Untreated depression may adversely affect pregnancy and offspring outcomes through several mechanisms; on the flip side, antidepressants used to treat depression may cross the placenta and affect the developing fetus and...Untreated depression may adversely affect pregnancy and offspring outcomes through several mechanisms; on the flip side, antidepressants used to treat depression may cross the placenta and affect the developing fetus and its brain. This article examines the research literature on gestational exposure to antidepressants and the risk of neurodevelopmental disorders (NDDs) in offspring. Two recent meta-analyses and 3 subsequently published observational studies, including 1 Asian study, are reviewed with especial focus on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Despite limitations of the literature, some conclusions can reasonably be drawn. In unadjusted analyses, which assist an understanding of real world risks, gestational exposure to antidepressant drugs is associated with an up to doubled risk of ASD and ADHD. However, in adjusted analyses, which assist an understanding of cause-effect relationships but not real world risks, the risks substantially attenuate and may lose statistical significance. The risks also lose statistical significance in analyses that address confounding by indication by comparing antidepressant-exposed and -unexposed pregnancies in women with psychiatric disorders. The likelihood of confounding by parental genes, parental environment, and parental health-related variables is suggested by findings that antidepressants remain significantly associated with NDDs when the exposure period is outside the pregnancy window (such as before or after but not during pregnancy) or when fathers are exposed to antidepressants during pregnancy. Finally, discordant sibling pair analyses suggest that whether or not a child develops an NDD is related to whether or not its sib has an NDD rather than whether or not the child was exposed to an antidepressant in utero. Discussion points are suggested for the shared decision-making process when counseling women about NDD risks associated with gestational exposure to antidepressant drugs. Take-home messages are summarized.
The purpose of this study is to evaluate obstetric outcomes in pregnant women who received second-generation long-acting injectable antipsychotics (LAIAs) compared to a control group who received second-generation oral a...The purpose of this study is to evaluate obstetric outcomes in pregnant women who received second-generation long-acting injectable antipsychotics (LAIAs) compared to a control group who received second-generation oral antipsychotics. This was a retrospective study utilizing a global cohort of 148 health care organizations grouped into a network within the TriNetX database. Pregnant patients of any trimester were grouped into 2 cohorts: (1) exposure to long-acting aripiprazole, risperidone, paliperidone, or olanzapine (n=2,082) and (2) exposure to the corresponding oral formulations (n=31,376) and propensity matched. The primary outcome was the occurrence of one of the following obstetric complications: gestational diabetes, preeclampsia, eclampsia, or a newly diagnosed hypertensive disorder. Cesarean section rates were also assessed. After propensity matching, each cohort yielded 2,025 patients. No intergroup differences were observed in the composite primary end point, performed postmatching (odds ratio 0.95; 95% CI, 0.76-1.18; =.61). No difference in rates of cesarean section was observed. Similar rates of gestational diabetes, eclampsia, preeclampsia, and maternal hypertensive disorders were observed in women receiving long-acting injectable and oral second-generation antipsychotics.
To provide an up-to-date evaluation of valproic acid (VPA) use trends, patterns, and predictors in females of reproductive age in ambulatory care settings in the US. A retrospective, cross-sectional study was conducted...To provide an up-to-date evaluation of valproic acid (VPA) use trends, patterns, and predictors in females of reproductive age in ambulatory care settings in the US. A retrospective, cross-sectional study was conducted using 2017 through 2022 Medical Expenditure Panel Survey data to examine trends in VPA use. Prescription rates were calculated per 1,000 prescription events with 95% confidence intervals. VPA prescriptions were stratified by clinical indication and recipient group (females aged 12-49 years, females aged ≥50 years, and males aged 12-49 years). Multivariable logistic regression was used to identify predictors of VPA use among females aged 12-49 years and all females with comorbid bipolar disorder, headache, or seizure conditions. The cumulative total of VPA prescription events across the 2017-2022 study period was 29,754,849 (95% CI, 23,843,243-35,666,455). Of these, 5,442,682 (95% CI, 2,879,340-8,006,024) were issued to females aged 12-49 years (18.3% of all VPA prescriptions). From 2017 to 2022, VPA prescribing decreased by nearly 50% ( =.037). Most VPA prescriptions filled by females aged 12-49 years were for migraine or other headache syndromes (27.2%), followed by bipolar disorder (24.6%) and convulsions or epilepsy (20.7%). Of the estimated 153,120 females aged 12-49 years who filled a prescription for VPA between 2017-2022, 85.9% were not using contraception. Approximately 1 in 5 VPA prescriptions between 2017 to 2022 were prescribed to females of reproductive age. VPA was most commonly used for the treatment of migraine or other headache syndrome, followed by bipolar disorder and convulsive disorder. Only 14.1% of females of reproductive age using VPA were also using contraception. Interventional studies aimed at reducing VPA use in females of reproductive age are needed.
