Human psychopharmacology最新文献

{"title":"No Evidence of Moderated Impulsivity Following Administration of the IMPase Inhibitor Ebselen in Healthy Adults.","authors":"Matthew P G John, Luke Earnshaw, Nikhil Gauri Shankar, Jawad Sultan Raja, Timothy J Davies, Phillip J Cowen, Trevor Sharp, Alberto Salmoiraghi, Robert D Rogers","doi":"10.1002/hup.70040","DOIUrl":"10.1002/hup.70040","url":null,"abstract":"<p><strong>Objective: </strong>Impulsivity is a transdiagnostic risk factor for numerous health morbidities and is strongly associated with early relapse and poor treatment outcomes in addictions and mood-disorders. Lithium carbonate can be helpful in moderating the impulsive behaviors associated with mania, possibly mediated by reduced myo-inositol activity following inhibition of the enzyme inositol monophosphatase (IMPase). We tested the hypothesis that impulsivity-as motor disinhibition, decisions without adequate information, and stronger preferences for small immediate rewards over larger later rewards-can be moderated by the IMPase inhibitor ebselen in healthy adult volunteers.</p><p><strong>Methods: </strong>One hundred and thirty healthy adults completed a between-subjects, double-blind, placebo-controlled protocol. Over 2 days, participants received a previously validated dose of 1800 mg of ebselen or placebo before completing tests of impulsivity and decision-making.</p><p><strong>Results: </strong>There were no substantive changes in any measure of impulsivity following treatment with ebselen compared with placebo. Neither was there any convincing evidence of stronger treatment effects in high-trait impulsive participants compared with low-trait participants.</p><p><strong>Conclusion: </strong>These results fail to replicate findings that ebselen administration moderates validated measures of impulsivity in healthy adults, at least at doses shown to reduce myo-inositol within the medial prefrontal cortex and produce changes in emotional processing and reward-based learning.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70040"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconceptualization of Drug Effects in Double Blind Randomized Placebo Controlled Trials for Psychiatric Illnesses: A Practical Suggestion.","authors":"Takefumi Suzuki","doi":"10.1002/hup.70048","DOIUrl":"10.1002/hup.70048","url":null,"abstract":"<p><p>Double blind randomized placebo controlled trials (RCTs) have been regarded as the gold standard for evaluation of potential treatments. Nevertheless RCTs for psychiatric illnesses, almost all of which sorely need better medications, have been plagued with high placebo response, practically diluting true drug effects (if any) and potentially discouraging novel drug developments. Various strategies have been considered to tackle this significant issue but none has been particularly successful to date. The author proposes to examine the belief of treatment allocation by the study participants, (at least) twice, during the study period. The results will be interpreted in terms of correctness and consistency, regardless of the actual treatment allocation. Whether response trajectory differs based on these parameters (e.g., robust placebo response stems from those who consistently guessed placebo as active drug) should be tested and analyzed. The concept could be useful regarding functional unblinding, another serious issue in psychiatric RCTs, for drugs with strong clinical effects.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70048"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Underprescription of Clozapine: A Narrative Review Regarding 'Clozaphobia'.","authors":"Rafael Brito Castro, Joaquim J Ferreira, João Gama-Marques","doi":"10.1002/hup.70050","DOIUrl":"10.1002/hup.70050","url":null,"abstract":"<p><p>This review aims to examine the appropriateness of the term 'clozaphobia' to characterise the obstacles contributing to the underprescription of clozapine (CLZ). English-language, peer-reviewed studies addressing clinicians', patients' and/or carers' attitudes toward CLZ were considered eligible for full-text review. In May 2025, a search was conducted using the keywords clozapine, clozaphobia, fear*, underus*, underprescri*, underutiliz*, and barrier*, restricted to titles and abstracts on PubMed, Web of Science, Scopus, and Cochrane. A total of 362 records were retrieved, and 30 records were identified through backward citation searching. After screening, 53 studies were eligible for review. This review identified several barriers to CLZ use, which were grouped into three broad domains: clinician-related, medication- and patient-related, and administrative-related barriers. Key barriers included difficulties in recognising Treatment-Resistant Schizophrenia (TRS) and identifying candidates for CLZ, lack of training and confidence, negative attitudes toward CLZ, variability in treatment pathways, concerns about CLZ's adverse effects, and challenges in convincing carers of the need for CLZ, insufficient resources, unclear professional roles, and fragmentation of services. The vast majority of identified barriers stem from misconceptions or negative attitudes toward CLZ, which unjustifiably limit patient access to this effective treatment, and can be addressed through the implementation of existing facilitating strategies. In such contexts, the term clozaphobia seems appropriate and its use may help to raise awareness and promote critical reflexion on this subject. With the end of the clozapine risk evaluation and mitigation strategy, it is now time to push society to start producing higher dose pills and a long-acting injectable version of clozapine.