International Clinical Psychopharmacology最新文献

{"title":"Association between anxious depression and clinical outcomes in subjects with treatment-resistant depression: a comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment-resistant depression (ASCERTAIN-TRD).","authors":"Stefania Chaikali, Clotilde Guidetti, Silvia Ioannou, Madhukar H Trivedi, Richard C Shelton, Dan V Iosifescu, Michael E Thase, Manish K Jha, Sanjay J Mathew, Charles DeBattista, Mehmet E Dokucu, Olga Brawman-Mintzer, Glenn W Currier, William Vaughn McCall, Matthew Macaluso, Alexander Bystritsky, Fidel Vila-Rodriguez, Erik B Nelson, Albert S Yeung, Leslie C MacGregor, Thomas Carmody, Maurizio Fava, George I Papakostas","doi":"10.1097/YIC.0000000000000628","DOIUrl":"10.1097/YIC.0000000000000628","url":null,"abstract":"<p><strong>Objective: </strong>Anxious depression is a negative prognostic factor linked to worse outcomes in major depressive disorder (MDD). However, its role in treatment-resistant depression (TRD) remains unclear. This secondary analysis of the ASCERTAIN-TRD trial investigates the role of anxious depression as a predictor or moderator of treatment response.</p><p><strong>Methods: </strong>A Hamilton Depression Rating Scale Anxiety and Somatization Subscale score of at least 7 identified subjects with the anxious depressive subtype. Treatment response was evaluated based on changes in Montgomery-Asberg Depression Rating Scale scores using mixed-effects models with repeated measures and included additional terms accounting for the presence or absence of anxious depression. Two hundred fifty-three patients, who had at least one post-baseline Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale score were included in the analysis. Of them, 182 subjects presented anxious and 71 nonanxious depression.</p><p><strong>Results: </strong>Treatment outcomes were similar across the three treatment groups regardless of anxious MDD status ( P -value > 0.5 for all comparisons) suggesting that anxious depression was not a significant predictor or moderator of treatment outcome.</p><p><strong>Conclusion: </strong>These findings indicate that anxious depression alone may be prognostic rather than predictive. These findings may be a useful guidance for clinicians, suggesting that standard TRD treatments remain applicable in the anxious MDD subtype.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"295-303"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928993","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":"Drug development in autism spectrum disorder: genetic heterogeneity, failed trials, and the case for stratified pharmacotherapy.","authors":"Riccardo Bortoletto, Giuseppe Fanelli, Marco Colizzi","doi":"10.1097/YIC.0000000000000627","DOIUrl":"10.1097/YIC.0000000000000627","url":null,"abstract":"<p><p>Despite three decades of clinical trials, no pharmacological treatment has shown consistent efficacy for the core features of autism spectrum disorder (ASD), and regulatory approvals remain limited to risperidone and aripiprazole for severe irritability. This limited efficacy likely reflects a mismatch between underlying biology and broad trial designs. ASD is a clinically defined neurodevelopmental condition with marked etiologic heterogeneity, shaped by highly polygenic liability and a long tail of rare, often de novo , high-impact variants. Genomic studies implicate synaptic signaling, chromatin regulation, and excitatory-inhibitory processes, but this partial biological convergence does not support a single therapeutic target across the diagnostic spectrum. Debate over environmental risk factors, including prenatal acetaminophen exposure, also shows how weak causal inference can distort research priorities. We propose three priorities for ASD pharmacotherapy: genetically stratified mechanism-linked interventions, pharmacogenomics-informed symptomatic prescribing, and trials using validated or biomarker-informed endpoints that capture outcomes regarded as meaningful by autistic people.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"308-311"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928996","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":"Methylphenidate treatment in adults with comorbid attention-deficit/hyperactivity disorder and borderline personality disorder: a prospective longitudinal study.","authors":"Giulio Emilio Brancati, Martina Marcenaro, Elena Costagli, Anna Magnesa, Pierpaolo Medda, Elisa Schiavi, Giulio Perugi","doi":"10.1097/YIC.0000000000000630","DOIUrl":"10.1097/YIC.0000000000000630","url":null,"abstract":"<p><p>Attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) frequently co-occur. However, evidence on the clinical effects of stimulant treatment in ADHD-BPD comorbidity remains limited. This prospective study aimed to investigate the longitudinal effects of methylphenidate (MPH) on borderline personality features in adults with ADHD-BPD. Thirty-six adults diagnosed with ADHD who also met the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for BPD were treated with MPH and followed for at least 16 weeks. Clinical ratings of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition BPD criteria and psychometric measures assessing symptom severity and personality functioning were obtained at baseline and follow-up. Twenty-four participants (66.7%) completed the follow-up. Follow-up duration ranged from 3.9 to 12.3 months, with a mean duration of 7.8 ± 2.48 months. The number of BPD criteria significantly decreased after treatment ( r  = 0.82, P  < 0.001). Nineteen participants no longer met the diagnostic threshold for BPD, and 10 achieved remission (≤2 BPD criteria). Baseline anger dysregulation ( P  = 0.009) and mood stabilizer use ( P  = 0.029) were associated with continued MPH treatment. Our findings preliminarily suggest that MPH, especially combined with mood stabilizers, may be associated with clinical benefits and acceptable tolerability in patients with comorbid ADHD-BPD. While causal conclusions cannot be drawn, replication in randomized controlled trials is warranted.