Journal of Clinical Psychiatry最新文献

{"title":"A Single-Dose, Randomized, Open-Label, Parallel Design Study to Characterize the Pharmacokinetics of an Investigational Olanzapine Intranasal Spray Compared to a Reference Dose of Olanzapine Intramuscular Injection in Healthy Adult Males.","authors":"Stuart Madden, Leslie Citrome, Christoph U Correll, Evelyn K Shih, Miguel Lopez-Toledano, Adrian L Rabinowicz, Enrique Carrazana","doi":"10.4088/JCP.24m15665","DOIUrl":"https://doi.org/10.4088/JCP.24m15665","url":null,"abstract":"<p><p><b>Objective:</b> Injectable olanzapine for acute agitation in psychiatric disorders is limited to delivery by health care professionals in supervised settings. Intranasal (IN) administration offers a potential needle free route of delivery with favorable pharmacokinetics and patient experience, including the possibility of self-administration in community settings. Two IN formulations of olanzapine containing the permeation enhancer dodecyl maltoside (DDM) were assessed, with intramuscular (IM) olanzapine as a reference.</p><p><p><b>Methods:</b> In this randomized phase 1 trial (conducted October 2023), healthy volunteers (N =24) were randomized 1:1: 1 to receive 1 dose of IN olanzapine 7.5 mg+0.25% DDM, IN olanzapine 7.5 mg+0.50% DDM, or olanzapine 7.5 mg IM. Plasma olanzapine concentrations were measured over time, and safety and tolerability were assessed.</p><p><p><b>Results:</b> Mean peak plasma olanzapine concentrations were 31.5, 32.3, and 20.5 ng/mL for 0.25% and 0.50% DDM sprays and IM dosing, respectively. Median times to peak plasma concentration were 4.8, 10.2, and 37.8 minutes. After a single dose of the 0.25% and 0.50% DDM formulations, bioavailability was 88.8% and 83.3% of a single IM dose. All reported treatment emergent adverse events were mild, transient, and deemed possibly related to the study drug, with the most frequent being sedation (n = 24) and nasal discomfort lasting seconds (n = 16, IN treatments). Nasal irritation scores were grade 0 (no sign of nasal irritation or mucosal erosion), and suicide risk assessment was negative for all time points.</p><p><p><b>Conclusion:</b> Two novel investigational IN formulations of olanzapine containing the permeation enhancer DDM showed favorable pharmacokinetics and an acceptable safety profile presenting no unexpected signals in healthy adults. Continued study is warranted.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT06600477.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Infant Distress to Limitation and Postpartum Depression Treatment Response.","authors":"Kian Yousefi Kousha, John E Krzeczkowski, Ryan J Van Lieshout","doi":"10.4088/JCP.24br15503","DOIUrl":"https://doi.org/10.4088/JCP.24br15503","url":null,"abstract":"","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Effects of Negative Ethnic-Racial Identity Affect on Internalizing Symptoms in Youth of Latiné Background Exposed to Interpersonal Trauma.","authors":"Sunita M Stewart, Nazan Aksan, Andrea Bancroft, Jeffrey D Shahidullah, Savannah M Krantz, Madelyn Guerra, Jessica Sandoval, Cynthia Garza, Andres G Viana, Myesha Morgan, Cecilia DeVargas, Justin F Rousseau, D Jeffrey Newport, Karen Dineen Wagner, Charles B Nemeroff","doi":"10.4088/JCP.24m15654","DOIUrl":"https://doi.org/10.4088/JCP.24m15654","url":null,"abstract":"<p><p><b>Objectives:</b> Latiné youth in the US are at elevated risk for trauma exposure, but factors that contribute to their symptoms are not well studied. We examined the effects of interpersonal trauma (IPT) burden and negative affect about ethnic-racial identity (NERI-A) on internalizing symptoms following trauma exposure.</p><p><p><b>Method:</b> Participants were 1,006 US-born youth of Latiné background (mean age 15.4 years, 60% female at birth, and 70% identified as White) from the Childhood Trauma Research Network, a research consortium examining long-term outcomes of childhood trauma in Texas. Participants were enrolled between October 2020 and February 2024. Analyses controlled for sex, age, race, non-interpersonal trauma, whether parents were of the immigrant generation, and mental health treatment received.