J Clin Psychiatry
· 2025 Dec · PMID 41396185
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Bipolar disorder (BD) is a severe and chronic mental illness characterized by periods of mania/ hypomania and depression. Both disease phases are associated with increased risk of acquiring HIV. Despite this, use of high...Bipolar disorder (BD) is a severe and chronic mental illness characterized by periods of mania/ hypomania and depression. Both disease phases are associated with increased risk of acquiring HIV. Despite this, use of highly effective preexposure prophylaxis (PrEP) for HIV prevention among people with BD is poorly understood. We performed a retrospective cohort study using the Merative MarketScan Claims Database from 2010-2022 to identify people with BD. Additional clinical variables including outpatient encounters for sexually transmitted infections (STIs), use of long-acting injectable agents, psychiatric hospitalizations, and outpatient encounters with primary care providers (PCPs) and psychiatrists were included. There were 333,867 people with BD (61.9% female) in the cohort. A total of 435 new HIV diagnoses were identified, with diagnoses more common among males (adjusted odds ratio [aOR] [95% CI]=5.30 [4.22-6.65], <.001) and those with comorbid stimulant use disorder (aOR [95% CI]=2.40 [1.71-3.39], <.001). A total of 1,337 people with BD were prescribed PrEP, and 909 were prescribed at least 3 months of PrEP. Among people with ≥4 encounters for STIs, 3.53% (n=246) were prescribed PrEP of any duration, and 2.73% (n=190) were prescribed PrEP for at least 3 months. People with BD who had outpatient encounters only with psychiatrists had greater odds of HIV diagnosis compared to those who had follow-up encounters with PCPs only (aOR [95% CI]=1.58 [1.11-2.27], =.01) and lower odds of receiving PrEP prescription (aOR [95% CI]=0.74 [0.56-0.98], =.03). PrEP use among commercially insured people with BD was critically low, with <1% prescribed PrEP. Even among those with multiple encounters for STIs, <4% were prescribed PrEP, despite this being an indication for prescription. Engagement of people with BD in the PrEP care continuum is essential for ending the HIV pandemic, and integration of PrEP prescription with psychiatric care may represent an efficient method for increasing PrEP use.
