Journal of Clinical Psychopharmacology最新文献

{"title":"The Antidepressant Effects of the mGlu2/3 Receptor Antagonist TS-161 in Treatment-Resistant Depression: A Phase IIa Proof-of-Concept Clinical Trial.","authors":"Mark D Kvarta, Mai Watanabe, Satoshi Ozaki, Dede Greenstein, Adam Fijtman, Gregory Jones, Hiroe I Hu, Solaleh Azimipour, Peixiong Yuan, Jenessa N Johnston, Jennifer W Evans, Jessica R Gilbert, Carlos A Zarate","doi":"10.1097/JCP.0000000000002246","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002246","url":null,"abstract":"<p><strong>Background: </strong>Like ketamine, group II metabotropic glutamate receptor (mGluR2/3) antagonists increase glutamate release and monoaminergic signaling, promote synaptic plasticity, and show antidepressant-related activity in preclinical models. A recent phase I trial of the orthosteric mGluR2/3 antagonist prodrug TS-161 established its safety, tolerability, and pharmacokinetic profile.</p><p><strong>Methods: </strong>This phase IIa randomized, placebo-controlled, double-blind, crossover, proof-of-concept, single-site trial was designed to evaluate the antidepressant effects of TS-161. Eleven unmedicated adults with treatment-resistant depression received either oral TS-161 (50 to 100 mg daily) or a placebo for 3 weeks before crossing over to the other condition. The study was halted early due to low recruitment.</p><p><strong>Results: </strong>Adverse events were mild and consistent with the prior phase I study. Linear mixed models using drug×time interaction to estimate mean Montgomery-Åsberg Depression Rating Scale scores per treatment identified no significant difference between treatment conditions at any timepoint, including the primary endpoint, day 21 (P=0.91). One of the 11 participants responded to TS-161 by day 7 (vs. 0/9 receiving placebo); no participants achieved remission. Magnetic resonance spectroscopy suggested a qualitative trend for increased glutamate metabolite values, and TS-161 increased gamma power during magnetoencephalography relative to baseline and placebo (pFDR<0.01) in lateral cortical regions. Peripheral brain-derived neurotrophic factor levels trended toward elevation (overall drug effect P=0.055). No advantages were seen in secondary clinical or cognitive outcomes.</p><p><strong>Conclusions: </strong>The findings suggest potential central nervous system engagement through proxy biomarkers and increased glutamatergic tone, but this did not translate to clinical improvement.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905530","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":"Laryngospasm and Generalized Dystonia After Risperidone ER in the Setting of Fluphenazine Therapy.","authors":"Benjamin Cutler, Emily Schroeder, John Mauch","doi":"10.1097/JCP.0000000000002248","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002248","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905570","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":"Dose-Dependent Efficacy of Aripiprazole in Jealous-Type Delusional Disorder: A Case Study Guided by PSYRATS-DS.","authors":"Metehan Kopan, Berivan Gündürü","doi":"10.1097/JCP.0000000000002257","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002257","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905523","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":"Clozapine-induced Nephritis During Titrations May Be More Frequent Than What Was Described But Is Essentially Preventable.","authors":"Jose de Leon","doi":"10.1097/JCP.0000000000002254","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002254","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887597","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":"GLP-1 Receptor Agonists, Lithium, and the Kidneys: A Tale of Two Signals.","authors":"Jonathan G Leung, Balwinder Singh","doi":"10.1097/JCP.0000000000002253","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002253","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887646","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":"The Randomization Effect in a Double-Blind Placebo-Controlled Depression Study.","authors":"Steven D Targum, Paulette Ceesay, Christopher Lines, Michael E Thase, Gerard Sanacora, Aristide Merola","doi":"10.1097/JCP.0000000000002250","DOIUrl":"https://doi.org/10.1097/JCP.0000000000002250","url":null,"abstract":"<p><strong>Background: </strong>Double-blind, placebo-controlled trials are often affected by higher-than-anticipated placebo responses that may contribute to study failure. It is common to observe symptomatic improvement immediately after randomization regardless of treatment allocation.</p><p><strong>Methods: </strong>This post hoc analysis examined the early randomization effect in a recent 4-week double-blind, placebo-controlled study that examined a novel presynaptic mGluR2 inhibitor, MK-1942, in a daily or twice-weekly dosing strategy versus placebo as an adjunctive treatment in acutely depressed participants with major depressive disorder who had not adequately responded to antidepressant treatment.</p><p><strong>Results: </strong>The original study failed to meet its primary endpoints, but a post hoc analysis revealed an early randomization effect that may have impeded signal detection. Over 60% of the overall Montgomery Asberg Depression Rating Scale (MADRS) score improvement observed in the placebo group occurred within the first week of this 4-week study, and >20% of placebo-assigned participants met criteria as treatment responders within 1 week after randomization. Using week 1 as an alternative (\"revised\") baseline, the percentage of placebo responders at week 4 was reduced from 48.6% to 31.4%. Cohen standardized effect size favoring the twice-weekly MK-1942 dosing over placebo improved from -0.33 (original baseline) to -0.54 at week 4 by applying the revised baseline.</p><p><strong>Conclusions: </strong>These post hoc results suggest an early randomization effect may complicate the interpretation of studies that examine treatment effects of drugs in development. Masking the timing of randomization with blinded, placebo-lead-in designs may warrant consideration for depression studies, particularly for rapid-acting antidepressants.