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"284-294"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928990","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":"Not all antipsychotic polypharmacy is the same.","authors":"Norio Yasui-Furukori","doi":"10.1097/YIC.0000000000000629","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000629","url":null,"abstract":"","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":"41 5","pages":"304-307"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669353","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":"Resistant depression, biomarkers, and comorbidity in clinical practice.","authors":"Alessandro Serretti","doi":"10.1097/YIC.0000000000000633","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000633","url":null,"abstract":"","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":"41 5","pages":"265-268"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669459","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":"Efficacy and safety of intramuscular and intravenous midazolam for acute agitation in emergency settings: a systematic review.","authors":"Federico Bottaro, Guido Nosari, Isidora Tesic, Paolo Brambilla, Giuseppe Delvecchio","doi":"10.1097/YIC.0000000000000638","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000638","url":null,"abstract":"<p><p>Acute agitation often requires parenteral sedation in emergency care. Midazolam is widely used for its rapid onset, short duration of action, and availability for intramuscular and intravenous administration, but its efficacy and safety across emergency settings remain incompletely understood. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines, we searched PubMed, Scopus, and Web of Science for original studies evaluating intramuscular or intravenous midazolam, as monotherapy or in combination regimens, for acute agitation in emergency department (ED), psychiatric emergency service (PES), and prehospital emergency medical service (EMS) settings. Twenty-three studies met the inclusion criteria. Intramuscular midazolam was generally associated with rapid early sedation in ED studies, although this advantage was sometimes offset by less sustained clinical effects and higher need for rescue or additional sedation. Intravenous midazolam monotherapy showed a greater need for active airway management in its main direct comparison with intravenous droperidol. Midazolam-droperidol combinations showed more consistent advantages for rapid early sedation in monitored ED settings. In PES and EMS, midazolam's role was more dependent on clinical context, operational constraints and postsedation monitoring. Midazolam appears a useful rapid-onset option, but should not be considered a consistently superior standalone strategy. Future multicenter studies should better elucidate its safest and most effective use.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818219","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":"Expanding the horizon of brexpiprazole augmentation in treatment-resistant disorders: from obsessive-compulsive disorder to adolescent bipolar disorder.","authors":"Yiğit Özaydin, Fevzi Tuna Ocakoğlu, Eyüp Sabri Ercan","doi":"10.1097/YIC.0000000000000615","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000615","url":null,"abstract":"","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":"41 4","pages":"256-257"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054309","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":"Antipsychotic polypharmacy in Japanese outpatients with schizophrenia: prevalence and sex- and age-related patterns.","authors":"Rintaro Sogawa, Junji Uno, Akira Yoshimi, Kenta Umeda, Shusuke Uekusa, Mami Kobayashi, Michinori Tokizaki, Masami Tensho, Takashi Yoshio, Toshiya Inada, Chisato Shimanoe, Masahiro Kurosawa","doi":"10.1097/YIC.0000000000000616","DOIUrl":"10.1097/YIC.0000000000000616","url":null,"abstract":"<p><p>Antipsychotic polypharmacy (APP), defined as the concurrent use of two or more antipsychotic agents, remains common in clinical practice despite antipsychotic monotherapy being the recommended standard for schizophrenia treatment. This nationwide cross-sectional survey examined the prevalence and determinants of APP among outpatients with schizophrenia in Japan. Data were collected from 3657 patients across 36 medical institutions between 21 and 25 October 2024. Patients were categorized into antipsychotic monotherapy and APP groups, and demographic and clinical characteristics, including age, sex, medication administration frequency, use of long-acting