Aasim Ali, Abdullah Shahid, Muhammad Usman, Asad Ullah Ansari, Labeeba Abdul Ghafoor, Csilla Dézsi, Viktor Gulyás-Oldal, Károly Szili, Muhammad Abdullah Ali, Usama Saleem, Muhammad Asad Shabbir, Armaghana Abdullah, Mukesh Kumar Sharma, Muhammad Talha
{"title":"Efficacy and safety of ecopipam for Tourette syndrome: An updated systematic review and meta-analysis of randomized controlled trials.","authors":"Aasim Ali, Abdullah Shahid, Muhammad Usman, Asad Ullah Ansari, Labeeba Abdul Ghafoor, Csilla Dézsi, Viktor Gulyás-Oldal, Károly Szili, Muhammad Abdullah Ali, Usama Saleem, Muhammad Asad Shabbir, Armaghana Abdullah, Mukesh Kumar Sharma, Muhammad Talha","doi":"10.1177/20451253261487299","DOIUrl":"10.1177/20451253261487299","url":null,"abstract":"<p><strong>Background: </strong>Tourette syndrome is a neurodevelopmental disorder characterized by persistent motor and vocal tics. Dopamine D2 receptor antagonists can reduce tic severity but are frequently limited by metabolic, sedative, and extrapyramidal adverse effects. Ecopipam is a selective dopamine D1/D5 receptor antagonist with a potentially distinct tolerability profile.</p><p><strong>Objectives: </strong>To evaluate the efficacy and safety of ecopipam in patients with Tourette syndrome using updated randomized evidence.</p><p><strong>Design: </strong>Systematic review and random-effects meta-analysis of randomized placebo-controlled trials.</p><p><strong>Data sources and methods: </strong>PubMed/MEDLINE, Embase, Scopus, ClinicalTrials.gov, reference lists, and conference sources were searched from database inception to May 31, 2026. The primary outcome was change in Yale Global Tic Severity Scale Total Tic Score. Headache and insomnia were evaluated as safety outcomes. Treatment estimates were pooled using random-effects models with Hartung-Knapp adjustment. Risk of bias was assessed using the Cochrane RoB 2 tool.</p><p><strong>Results: </strong>Three randomized trials involving 297 unique randomized participants were included. Ecopipam improved tic severity compared with placebo (mean difference, -3.72; 95% confidence interval, -5.96 to -1.47). The result remained significant after exclusion of the phase 3 randomized-withdrawal trial (mean difference, -3.33; 95% confidence interval, -4.85 to -1.81). No statistical heterogeneity was detected for efficacy outcomes, although the small number of trials limits interpretation. Headache was not significantly increased (risk ratio, 1.36; 95% confidence interval, 0.52-3.51). Insomnia showed an imprecise, nonsignificant association (risk ratio, 2.44; 95% confidence interval, 0.07-79.93; I<sup>2</sup>=62.2%).</p><p><strong>Conclusion: </strong>Short-term randomized evidence suggests that ecopipam reduces tic severity. Evidence concerning insomnia and long-term psychiatric and metabolic safety remains insufficient, requiring larger independent trials with longer follow-up.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261487299"},"PeriodicalIF":5.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888343","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":"Informing the patient of the placebo option: an ethical necessity likely to reduce inappropriate psychotropic prescriptions?","authors":"Fabrice Berna, Guillaume Durand, Rémy Boussageon, Julien Nizard, François Paille, Laurence Verneuil","doi":"10.1177/20451253261436150","DOIUrl":"10.1177/20451253261436150","url":null,"abstract":"<p><p>The growing interest in deprescribing drugs highlights the importance of re-evaluating prescriptions, but also of limiting inappropriate prescribing. This paper reflects on the ethical use of a placebo as a way of limiting inappropriate prescribing. We focus on psychotropic drugs, but our reasoning may also concern other medical conditions. We analyze the conditions in which placebos are usually prescribed in medicine and analyze four situations to determine which would be best ethical. Although the use of placebos, whether pure (i.e., containing no active substance) or impure (i.e., containing active substances but used in a non-specific manner), is commonplace in medicine, patients are not duly informed: this practice respects neither patient autonomy nor freedom of choice. In contrast, the use of open-label placebos (i.e., prescribed to the patient in full transparency) solves this ethical problem. Importantly, informing the patient about the placebo does not seem to alter its therapeutic effect. Furthermore, the information given to the patient as part of the shared-medical decision generally does not mention the benefits that a placebo could bring to the patient in place of a pharmacologically active drug. However, scientific data on the efficacy of a placebo is available in randomized controlled trials or meta-analyses for almost all drugs. This effect is sometimes high under specific clinical conditions. We conclude that there is an ethical imperative to inform patients of the efficacy of a placebo in a clinical context where the prescription of a pharmacologically active drug is discussed. The open-label placebo option should become more systematic in medicine, particularly in psychological symptoms or conditions with a well-documented significant placebo effect. Aside from this ethical aspect, prescribing more placebos could be a way of combating overprescription, reducing inappropriate drug use and iatrogenia, and supporting the eco-responsible approach to prescribing in medicine.