This meta-analysis assessed the effectiveness of peer-administered interventions for treating perinatal depression or anxiety and whether variations in intervention characteristics impacted their effectiveness. Records...This meta-analysis assessed the effectiveness of peer-administered interventions for treating perinatal depression or anxiety and whether variations in intervention characteristics impacted their effectiveness. Records were identified through MEDLINE, EMBASE, PsycINFO, CINAHL, and Web of Science until October 2024. We used terms related to the perinatal period, depression, anxiety, and peer support. We identified 5,700 articles, of which 19 were included and 18 were meta-analyzed. A total of 3,821 participants were included, with the majority from high-income countries. Studies involving a peer-administered intervention for perinatal depression or anxiety with a randomized controlled trial (RCT) design were eligible. Three intervention types were identified: peer-delivered psychotherapies, individual peer support, and peer discussion groups. Random-effects meta-analyses suggested that peer-administered interventions were more effective at improving depression symptoms than standard care (standardized mean difference [SMD]: -0.35; 95% CI, -0.54 to -0.17). Peer-delivered psychotherapy had the largest effect sizes (SMD: -0.51; 95% CI, -0.79 to -0.24), followed by individual support (SMD: -0.30; 95% CI, -0.63 to 0.04) and discussion groups (SMD: -0.09; 95% CI, -0.42 to 0.25). Subgroup analyses suggest that group interventions may lead to the greatest improvement. On the whole, peer-administered interventions were not effective for anxiety (SMD: -0.25; 95% CI, -0.57 to 0.08), but peer-delivered psychotherapies specifically improved anxiety symptoms (SMD: -0.63; 95% CI, -0.95 to -0.31). Peer-administered interventions are effective at improving perinatal depression, with peer-delivered psychotherapies being the most effective. Large-scale RCTs are needed to explore long-term effectiveness on perinatal depression and anxiety.
To investigate the alignment of self-harm ideation ratings with clinical assessments of suicidality in postpartum women diagnosed with unipolar and bipolar depression and the impact of trauma and psychiatric diagnosis on...To investigate the alignment of self-harm ideation ratings with clinical assessments of suicidality in postpartum women diagnosed with unipolar and bipolar depression and the impact of trauma and psychiatric diagnosis on this alignment. Data from the largest postpartum depression screening study (n=10,000) in the US were examined in this secondary analysis. Inclusion criteria were a positive depression screen (Edinburgh Postnatal Depression Scale [EPDS] ≥10), a psychiatric diagnosis (Structured Clinical Interview for ), and a suicidality assessment derived from the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS). Trauma exposure, including both childhood and adult physical and sexual abuse, was measured using 4 yes/no questions from the Dissociative Disorders Interview Schedule. Associations between key variables were examined using independent samples tests, analysis of variance, χ tests, or Fisher exact tests. Nonparametric tests were used for skewed continuous data. To assess the consistency between the EPDS and SIGH-ADS scales, Cohen κ statistics were used, with weighted κ applied to severity ratings and simple κ for binary categorizations. Among 1,155 screen-positive postpartum women (68% White, 25.5% African American, 6.6% other; mean age 27.93 years), 21% endorsed self-harm ideation and 10.1% reported suicidality. Compared to those with unipolar depression, women with bipolar disorder had more than twice the odds of suicidality (odds ratio [OR] 2.77, 95% CI, 1.86 to 4.13, <.001) and nearly 4 times the odds (OR 3.92, 95% CI, 1.18 to 13.00, <.001) of not self-reporting self-harm ideation. Overall concordance between self-report (EPDS10) and clinical evaluation (SIGH-ADS11) was 78.6% (κ=0.28, 95% CI, 0.21 to 0.34, fair agreement) but varied significantly by diagnosis (<.001), with lower concordance in the bipolar group (67.3%; κ=0.21) compared to the unipolar group (80.4%; κ=0.31). In the high-risk bipolar disorder group, concordance was no longer statistically significant, indicating poor alignment between self-report and clinical evaluation for these patients. Trauma was strongly associated with suicidality and a bipolar diagnosis. The EPDS does not consistently detect suicidality in perinatal bipolar patients, with our study showing only slight and nonsignificant agreement with clinical assessment in this high-risk group. Given that risk can change quickly in postpartum bipolar patients, timely and frequent clinical assessments are needed to identify high-risk individuals. Tracking and integrating routine bipolar disorder screening and trauma assessments in perinatal care may enhance early identification of suicide risk and improve maternal mental health outcomes.
