evaluate the reproductive safety of atypical antipsychotics. Exposed and control participants were systematically queried about the use of vitamins and supplements. Slightly greater than half (53.2 %) of the participants eligible for analysis (N = 534) were using at least one vitamin or supplement at the time of enrollment, not including prenatal vitamins or folic acid. The most common supplements used were omega-3 fatty acids (38.0 %), vitamin D (11.0 %), calcium (8.2 %), and iron (4.7 %). Probiotics and melatonin were used by 2.6 and 0.9 %, respectively. In this prospective pregnancy registry, we found that over half of the participants were taking supplements or vitamins other than prenatal vitamins and folic acid. These findings underscore the need for active query on the part of health care providers about the use of supplements during pregnancy, and the need to obtain rigorous reproductive safety and efficacy data for supplements used by pregnant women and reproductive aged women.

Comparison of Electronic Screening for Suicidal Risk With the Patient Health Questionnaire Item 9 and the Columbia Suicide Severity Rating Scale in an Outpatient Psychiatric Clinic.

BACKGROUND: Patient-reported data can improve clinical care, including identifying patients who are at risk for suicide. METHODS: In a tertiary care, psychiatric outpatient clinic, we compared computerized self-assessments of suicidal risk based on item 9 of the Patient Health Questionnaire-9 and an electronic version of the Columbia Suicide Severity Rating Scale (C-SSRS), using retrospective medical record review of clinical psychiatric assessments as the reference standard. We also surveyed patients׳ attitudes about participating in the process. We compared prevalence of suicidal risk rates by the 3 assessment methods as well as their sensitivity, specificity, and predictive value. RESULTS: Observed prevalence of positive suicidal risk screenings differed significantly, ranking (1) Patient Health Questionnaire-9 item 9, 24% (343/1416; 95% CI: 22%-26%) < (2) C-SSRS, 6.0% (85/1416; 95% CI: 5.0%-7.4%) < (3) clinical assessment, 1.4% (20/1416; 95% CI: 0.9%-2.2%). The sensitivity of Patient Health Questionnaire-9 item 9 was 92% (78/85; 95% CI: 86%-98%) and the specificity was 81% (1107/1376; 95% CI: 78%-82%). The sensitivity of the C-SSRS was 95.0% (19/20; 95% CI: 75%-100%) and the specificity was 95% (1330/1396; 95% CI: 94%-96%). Of 100 patients surveyed, the screening was well accepted, with some concerns about confidentiality and adequate clinical follow-up. CONCLUSIONS: As expected, Patient Health Questionnaire-9 item 9 generated much higher rates of apparently false-positive findings than the C-SSRS did, when compared with clinical assessment. C-SSRS backed with timely clinical assessment may be a useful and efficient method of screening for suicidal risk, provided that adequate, immediate clinical follow-up is available.

Thoughts of death and self-harm in patients with epilepsy or multiple sclerosis in a tertiary care center.

BACKGROUND: Patients with epilepsy or multiple sclerosis (MS) have high risks of depression and increased risks of suicide, but little is known about their risks of suicidal ideation. OBJECTIVE: We sought to (1) estimate the prevalence of thoughts of being better off dead or of self-harm among patients with epilepsy or MS, (2) identify risk factors for such thoughts, and (3) determine whether any risk factors interact with depression to predict such thoughts. METHODS: A Cleveland Clinic database provided information on 20,734 visits of 6586 outpatients with epilepsy or MS. Outcome measures were thoughts of death or self-harm (Patient Health Questionnaire [PHQ] item-9), and total score ≥10 for the 8 remaining PHQ items (probable major depression). Generalized estimating equations accounted for repeat visits in tests of associations of PHQ item-9 responses with depression, age, sex, race, household income, disease severity, and quality of life. RESULTS: Prevalence of thoughts of death or self-harm averaged 14.4% overall (epilepsy, 14.0% and MS, 14.7%). Factors associated with positive PHQ item-9 responses in epilepsy were depression and male sex, modified by poor quality of life. Factors associated with positive PHQ item-9 in MS were depression, male sex, medical comorbidity, and poor quality of life; the effect of depression was worse with greater MS severity and being unmarried. CONCLUSIONS: Among patients with common neurologic disorders (epilepsy or MS), 14%-15% reported thoughts of death or self-harm associated with illness severity, depression, quality of life, male sex, and being unmarried. Such patients require further evaluation of clinical outcomes and effects of treatment.

Prevalence of atypical antipsychotic use in psychiatric outpatients: comparison of women of childbearing age with men.

To characterize current treatment practices, we compared the use of atypical antipsychotic drugs among women of childbearing age to men based on electronic medical records of 1073 hospital-based psychiatric outpatients given at least one second-generation antipsychotic drug. One quarter of psychiatric outpatients sampled were prescribed at least one atypical antipsychotic, in more than half of cases for off-label indications. Women were significantly more likely than men to be diagnosed with mood or anxiety disorders than psychotic disorders and to be prescribed quetiapine (60.7 vs. 48.0 %) or aripiprazole (31.2 vs. 23.9 %), but less likely risperidone (15.8 vs. 26.1 %) or ziprasidone (10 vs. 14 %).

Effects of Prenatal Exposure to Second-Generation Antipsychotics on Development and Behavior Among Preschool-Aged Children: Preliminary Results From the National Pregnancy Registry for Psychiatric Medications.

