Journal of Psychopharmacology最新文献

{"title":"The anti-inflammation pharmacodynamics of lithium: Therapy of bipolar disorder.","authors":"Yuyang Zhou, Weizhi Zheng, Feichang Guo, Shijin Wu, Congjie Zhong","doi":"10.1177/02698811251326942","DOIUrl":"https://doi.org/10.1177/02698811251326942","url":null,"abstract":"<p><p>Bipolar disorder is a severe mental disorder that necessitates effective long-term treatment strategies. Clinically, lithium has demonstrated favorable outcomes in managing this condition. The inflammatory theory posits that bipolar disorder is influenced by an inflammatory response, and lithium is thought to mitigate this disorder by inhibiting such responses. In terms of the pharmacodynamics of blocking inflammatory mediators, lithium mainly acts on GSK-3β. Upon interaction with GSK-3β, lithium can suppress the gene expression of inflammatory mediators, subsequently reducing their secretion. This mechanism influences multiple downstream pathways, ultimately contributing to the therapeutic effects observed in bipolar disorder. Specifically, these pathways include the arachidonic acid pathway, nitric oxide synthase pathway, neurotransmitter pathway, and so on. This article reviews the pharmacodynamic targets and mechanisms of lithium, offering insights into the appropriate clinical application of lithium and the advancement of lithium pharmacotherapies.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251326942"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730691","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":"Monoamine neurotransmitter-related gene-based genome-wide association study of low-dose ketamine in patients with treatment-resistant depression.","authors":"Chung-Feng Kao, Shih-Jen Tsai, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Chen-Jee Hong, Ya-Mei Bai, Pei-Chi Tu, Mu-Hong Chen","doi":"10.1177/02698811251326939","DOIUrl":"https://doi.org/10.1177/02698811251326939","url":null,"abstract":"<p><strong>Background: </strong>Low-dose ketamine is an N-methyl-D-aspartate receptor antagonist that exerts an antidepressant effect on patients with treatment-resistant depression (TRD). This antidepressant effect may extend beyond the glutamatergic hypothesis. Nevertheless, the roles of genes encoding other monoamine neurotransmitters (i.e., serotonin and dopamine) in the neuromechanism of low-dose ketamine remain unknown.</p><p><strong>Methods: </strong>In this clinical trial, which involved 65 patients with TRD, 21 patients received 0.5 mg/kg ketamine, 20 received 0.2 mg/kg ketamine, and 24 received normal saline. All patients were genotyped for 684,616 single-nucleotide polymorphisms (SNPs). A total of 50 monoamine neurotransmitter-related candidate genes, including HTR2A and HTR2C from the serotoninergic system, CHRM4 and CHRNB1 from the cholinergic system, and DRD2 from the dopaminergic system, were selected to conduct a gene-based genome-wide association study of the antidepressant effects of ketamine.</p><p><strong>Results: </strong>Gene-set enrichment analysis revealed that the pathway underlying neuroactive ligand-receptor interaction (KEGG) played a pivotal role in the biomechanisms underlying ketamine's antidepressant effect. Specifically, the genes and SNPs related to the cholinergic system (e.g., rs2644247 in CHRM5), μ1 opioid receptor (e.g., rs2473546 in OPRM1), dopaminergic system (e.g., rs2617577 in SLC6A3), serotonergic system (HTR2A), cannabinoid receptor (CNR2), and σ1 receptor (SIGMAR1) were associated with the antidepressant effect of low-dose ketamine.</p><p><strong>Discussion: </strong>Low-dose ketamine has an antidepressant effect, which may be associated with multiple monoamine neurotransmitter systems and the σ1 receptor.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251326939"},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700583","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":"Evaluating the efficacy of metformin in reducing hyperprolactinemia among patients with schizophrenia: A meta-analysis of randomized controlled trials.","authors":"Kah Kheng Goh, Chun-Hsin Chen, Mong-Liang Lu","doi":"10.1177/02698811251326945","DOIUrl":"https://doi.org/10.1177/02698811251326945","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic treatment is commonly associated with hyperprolactinemia, leading to menstrual disturbances, sexual dysfunction, and decreased bone mineral density. Nearly all antipsychotic drugs can elevate prolactin levels, affecting up to 70% of patients with schizophrenia. We aim to evaluate the potential therapeutic role of metformin in reducing hyperprolactinemia among these patients.