International Clinical Psychopharmacology最新文献

{"title":"Critical reassessment of manic and psychotic episodes related to levetiracetam: a systematic review of published case reports.","authors":"Aldo Stoppa, Tábatha Fernández-Plaza, Anna Giménez-Palomo, Isabella Pacchiarotti, Gerard Anmella, Giovanna Fico, Maria Sagué-Vilavella, Mireia Vázquez, Diego Hidalgo-Mazzei, Luis Pintor, Eduard Vieta","doi":"10.1097/YIC.0000000000000632","DOIUrl":"10.1097/YIC.0000000000000632","url":null,"abstract":"<p><p>Levetiracetam (LEV) is a widely used antiepileptic but associated with psychiatric side effects. While mild reactions are common, manic and psychotic episodes are less frequent, though clinically significant. This review critically assesses published cases of (hypo)manic and psychotic episodes related to LEV. A systematic review was conducted using MEDLINE (PubMed), Cochrane Library, and Web of Science (up to 1 June 2025), restricted to studies with primary clinical data on (hypo)manic or psychotic episodes associated with LEV. The quality of each case was assessed using a critical appraisal checklist, and the Naranjo Adverse Drug Reaction Probability Scale was applied to evaluate causality. A total of 50 cases met the inclusion criteria: Eight (hypo)manic and 42 psychotic episodes. The most frequent psychiatric manifestations were delusions (48%), aggressiveness (44%), and manic symptoms (38%). Temporal lobe epilepsy was present in 26% of patients, and 66% had uncontrolled seizures. Although case reports describe an association between LEV and (hypo)manic and psychotic episodes, causality assessment based on the methodological approach applied indicated a low probability that LEV alone was responsible. Alternative explanations, including epilepsy-related factors and comorbid medical conditions, were frequently cited. In some cases, an alternative diagnosis might be manic episode with psychotic features .</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"324-346"},"PeriodicalIF":3.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251446","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":"Lithium and GLP-1-based therapies in bipolar disorder: an emerging pharmacovigilance signal and monitoring considerations.","authors":"Ervin Cotrik, Antônio Geraldo da Silva, Jair C Soares","doi":"10.1097/YIC.0000000000000636","DOIUrl":"10.1097/YIC.0000000000000636","url":null,"abstract":"<p><p>Lithium remains a cornerstone of bipolar disorder treatment, yet it has a narrow-therapeutic index and depends on renal and volume status. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists are now widely coprescribed in this population. Six bibliographically distinct reports published since 2025 describe lithium elevation or toxicity after initiation, switching, or escalation, and in June 2026 the European Medicines Agency's Pharmacovigilance Risk Assessment Committee opened a signal of a drug interaction leading to increased lithium levels. We separate three levels of evidence: (a) an uncontrolled pharmacovigilance signal; (b) plausible mechanistic pathways; and (c) a speculative temporal model. The candidate mechanisms are more constrained than previously appreciated: delayed gastric emptying alters absorption rate without demonstrably altering total exposure; GLP-1-mediated natriuresis acts in the opposite direction and does not persist; reduced lithium clearance after weight loss is sustained but quantitatively insufficient. The temporal framing is speculative and may partly reflect ascertainment bias. The reports describe two separable phenomena: acute toxicity events, largely explicable by intake and volume effects, and a sustained upward shift in concentration per unit dose, which is not. We set out falsifiable predictions and monitoring considerations, adopting rather than claiming the schedule proposed elsewhere.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"365-370"},"PeriodicalIF":3.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653225","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":"Attributing benefit and harm in clinical practice: medication burden, causality, and pharmacovigilance.","authors":"Alessandro Serretti","doi":"10.1097/YIC.0000000000000639","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000639","url":null,"abstract":"","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":"41 6","pages":"319-323"},"PeriodicalIF":3.