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261436150"},"PeriodicalIF":5.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875679","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":"Consent beyond the written form: Implications for ketamine trials in the Philippines.","authors":"Abegail A Pagallaman, John Noel E Fermin","doi":"10.1177/20451253261486613","DOIUrl":"10.1177/20451253261486613","url":null,"abstract":"","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261486613"},"PeriodicalIF":5.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875579","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}
Pierre-Michel Llorca, Anne Sauvaget, Emilie Olié, Lila Mékaoui, Ludovic Samalin, Maud Rothärmel, Anne-Laure Boitez, Julien Dupin, Clotilde Wicart, Emeline Gaudre-Wattinne, Hugo Lacour, Benjamin Grenier, Bernard Astruc, Bruno Falissard, Pierre de Maricourt
{"title":"Real-world clinical practice, effectiveness and safety of esketamine nasal spray in major depressive disorder patients: a French prospective cohort (ELLIPSE study).","authors":"Pierre-Michel Llorca, Anne Sauvaget, Emilie Olié, Lila Mékaoui, Ludovic Samalin, Maud Rothärmel, Anne-Laure Boitez, Julien Dupin, Clotilde Wicart, Emeline Gaudre-Wattinne, Hugo Lacour, Benjamin Grenier, Bernard Astruc, Bruno Falissard, Pierre de Maricourt","doi":"10.1177/20451253261463652","DOIUrl":"10.1177/20451253261463652","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is highly prevalent and associated with significant disability and mortality. Treatment-resistant depression (TRD), defined as inadequate response to ⩾2 antidepressant lines, remains a major therapeutic challenge. Esketamine nasal spray, approved in 2019 for TRD, demonstrated efficacy and safety in randomized trials, but real-world evidence remains limited.</p><p><strong>Objectives: </strong>The ELLIPSE study aimed to describe patient characteristics, treatment patterns, and 12-month outcomes of esketamine in routine clinical practice in France.</p><p><strong>Design: </strong>ELLIPSE was a prospective, multicenter, observational cohort study including adults with unipolar MDD initiating esketamine between Dec 2021 and Jul 2023, followed for 12 months.</p><p><strong>Methods: </strong>Data were collected via standardized clinical assessments. Effectiveness was evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS). Response was defined as ⩾50% MADRS reduction; remission as MADRS ⩽ 10.</p><p><strong>Results: </strong>A total of 200 patients (mean age 46.6 years; 56.5% female) were enrolled; 97.5% met TRD criteria. Median esketamine exposure was 4.5 months. Mean MADRS decreased from 31.9 at baseline to 12.4 at month 12 (mean change -17.9; 95% CI: -21.6 to -14.2). Response and remission rates reached a plateau at month 2, where the response rate was 55.2% and the remission rate was 33.6%, maintained up to month 12. Adverse events (AEs) occurred in 65.7% of patients, most commonly dissociative states (28.0%) and transient blood pressure increases (11.6%).</p><p><strong>Conclusion: </strong>This real-world study in patients with treatment-resistant depression, including those with comorbidities/prior suicide attempts, showed clinically relevant improvement from month 2, sustained through 12 months. Dissociative symptoms were the most frequent treatment-related AE.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261463652"},"PeriodicalIF":5.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875702","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}
Allison S Brandt, Gopal Vyas, Taiwo Oduguwa, Adeola O Adebayo, Heather A Adams, Raymond C Love, Russell L Margolis, Robert W Buchanan, Richard Adebayo, Deanna L Kelly
