Christoph U Correll, Suresh Durgam, Susan G Kozauer, Hassan D Lakkis, Changzheng Chen, Kimberly E Vanover, Sharon Mates, Robert E Davis
{"title":"Lumateperone monotherapy for major depressive episodes associated with bipolar disorder: efficacy and safety in a randomized placebo-controlled trial.","authors":"Christoph U Correll, Suresh Durgam, Susan G Kozauer, Hassan D Lakkis, Changzheng Chen, Kimberly E Vanover, Sharon Mates, Robert E Davis","doi":"10.1097/YIC.0000000000000597","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000597","url":null,"abstract":"<p><p>This Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of lumateperone to treat bipolar depression. Patients (18-75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1:1 to 6-week lumateperone 28 mg (n = 183), lumateperone 42 mg (n = 185), or placebo (n = 186). Primary and key secondary endpoints were change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total score and time to first sustained response (≥50% reduction from baseline in MADRS Total score), respectively. Safety assessments included adverse events, extrapyramidal symptoms (EPS), laboratory evaluations, and vital signs. Neither dose of lumateperone achieved significant improvement vs. placebo (P > 0.05) in the primary endpoint (MADRS Total score, least squares mean difference vs. placebo: 28 mg, 0.9; 42 mg, -1.0) or in the key secondary endpoint (MADRS Total time to first sustained response hazard ratio vs. placebo: 28 mg, 1.00; 42 mg, 0.93), likely due to a high placebo response. Both lumateperone doses were well tolerated, with low EPS risk and minimal changes in weight, prolactin, and cardiometabolic or endocrine parameters. While study efficacy objectives were not met, both doses of lumateperone were generally safe and well tolerated in patients with bipolar depression.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690111","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}
Mauricio Tohen, Suresh Durgam, Susan G Kozauer, Changzheng Chen, Robert E Davis, Sharon Mates
{"title":"Long-term safety and tolerability of lumateperone 42 mg in patients with bipolar disorder: results from a 6-month open-label extension study.","authors":"Mauricio Tohen, Suresh Durgam, Susan G Kozauer, Changzheng Chen, Robert E Davis, Sharon Mates","doi":"10.1097/YIC.0000000000000596","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000596","url":null,"abstract":"<p><p>This 6-month open-label extension (OLE) period of a Phase 3 placebo-controlled study (NCT02600494) examined the safety of lumateperone in patients with bipolar I or bipolar II depression. Eligible patients completing the placebo-controlled period received lumateperone 42 mg once daily up to 175 days. The primary endpoint was safety and tolerability, assessed by adverse events (AEs) and clinical laboratory evaluations analyzed by imputing missing data using a last observation carried forward approach. The secondary endpoint was efficacy measured by Montgomery-Åsberg Depression Rating Scale (MADRS) total and Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) scores. Of 127 patients in the OLE, 58.3% completed treatment, and 42.5% experienced a drug-related treatment-emergent AE (TEAE); the most common TEAEs were headache (20.5%), dry mouth (11.8%), dizziness (10.2%), and nausea (10.2%). The majority (92%) of TEAEs were of mild or moderate severity. There were no notable changes in extrapyramidal symptom scores, cardiometabolic parameters, or body morphology. MADRS total score (mean change, -8.9, nominal P < 0.0001), CGI-BP-S total score (-2.3, nominal P < 0.0001), and CGI-BP-S depression subscore (-1.3, nominal P < 0.0001) improved over time, from baseline to Day 175. Overall, 6-month lumateperone 42 mg was generally well tolerated, and depressive symptoms based on MADRS total score and CGI-BP-S improved over time.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636951","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, suicidality, tolerability, and acceptability of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors for children and adolescents with anxiety disorders: a systematic review and meta-analysis.","authors":"Nuntaporn Karawekpanyawong, Chawanun Charnsil, Sirijit Suttajit, Manit Srisurapanont","doi":"10.1097/YIC.0000000000000599","DOIUrl":"10.1097/YIC.0000000000000599","url":null,"abstract":"<p><p>This systematic review and meta-analysis included randomized controlled trials (RCTs) to compare the efficacy, (treatment-emergent) suicidality, tolerability, and acceptability of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) against placebo in treating children and adolescents with anxiety disorders. We searched multiple electronic databases on July 15 2024. The outcomes included anxiety reduction (efficacy), suicidality rate, dropout rate because of adverse effects (tolerability), and overall dropout rate (acceptability). This study included 15 trials involving 2083 participants (median age = 11.61 years), investigating five SSRIs and two SNRIs. SSRIs/SNRIs significantly reduced anxiety symptoms [14 trials, standardized mean difference = -0.49, 95% confidence interval (CI): -0.65 to -0.33, I2 = 60%], with no significant difference between the two classes. Compared with placebo, they showed a higher risk of suicidal ideation [eight trials, risk ratio = 3.51, 95% confidence interval (CI): 1.51-8.16, I2 = 0%], greater acceptability (15 trials, risk ratio = 0.86, 95% CI: 0.75-0.99, I2 = 0%), and similar tolerability (14 trials, risk ratio = 1.30, 95% CI: 0.68-2.46, I2 = 35%). SSRIs and SNRIs effectively reduce anxiety symptoms in children and adolescents, with good tolerability and acceptability; however, they may increase the risk of suicidal ideation.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636950","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}