</p><p><p><b>Results:</b> Greater IPT burden and higher baseline NERI-A were associated with greater baseline anxiety (<i>P</i> < .001, <i>P</i> = .026) and depressive (<i>P</i> < .001, <i>P</i> = .040) symptoms. The effect of baseline IPT burden on direction and magnitude of longitudinal change in anxiety (0.038) and depression (0.002) differed for those with high NERI-A vs low NERI-A. In the context of low NERI-A, IPT burden showed steady or decreasing associations with symptoms over time. In contrast, for those reporting high NERI-A, IPT burden showed strengthening associations with both anxiety and depression over time.</p><p><p><b>Conclusion:</b> Our study highlights the vulnerability of youth who experience IPT and report NERI-A. Further research is needed to determine how NERI-A develops, changes, and is moderated in the diverse groups of individuals of Latiné descent.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discordant Sibling Pair Comparisons in Observational Studies: A Research Design Simply Explained.","authors":"Chittaranjan Andrade","doi":"10.4088/JCP.25f15843","DOIUrl":"https://doi.org/10.4088/JCP.25f15843","url":null,"abstract":"<p><p>When studying how (eg) gestational exposure to antidepressant drugs influences the risk of (eg) autism spectrum disorder (ASD) in offspring, conventional observational studies adjust analyses for available covariates and confounds. In such analyses, a significant association between antidepressant exposure and ASD outcome can never be asserted to be causal because of the possibility of residual confounding arising from confounding by indication (or severity thereof), confounding by genetic risk factors, and confounding by environmental risk factors. Confounding by indication and severity thereof can sometimes be addressed through propensity score matching, but the adjustment can never be perfect. Additionally, adjustment for genetic and environmental risk factors is hard or impossible to do because these are inadequately measured, unmeasured, and/or unknown variables. Sibling comparison studies have recently emerged as an option to address the genetic and environmental risk factors. In such studies, sibs discordant for exposure are compared for risk of outcome (cohort design) or sibs discordant for outcome are compared for odds of exposure (case-control design). The assumption is that sibs share similar genetic and environmental risk factors and so, when sibs are compared, these risk factors cancel out whether they are measured or not, known or unknown. If antidepressant exposure remains significantly associated with ASD in sibling comparisons, a possible conclusion is that antidepressants and not genetic or environmental factors drive the ASD risk. If antidepressant exposure loses significance in the sibling comparisons, it suggests that shared genetic and/or environmental factors, rather than antidepressant exposure, explain the ASD risk. The interpretation, however, is nuanced. Strengths, limitations, and interpretations of sibling comparison studies are explained. To illustrate the usefulness of sibling comparisons, results are presented from a recent study of ASD risk after gestational or early infancy exposure to antibiotics.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suicide Among Veterans Health Administration Patients With Bipolar Disorder: Evidence for Increased Risk Associated With Benzodiazepine Receipt.","authors":"Kevin G Saulnier, Anna L Philibert, Peter P Grau, Nicholas W Bowersox","doi":"10.4088/JCP.24m15424","DOIUrl":"https://doi.org/10.4088/JCP.24m15424","url":null,"abstract":"<p><p><b>Objective:</b> To evaluate factors associated with suicide mortality among Veterans Health Administration (VHA) patients with bipolar disorder.</p><p><p><b>Methods:</b> VHA patients diagnosed with bipolar disorder in calendar year (CY) 2014 who utilized VHA health care services in CY2013 were included in the study cohort. Suicide mortality in the 5 years following the first documented bipolar disorder diagnosis during CY2014 was examined using Cox proportional hazards regression.</p><p><p><b>Results:</b> 725 of 126,655 VHA patients who had a bipolar disorder diagnosis in CY2014 (0.6%) died by suicide in the following 5 CYs (2014-2019). Suicide was associated with suicide high-risk flags (hazard ratio [HR] = 2.21), prior year emergency department visit (HR = 1.25), having a new bipolar disorder diagnosis (HR= 1.23), and receiving a benzodiazepine prescription of ≥30 days of supply (HR = 1.58). Prescriptions of benzodiazepines of <30 days of supply, other anxiolytics (ie, buspirone), and sedatives were not significantly associated with suicide mortality in the multivariable model.