{"title":"Clinical response to clozapine in Black people with psychosis: A secondary analysis of an open-label clinical trial.","authors":"Allison S Brandt, Gopal Vyas, Taiwo Oduguwa, Adeola O Adebayo, Heather A Adams, Raymond C Love, Russell L Margolis, Robert W Buchanan, Richard Adebayo, Deanna L Kelly","doi":"10.1177/20451253261481518","DOIUrl":"10.1177/20451253261481518","url":null,"abstract":"<p><strong>Background: </strong>Clozapine is the most effective treatment for people with treatment-resistant schizophrenia (TRS). However, clozapine is underutilized, and there are stark racial disparities: Black people with psychosis are less likely to receive clozapine than White people with psychosis. Because of the lack of data on the effectiveness of clozapine in Black people, we sought to determine the clinical response to clozapine in this population.</p><p><strong>Objectives: </strong>To evaluate clinical response to clozapine in Black people with psychosis to provide evidence that may help reduce disparities in clozapine access.</p><p><strong>Design: </strong>Secondary analysis of a six-month, prospective, open-label clinical trial examining the safety of clozapine use in Black people.</p><p><strong>Methods: </strong>We analyzed data from Black people with schizophrenia spectrum disorders (<i>n =</i> 184) from sites in Maryland, USA (n = 97) and Lagos, Nigeria (n = 87). The primary outcome was reduction in symptom severity as measured by the Brief Psychiatric Rating Scale (BPRS) total score over time on clozapine. Additional outcomes included changes in BPRS subscales over time, predictors of 30% improvement in BPRS, clozapine level most predictive of clinical improvement, and the burden of side effects.</p><p><strong>Results: </strong>BPRS total scores decreased significantly with time on clozapine, with a mean reduction of 8.1 points across sites. BPRS positive and resistance subscale scores also improved significantly. Nigerian participants had higher odds of 30% BPRS improvement and showed a faster response to clozapine compared with USA participants. CGI-S improved significantly from baseline to 24 weeks, and weight increased significantly.</p><p><strong>Conclusions: </strong>Black participants experienced significant symptomatic benefit over 24 weeks on clozapine. These findings suggest that Black individuals eligible for clozapine may experience meaningful clinical improvement, supporting efforts to reduce disparities in clozapine access.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261481518"},"PeriodicalIF":5.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814234","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}
Fasil Bayafers Tamene, Getachew Yitayew Tarekegn, Tilaye Arega Moges, Samuel Berihun Dagnew, Tigabu Eskeziya Zerihun, Abel Temeche Kassaw, Desalegn Addis Mussie, Woretaw Sisay Zewdu, Samuel Agegnew Wondm
{"title":"Anticholinergic burden and its predictors among patients with schizophrenia in Northwest Ethiopia: An institutional-based cross sectional study.","authors":"Fasil Bayafers Tamene, Getachew Yitayew Tarekegn, Tilaye Arega Moges, Samuel Berihun Dagnew, Tigabu Eskeziya Zerihun, Abel Temeche Kassaw, Desalegn Addis Mussie, Woretaw Sisay Zewdu, Samuel Agegnew Wondm","doi":"10.1177/20451253261481515","DOIUrl":"10.1177/20451253261481515","url":null,"abstract":"<p><strong>Background: </strong>Many drugs prescribed for individuals with schizophrenia have anticholinergic effects. When these medications are used together, they can create a substantial overall Anticholinergic Burden (ACB).</p><p><strong>Objective: </strong>The aim of this study was to assess the prevalence of ACB and its predictors among patients with schizophrenia at selected comprehensive specialized hospitals in Northwest Ethiopia.</p><p><strong>Design: </strong>A multicenter cross sectional study was conducted.</p><p><strong>Methods: </strong>The study included 406 patients with schizophrenia at selected specialized hospitals in Northwest Ethiopia between June and August 2022. Study participants were recruited using systematic random sampling. The Anticholinergic Cognitive Burden Score (ACBS) was used to assess ACB. Data were entered using EpiData version 4.6.0 and analyzed with SPSS version 26. Multivariable logistic regression analysis was performed to determine the predictors of high ACB, with variables having a p-value < 0.05 at a 95% confidence interval considered statistically significant.</p><p><strong>Results: </strong>The prevalence of high ACB was 34.2%. Older patients [Adjusted Odds Ratio (AOR) = 3.26, 95% CI: 1.17, 9.08 P: 0.024], comorbidity [AOR =2.29, 95% CI: 1.24, 4.24, P: 0.008], polypharmacy [AOR = 2.54, 95% CI: 1.35, 4.76, P: 0.004], and Antipsychotic Polypharmacy (APP) [AOR = 2.15, 95% CI: 1.21, 3.82, P: 0.009] were significantly associated with ACB.</p><p><strong>Conclusion: </strong>In this study, one-third of patients were exposed to high ACB. Old aged patients, those with comorbidity, polypharmacy, and APP need routine follow-up and screening in order to reduce high anticholinergic exposure.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261481515"},"PeriodicalIF":5.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798193","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}
Feng Ji, Lijuan Ma, Xuning Shen, Xiaoling Liang, Wei Cui, Yucong Zhou, Xi-En Wang, Hao Liu