</p><p><strong>Methods: </strong>We systematically searched PubMed, CNKI, Embase, Cochrane, and Web of Science through January 31, 2024, for randomized controlled trials (RCTs) evaluating metformin's effect on prolactin levels in patients with schizophrenia. Data were extracted and synthesized using random-effects meta-analysis.</p><p><strong>Results: </strong>This meta-analysis included 10 RCTs with 1046 participants (584 received metformin and 462 received placebo or no treatment). Metformin significantly reduced prolactin levels compared to control groups (SMD = -0.98, 95% CI: -1.62, -0.35, <i>p</i> = 0.002; transformed MD = -34.88 ng/mL, 95% CI: -57.65, -12.46). Subgroup analyses indicated that higher doses (1500 mg), shorter treatment durations (<24 weeks), higher BMI (>25 kg/m²), and longer illness duration (>1 year) were associated with more significant prolactin reductions. Metformin was well tolerated with no significant increase in adverse events or all-cause discontinuation rates compared to the control group.</p><p><strong>Conclusion: </strong>This meta-analysis suggests that metformin shows potential as a treatment for antipsychotic-induced hyperprolactinemia, with a favorable tolerability profile in patients with schizophrenia, particularly at higher doses, shorter treatment durations, higher BMI, and longer illness duration. Despite the robustness of the findings, high heterogeneity necessitates cautious interpretation. Future research should explore demographic and clinical factors influencing the response to metformin for optimizing treatment.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251326945"},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700046","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":"Lifetime classic psychedelic use and headaches: A cross-sectional study.","authors":"Zusanna Bjurenfalk, Alva Cosmo, Otto Simonsson, Caroline Ran","doi":"10.1177/02698811251324372","DOIUrl":"https://doi.org/10.1177/02698811251324372","url":null,"abstract":"<p><strong>Background: </strong>Migraine and cluster headache are two primary headache disorders for which conventional treatments are limited. Classic psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin are potentially promising new treatment candidates for these conditions.</p><p><strong>Aims: </strong>The aim of the present study was to investigate the possible relationship between the lifetime use of classic psychedelics and frequent bad headaches in a large British cohort sample.</p><p><strong>Methods: </strong>Using data (<i>N</i> = 11,419) collected in 1999-2000 as part of the 1958 British National Child Development Study, this cross-sectional study used multiple logistic regression, controlling for a range of potential confounders, to test the hypothesis that lifetime use of classic psychedelics would be associated with lower odds of having frequent bad headaches.</p><p><strong>Results: </strong>Lifetime use of classic psychedelics was associated with 25% lower odds of having frequent bad headaches (adjusted odds ratio = 0.75, 95% CI: 0.59-0.95, <i>p</i> = 0.016).</p><p><strong>Conclusions: </strong>The results of the present study add to the literature suggesting classic psychedelics as a possible future prophylactic treatment option for primary headache disorders.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251324372"},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604937","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":"Habitual caffeine intake, genetics and cognitive performance.","authors":"Angeliki Kapellou, Leta Pilic, Yiannis Mavrommatis","doi":"10.1177/02698811241303601","DOIUrl":"10.1177/02698811241303601","url":null,"abstract":"<p><strong>Background: </strong>Research on caffeine and cognitive performance remains controversial. Variations in genes associated with caffeine metabolism and response such as <i>CYP1A2, AHR</i> and <i>ADORA2A</i> may account for variable findings.</p><p><strong>Aim: </strong>To investigate caffeine × gene interactions on cognitive performance in all key domains of cognition in healthy individuals.</p><p><strong>Methods: </strong>Participants completed a lifestyle and food frequency questionnaire and a cognitive test battery including validated tasks to assess the domains of social cognition, memory, attention and executive function. Genotyping was performed for <i>AHR</i> rs6968554, <i>CYP1A2</i> rs2472297, <i>ADORA2A</i> rs5751876, <i>ADA</i> rs73598374 and <i>APOE</i> rs429358 and rs7412.