OBJECTIVE:Systematically collected pregnancy safety data for cariprazine have been lacking, despite growing use of this medication across psychiatric indications. The goal of this analysis was to determine the risk of major malformations among infants of mothers with psychiatric illness who used cariprazine during the first trimester of pregnancy compared to unexposed controls. METHODS:The National Pregnancy Registry for Psychiatric Medications (NPRPM) is a prospective pharmacovigilance program in which pregnant women with psychiatric diagnoses are enrolled during pregnancy and followed through the postpartum period. Labor and delivery and pediatric medical records are reviewed for evidence of major malformations followed by final adjudication by a dysmorphologist blinded to medication exposure. Infants with first-trimester exposure to cariprazine were compared to controls not exposed to second-generation antipsychotic medications. RESULTS:As of September 9, 2025, N = 4,125 have enrolled in the study. Of those enrolled, 58 cariprazine-exposed infants and 2,098 infants in the comparison group were eligible for inclusion in this analysis. There were no major malformations in the cariprazine-exposed group (absolute risk 0.00%; 95% confidence interval, 0.00%-6.16%) compared to 32 infants with major malformations in the control group (1.53%; 1.05%-2.15%). CONCLUSIONS:In this prospective cohort, 0 of 58 infants exposed to cariprazine during the first trimester had major malformations, compared with 32 of 2,098 (1.53%) unexposed infants. Although these data are preliminary and cannot rule out modest teratogenic effects, they are nonetheless important to provide to health care providers and the public, as cariprazine use has been rising among women of reproductive age.

PURPOSE:Vortioxetine is an antidepressant used to treat major depressive disorder (MDD), a disorder that is common among women of reproductive age. To date, the reproductive safety of vortioxetine in humans has been limited. We sought to provide preliminary systematic data from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications (NPRPM) on the risk of major malformations after exposure to vortioxetine in the first trimester of pregnancy. MATERIALS AND METHODS:The NPRPM is a longitudinal, ongoing study in which pregnant women with psychiatric disorders are enrolled to prospectively assess for major congenital malformations after in utero exposure to psychotropics. Data regarding women who took vortioxetine during the first trimester were extracted from the NPRPM database. Data for this analysis were assessed as rigorously ascertained case series to determine the incidence of major malformations. The primary outcome of major malformations following first-trimester exposure was obtained by maternal postpartum interview and medical record review and adjudicated by a dysmorphologist blinded to exposure status. RESULTS:As of March 26, 2026, 56 women who reported taking vortioxetine during the first trimester had evaluable data. Among this sample, there were no major malformations. CONCLUSIONS:These preliminary data represent the only rigorous and prospectively ascertained pregnancy outcomes after first-trimester vortioxetine exposure. No major malformations were observed. While these data are reassuring, the relatively small sample size limits conclusions on the safety of vortioxetine in pregnancy.

About 1 in 10 adults in the United States report having used benzodiazepines in the past year. These medications carry substantial risks, including falls, cognitive impairment, overdose, and death, particularly when combined with alcohol or opioids. The American Society of Addiction Medicine, in collaboration with 9 other professional societies, has issued recommendations on when and how to taper and discontinue benzodiazepines. The authors of this article summarize important points from the guideline, aimed at all who provide long-term benzodiazepine prescriptions.

Purpose: Vortioxetine is an antidepressant used to treat major depressive disorder (MDD), a disorder that is common among women of reproductive age. To date, the reproductive safety of vortioxetine in humans has been limited. We sought to provide preliminary systematic data from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications (NPRPM) on the risk of major malformations after exposure to vortioxetine in the first trimester of pregnancy. Materials and Methods: The NPRPM is a longitudinal, ongoing study in which pregnant women with psychiatric disorders are enrolled to prospectively assess for major congenital malformations after in utero exposure to psychotropics. Data regarding women who took vortioxetine during the first trimester were extracted from the NPRPM database. Data for this analysis were assessed as rigorously ascertained case series to determine the incidence of major malformations. The primary outcome of major malformations following first-trimester exposure was obtained by maternal postpartum interview and medical record review and adjudicated by a dysmorphologist blinded to exposure status. Results: As of March 26, 2026, 56 women who reported taking vortioxetine during the first trimester had evaluable data. Among this sample, there were no major malformations. Conclusions: These preliminary data represent the only rigorous and prospectively ascertained pregnancy outcomes after first-trimester vortioxetine exposure. No major malformations were observed. While these data are reassuring, the relatively small sample size limits conclusions on the safety of vortioxetine in pregnancy.

