Journal of Clinical Psychopharmacology最新文献

{"title":"Predictive Validity of the 5-Factor PANSS Model in Acute Schizophrenia: Early Response to Aripiprazole and Brexpiprazole.","authors":"Yuri Kobayashi, Mizue Ichinose, Toshihiro Terui, Hiroshi Hoshino, Yuhei Suzuki, Sho Horikoshi, Masayuki Goto, Daijiro Yamaguchi, Yoichiro Hirata, Haruka Kaneko, Kenya Watanabe, Keiko Kanno-Nozaki, Satoshi Takeuchi, Itaru Miura","doi":"10.1097/JCP.0000000000002040","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002040","url":null,"abstract":"<p><strong>Background: </strong>Predicting early treatment response in acute schizophrenia is critical yet challenging. This observational study aimed to determine whether improvements in specific symptom domains after 2 weeks predict overall response at 6 weeks in patients treated with aripiprazole (ARI) or brexpiprazole (BRE).</p><p><strong>Methods: </strong>We included 65 patients (34 antipsychotic-naïve and 31 antipsychotic-free recurrent) treated with flexible doses of ARI or BRE. Benzodiazepines were used in 41 patients (64.1%), and their use did not significantly impact prediction. The Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Improvement were used to assess responses.</p><p><strong>Results: </strong>Receiver operating characteristic analysis revealed area under the curve values for PANSS total (PANSS-T), negative, excitement, cognitive, positive, and depressive/anxiety components of 0.788, 0.783, 0.603, 0.746, 0.738, and 0.735, respectively. Kendall's tau correlation and Cramer's V revealed significant predictive relationships for PANSS-T (0.413, P<0.001), negative (0.411, P<0.001), and therapeutic response dichotomized by this score (0.573, P <0.001), cognitive (0.364, P<0.001), positive (0.344, P<0.001), and depression/anxiety (0.344, P=0.001), but not for excitement (0.15, P=0.151). Benzodiazepine use did not significantly impact these predictive associations.</p><p><strong>Conclusions: </strong>This study is the first to evaluate the predictive validity of the PANSS 5-factor model in patients with acute schizophrenia treated with ARI/BRE. Early symptom improvements, particularly in negative domains, are stronger predictors of overall response, while excitement symptom improvements showed a weaker relationship. These findings underscore the importance of early, symptom-specific assessments to optimize treatment strategies for acute schizophrenia. Further studies with larger samples are necessary to validate these results.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concomitant Use of Dextromethorphan/Bupropion and Escitalopram Associated With Serotonin Toxicity in an Older Adult: A Case Report.","authors":"Demetrius Woodard, Lara Boyle, Samantha J Zwiebel","doi":"10.1097/JCP.0000000000002034","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002034","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Does Positive Mental Health Affect Next-Step Treatment Outcomes in Treatment-Resistant Depression? A VAST-D Report.","authors":"Sidney Zisook, Gary R Johnson, Beata Planeta, Somaia Mohamed","doi":"10.1097/JCP.0000000000002051","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002051","url":null,"abstract":"<p><strong>Background: </strong>Many patients view the return of \"positive mental health\" (PMH) to be their most important goal of treatment for major depressive disorder (MDD). However, few studies have systematically measured PMH or prospectively examined the added value of considering PMH as a treatment predictor of outcome. This report aims to fill those gaps by determining features associated with PMH and their contributions to outcomes in outpatients with treatment-resistant depression.</p><p><strong>Methods: </strong>The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to 1 of 3 next-step treatments: switching to bupropion (S-BUP), combining with bupropion (C-BUP), or augmenting with aripiprazole (A-ARI). PMH was measured by a novel, 7-item, self-rated questionnaire. The features and outcomes associated with PMH at baseline and during 12 weeks of treatment were explored.</p><p><strong>Results: </strong>Low PMH scores at baseline were associated with greater severity and chronicity of depression, suicidal ideation, increased anxiety, comorbid PTSD, grief, and lower quality of life. High PMH scores were associated with a greater likelihood of remission. PMH scores improved with treatment, especially if the next-step treatment was A-AUG as opposed to S-BUP. Improvement in PMH was associated with higher remission and response rates.</p><p><strong>Conclusions: </strong>Targeting deficiencies in PMH could help optimize outcomes in patients with MDD.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT01421342.