Valerio Ricci, Alessandro Sarni, Giovanni Martinotti, Giuseppe Maina
{"title":"Comparative analysis of third-generation antipsychotics in first-episode schizophrenia: efficacy, safety, and cognitive impacts. A narrative review.","authors":"Valerio Ricci, Alessandro Sarni, Giovanni Martinotti, Giuseppe Maina","doi":"10.1097/YIC.0000000000000559","DOIUrl":"10.1097/YIC.0000000000000559","url":null,"abstract":"<p><strong>Background and objectives: </strong>Schizophrenia is a chronic, complex mental health disorder requiring effective management to mitigate its broad personal and societal impacts. This narrative review assesses the efficacy, effectiveness, and side effects of third-generation antipsychotics (TGAs) like aripiprazole, brexpiprazole, and cariprazine, focusing on their use in first-episode schizophrenia. These drugs aim to reduce side effects typical of earlier antipsychotics while more effectively addressing positive and cognitive symptoms.</p><p><strong>Methods: </strong>Our extensive literature review, using PubMed and Scopus , includes randomized controlled trials and observational studies, showing TGAs may match older antipsychotics in efficacy with fewer side effects, notably in reducing extrapyramidal symptoms and enhancing cognitive outcomes.</p><p><strong>Results: </strong>Aripiprazole appears effective in both acute and maintenance phases of schizophrenia, while brexpiprazole and cariprazine show potential in managing negative symptoms and improving social functioning, essential for patient recovery.</p><p><strong>Conclusions: </strong>This review emphasizes the need for personalized treatment and further research to fully determine the long-term benefits and safety of TGAs. These findings can inform clinical decisions and underline the ongoing need for innovation in schizophrenia pharmacotherapy.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"191-206"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467738","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}
Leslie Citrome, Elena Álvarez-Barón, Irene Gabarda-Inat, Karthinathan Thangavelu, Michael Tocco
{"title":"The specific anti-hostility effect of lurasidone in patients with an acute exacerbation of schizophrenia: results of pooled post hoc analyses in adolescents and adults.","authors":"Leslie Citrome, Elena Álvarez-Barón, Irene Gabarda-Inat, Karthinathan Thangavelu, Michael Tocco","doi":"10.1097/YIC.0000000000000563","DOIUrl":"10.1097/YIC.0000000000000563","url":null,"abstract":"<p><p>Symptoms of hostility in patients during acute exacerbations of schizophrenia have been associated with aggressive behavior. Data suggest that some second-generation antipsychotics have specific anti-hostility effects, independent of sedation and positive symptom improvement. Two post hoc analyses were performed to examine the efficacy of lurasidone for reducing hostility in patients with schizophrenia. One analysis pooled adults ( N = 1168) from 5 placebo-controlled, 6-week trials of lurasidone (40-160 mg). Another analysis pooled younger patients (up to age 25 years, N = 427) from the adult studies and a similarly designed trial of lurasidone (40 or 80 mg) in adolescent patients (13-17 years old). The outcome measure was mean change in the hostility item (P7) of the Positive and Negative Syndrome Scale (PANSS). To address pseudospecificity, results were adjusted for positive symptom change and sedation. In adults with a baseline PANSS hostility score ≥2, significant improvement in hostility was observed for all doses with a dose-related increase in effect size (Cohen's d): lurasidone 40 mg = 0.18, 80 mg = 0.24, 120 mg = 0.36, and 160 mg = 0.53. The same dose-response pattern was observed for the more severe hostility subgroups (P7: ≥3, ≥4), and in the early-onset population. Results suggest that lurasidone has specific, dose-related anti-hostility effects.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"214-223"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758549","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":"COVID-19 and psychiatric disorders among young people: a cross-sectional study.","authors":"Tiziano Prodi, Filippo Dragogna, Beatrice Benatti, Alberto Varinelli, Simone Vanzetto, Letizia Gianfelice, Bernardo Dell'Osso","doi":"10.1097/YIC.0000000000000565","DOIUrl":"10.1097/YIC.0000000000000565","url":null,"abstract":"<p><p>During the COVID-19 pandemic, a significant rise in mental health issues was observed. Particularly, children and adolescents have shown a higher risk of developing mental disorders than adults. This study aimed to describe the evolving features of the requests for psychiatric emergency interventions during the COVID-19 pandemic in young people. We conducted a cross-sectional study comparing the number, characteristics, and symptoms of people aged between 12 and 18 years old attending one Emergency Department (ED) for psychiatric issues, considering three different periods: T0 (8 March 2019-7 March 2020), T1 (8 March 2020-7 March 2021), and T2 (8 March 2021-7 March 2022). Total admissions were 220: 99 (45%) during T0, 40 (18.1%) for T1, and 81 (36.8%) for T2 ( P < 0.001). A significant decrease in the mean age from T0 to T1 was found ( P < 0.01). Admissions for psychomotor agitation decreased, while admission due to anxiety disorder and nonsuicidal self-injury raised significantly ( P < 0.05), as for first psychiatric presentation ( P < 0.01). Regarding substance use, a significant reduction was observed ( P < 0.05). The rates of eating disorders ( P < 0.001) and early insomnia ( P < 0.01) increased from T0. These findings highlight the worsening of psychiatric symptoms in the young population during the COVID-19 pandemic.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"224-231"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909852","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}