Two recent studies demonstrated that brexpiprazole combined with sertraline was effective in reducing posttraumatic stress disorder (PTSD) symptoms, and an application has been submitted to the FDA for the combination tr...Two recent studies demonstrated that brexpiprazole combined with sertraline was effective in reducing posttraumatic stress disorder (PTSD) symptoms, and an application has been submitted to the FDA for the combination treatment. When reading the inclusion and exclusion criteria of these studies, we suspected that many patients that we treat in our clinical practice would not have been eligible for the studies establishing the efficacy of the brexpiprazole-sertraline combination. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we estimated how many patients with PTSD in our practice would have qualified for the brexpiprazole-sertraline trials. The sample was derived from the 3,800 psychiatric outpatients evaluated with semistructured diagnostic interviews, 417 of whom met criteria for PTSD upon presentation. The clinical protocol of the brexpiprazole-sertraline study listed the exclusion criteria. There were 11 exclusion criteria related to the patients' trauma history or psychiatric condition, almost all of which we assessed and applied to the sample. Three exclusion criteria were met by the majority of the patients: current major depressive disorder, PTSD age of onset before 16 years, and the interval between the onset of PTSD and patients' current age was 10 years or greater. Nearly 95% of patients met at least 1 of the exclusion criteria used in the brexpiprazole-sertraline studies. While the effectiveness of the brexpiprazole-sertraline combination offers hope for addressing a significant unmet need in the treatment of PTSD, it is concerning that so few of our patients would have qualified for the clinical trials. As a result, we remain uncertain about the medications' effectiveness for most patients treated in clinical practice. We urge regulatory agencies to require industry to conduct studies that better reflect the patient populations seen in clinical practice.
The association between functional dysconnectivity in the triple networks-the default mode network (DMN), salience network (SN), and frontoparietal network (FPN)-and current suicidal ideation (CSI) in young people with m...The association between functional dysconnectivity in the triple networks-the default mode network (DMN), salience network (SN), and frontoparietal network (FPN)-and current suicidal ideation (CSI) in young people with major affective disorders remains unclear. This study included 158 young people (mean age: ∼18 years) with major affective disorders (101 with CSI and 57 without CSI) and 64 age- and sex-matched healthy control individuals. Both major depressive disorder and bipolar disorder were diagnosed according to the criteria. CSI was defined by a Montgomery-Åsberg Depression Rating Scale suicide item score of ≥2. All participants underwent resting-state functional connectivity magnetic resonance imaging. Seed-based connectivity analyses were performed, with adjustment for diagnosis and prior suicide attempts. Compared with the non-CSI group, the CSI group exhibited hyperconnectivity between the anterior insula (SN) and hippocampus as well as between the posterior parietal cortex (FPN) and rectus gyrus (DMN) and hypoconnectivity between the amygdala (SN) and cerebellum crus II. Both the CSI and non-CSI groups exhibited increased functional connectivity between the posterior parietal cortex and emotional perception-related regions, specifically, the superior and middle temporal gyri, compared with healthy control individuals. Suicidality is associated with extensive and pronounced functional dysconnectivity in the SN, FPN, and DMN in young people with major affective disorders.