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70050"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating Hypo-Egoic Features: Ayahuasca's Psychedelic Path Versus Meditation's Mindful Journey.","authors":"María Arqueros, Joaquim Soler, Ausiàs Cebolla, Javier Garcia-Campayo, Elisabet Domínguez-Clavé, Juan C Pascual","doi":"10.1002/hup.70046","DOIUrl":"10.1002/hup.70046","url":null,"abstract":"<p><strong>Objective: </strong>'Ego dissolution' refers to a temporary state characterized by diminished self-referential processing, which leads to a breakdown of personal boundaries and an enhanced sense of unity with the environment. Both psychedelics, such as ayahuasca, and contemplative practices, like meditation, have been proposed as mechanisms for modulating the ego. While ayahuasca induces transient self-perception alterations, meditation promotes more sustained changes through cognitive and emotional regulation. This study examines whether ayahuasca consumption modulates the ego and compares its effects with those of meditation.</p><p><strong>Methods: </strong>A total of 37 ayahuasca users and 137 meditators participated. We used the \"Delusion of Me\" (DoM) index, a unidimensional self-report measure comprising three domains: acceptance, decentering, and non-attachment. It could be considered closely related to the concept of self 'as a content' and may potentially serve as a measure of ego.</p><p><strong>Results: </strong>Meditators exhibited significantly higher DoM scores than ayahuasca users. The quadratic regression did not show a cumulative effect, with no significant relationship found between the number of ayahuasca sessions and DoM scores.</p><p><strong>Conclusions: </strong>Meditation practice correlated with higher DoM scores and cumulative practice showed a significant non-linear association with DoM. Conversely, repeated ayahuasca exposure demonstrated no evidence of a cumulative association in this sample.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70046"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychopathological Concomitants and Motivations Related to Misuse of Non-Steroidal Anti-Inflammatory Drugs and Paracetamol.","authors":"Francesco Saverio Bersani, Elisabeth Prevete, Tommaso Accinni, Simone Montaldo, Irene Pinucci, Annalisa Maraone, Lorenzo Tarsitani, Massimo Pasquini, Claudio Imperatori","doi":"10.1002/hup.70043","DOIUrl":"10.1002/hup.70043","url":null,"abstract":"<p><strong>Introduction: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are among the most commonly used medications worldwide. It has been suggested that the misuse of such medications is not uncommon. The objective of the present research was to explore prevalence, reported reasons and psychopathological concomitants related to NSAIDs/paracetamol misuse in a sample of users.</p><p><strong>Methods: </strong>The sample was made of 346 NSAIDs or paracetamol users (age range: 18-64 years); assessments included the 4-item Perceived Stress Scale (PSS-4), the 10-item version of the Adverse Childhood Experiences International Questionnaire (ACE-IQ-10), the Body Image Concern Inventory (BICI), the Alcohol Use Disorders Identification Test-C (AUDIT-C), and questions related to NSAIDs/paracetamol misuse.</p><p><strong>Results: </strong>Forty-eight individuals (13.9%) were categorized as NSAIDs/paracetamol misusers. A logistic regression model showed that higher scores in AUDIT-C, BICI and ACE-IQ-10, and the use of psychiatric medications, were significantly associated with the likelihood of NSAIDs/paracetamol misuse. Specific reasons related to the misuse are also reported.</p><p><strong>Discussion: </strong>Our findings provide novel insights into the relationship between NSAIDs/paracetamol misuse and psychopathology, with potential clinical implications for prevention and treatment.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70043"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin as an Alternative to Metformin for Antipsychotic-Related Weight Gain: Double-Blind Randomized Controlled Trial.","authors":"Atena Dolati, Davoud Ahmadimoghaddam, Maryam Zamanirafe, Shabnam Rezaie, Salman Khazaie, Maryam Mehrpooya, Mona Doostizadeh","doi":"10.1002/hup.70047","DOIUrl":"10.1002/hup.70047","url":null,"abstract":"<p><strong>Background: </strong>Weight gain and metabolic disturbances are common adverse effects of antipsychotic medications such as clozapine and olanzapine. Beyond their primary role in glycemic control, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been associated with weight loss and improvements in various metabolic parameters. This study compared the efficacy and safety of empagliflozin and metformin in patients with antipsychotic-induced weight gain (AIWG).