Juan Carlos Rivas, Juliana Galindo-A, Luis Fernando Zambrano, Carlos Alberto Miranda-B, Sandra Milena Ramírez, Ana María Rivas-Grajales, Mauricio Hernández-Carrillo, Erika Andrea Rincón, Pablo Eduardo Perafán, Juan Esteban Gómez-Mesa
{"title":"Risk of corrected QT interval prolongation in patients receiving antipsychotics.","authors":"Juan Carlos Rivas, Juliana Galindo-A, Luis Fernando Zambrano, Carlos Alberto Miranda-B, Sandra Milena Ramírez, Ana María Rivas-Grajales, Mauricio Hernández-Carrillo, Erika Andrea Rincón, Pablo Eduardo Perafán, Juan Esteban Gómez-Mesa","doi":"10.1097/YIC.0000000000000564","DOIUrl":"10.1097/YIC.0000000000000564","url":null,"abstract":"<p><p>Antipsychotic (AP) use has been associated to QT interval prolongation on the surface electrocardiogram (ECG). Our study aimed to determine the incidence of corrected QT (QTc) interval prolongation among patients admitted to a psychiatric hospitalization unit requiring AP treatment and to assess the relationship between administered dose and QTc interval changes. We enrolled 179 patients admitted to the Hospital Psiquiátrico Departamental Universitario del Valle in Cali, Colombia. ECGs were conducted upon admission, and again at 3 and 7 days postadmission. The QT interval was measured, and QTc interval correction was performed using Bazzet's formula. QTc interval prolongation at time points B or C was observed in 9.5% of patients. Clozapine was the most common AP associated with QTc interval prolongation (20.59%), followed by olanzapine (15.38%). The relative risk of QT interval prolongation with clozapine compared to haloperidol was 4.17 (95% confidence interval, 1.14-15.17, P = 0.02). AP use upon hospital admission was linked to early (within 3 days) QTc interval prolongation. Clozapine and olanzapine were associated with a greater increase in QTc interval compared to haloperidol, indicating a need for rigorous electrocardiographic monitoring with their use.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"207-213"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855386","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}
Nicolaja Girone, Maddalena Cocchi, Francesco Achilli, Edoardo Grechi, Chiara Vicentini, Beatrice Benatti, Matteo Vismara, Alberto Priori, Bernardo Dell'Osso
{"title":"Treatment adherence rates across different psychiatric disorders and settings: findings from a large patient cohort.","authors":"Nicolaja Girone, Maddalena Cocchi, Francesco Achilli, Edoardo Grechi, Chiara Vicentini, Beatrice Benatti, Matteo Vismara, Alberto Priori, Bernardo Dell'Osso","doi":"10.1097/YIC.0000000000000557","DOIUrl":"10.1097/YIC.0000000000000557","url":null,"abstract":"<p><p>Approximately 50% of patients with psychiatric disorders do not fully adhere to the prescribed psychopharmacological therapy, significantly impacting the progression of the disorder and the patient's quality of life. The present study aimed to assess potential differences in terms of rates and clinical features of treatment adherence in a large cohort of psychiatric patients with different diagnoses attending various psychiatric services. The study included 307 psychiatric patients diagnosed with a primary major depressive disorder, bipolar disorder, anxiety disorder, schizophrenic spectrum disorder, or personality disorder. Patient's adherence to treatment was evaluated using the Clinician Rating Scale, with a cutoff of at least five defining adherence subgroups. One-third of the sample reported poor medication adherence. A lower rate of adherence emerged among patients with schizophrenic spectrum disorder and bipolar disorder. Subjects with poor adherence were more frequently inpatients and showed higher current substance use, a greater number of previous hospitalizations, and more severe scores at psychopathological assessment compared with patients with positive adherence. Poor adherence was associated with symptom severity and increased rates of relapses and rehospitalizations. In addition, substance use appears to be an unfavorable transdiagnostic factor for treatment adherence.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"232-241"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175639","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":"Innovations and challenges in antipsychotic treatments and external modulating factors.","authors":"Alessandro Serretti","doi":"10.1097/YIC.0000000000000593","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000593","url":null,"abstract":"","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":"40 4","pages":"187-190"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158426","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}