Second-generation antipsychotic (SGA)-induced weight gain (AIWG) is a major factor contributing to SGA nonadherence. The aim of the study was to evaluate the effect of concurrent metformin treatment on SGA adherence and...Second-generation antipsychotic (SGA)-induced weight gain (AIWG) is a major factor contributing to SGA nonadherence. The aim of the study was to evaluate the effect of concurrent metformin treatment on SGA adherence and persistence. A retrospective cohort study using MarketScan Commercial and Medicaid claims data included nondiabetic adults (≥18 years) with ≥30 days of overlapping prescriptions for SGAs and metformin. SGA-metformin concurrent users were 1:4 matched to SGA-only users and followed for 180 and 365 days to assess SGA adherence using proportion of days covered (PDC) and persistence (days until a 60-day gap). Additionally, concurrent users were classified into early (<30 days) and delayed (≥30 days) initiators based on the duration between SGA and metformin initiation. The differences between study groups were adjusted by propensity score using inverse probability of treatment weights (IPTW). In commercially insured patients, 575 concurrent users were matched to 2,300 SGA-only users, whereas Medicaid had 972 concurrent users matched to 3,888 SGA-only users. During the 180-day follow-up period, concurrent users demonstrated higher PDC and persistence to SGA than SGA-only users (PDC: commercial: 80.9% vs. 67.61%; Medicaid: 78.41% vs 68.27%; persistence: commercial: 139.0 vs 106.4 days; Medicaid: 149.1 vs 115.7 days). After IPTW adjustment, the differences in PDC between the study groups were 11.79% (commercial) and 9.64% (Medicaid), with corresponding differences in persistence of 32.14 (commercial) and 33.78 (Medicaid) days. The findings for the early and delayed initiators and the 365-day follow-up period were consistent with the main analysis. The concurrent use of metformin with SGA drugs was associated with improved adherence and persistence to SGAs at both 180-and 365-day follow-up periods in adults with Medicaid and commercial insurance. Additionally, the observed improvement in SGA adherence among both early and delayed metformin initiators supports the effectiveness of metformin in enhancing adherence, whether used on a preventive basis or as a treatment for AIWG.
Distinguishing between primary and secondary mood disorders (illness-or substance-induced) is important for appropriate treatment, yet their prevalence and outcomes in the general population remain understudied. To comp...Distinguishing between primary and secondary mood disorders (illness-or substance-induced) is important for appropriate treatment, yet their prevalence and outcomes in the general population remain understudied. To compare psychiatric and mental health outcomes between primary and secondary mood disorders over a 3-year follow-up. We used longitudinal data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey of the US adult population (Wave 1, 2001-2002; Wave 2, 2004-2005). Primary and secondary mood disorders were assessed following criteria. Outcomes assessed 3 years later included recurrence and persistence of mood disorders, suicide attempt, mental and physical health-related quality of life, and mental health help-seeking behavior. All analyses were adjusted for a wide range of sociodemographic and clinical characteristics. Among 3,602 participants with mood disorders during the 12 months before Wave 1, 298 (8.3%) had secondary and 3,304 (91.7%) primary mood diagnoses. Following adjustments, secondary mood disorders were associated with significantly poorer physical health-related quality of life (β=-2.75; 95% CI, -4.27 to -1.23) and lower 3-year recurrence (adjusted odds ratio [AOR]=0.51; 95% CI, 0.36 to 0.72) and persistence rates (AOR=0.49; 95% CI, 0.31 to 0.79) compared to primary mood disorders. Other outcomes showed no significant differences (all >.05). Secondary mood disorders were not rare and associated with poorer physical health-related quality of life than primary mood disorders. However, both groups showed similar risks of suicide attempts, impaired mental health-related quality of life, and rates of mental health help-seeking behavior. The findings for adults with secondary mood disorders align with efforts to integrate physical and mental health care.
The US Administration has moved to declare gestational exposure to acetaminophen (paracetamol) a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children. This articl...The US Administration has moved to declare gestational exposure to acetaminophen (paracetamol) a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children. This article examines the science on the subject. Studies suggest that about half of women use acetaminophen during pregnancy; nevertheless, there is no epidemic of neurodevelopmental disorders (NDDs) in offspring. Two large population-based studies, one Swedish and the other Japanese, found that maternal use of acetaminophen during pregnancy was associated with an increased risk of ASD, ADHD, and intellectual disability (ID) in children. However, the risks were very small in fully adjusted analyses; hazard ratios (HRs) were mostly in the 1.05-1.07 range. Importantly, maternal use of aspirin, other NSAIDs, opioids, or antimigraine drugs during pregnancy was also associated with an increased risk of ASD and ADHD (but not ID). Most importantly, in sibling analyses, gestational exposure to acetaminophen, aspirin, and other analgesic drug categories was not associated with an increased risk of NDDs. There are many key points. Acetaminophen has a safety profile that is better than that of alternative treatments. The magnitude of increase in absolute risk for NDDs is very small (eg, by 0.09% at age 10, for ASD). There are many unmeasured confounds that, evenif weak, could nullify the relationship between acetaminophen and NDDs. Sibling analyses suggest that shared genetic and shared environment risk factors (rather than acetaminophen exposure) may explain the NDD risk. Analyses of other analgesic drug groups suggest that pain and inflammation, rather than drug exposure, may also explain the NDD risk. Finally, for reasons that are explained, making acetaminophen unavailable during pregnancy does not mean that the NDD risk will reduce. These points need to be discussed with women in a shared decision-making process that is both equitable and free from guilting.
