Journal of Clinical Psychiatry最新文献

Background: 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.

Methods: The sample was derived from the 3,800 psychiatric outpatients evaluated with semistructured diagnostic interviews, 417 of whom met DSM-IV 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.

Results: 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.

Conclusions: 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.

Background: 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.

Methods: 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 DSM-5 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.

Results: 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.

Discussion: Suicidality is associated with extensive and pronounced functional dysconnectivity in the SN, FPN, and DMN in young people with major affective disorders.

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Background: 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.

Aim: To compare psychiatric and mental health outcomes between primary and secondary mood disorders over a 3-year follow-up.

Methods: 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 DSM-IV 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.

Results: 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 P>.05).

Conclusion: 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 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 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.

Objective: 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).

Methods: 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.

Results: CBT-IU significantly reduced the risk of postpartum anxiety disorder onset compared to CAU (P<.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 (P=.003), worry symptoms (P<.001), emotion dysregulation (P=.018), and interviewer-rated anxiety symptoms (P<.001) compared to CAU. Treatment satisfaction among CBT-IU participants was high.

Conclusion: 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.

Trial Registration: ClinicalTrials.gov identifier: NCT05691140.