</p><p><strong>Methods: </strong>In this 12-week, double-blind, randomized controlled trial, 84 adults with schizophrenia or bipolar disorder and established weight gain from clozapine or olanzapine were assigned to receive either empagliflozin (10 mg daily) or metformin (1000 mg daily). The primary outcome was the percentage change in body weight from baseline to week 12. Secondary outcomes included changes in absolute body weight, body mass index (BMI), waist circumference, waist-hip ratio, and the proportion of patients achieving ≥ 5% weight loss. Exploratory outcomes assessed changes in glycemic and lipid parameters, fasting insulin, and insulin resistance (HOMA-IR). Safety was evaluated by monitoring adverse events, treatment discontinuations, and serious adverse events.</p><p><strong>Results: </strong>Of the 84 randomized participants, 38 (90.5%) in the empagliflozin group and 39 (92.9%) in the metformin group completed the 12-week study. Both treatments produced significant within-group reductions in anthropometric measures (all p < 0.001) and there were no statistically significant differences between groups in the magnitude of change for body weight, BMI, waist circumference, hip circumference, or waist-hip ratio (all p > 0.05). Both groups showed improvements in glycemic and lipid parameters, but empagliflozin resulted in significantly greater reductions in TG (p = 0.004), fasting insulin (p = 0.005), and HOMA-IR (p = 0.012), as well as a greater increase in HDL-C (p < 0.001) compared to metformin. The overall incidence of adverse effects was comparable (33.3% vs. 38.1%; p = 0.650), with no serious adverse events reported.</p><p><strong>Conclusions: </strong>These findings suggest that empagliflozin is a promising alternative to metformin for managing metabolic complications in patients treated with clozapine or olanzapine. These findings warrant confirmation and further investigation in larger, long-term studies.</p><p><strong>Trial registration: </strong>The trial was registered prospectively at the Iranian Registry of Clinical Trials (IRCT) with the ID code IRCT20120215009014N538 on November 12, 2024.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70047"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rivastigmine for Behavioural Symptoms in Parkinson's Disease: Evidence and Open Questions.","authors":"Antonina Luca","doi":"10.1002/hup.70049","DOIUrl":"10.1002/hup.70049","url":null,"abstract":"<p><strong>Introduction: </strong>Behavioural symptoms, including hallucinations, apathy, and depression, are frequent in Parkinson's disease (PD). This review evaluated the effectiveness of rivastigmine in treating neuropsychiatric symptoms in PD.</p><p><strong>Methods: </strong>A search of PubMed, MEDLINE and EBSCO (1 January 2000-1 October 2025) using terms related to PD and intervention (rivastigmine, anticholinesterase) was conducted. Case reports and case series were excluded.</p><p><strong>Results: </strong>Eight studies (5 randomized controlled trials and three open-label studies) were selected. Due to the heterogeneity of the outcomes and methodological differences between studies, findings were summarized in a narrative way. In almost all studies, rivastigmine improved hallucinations. Data on the effect of apathy are mixed.</p><p><strong>Conclusions: </strong>The present review suggests that rivastigmine may improve hallucinations in selected PD patients. Future multicentre, adequately powered randomized controlled trials with a stratification by cognitive status, formulation, and dose of rivastigmine are needed. Despite the limited number of high-quality studies and methodological heterogeneity, clinical practice consistently suggests the beneficial role of rivastigmine in managing behavioural disturbances in PD. In real-world settings, rivastigmine is frequently associated with improvement of hallucinations and affective symptoms, particularly in individuals with co-occurring cognitive impairment. While these observations cannot substitute for robust controlled evidence, they provide additional support for the therapeutic value of rivastigmine.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70049"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147950688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D Deficiency in Bipolar Disorder: Prevalence, Sociodemographic and Clinical Characteristics.","authors":"Zorana Pavlović, Milena Stevanović, Aleksandar Krstić, Isidora Ivković, Milica Vujčić, Zorana Bukurecki, Branko Jakovljević, Milan Latas","doi":"10.1002/hup.70045","DOIUrl":"10.1002/hup.70045","url":null,"abstract":"<p><strong>Objective: </strong>To assess the prevalence and severity of vitamin D deficiency in patients with bipolar disorder and examine potential associations with their sociodemographic and clinical characteristics.</p><p><strong>Methods: </strong>A retrospective study was conducted on 185 inpatients aged 18-65, diagnosed with bipolar disorder and hospitalized at the Clinic for Psychiatry, University Clinical Center of Serbia, between 2022 and 2024. Data were obtained by analyzing medical records using the hospital information system \"Heliant\".</p><p><strong>Results: </strong>Vitamin D deficiency was observed in 76.8% of patients, with 14.6% having severe deficiency, 36.8% deficiency, and 25.4% insufficiency. Significant associations were found between vitamin D deficiency and the autumn/winter season, as well as lower education levels. Additionally, manic episodes were more frequently observed during spring and summer. No other significant associations were identified.