injectables, clozapine, and concomitant psychotropic medications, were compared. Antipsychotic doses were standardized to chlorpromazine equivalents and analyzed by sex and age group. APP was observed in 40.8% of patients. Multivariable analyses showed that APP was significantly associated with male sex, older age, long-acting injectable use, and concomitant use of antiparkinsonian agents, anxiolytics/hypnotics, and mood stabilizers, whereas clozapine use was inversely associated with APP. Chlorpromazine equivalent doses increased with the number of antipsychotics prescribed, peaking in patients aged 40-59 years and declining thereafter. Second-generation antipsychotics predominated overall, although first-generation antipsychotic use increased with polypharmacy. These findings underscore the importance of careful management of APP, taking sex- and age-related prescribing patterns into consideration.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"225-231"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316859","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":"An observational study on the effects of as-needed use of various antipsychotic drugs for agitation due to psychotic disorders.","authors":"Kotaro Hatta, Fumiyoshi Morikawa, Satoshi Yamasaki, Takuya Ishizuka, Mitsuru Nakamura, Kosuke Hino, Shigemasa Katayama, Atsushi Imai, Kiyoshi Fujita, Naoya Sugiyama","doi":"10.1097/YIC.0000000000000613","DOIUrl":"10.1097/YIC.0000000000000613","url":null,"abstract":"<p><p>This multicenter, 6-month naturalistic observational study investigated the time from as-needed (PRN) administration of psychotropic medications to the onset of calming in patients with acute psychotic disorders. Newly admitted patients exhibiting moderate to marked agitation on the Agitation-Calmness Evaluation Scale (ACES) and requiring PRN treatment were included, and 170 first agitation episodes were analyzed. The primary outcome was time to onset of effect, defined as achieving ACES = 3. Medication refusal at baseline was far more frequent in patients with injectable formulations than those with oral or sublingual agents (65.5% vs. 4.3%). Kaplan-Meier estimates showed mean onset times (minutes) for oral/sublingual drugs as follows: asenapine sublingual, 30.0; olanzapine orally disintegrating tablet, 31.9; quetiapine, 46.6; and risperidone oral solution, 34.5. Using Cox proportional hazards models with asenapine as reference, quetiapine demonstrated a significantly lower hazard of achieving calming (hazard ratio 0.39), while risperidone showed a nonsignificant trend. For injectable antipsychotics, mean onset times were: olanzapine intramuscular, 36.3; haloperidol intramuscular, 47.5; and haloperidol intravenous, 45.0, with no significant differences among them. No serious adverse events were observed. The findings suggest that asenapine sublingual may offer faster calming in patients without refusal, and that future studies with shorter assessment intervals are warranted.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"204-212"},"PeriodicalIF":3.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13207436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085665","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":"Depression severity and efficacy outcomes: post hoc analyses from a phase 3 trial of esmethadone for the adjunctive treatment of major depressive disorder with inadequate response to standard antidepressants.","authors":"Clotilde Guidetti, George I Papakostas, Steven Stahl, Luca Pani, Sara De Martin, Andrea Mattarei, Stefano Comai, Cornelia Kröger, Paggard Champasa, Charles W Gorodetzky, Frank J Vocci, Thomas R Kosten, David Bushnell, Martin Kappler, Franco Folli, Charles E Inturrisi, Marco Pappagallo, Paolo L Manfredi, Maurizio Fava","doi":"10.1097/YIC.0000000000000618","DOIUrl":"10.1097/YIC.0000000000000618","url":null,"abstract":"<p><p>Esmethadone is under development as an adjunctive treatment for major depressive disorder in patients with inadequate response to standard antidepressants. In the phase 3 study REL-1017-301, esmethadone did not meet the primary endpoint of mean change from baseline (CFB) in Montgomery-Åsberg Depression Rating Scale (MADRS) at day 28, although it showed statistically significant results on the key secondary endpoint of response rate. Post hoc exploratory analyses suggested efficacy in patients with baseline MADRS greater than or equal to 35 (severe depression) ( P  = 0.006). The objective of this study was to enhance the reliability of these post hoc analyses through sensitivity analyses. (a) Sensitivity analyses for the primary endpoint using baseline MADRS cutoffs 31-37 showed larger treatment effects with higher baseline severity. Mixed model for repeated measures and per-protocol results were consistent. (b) CFB in MADRS was modeled for each treatment arm individually using all available data. The mean CFB in MADRS demonstrated separation between esmethadone and placebo arms for patients with a baseline score of 35 or higher. These exploratory, hypothesis-generating sensitivity analyses support the potential efficacy of esmethadone in patients with severe depression.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"213-224"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305536","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}