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108925","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":"Association between the number of delirium-associated medications and postoperative delirium in older adults: a multicenter retrospective study.","authors":"Masakazu Hatano, Rintaro Sogawa, Haruna Araki, Toshiki Matsumura, Satoru Esumi, Kenji Shin, Hironori Tabuchi, Kiyotaka Tsubouchi, Taisuke Ozaki, Hiroyuki Kamei, Kensuke Suga, Tomo Okochi, Shigeki Yamada","doi":"10.1097/YIC.0000000000000624","DOIUrl":"10.1097/YIC.0000000000000624","url":null,"abstract":"<p><p>A variety of medications contribute to the risk of postoperative delirium (POD) in older adults. This multicenter retrospective study aimed to investigate the relationship between the number of delirium-associated medication types and the incidence of POD. Patients aged greater than or equal to 70 years who underwent surgery under general anesthesia were included. Odds ratios (ORs) and 95% confidence intervals were estimated via multivariate logistic regression analysis, using patients not receiving delirium-associated medications as the reference group. Delirium-associated medications were selected from seven medication classes: benzodiazepines, non-benzodiazepines, opioids, antiparkinsonian agents, glucocorticoids, H 1 -antihistamines, and H 2 -antihistamines. A total of 4562 patients were included in the analysis. The overall incidence of POD was 7.7% (352/4562) and increased progressively with the number of delirium-associated medication types, from 6.0% among patients receiving none to 31.0% among those receiving four or more types. After adjusting for other delirium-related factors, the ORs of POD were significantly higher in patients receiving delirium-associated medications than in those receiving none and increased with the number of medication types. Sensitivity analyses confirmed the robustness of these findings. Our findings suggest that a higher number of delirium-associated medications is associated with an increased risk of POD in older adults, warranting preoperative medication review.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"347-352"},"PeriodicalIF":3.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574012","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":"Effectiveness and safety of long-acting aripiprazole 960 mg: preliminary findings from a prospective real-world observational study.","authors":"Tiziano Prodi, Miriam Olivola, Rodolfo Leuzzi, Monica Biseo, Edoardo Grechi, Nicolaja Girone, Cesare Galimberti, Chiara Di Genova, Kevin La Monica, Federica Calorio, Emma Zuliani, Giada Versaci, Pietro Gallazzi, Norbert Gabriel Kereszteny, Marco Franchini, Andrea Crippa, Gianluca Termine, Roberta Anniverno, Annamaria Cattaneo, Bernardo Dell'Osso","doi":"10.1097/YIC.0000000000000635","DOIUrl":"10.1097/YIC.0000000000000635","url":null,"abstract":"<p><p>Poor treatment adherence is a major challenge in the management of severe mental disorders, as it is associated with an increased risk of relapse, rehospitalization, symptom worsening, treatment resistance, and all-cause mortality. In 2023 a 2-month 960 mg formulation of aripiprazole 2 months ready-to-use (Ari 2MRTU) was introduced. Compared with monthly long-acting injectable (LAI) drugs, Ari 2MRTU may improve adherence and patient satisfaction by reducing the frequency of healthcare visits. The aim of this prospective longitudinal study was to provide preliminary real-world data on the effectiveness, safety, and acceptability of Ari 2MRTU. Fifty patients, most of whom had previously received aripiprazole, were assessed at baseline, 2 months, and 4 months. Data regarding effectiveness, safety, and acceptability outcomes were collected. Psychometric scores changes were analyzed employing linear mixed-effect regression models accounting for time, age, sex, and previous oral treatment with aripiprazole. Our preliminary findings suggest that Ari 2MRTU is associated with improvements in psychotic symptoms over time, while changes in affective symptoms were less consistent. The findings were also consistent with an overall favorable tolerability profile of Ari 2MRTU. Although adverse events were commonly reported, no unexpected safety signals emerged during the follow-up period, and patients' attitudes toward LAI treatment generally improved over time.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"353-364"},"PeriodicalIF":3.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561975","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":"Lithium-associated peripheral transcriptional signatures correlate with brain white matter microstructure in bipolar disorder.","authors":"Diana Betelli, Serena Furno, Beatrice Bravi, Carlo Di Carlo, Cristina Lorenzi, Sara Spadini, Annamaria Finardi, Cristina Colombo, Roberto Furlan, Sara Poletti, Francesco Benedetti","doi":"10.1097/YIC.0000000000000637","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000637","url":null,"abstract":"<p><p>Lithium is the mainstay treatment for bipolar disorder, improving brain white matter microstructure and regulating genes involved in immune response and cell signaling. In 116 patients affected by a major depressive episode in the course of bipolar disorder, we investigated the effect of long-term lithium treatment on gene expression in peripheral blood mononuclear cells and their association with white matter microstructure. Differential gene expression analysis identified three genes significantly upregulated in lithium-treated compared