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zopiclone Discontinuation-Associated Transient Sleepwalking Behavior: A Case Report.","authors":"Wangwang Xu, Xinqi Wang, Jingjing Xu, Yang Zhang, Jin Gao","doi":"10.1097/JCP.0000000000002045","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002045","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 2 Randomized Trial of NBI-1065846 (TAK-041) in Patients With Anhedonia Associated With Major Depressive Disorder: Results of the TERPSIS Study.","authors":"Shannon R Benedetto, Adrian Ionescu, Tingting Ge, Maura Furey, Swan Lin, Manish K Jha, Andrew Krystal, Asim A Shah, David P Walling, Neel Shah, Sakina J Rizvi, Sidney Kennedy, Antonio Laurenza, Venkatesha Murthy, Eiry Roberts, Jaskaran B Singh","doi":"10.1097/JCP.0000000000002046","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002046","url":null,"abstract":"<p><strong>Background: </strong>Anhedonia is a core symptom of major depressive disorder (MDD) that may result from aberrant lateral habenula hyperactivity. Targeting G-protein coupled receptor 139 (GPR139) may improve anhedonia by modulating lateral habenula activity. NBI-1065846 is an investigational GPR139 agonist that improved anhedonia, anxiety, and depression in rodent models.</p><p><strong>Methods: </strong>TERPSIS was a phase 2, proof-of-concept clinical study. Adults with MDD experiencing a major depressive episode with anhedonia were randomized 1:1 to NBI-1065846 or placebo for 8 weeks. The primary endpoint was the change in the Dimensional Anhedonia Rating Scale (DARS) score. Secondary endpoints were change in total Montgomery Åsberg Depression Rating Scale (MADRS) score in participants with a baseline 17-item Hamilton Depression Rating Scale (HAM-D17) score of ≥19 (moderate to severe) and change in Clinical Global Impression of Severity (CGI-S) score. All changes were from baseline to Day 57.</p><p><strong>Results: </strong>In total, 93 participants received study treatment (NBI-1065846, n = 46; placebo, n = 47). Both groups showed notable improvements in DARS scores from baseline to day 57 (least-squares mean change: NBI-1065846, 13.5; placebo, 17.4), with no statistically significant difference (NBI-1065846 vs. placebo, P = 0.8663). Similarly, MADRS (P = 0.7008) and CGI-S (P = 0.9051) scores showed no significant difference between groups. All treatment-emergent adverse events in the NBI-1065846 group were mild or moderate in severity.</p><p><strong>Conclusions: </strong>The TERPSIS study did not meet its primary or secondary endpoints. NBI-1065846 was generally well tolerated. Addressing the lack of treatment options for anhedonia remains an important unmet clinical need.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blepharospasm Arising From Escitalopram Use: A Case Report.","authors":"Anastasia Zent, Sean Nutting","doi":"10.1097/JCP.0000000000002043","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002043","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RE104: A Double-Blind, Randomized, Single Ascending Dose Placebo-Controlled Study.","authors":"Guy Ludbrook, Nathan Bryson, Beatrix Taylor, Jasna Hocevar-Trnka, Matthew W Johnson, Joe Hirman, Glynn Morrish, Robert Alexander, Mark Pollack","doi":"10.1097/JCP.0000000000002047","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002047","url":null,"abstract":"<p><strong>Background: </strong>This study is the first to formally evaluate in humans the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RE104, a prodrug of the synthetic psychedelic known as 4-hydroxy-N,N-diisopropyltryptamine or 4-OH-DiPT.</p><p><strong>Methods: </strong>This double-blind, randomized, placebo-controlled, phase 1 study of single subcutaneous (SC) doses of RE104 (5 to 40 mg) included 6 cohorts and a total of 48 healthy adult participants with prior experiences with hallucinogenic or psychedelic compounds.</p><p><strong>Results: </strong>SC doses of RE104 were generally safe up to 40 mg with no serious adverse events (AEs) or deaths. Most AEs occurred acutely under supervision and were mild to moderate. The Columbia-Suicide Severity Rating Scale score did not increase during the study, and the Assessment of Alertness and Sedation Scale was largely normal at all timepoints regardless of dose. RE104 exposure, based on Cmax, AUC0-t, and AUC0-inf, increased with dose from 5 to 40 mg RE104. 4-OH-DiPT appeared rapidly in plasma (median Tmax ranged from 1.0 to 1.25 hours across dose groups). Mean plasma 4-OH-DiPT t½ ranged from 2.72 hours to 4.12 hours. PKs appeared linear at the doses examined. Plasma levels of 4-OH-DiPT correlated with the Drug Effect Questionnaire and Mystical Experience Questionnaire (MEQ). Dose-related increases were observed in frequency of the MEQ 30 \"complete mystical experience\" responders.