Xanomeline-trospium (XT) is the first muscarinic-based therapy approved for schizophrenia. It combines M1 and M4 receptor agonism with peripheral antagonism to limit cholinergic side effects. By modulating circuits upstr...Xanomeline-trospium (XT) is the first muscarinic-based therapy approved for schizophrenia. It combines M1 and M4 receptor agonism with peripheral antagonism to limit cholinergic side effects. By modulating circuits upstream of dopamine release, XT offers a mechanism that differs from traditional antipsychotics and may address positive, negative, and cognitive symptoms. In July 2025, a consensus panel of clinicians with expertise in treating schizophrenia and real-world experience using XT convened to discuss practical strategies for its use across treatment settings. The panel concluded that XT should be considered early in the course of illness, particularly in first-episode psychosis, because it may alter long-term outcomes while reducing reliance on high-dose dopamine antagonists. Outpatient strategies emphasize individualized titration and proactive management of gastrointestinal side effects to support adherence. Inpatient use allows for more rapid titration and has shown rapid benefits in both positive and negative symptoms, facilitating earlier stabilization and discharge. Cross-titration experience suggests that XT can be dose-sparing when combined with dopamine blockers, reducing the burden of metabolic and motor side effects. These real-world insights highlight XT as a versatile treatment option that expands the therapeutic possibilities for schizophrenia.
Postpartum anxiety is common, often underrecognized, and associated with numerous negative outcomes for both the perinatal individual and their infant. Despite its high prevalence and burden, research focused on preventa...Postpartum anxiety is common, often underrecognized, and associated with numerous negative outcomes for both the perinatal individual and their infant. Despite its high prevalence and burden, research focused on preventative strategies for postpartum anxiety remains very limited. This study investigated whether a 6-week cognitive behavioral therapy protocol targeting intolerance of uncertainty (CBT-IU) during pregnancy could reduce risk for postpartum anxiety disorders among individuals with heightened intolerance of uncertainty (IU). In this investigator-initiated, single-site, proof-of-concept, randomized controlled trial (RCT), eligible participants (n=37), between 14 and 32 weeks' gestation, with heightened IU (baseline score of ≥64 on the 27-item Intolerance of Uncertainty Scale) were randomized to a 6-session individual CBT-IU or care as usual (CAU), of whom 35 completed measures and were included in analyses. The primary objective of this study was to evaluate whether CBT-IU for pregnant individuals with elevated IU could reduce the risk of postpartum anxiety disorder compared to CAU. Secondary outcomes included changes in worry, depression, and emotion regulation. CBT-IU significantly reduced the risk of postpartum anxiety disorder onset compared to CAU (<.001), with none of the participants in the CBT-IU group meeting diagnostic (or provisional) criteria for an anxiety or related disorder, compared to 31.6% of participants in the CAU group. CBT-IU participants showed clinically significantly reductions in IU (=.003), worry symptoms (.001), emotion dysregulation (.018), and interviewer-rated anxiety symptoms (<.001) compared to CAU. Treatment satisfaction among CBT-IU participants was high. These findings suggest that targeting IU during pregnancy may be an effective preventive strategy for reducing the risk of postpartum anxiety disorder onset. This proof-of-concept RCT supports a large-scale RCT to ultimately test CBT-IU as an effective intervention for prevention of postpartum anxiety disorders. ClinicalTrials.gov identifier: NCT05691140.