to nontreated patients: SEPTIN11, DGKK, and TPPP3; and two downregulated genes: LEF1-AS1 and PLXDC1. At tract-based spatial statistics, significant lithium-by-gene expression interactions were observed for SEPTIN11, LEF1-AS1, PLXDC1, and DGKK, indicating that the relationship between gene expression and white matter microstructure differed depending on lithium treatment status. Only in lithium-treated participants, LEF1-AS1 and PLXDC1 expression were associated with increased fractional anisotropy and decreased radial diffusivity and mean diffusivity, while SEPTIN11 expression was associated with increased axial diffusivity, mean diffusivity, and radial diffusivity. These genes are widely expressed in the brain, and their peripheral expression correlates with white matter microstructure measures associated with lithium treatment. This observation supports the potential usefulness of peripheral transcriptomic signatures to mark the individual biological impact of lithium treatment on the brain.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976327","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":"Use of risperidone in-situ microparticles in real world: patterns of prescription and dose selection in patients with psychotic disorders.","authors":"Ilaria Di Bernardo, Paolo Brambilla, D'Agostino Armando, Mauro Percudani, Giancarlo Cerveri, Giovanni Migliarese, Virginio Salvi, Annabella Di Giorgio, Valentina Dalò, Federica Calorio, Adelaide Panariello, Alessandro Galluzzo, Silvia Paletta, Simone Cavallotti, Antonio Callari, Laura Celebre, Alberto Costa, Luca Belmonte, Giada Versaci, Maurizio Proto, Chiara Nostro, Barbara Scaramelli, Filippo Dragogna, Giorgio Ratti, Michele Scalera, Antonio Vita, Bernardo Dell'osso","doi":"10.1097/YIC.0000000000000634","DOIUrl":"https://doi.org/10.1097/YIC.0000000000000634","url":null,"abstract":"<p><p>Long-acting injectable (LAI) antipsychotics are important for improving adherence and preventing relapse. Risperidone in-situ microparticles (ISM), a once monthly LAI using ISM technology, rapidly achieves therapeutic plasma levels without loading doses or oral supplementation. Real-world evidence on its use remains limited. This multicenter observational-naturalistic-retrospective study assessed prescribing patterns of risperidone-ISM across nine Public Mental Health Departments in Lombardy, Italy. Data from 218 inpatients and outpatients with psychotic disorders diagnosed according to diagnostic and statistical manual of mental disorders, fifth edition, text revision criteria were collected. Demographic, clinical, and pharmacological variables were analyzed. Patients were stratified by dose (75 vs. 100 mg), and group differences were assessed using χ2 and analysis of variance tests. Multivariable logistic regression identified independent correlates of prescription of the 100 mg dose. Sample's mean age was 41.8 years (69% male), with 71.1% receiving 100 mg. LAI initiation was primarily intended to improve adherence in 77.7% of cases. Among hospitalized patients, Brief Psychiatric Rating Scale scores decreased between admission and discharge (59.35 vs. 33.48); however, causality could not be inferred. The 100 mg group had significantly more male patients and showed higher rates of substance use and involuntary hospitalization, while the 75 mg group more often presented depressive symptoms and antidepressant use. In multivariable analysis, only involuntary hospitalization remained independently associated with receiving the 100 mg dose. This study provides real-world evidence on prescribing patterns of different risperidone-ISM doses and short-term clinical outcomes among treated patients.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880225","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":"Preliminary evidence that blood extracellular nicotinamide phosphoribosyltransferase increases with antidepressant response to chronotherapeutics and to monoaminergic drugs.","authors":"Francesco Benedetti, Igor Branchi, Ha Kyung Shin, Cristina Lorenzi, Edoardo Venturelli, Sara Dallaspezia, Cristina Colombo, Raffaella Zanardi, Sara Poletti","doi":"10.1097/YIC.0000000000000622","DOIUrl":"10.1097/YIC.0000000000000622","url":null,"abstract":"<p><p>The purpose of the present study is to provide a preliminary evidence of the possible involvement of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) in antidepressant response. NAMPT is the major regulator of the cellular availability of nicotinamide adenine dinucleotide (NAD+), and, when released from the cells, it influences activity, energy expenditure, and neurotransmitter levels in mammals. We studied changes of blood circulating eNAMPT before and after treatment in 46 patients with major depressive disorder, treated with monoaminergic antidepressant drugs for 1 month, or with Bipolar Disorder, treated with antidepressant chronotherapeutics (repeated total sleep deprivation combined with light therapy) for 1 week. Participants showed high individual variation in eNAMPT before and after treatment. The increase in circulating eNAMPT concentration was associated with individual benefit from treatment independent of diagnosis or type of treatment. eNAMPT increase was not necessary to achieve response, but the best antidepressant effects were observed in patients showing the highest increase. These findings suggest that eNAMPT may facilitate treatment efficacy rather than acting as a direct mechanism of symptom reduction. Results are in agreement with the literature affirming a possible role of NAD+ homeostasis and mitochondrial mechanisms in mood disorders. If confirmed, they may pave the way to identify new targets for the treatment of depression.