</p><p><strong>Conclusions: </strong>Single SC doses of RE104 resulted in a psychoactive experience and a favorable safety profile similar to psilocybin but with a shorter duration of psychoactive effect (3 to 4 hours). Results suggest a potential for therapeutic effect, warranting further study.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"52-Week Open-Label Safety and Tolerability Study of Centanafadine Sustained Release in Adults With Attention-Deficit/Hyperactivity Disorder.","authors":"Gregory W Mattingly, Osman Turkoglu, Denise Chang, Caroline Ward, Taisa Skubiak, Zhen Zhang, Andrew J Cutler","doi":"10.1097/JCP.0000000000002020","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002020","url":null,"abstract":"<p><strong>Background: </strong>Centanafadine (CTN) is a potential first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) currently in development for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults. Safety, tolerability, and exploratory efficacy of CTN sustained release (SR) in adults were assessed over 52 weeks.</p><p><strong>Methods: </strong>Adults were enrolled after completing a phase 3 pivotal trial or de novo. The monitoring schedule employed a screening (up to 28 d for de novo group only), 52-week open-label, and 10-day safety follow-up periods. Participants received CTN SR 400 mg total daily dose, twice daily. Safety assessments included treatment-emergent adverse events (TEAEs), clinical laboratories, vital signs, electrocardiogram measures, the Study Medication Withdrawal Questionnaire, and the Columbia-Suicide Severity Rating Scale. Exploratory efficacy was assessed using the Adult Investigator Symptom Rating Scale (AISRS) and the Clinical Global Impression of Severity (CGI-S). Safety was analyzed with a mixed-effect model; efficacy was reported using summary statistics.</p><p><strong>Results: </strong>Of 662 adults enrolled [mean (SD) age, 36.7 (10.1) y; 51.1% female; 82.9% white], 653 received CTN SR, and 345 completed the trial. Altogether, 61.4% reported ≥1 TEAE, mostly mild or moderate in severity; insomnia (8.0%), nausea (7.7%), diarrhea and headache (7.0% each) were most common. Eighty (12.3%) discontinued because of TEAEs. Serious adverse events occurred in 12 (1.8%) participants; none were CTN SR-related per investigators. AISRS total scores improved up to 57% and CGI-S by 1.5 points from baseline.</p><p><strong>Conclusions: </strong>Results from this trial demonstrate that CTN SR 400 mg is safe and effective for long-term treatment of adults with ADHD.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pisa Syndrome After Discontinuation of Low-Dose Sulpiride: A Case Report.","authors":"Genki Koyama, Masaki Nakano, Taketo Takata, Yu Mimura, Hiroyuki Uchida, Michitaka Funayama","doi":"10.1097/JCP.0000000000002044","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002044","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weekly Changes in the Clozapine Concentration-to-Dose Ratio During Clozapine Titration in Japanese Patients With Schizophrenia.","authors":"Yuki Kikuchi, Mutsumi Sakata, Kazuro Ikawa, Daisuke Kume, Naoki Horikawa, Hiroshi Komatsu, Hiroaki Tomita","doi":"10.1097/JCP.0000000000002003","DOIUrl":"10.1097/JCP.0000000000002003","url":null,"abstract":"<p><strong>Background: </strong>To prevent inflammatory side effects early in the titration phase of clozapine, international guidelines recommend measuring clozapine blood levels weekly. However, data on such measurements are lacking.</p><p><strong>Methods: </strong>We retrospectively reviewed the medical records of all patients with schizophrenia who were treated with clozapine for the first time and whose clozapine blood levels were measured for at least 2 consecutive weeks from clozapine initiation at our institution from 2020 to 2024. Patients were divided into 2 groups based on whether they had a fever during the first 6 weeks of clozapine treatment. The clozapine concentration-to-dose (C/D) ratios were compared weekly within 6 weeks after starting clozapine.</p><p><strong>Results: </strong>A total of 28 patients were included in the study, of whom 6 developed a fever and 22 did not. The median C/D ratios in weeks 1 and 2 were significantly higher in patients with a fever than in those without (week 1: 2.12 vs 1.31, P  = 0.0217; week 2: 3.48 vs 1.23, P  = 0.01). There was no significant difference in C/D ratios between the groups from week 3 to week 6. During the first 6 weeks of treatment, C/D ratios increased markedly and showed peaks in patients with fever but remained stable in patients without fever.</p><p><strong>Conclusions: </strong>Measuring clozapine blood levels early in the titration phase helps estimate the metabolic capacity of patients. Furthermore, it is essential to pay attention to inflammation, which may increase clozapine C/D ratios.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"345-348"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}