</p><p><strong>Results: </strong>Significant gene × caffeine interactions were observed for the domains of social cognition, (<i>F</i>_{2, 123} = 5.848, <i>p</i> = 0.004) and executive function (<i>F</i>_{2, 109} = 3.690, <i>p</i> = 0.028). 'Slow' metabolisers had a higher performance in social cognition compared with 'fast' metabolisers among high-caffeine consumers (<i>p</i> = 0.004), while 'fast' metabolisers had a higher performance in executive function compared with 'slow' metabolisers among moderate caffeine consumers (<i>p</i> = 0.002).</p><p><strong>Conclusions: </strong>The present findings suggest an association between genetic caffeine metabolism, habitual caffeine intake and cognitive function in the domains of social cognition and executive function. More research in naturalistic environments using larger cohorts is needed to confirm these findings to add to our understanding of how habitual caffeine may influence cognitive function based on individual genotype.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"233-243"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794500","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":"Brain serotonin, oxytocin, and their interaction: Relevance for eating disorders.","authors":"Elmira Ismaylova, Zsofia Nemoda, Linda Booij","doi":"10.1177/02698811241309617","DOIUrl":"10.1177/02698811241309617","url":null,"abstract":"<p><strong>Introduction: </strong>Eating disorders are characterized by maladaptive eating behaviors and preoccupations around body shape, weight, and eating. The serotonin system has been among the most widely studied neurobiological factors in relation to eating disorders. Recent research also highlighted the role of oxytocin.</p><p><strong>Aims and methods: </strong>This article aims to review animal and human studies on the involvement of central serotonin and oxytocin, and their interplay in eating disorders in particular. We synthesize results from studies using animal models of eating disorders and from research conducted in healthy individuals and clinical populations.</p><p><strong>Results/outcomes: </strong>Altered serotonin neurotransmission and oxytocin levels in the brain-particularly in the hypothalamus, brainstem, and limbic regions-were associated with disturbances in eating behaviors and related maladaptive cognitions and emotions. These brain regions were found to constitute a typical neural network through which both central serotonin and oxytocin might operate in a bidirectional manner.</p><p><strong>Conclusions/interpretation: </strong>Based on the preceding findings, we describe a developmental biopsychosocial model relevant to eating disorders, including the role of serotonin-oxytocin interactions in the brain. While it is clear that eating disorders are multifactorial in which many biopsychosocial pathways are involved, the current review highlights the importance of well-designed translational research when studying mechanisms of serotonin-oxytocin interactions in the brain. Such research would help to better understand the effects of joint central oxytocin and serotonin administration as a possible preventive or therapeutic intervention for eating disorders.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"187-200"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915144","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":"Metformin efficacy and safety as an adjunctive treatment for irritability in children with autism spectrum disorder: A randomized, double-blind, placebo-controlled trial.","authors":"Zahra Bazrafshan, Parsa Mohammadi, Alireza Hasanzadeh, Mohammad Sanjari Moghaddam, Maryam Kabiri, Hossein Sanjari Moghaddam, Amir Hossein Abdolghaffari, Mohammad-Reza Mohammadi, Shahin Akhondzadeh","doi":"10.1177/02698811241303593","DOIUrl":"10.1177/02698811241303593","url":null,"abstract":"<p><strong>Background: </strong>Antidiabetic medications have shown efficacy in alleviating autism symptoms. However, there is a lack of clinical research on the impact of metformin on irritability associated with autism. This study aimed to assess the efficacy and safety of metformin as an adjuvant therapy with risperidone for managing irritability in children diagnosed with Autism Spectrum Disorder (ASD).</p><p><strong>Methods: </strong>This is a randomized, 10-week, double-blind, placebo-controlled trial conducted at the children's autism clinic of Roozbeh Hospital (Tehran, Iran) from March 2024 to May 2024. Participants were divided into two groups of risperidone plus metformin (500 mg per day) and risperidone plus placebo and were assessed at baseline, weeks 5 and 10 with the aberrant behavior checklist-community scale (ABC-C).