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874506","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":"Cognitive Effects of Esketamine in Treatment-Resistant Depression: A Systematic Review.","authors":"Riccardo Guglielmo, Emma Laura Facchinetti, Daniele Cioci, Miriam Olivola, Beatriz Pereira da Silva, Alessandra Mazzocchi, Bernardo Dell'Osso, Mario Amore, Gianluca Serafini","doi":"10.1097/JCP.0000000000002165","DOIUrl":"10.1097/JCP.0000000000002165","url":null,"abstract":"<p><strong>Background: </strong>Treatment-resistant depression affects up to one third of patients with major depressive disorder and is frequently accompanied by persistent cognitive impairments that significantly hinder functional recovery. Emerging evidence suggests that sub-anesthetic esketamine does not appear to be associated with cognitive deterioration and may be associated with procognitive effects; however, no systematic review has specifically synthesized cognitive outcomes in this population.</p><p><strong>Methods: </strong>A systematic search was conducted. Eligible studies included adults aged 18 to 80 years receiving intranasal or intravenous esketamine, with cognitive assessments performed at least 1 month after treatment initiation. Six studies met the inclusion criteria. Cognitive outcomes were grouped into attention/processing speed, memory, and executive functions.</p><p><strong>Results: </strong>Across studies, available evidence suggests that esketamine does not appear to be associated with cognitive deterioration in any assessed domain. Improvements in attention and processing speed were the most frequent and robust findings, observed in both RCT-derived datasets and naturalistic longitudinal studies. Memory remained stable in short-term designs but improved in studies with extended follow-up. Executive functions showed gains primarily among participants with baseline impairments and in long-term assessments. All remaining evaluations indicated cognitive stability.</p><p><strong>Conclusions: </strong>Current evidence, albeit limited, suggests that esketamine appears to be cognitively safe in adults with treatment-resistant depression and may confer selective improvements, particularly in attention and processing speed, with more variable benefits in memory and executive functioning over sustained treatment. These effects may support functional recovery and complement esketamine's antidepressant action. Further research using harmonized cognitive batteries, larger samples, and longer follow-up periods is needed to better characterize cognitive trajectories and their relevance for personalized treatment strategies.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"612-624"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to \"Reading the Signal: What Psychedelic Trials in Depression Still Can't Tell Us\".","authors":"Natia Horato, Felipe Dalvi-Garcia, Pablo E P Dutra, Antonio E Nardi","doi":"10.1097/JCP.0000000000002240","DOIUrl":"10.1097/JCP.0000000000002240","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"656"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591993","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 Manic Episode Associated With Levetiracetam Treatment in a Patient With Brain Tumor.","authors":"Cristina Centomo, Giovanni Di Caprio, Paola Bini, Enrico Marchioni, Pierluigi Politi, Cristiano Nichini","doi":"10.1097/JCP.0000000000002226","DOIUrl":"10.1097/JCP.0000000000002226","url":null,"abstract":"","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"644-647"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592019","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":"Cariprazine in Human Milk: Cautionary Implications for Use During Lactation.","authors":"Shreya Balamurali, Shraddha Trehan, Amy Stark, Palika Datta, Kaytlin Krutsch","doi":"10.1097/JCP.0000000000002174","DOIUrl":"10.1097/JCP.0000000000002174","url":null,"abstract":"<p><strong>Background: </strong>Cariprazine is a dopamine D2/D3 partial agonist approved for treatment-resistant depression, bipolar disorder (BD) and schizophrenia. Women with bipolar disorder face an increased risk of postpartum mania and psychosis, as childbirth often triggers episodes. While continuing cariprazine can be crucial for maternal well-being, limited data exist on its peripartum safety. The objective of this research is to assess the risk of infant exposure to maternal cariprazine via breast milk.</p><p><strong>Methods: </strong>Breast milk samples were released from the InfantRisk Human Milk Biorepository from 5 lactating women who were taking cariprazine 1.5 to 4.5 mg daily, 4 of whom continued the drug since pregnancy. Timed samples were collected and analyzed using liquid chromatography-tandem mass spectrometry for cariprazine and its active metabolites, desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR). Infant risk was assessed by determining relative infant dose (RID%) and maternal reports of infant outcomes.</p><p><strong>Results: </strong>Cariprazine and its metabolites were detectable in all participants' milk samples. Mean RID% was 1.23% for cariprazine, 0.09% for DCAR, and 1.22% for DDCAR, yielding a cumulative exposure of 2.54% RID; the highest individual dose-standardized RID was 3.99% (cumulative). Two mothers self-reported infant lethargy, one of which resolved after maternal dose reduction.</p><p><strong>Conclusions: </strong>Estimated infant exposure to cariprazine and its active metabolites falls below standard safety thresholds. However, reported infant adverse effects and the potential for metabolite accumulation due to DDCAR's long half-life necessitate further research to examine potential long-term adverse effects while breastfeeding, particularly in infants exposed to higher maternal doses. These findings represent the first empirical data on cariprazine during lactation and highlight the need for further studies, including pharmacokinetic modeling, to inform clinical guidance.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":"549-555"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838520","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}