Objective: Data are lacking on the neurodevelopmental outcomes of children prenatally exposed to second-generation antipsychotics (SGAs). The objective of this study is to examine neurodevelopmental outcomes of children exposed in utero to SGAs compared to those unexposed in a cohort of mothers with psychiatric morbidity.Methods: We conducted a cross-sectional assessment of preschool-aged children whose mothers were enrolled in the National Pregnancy Registry for Psychiatric Medications. Two validated, parent-report developmental and behavioral screening assessments, the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Preschool Child Behavior Checklist for Ages 1½-5 (CBCL/1½-5), respectively, were delivered electronically to eligible participants. Outcomes of children exposed in utero to SGAs were compared to those unexposed to SGAs in a cohort of mothers with a history of psychiatric illness. Exposure to other psychotropic medications during pregnancy was not an exclusion criterion for either group.Results: From January 2, 2018, to February 2, 2021, 520 children were eligible, and 352 responses were collected (67.7%), including 178 children in the SGA-exposed group (mean age = 2.6 years) and 174 children in the unexposed comparison group (mean age = 2.1 years). No significant differences between groups were detected (OR = 1.24, 95% CI, 0.74-2.09) with respect to developmental outcomes assessed by the ASQ-3. Similarly, for behavioral outcomes, adjusted analysis showed no significant differences in odds of an abnormal "clinical" score on the CBCL/1½-5 composite scales.Conclusions: The current study is the first to examine neurobehavioral outcomes of preschool-aged children exposed prenatally to SGAs. No significant differences in overall development or behavior were detected in the exposed versus unexposed group. These preliminary findings are an important step in delineating neurodevelopmental effects of prenatal SGA exposure.

Risk of Poor Neonatal Adaptation Syndrome Among Infants Exposed to Second-Generation Atypical Antipsychotics Compared to Antidepressants: Results From the National Pregnancy Registry for Psychiatric Medications.

Objective: While poor neonatal adaptation syndrome (PNAS) has been particularly well described among infants exposed to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), this is not the case for second-generation antipsychotics (SGAs). In 2011, the US Food and Drug Administration (FDA) issued a drug safety warning regarding fetal antipsychotic exposure and risk for PNAS and extrapyramidal symptoms (EPS). The primary objective of this study was to examine the risk for PNAS among infants exposed to SGAs compared to SSRI/SNRI-exposed infants, leveraging the prospective, longitudinal design of the National Pregnancy Registry for Psychiatric Medications (NPRPM).Methods: The NPRPM is a prospective pharmacovigilance program in which pregnant women, aged 18-45 years, are enrolled and followed prospectively. Medical records were systematically reviewed and data abstracted using a checklist of PNAS and EPS symptoms specifically outlined in the FDA drug safety warning. The two study groups included infants exposed to an SGA during pregnancy and infants exposed to an SSRI/SNRI during pregnancy. The primary outcome was the presence of at least one or more PNAS symptoms during the first month of life. Other neonatal outcomes following exposure to the medication of interest, including preterm birth, neonatal intensive care unit (NICU) admission, rates of EPS, and whether infants were discharged home with their mothers, are also reported.Results: Of the 2,145 women enrolled in this study as of December 16, 2020, a total of 373 women and their infants (n = 384) were eligible for inclusion (n = 193 SGA-exposed infants and 191 SSRI/SNRI-exposed infants). Among SGA-exposed infants, 32.6% (63/193) experienced at least 1 PNAS sign compared to 34.6% of infants (66/191) in the SSRI/SNRI-exposed group. The majority of infants in each group showed no symptoms of PNAS. No differences were observed between the two groups with respect to rates of preterm birth, NICU admission, prevalence of EPS, and timing of infants being discharged home with their mothers.Conclusions: PNAS symptomatology was comparable among infants exposed prenatally to an SGA or to an SSRI/SNRI. These preliminary findings provide an estimated risk of PNAS among infants exposed to SGAs of roughly 30%. Interestingly, these findings are also consistent with estimates in the literature of PNAS in SSRI/SNRI-exposed infants, suggesting a possible common pathway underlying this phenomenon.Trial Registration: ClinicalTrials.gov identifier: NCT01246765.

Reproductive Safety of Lurasidone and Quetiapine: Update from the National Pregnancy Registry for Psychiatric Medications.

Background: Second-generation antipsychotics (SGAs), also called atypical antipsychotics, are common therapies for women with a spectrum of psychiatric disorders. No systematically ascertained human reproductive safety data are available for lurasidone, and prospective data for quetiapine are limited, making decisions regarding use of these medications during pregnancy complicated. Materials and Methods: The National Pregnancy Registry for Psychiatric Medications is a prospective cohort study designed to collect reproductive safety data relative to SGAs. Pregnant women aged 18-45 years, with psychiatric illness and prenatal psychotropic medication exposure completed three phone interviews during pregnancy and the postpartum period. Cases of presumed malformations are abstracted from medical records for adjudication by a teratologist blinded to medication exposure. Results: Of 2,293 women enrolled at the time of analysis, 134 in the lurasidone group, 264 in the quetiapine group, and 886 controls completed the postpartum interview and were therefore eligible for inclusion. Dropped or lost-to-follow-up participants (13%) and those currently pregnant were excluded. Participants were predominantly White, college-educated, and married (lurasidone = 88.1%, 76.9%, 77.6%; quetiapine = 89.8%, 71.2%, 75.0%; controls = 92.7%, 86.7%, 89.1%). Absolute risks of major malformations were 2.19% (lurasidone), 1.85% (quetiapine), and 1.77% (controls). Odds ratios comparing lurasidone and quetiapine with controls were 1.24 (95% confidence interval [CI] = 0.36-4.32) and 1.04 (95% CI = 0.38-2.85), respectively. Conclusions: No specific patterns of malformations were observed in infants exposed to the medications of interest. Lurasidone and quetiapine did not appear to be major teratogens, but further information is needed to refine risk estimates. Food and Drug Administration guidance underscores the importance of pregnancy registries. Clinical trial number: NCT01246765.