</p><p><strong>Results: </strong>A total of 55 patients were included in the final analysis. Irritability (primary outcome measure) sharply decreased in the metformin compared to the placebo group (<i>p</i> = 0.008). Among the other four subscales of ABC-C, the hyperactivity/noncompliance score showed a significant drop during the baseline-to-week-5 period (<i>p</i> = 0.021). In addition, inappropriate speech subscales decreased significantly from baseline-to-week 5 in the metformin compared to the placebo group (<i>p</i> = 0.045). No other significant finding was observed among ABC-C scores for lethargy/social withdrawal or stereotypic behavior subscales.</p><p><strong>Conclusion: </strong>Metformin demonstrated promising results in reducing irritability in ASD patients, which is in concordance with previous studies. However, further studies are required before any broad clinical recommendation.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"214-222"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829039","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":"Nighttime safety of daridorexant: Evaluation of responsiveness to an external noise stimulus, postural stability, walking, and cognitive function.","authors":"Massimo Magliocca, Ingrid Koopmans, Cedric Vaillant, Vincent Lemoine, Rob Zuiker, Jasper Dingemanse, Clemens Muehlan","doi":"10.1177/02698811241293997","DOIUrl":"10.1177/02698811241293997","url":null,"abstract":"<p><strong>Background: </strong>Daridorexant is a dual orexin receptor antagonist approved for the treatment of chronic insomnia disorder.</p><p><strong>Aims: </strong>Investigate the auditory awakening threshold (AAT), postural stability, and cognitive function during the night following evening administration of daridorexant 25 and 50 mg.</p><p><strong>Methods: </strong>Double-blind, placebo-controlled, randomized, 3-way (placebo, 25, 50 mg) crossover study in 36 healthy male and female nonelderly adult and elderly subjects (1:1 sex/age ratio). Four hours after bedtime administration, the AAT was determined, followed by investigation of the main pharmacodynamic endpoint nocturnal postural stability (body sway) as well as functional mobility using the Timed Up and Go (TUG) test, and cognitive function/memory using the Visual Verbal Learning Test (VVLT).</p><p><strong>Results: </strong>All 36 subjects completed the study. The average AAT was approximately 60 dB across treatments, i.e., there were no differences between daridorexant and placebo. Daridorexant marginally increased body sway by approximately 22%, while it had no clinically meaningful effect on the time to complete the TUG test (⩽1 s increase), and the VVLT (immediate and delayed number of correctly recalled words) showed minimal and clinically not meaningful differences of up to one word, all compared to placebo. Delayed word recognition was not different from placebo. The increase in body sway in the overall population was driven by nonelderly adults, as effects in elderly subjects were similar to placebo.</p><p><strong>Conclusions: </strong>Following bedtime administration, daridorexant maintained the ability to awaken to an external noise stimulus in the middle of the night, allowing subjects to function safely.</p><p><strong>Clinicaltrials.gov identifier: </strong>NCT05702177.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"223-232"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786006","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":"Haloperidol dopamine receptor occupancy and antagonism correspond to delirium agitation scores and EPS risk: A PBPK-PD modeling analysis.","authors":"Paul M Burkat","doi":"10.1177/02698811241309620","DOIUrl":"10.1177/02698811241309620","url":null,"abstract":"<p><strong>Background: </strong>Delirium is a severe neuropsychiatric disorder associated with increased morbidity and mortality. Numerous precipitating factors and etiologies merge into the pathophysiology of this condition which can be marked by agitation and psychosis. Judicious use of antipsychotic medications such as intravenous haloperidol reduces these symptoms and distress in critically ill individuals.</p><p><strong>Aims: </strong>This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model for the antipsychotic medication haloperidol; estimate plasma and unbound interstitial brain concentrations for repetitive haloperidol administrations used in hyperactive delirium treatment; determine dopamine receptor occupancy and antagonism under these conditions; and correlate these results with Richmond Agitation-Sedation Scale (RASS) scores and the risk of developing extrapyramidal symptoms (EPSs).