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"277-283"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573605","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":"Aripiprazole‑induced akathisia associated with bilateral putaminal hypermetabolism on PET.","authors":"Nicola Meda, Marialaura Lussignoli, Alessio A Gugliotta, Diego Cecchin, Giorgio Pigato, Fabio Sambataro","doi":"10.1097/YIC.0000000000000626","DOIUrl":"10.1097/YIC.0000000000000626","url":null,"abstract":"<p><p>Akathisia is a common and often disabling adverse effect of antipsychotic treatment. Although previous studies have linked akathisia to dopamine D 2 ‑receptor blockade in the basal ganglia, there is limited evidence from [18F]fluorodeoxyglucose PET ([18F]FDG PET) acquired during clinically manifest akathisia. We report the case of a woman in her 50s with bipolar disorder and autoimmune diseases who developed marked akathisia after augmenting lithium with aripiprazole 10 mg/day. During the symptomatic period, a whole‑body [18F]FDG PET computed tomography was performed to investigate recurrent fevers and gastrointestinal symptoms. Brain images incidentally showed bilateral putaminal hypermetabolism relative to the cerebral cortex. Neurological and rheumatology consultations were negative. No other medications were modified during the same timeframe. Akathisia remitted completely after aripiprazole discontinuation and clonazepam up‑titration, and the Naranjo Adverse Drug Reaction Probability Scale score indicated a probable adverse drug reaction. Basal ganglia hypermetabolism relative to the cerebral cortex is reminiscent of PET findings in reversible hyperkinetic disorders. To our knowledge, this is the first case report showing an association between bilateral putaminal hypermetabolism on [18F]FDG PET and aripiprazole-induced akathisia. This hypothesis-generating observation warrants replication in prospective studies to elucidate how dopaminergic dysfunction in the basal ganglia may contribute to the emergence of akathisia.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"312-317"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770570","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":"Defining treatment-resistant depression in a real-world setting: impact of a staging model on clinical features and treatment trajectories.","authors":"Matteo Carminati, Mattia Tondello, Chiara Morana, Alessandro Serretti, Raffella Zanardi","doi":"10.1097/YIC.0000000000000625","DOIUrl":"10.1097/YIC.0000000000000625","url":null,"abstract":"<p><p>Operationalizing treatment-resistant depression (TRD) is essential to guide the rational use of pharmacological and somatic interventions. This study applied a staged TRD model in a real-world inpatient setting to disentangle patterns associated with different degrees of resistance. We prospectively included 538 depressed inpatients and classified them as nonresistant, TRD1 (≥2 antidepressant failures at minimally licensed dose for ≥4 weeks), or TRD2 (≥2 failures of antidepressants from different classes at maximum tolerated dose for ≥4 weeks). Baseline features, comorbidities, and treatments were compared across groups. Depressive symptoms were assessed at admission and at 2, 4, and 8 weeks. TRD1 patients (24%) had an earlier onset and showed the highest prevalence of personality disorders, anxiety disorders, tobacco smoking, AUD, and substance use disorder. In contrast, TRD2 patients (29%) presented with more severe and longer depressive episodes and required more intensive pharmacological and somatic strategies. Only the TRD2 group displayed a significantly attenuated symptomatic improvement over time (time × group interaction; P  < 0.001) compared with nonresistant. In a real-world cohort, a simple two-stage TRD model differentiated a \"complex but responsive\" subgroup (TRD1) from a more biologically refractory profile (TRD2). Graded definitions may reduce misclassification, supporting more tailored management of comorbid conditions.</p>","PeriodicalId":13698,"journal":{"name":"International Clinical Psychopharmacology","volume":" ","pages":"269-276"},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573171","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}