</p><p><p><b>Conclusions:</b> Among VHA patients diagnosed with bipolar disorder, receipt of a benzodiazepine prescription of ≥30 days was associated with increased suicide risk, even after controlling for clinical and demographic factors. Elucidating mechanisms through which benzodiazepine prescriptions increase suicide risk is an important avenue for future investigations. Additionally, VHA patients with newly diagnosed bipolar disorder may benefit from increased clinical attention, given the elevated suicide risk among this subgroup. Findings highlight targets for suicide prevention initiatives.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eating Disorders Among Transgender and Gender Diverse People: A Qualitative Analysis of Reddit Threads.","authors":"Nora Y Sun, Sofia E Guerra, Alex S Keuroghlian","doi":"10.4088/JCP.24com15640","DOIUrl":"https://doi.org/10.4088/JCP.24com15640","url":null,"abstract":"","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and Risk Factors for Suicide Attempt During Pregnancy and the Postpartum Period.","authors":"Sidra Goldman-Mellor, Mark Olfson, Alison Gemmill, Claire Margerison","doi":"10.4088/JCP.24m15633","DOIUrl":"https://doi.org/10.4088/JCP.24m15633","url":null,"abstract":"<p><p></p><p><p><b>Background:</b> In the United States, suicide accounts for 1 out of every 20 deaths that occur during pregnancy and the first 12 months postpartum. Although nonfatal suicide attempts are the strongest known predictor of death by suicide, there are no prior population based estimates of the incidence of and clinical risk factors for pregnancy associated suicide attempts.</p><p><p><b>Methods:</b> This retrospective cohort study used statewide, all-payer, longitudinally linked hospital and emergency department (ED) patient records from California. Participants included all California residents with an index hospital delivery of a live infant between 2010 and 2020. Outcomes included ED presentation for nonfatal suicide attempt during pregnancy or up to 12 months postpartum. Clinical risk factors of interest included healthcare utilization patterns during pregnancy and behavioral health diagnoses recorded at index delivery.</p><p><p><b>Results:</b> Among delivering patients with an index delivery (N = 3,737,792), 0.13% (n = 4,968) had a suicide attempt during pregnancy or the postpartum period. After adjusting for background demographic characteristics, risks of a postpartum suicide attempt were increased 4- to 30-fold by several clinical factors, including prenatal suicide attempt ED visits, psychiatric ED visits, and assault ED visits, and by psychotic disorders, bipolar disorder, alcohol use disorder, recurrent and single-episode major depressive disorder, and anxiety disorders recorded at delivery.</p><p><p><b>Conclusions:</b> Risks of postpartum suicide attempt were substantially elevated for patients who had behavioral health related ED visits during pregnancy and by several psychiatric disorders at delivery. Clinical consideration should be given to monitoring these patients for suicide attempt risk.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma NfL, P-tau181, and P-tau181/Aβ42 Ratio in Predicting Mild Behavioral Impairment in Dementia-Free Multiethnic Asian Older Adults With Mixed Pathology in a 5-Year Clinical Cohort.","authors":"Yingqi Liao, Joyce R Chong, Cheuk Ni Kan, Xuhao Zhao, Yuek Ling Chai, Saima Hilal, Mitchell K P Lai, Christopher P Chen, Xin Xu","doi":"10.4088/JCP.24m15558","DOIUrl":"https://doi.org/10.4088/JCP.24m15558","url":null,"abstract":"<p><p><b>Objective:</b> The underlying mechanisms of mild behavioral impairment (MBI), a marker for cognitive impairment and dementia, have remained unclear especially in a multiethnic Asian population. The study aimed to examine whether baseline Alzheimer disease biomarkers, including plasma neurofilament light (NfL) chain, phosphorylated tau-181 (p-tau181), and the p-tau181-to-amyloid-β42 (p-tau181/Aβ42) ratio, could predict MBI incidence in dementia-free Asian older adults.</p><p><p><b>Methods:</b> Participants were recruited from the community and memory clinics from August 2010 to April 2022. All participants underwent cognitive, neuropsychiatric, and clinical assessments annually and neuroimaging scans biennially at baseline and over a maximum of 5 years. Neuropsychiatric symptoms (NPS) and incident MBI were examined using Neuropsychiatric Inventory. Plasma NfL, p-tau181, and Aβ42 were measured using single molecule array assays. Neuroimaging measures of hippocampal volume (HV) and white matter hyperintensities (WMH) were obtained.