</p><p><strong>Methods: </strong>The PBPK model for single and repetitive administrations of peroral and intravenous haloperidol was developed with PK-Sim software. The pharmacodynamic (PD) model for RASS scores with haloperidol unbound interstitial brain concentration passed as the regressor was developed with the MonolixSuite 2021R platform.</p><p><strong>Results: </strong>Peak haloperidol plasma and unbound interstitial brain concentrations following a single 2 mg intravenous dose are 32 ± 5 nM and 2.4 ± 0.4 nM. With repetitive administrations, dopamine receptor occupancy is 70%-83% and D2_LR antagonism is 1%-10%. Variations in dopamine receptor occupancy correlate with changes in RASS scores in individuals with hyperactive delirium. There is a linear association between the odds ratio of developing EPS and peak D2_LR antagonism as functions of dopamine receptor occupancy.</p><p><strong>Conclusions: </strong>Haloperidol dopamine receptor occupancy time course and D2_LR antagonism parallel RASS score changes and EPS risk, respectively.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"244-253"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927195","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":"Navigating agitation in neurodevelopmental disorders: A comparative study of pharmacotherapies via network meta-analysis in children and adults with autism spectrum disorder or intellectual disabilities.","authors":"Anees Bahji, Evan Forth, Amina Nasar, Ahmed Waqas, Emily R Hawken, Muhammad Ayub","doi":"10.1177/02698811241303654","DOIUrl":"10.1177/02698811241303654","url":null,"abstract":"<p><strong>Importance: </strong>Individuals with autism spectrum disorder (ASD) and intellectual disability often experience persistent challenges related to aggressive behaviour and agitation, highlighting the critical need for evidence-based pharmacological interventions among other strategies. Despite previous network meta-analyses (NMAs), the rapidly evolving landscape of treatment options necessitates ongoing and updated assessments.</p><p><strong>Objective: </strong>To evaluate the efficacy and tolerability of various pharmacotherapies in managing agitation in children and adults with ASD or intellectual disabilities (ID).</p><p><strong>Methods: </strong>Employing a systematic review and network meta-analysis methodology, we conducted an exhaustive search across multiple databases for double-blind, randomized controlled trials focusing on pharmacotherapies targeting agitation in these neurodevelopmental disorders. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, our assessment of study quality utilized the Cochrane Risk of Bias Tool to ensure methodological rigour and accuracy in data synthesis. Primary outcomes encompassed measures of reduced agitation, as indicated by treatment response on standardized agitation scales, alongside dropout rates, providing a comprehensive overview of treatment efficacy and tolerability.</p><p><strong>Results: </strong>Our analysis included data from 38 eligible trials, involving 2503 participants across both pediatric and adult populations. Key pharmacological interventions, such as arbaclofen, risperidone plus buspirone, omega-3 fatty acids, risperidone plus palmitoylethanolamide, aripiprazole and risperidone, demonstrated significant efficacy in reducing agitation compared to placebo. Importantly, these treatments were generally well-tolerated, with no significant increase in all-cause dropouts compared to placebo, highlighting their suitability for clinical use in managing agitation in individuals with ASD or ID.</p><p><strong>Conclusions: </strong>This study underscores the efficacy and tolerability of several pharmacotherapies in managing agitation among children and adults with ASD or ID. Our findings provide robust evidence that specific treatments, such as arbaclofen, risperidone plus buspirone and omega-3 fatty acids, are both effective and well-tolerated, offering valuable therapeutic options for clinicians. The study emphasizes the need for ongoing research to ensure that treatment strategies remain aligned with the evolving clinical landscape, ultimately improving patient outcomes in this challenging population.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"201-213"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846831","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}