Objective: Data are lacking on the neurodevelopmental outcomes of children prenatally exposed to secondgeneration 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 crosssectional 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 1 1 / 2 -5 (CBCL/1 1 / 2 -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/1 1 / 2 -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.

Background: Previous studies suggest an association between late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and increased postpartum hemorrhage (PPH) risk. This is the first pregnancy registry study to compare PPH outcomes among women with psychiatric illness exposed or unexposed to SSRIs/SNRIs proximate to delivery. Methods: This study used data from the National Pregnancy Registry for Psychiatric Medications to evaluate the relationship between SSRI/SNRI exposure in late pregnancy and PPH risk. The sample included n = 953 participants with retrospectively collected medical record data on postpartum blood loss, n = 453 unexposed to SSRIs/SNRIs during pregnancy, and n = 500 exposed at least during the week of delivery. PPH was defined as an estimated blood loss ≥500 mL following vaginal delivery or ≥1,000 mL following cesarean section (C-section), with onset of excessive bleeding occurring within the first 24 hours postpartum. Univariate and multivariate logistic regression analyses were performed to determine odds ratios. Results: Overall PPH incidence was 13.1%. SSRI/SNRI exposure was associated with a PPH unadjusted odds ratio of 1.42 compared to no exposure (95% confidence interval [CI: 0.97, 2.08]) and an adjusted odds ratio of 1.33 (95% CI [0.90, 1.97]). When stratified by delivery type, the odds ratio following vaginal delivery among women exposed to SSRIs/SNRIs was 1.04 (95% CI [0.63, 1.70]) versus 2.31 (95% CI [1.25, 4.26]) for C-section delivery; the adjusted C-section odds ratio was 2.21 (95% CI [1.18, 4.13]). Conclusions: Although these findings align with accumulating evidence suggesting SSRI/SNRI exposure may confer a modestly increased risk of PPH, particularly after C-section, the study was underpowered to make definitive conclusions. These preliminary data highlight the need for further research with larger sample sizes. Nevertheless, the findings underscore the importance of greater clinical monitoring for PPH following C-section, especially in women who may have other known PPH risk factors and are exposed to SSRIs/SNRIs in late pregnancy.

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.

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 mecha-nisms 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.

Purpose/BackgroundSince 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/ProceduresThe 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/ResultsAs 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/ConclusionsIn 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.

Many women with bipolar disorder experience episodes of illness or relapses over the perinatal period, especially in the immediate postpartum period. Risks associated with treated/untreated psychopathologies and fetal exposure to bipolar medications make the management of bipolar disorder during these periods challenging for clinicians and patients. In light of the available effectiveness and reproductive safety data, the current clinical update based on the opinions of a group of international perinatal psychiatry authors recommends general considerations and specific management strategies for each possible clinical scenario, including mixed features, predominant polarity, diagnosis of subtypes of bipolar disorder, severity of previous episodes, and risk of recurrence of mood episodes.

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.

Abstract 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.

Stopping antidepressants can be challenging due to the high rate of discontinuation symptoms. Patients with antidepressant discontinuation syndrome (ADS) commonly experience insomnia, flu-like symptoms, mood disturbances, dizziness, and paresthesias, but a broad array of adverse effects is possible. Symptoms can last for days to months, and different symptoms have different durations. Patient education, identification of patients most at risk for developing symptoms, and a slow antidepressant taper or cross-taper are important steps in mitigating the risk of ADS and managing patient concerns about ADS. Tapers should be carried out over weeks to months. Discontinuation symptoms should be managed with restarting the prior dose of antidepressant and then tapering even more slowly, with additional symptomatic management as needed.

This commentary on an article by Yakuwa and colleagues calls for an acceleration of the acquisition of clinical data on the safety of second-generation antipsychotics for pregnant women and their infants.