</p><p><p><b>Results:</b> A total of 305 dementia-free participants were included (age 72.1 ± 7.8 years, 52.5% female, 27.9% no cognitive impairment). Among 248 MBI-free participants at baseline, 55 (25.3%) participants developed incident MBI in 5 years. Higher baseline p-tau181, p-tau181/Aβ42 ratio, and NfL were predictive of increased NPS severity longitudinally and MBI incidence (<i>P</i> < .05). Higher p-tau181 levels (hazard ratio [HR] [95% CI], 2.40 [1.00-5.75], <i>P</i> = .05) were independently associated with an increased likelihood of incident MBI after accounting for incident dementia and plasma NfL. This relationship remained significant when controlling for HV and WMH (HR [95% CI], 2.69 [1.08-6.70], <i>P</i> = .03).</p><p><p><b>Conclusions:</b> Our findings highlighted the relationship between amyloid burden and neuroaxonal degeneration with neurobehavioral changes in multiethnic Asian older adults with underlying mixed pathology.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Tool to Refine Lithium Therapy: A Simple Formula for a Complex Problem.","authors":"Gin S Malhi, Erica Bell, Kinga Szymaniak","doi":"10.4088/JCP.24com15743","DOIUrl":"https://doi.org/10.4088/JCP.24com15743","url":null,"abstract":"","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Results From a Long-Term Observational Follow-Up Study of a Single Dose of Psilocybin for a Treatment-Resistant Episode of Major Depressive Disorder.","authors":"Guy M Goodwin, Ania Nowakowska, Merve Atli, Boadie W Dunlop, David Feifel, David J Hellerstein, Lindsey Marwood, Zainib Shabir, Sunil Mistry, Susan C Stansfield, Emma Teoh, Joyce Tsai, Matthew B Young, Ekaterina Malievskaia","doi":"10.4088/JCP.24m15449","DOIUrl":"https://doi.org/10.4088/JCP.24m15449","url":null,"abstract":"<p><p><b>Background:</b> The largest randomized study of psilocybin to date demonstrated the efficacy of COMP360 25 mg (Compass Pathways' investigational proprietary pharmaceutical-grade synthesized psilocybin formulation) in participants with treatment-resistant depression (COMP 001), compared with 10 mg and 1 mg doses. Here, we report findings from COMP 004, a 52-week observational follow-up of patients from COMP 001 and COMP 003, a small open-label study of the coadministration of 25 mg COMP360 with continuing antidepressant treatment.</p><p><p><b>Methods:</b> Adverse events (AEs) were collected over the full 52-week period. The primary efficacy endpoint was time to a prespecified depressive event over the 52 weeks following COMP360 administration in COMP 001 participants, presented as Kaplan-Meier estimates. A post hoc analysis included only participants that entered COMP 004. Data were collected from July 2020 to July 2022.</p><p><p><b>Results:</b> Sixty-six participants entered COMP 004 (COMP 001, n = 58 [25 mg group n = 22, 10 mg group n = 19, 1 mg group n = 17]; COMP 003, n = 8). Few AEs were reported post-entry into COMP 004, with 1 AE of mild suicidal ideation in the 1 mg group deemed possibly related to study drug. For all COMP 001 patients (n = 233), median time to depressive event was greater for the 25 mg group (92 days) compared to the 10 mg (83 days) and 1 mg (62 days) groups, with the majority of participants having had a depressive event by Week 12 (25 mg n = 37/75, 10 mg n = 38/79, 1 mg n = 44/75). The post hoc supplementary analysis of those who enrolled in COMP 004 from COMP 001 exhibited the difference between groups more strikingly (25 mg, 189 days; 10 mg, 43 days; 1 mg, 21 days); however, only 10 participants experienced a depressive event post-COMP 004 enrollment (25 mg n = 6, 10 mg n = 3, 1 mg n = 1) from COMP 001 and none from COMP 003. At COMP 004 entry, the 1 mg group had the highest number of participants on antidepressant medication (n = 10; 10 mg, n = 9; 25 mg, n = 6) and generally initiated treatment earlier.</p><p><p><b>Conclusion:</b> Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg. Larger long-term studies are required to confirm these findings and provide clarity on the longer-term effects of psilocybin.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT04519957.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"86 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}