</p><p><strong>Conclusion: </strong>A high prevalence of vitamin D deficiency was found among patients with bipolar disorder. Routine screening and early intervention should be considered, including education, supplementation, and lifestyle modifications. Integrating preventive strategies into psychiatric care may improve clinical outcomes and mood stability. Further longitudinal and interventional research is needed to clarify the potential role of vitamin D and to guide evidence-based prevention and treatment in bipolar disorder.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70045"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Cardiac Surveillance in Child Psychiatry: Role of Frontal QRS Angle During Atypical Antipsychotic Treatment.","authors":"Duygu Özge Asena, Duygu Ali, Dilli Gürkan Merve, Er Fahri, Çetinkaya Barış Begüm","doi":"10.1002/hup.70042","DOIUrl":"10.1002/hup.70042","url":null,"abstract":"<p><strong>Introduction: </strong>Atypical antipsychotics are widely prescribed in child and adolescent psychiatry and are known to affect cardiac repolarization, most commonly reflected by QTc prolongation. However, QTc alone may not fully capture repolarization heterogeneity. The frontal QRS-T angle f(QRS-T) is an electrocardiographic marker reflecting ventricular depolarization-repolarization mismatch. This study aimed to evaluate and compare f(QRS-T) alongside other repolarization parameters in children and adolescents receiving atypical antipsychotics versus healthy controls.</p><p><strong>Methods: </strong>This retrospective observational study included 45 children and adolescents (6-17 years) receiving atypical antipsychotics for at least six months and 45 age- and sex-matched healthy controls. Standard 12-lead ECG recordings were obtained to measure f(QRS-T), QTc, Tp-e interval, and Tp-e-based ratios. Correlation analyses assessed associations between f(QRS-T), QTc, and duration of antipsychotic use. Hierarchical multiple linear regression was performed to identify independent predictors of f(QRS-T) in the patient group. Receiver operating characteristic (ROC) analysis evaluated the discriminative ability of f(QRS-T) for QTc prolongation (QTc ≥ 440 ms).</p><p><strong>Results: </strong>Children receiving atypical antipsychotics exhibited significantly higher f(QRS-T), QTc interval, Tp-e interval, Tp-e(c), Tp-e(c)/QT, and iCEBc ratios compared with healthy controls (p < 0.05). Frontal QRS-T angle was positively correlated with QTc (r = 0.406, p < 0.001) but not with the duration of antipsychotic treatment. In hierarchical regression analysis, age, sex, QTc and duration of antipsychotic use were not independent predictors of f(QRS-T). ROC analysis demonstrated that f(QRS-T) moderately discriminated patients with QTc prolongation (AUC = 0.735); a cut-off value of 26.5° yielded a sensitivity of 72% and a specificity of 60%.</p><p><strong>Conclusion: </strong>f(QRS-T) is significantly increased in children and adolescents receiving atypical antipsychotics and is associated with QTc prolongation, although it is not independently predicted by treatment duration or conventional QT-based indices. These findings suggest that f(QRS-T) may serve as a complementary electrocardiographic marker of repolarization heterogeneity alongside QTc in the cardiac safety monitoring of pediatric patients treated with atypical antipsychotics.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70042"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Influence of CYP2D6 on Risperidone Metabolism: Pharmacokinetic and Pharmacodynamic Study in a Healthy South Indian Population.","authors":"Ramanujam Narayanan, Habibur Rahman, Susipriya Palanisamy, R Ranjithkumar, Sivaselvakumar Muthusamy","doi":"10.1002/hup.70044","DOIUrl":"10.1002/hup.70044","url":null,"abstract":"<p><strong>Objective: </strong>The CYP2D6*10 allele, which is prevalent in the Indian population, is of particular clinical significance. This study aims to investigate the effect of the CYP2D6*10 allele on the pharmacokinetics of risperidone and its metabolites following single-dose administration in healthy South Indian volunteers.</p><p><strong>Methods: </strong>The study was conducted with twenty healthy volunteers who were administered a single 2 mg dose of risperidone. CYP2D6 genotyping was performed using the PCR-RFLP method. Plasma levels of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OHRIS) were quantified using a UPLC-DAD system.</p><p><strong>Results: </strong>Significant differences in pharmacokinetic parameters were observed across the CYP2D6*10 genotypes. For intermediate metabolizers, the C_max, AUC_0-t, and T_1/2 were approximately 1.2 times higher, and the metabolic ratio was double compared to normal metabolizers. Notably, the C_max of the active moiety was significantly higher in intermediate metabolizers compared to normal metabolizers (p < 0.05). These findings indicate that CYP2D6 polymorphisms are associated with altered pharmacokinetic profiles of risperidone, with a reduced metabolic activation in individuals carrying the *10 allele.</p><p><strong>Conclusion: </strong>The results suggest that CYP2D6 genotyping could help inform personalized dosing strategies for risperidone, though further randomized controlled trials are required to confirm these findings.</p>","PeriodicalId":520641,"journal":{"name":"Human psychopharmacology","volume":"41 3","pages":"e70044"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}