{"title":"The mechanism of action and clinical efficacy of xanomeline-trospium in schizophrenia: A comprehensive review.","authors":"Feng Ji, Lijuan Ma, Xuning Shen, Xiaoling Liang, Wei Cui, Yucong Zhou, Xi-En Wang, Hao Liu","doi":"10.1177/20451253261478086","DOIUrl":"https://doi.org/10.1177/20451253261478086","url":null,"abstract":"<p><p>This narrative review summarizes the latest clinical evidence on xanomeline-trospium in schizophrenia, a first-in-class centrally acting dual-target muscarinic receptor modulator. Xanomeline-trospium combines the muscarinic receptor agonist xanomeline, with with functional preference for M1/M4 subtypes, and the peripherally acting muscarinic antagonist trospium chloride in a 4.2:1 ratio. Xanomeline mediates central therapeutic effects, whereas trospium mitigates xanomeline-induced peripheral adverse effects, including nausea, vomiting, and diarrhea. Five EMERGENT trials were reviewed, comprising three short-term efficacy studies and two long-term extension studies evaluating efficacy and safety. In five-week short-term trials, xanomeline-trospium significantly reduced total Positive and Negative Syndrome Scale (PANSS) total scores, with reductions in positive symptoms approximately 1.5-2 times greater and negative symptoms 1.5-3.5 times greater than those observed with placebo. In the EMERGENT-4 and EMERGENT-5 long-term extension trials, sustained therapeutic effects were observed along with potential improvements in quality of life in patients with mild-to-moderate schizophrenia over 52 weeks. Nevertheless, tolerability remains a major challenge, with high overall discontinuation rates (EMERGENT-4: 78.2% discontinuation; EMERGENT-5: 51% withdrawal). Notably, voluntary withdrawal accounted for a substantial proportion of discontinuations, exceeding adverse event-related withdrawals in certain subgroups. The most common adverse events included gastrointestinal symptoms (nausea, constipation, vomiting) and syncope. Compared with traditional dopamine D2 antagonists, xanomeline-trospium was associated with lower risks of weight gain, hyperprolactinemia, and extrapyramidal symptoms. Key limitations of this review include reliance on placebo-controlled trials without head-to-head comparisons, exclusion of treatment-resistant schizophrenia populations, and limited generalizability to outpatient settings due to the focus on acute inpatient cohorts. Future research should focus on identifying risk factors for early discontinuation and developing both pharmacological and non-pharmacological strategies to improve long-term adherence. Overall, as a novel non-dopaminergic antipsychotic strategy, xanomeline-trospium offers an important therapeutic option for patients who are intolerant to the metabolic or motor adverse effects of traditional antipsychotics, although challenges related to long-term adherence remain to be addressed.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261478086"},"PeriodicalIF":5.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798210","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":"Psychoactive drug use and substance-induced psychosis: Emerging challenges in a low-middle-income country.","authors":"Nabin Pathak, Sunil Shrestha","doi":"10.1177/20451253261473921","DOIUrl":"https://doi.org/10.1177/20451253261473921","url":null,"abstract":"<p><p>The Ministry of Home Affairs, Nepal<i>, \"The National Master Plan on Prevention and Control of Narcotic Drugs 2012-2019″</i> reports that cannabis accounts for the highest prevalence of initial narcotic drug use (80.4%), followed by diazepam (9.4%). Narcotic drug users increased by 5.06% annually over the seven-year period, with most users initiating use below the age of 19, posing a significant challenge for drug-induced psychosis. Health policies also influence the use of psychoactive agents. With growing calls for cannabis legalisation in Nepal, policymakers must carefully consider evidence from high-income countries, including the associated public health and mental health consequences. The 12-directive Mandamus issued by the Supreme Court of Nepal for individuals with mental health conditions represents a pivotal step in strengthening mental health in Nepal. It focuses on upholding mental health rights under the constitution and aligning national policies and regulations with international human rights treaties. Effective mental health care requires multidisciplinary teams comprising psychiatrists, psychologists, psychiatric nurses, psychotherapists, and pharmacists.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261473921"},"PeriodicalIF":5.0,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798168","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}
Matthew Atkins, James Fritz, Mary Rose Hilaire, David Taylor
{"title":"Same sample, different result: Variation in clozapine assay measurement in four UK laboratories.","authors":"Matthew Atkins, James Fritz, Mary Rose Hilaire, David Taylor","doi":"10.1177/20451253261473111","DOIUrl":"https://doi.org/10.1177/20451253261473111","url":null,"abstract":"<p><strong>Background: </strong>Laboratory measurement of clozapine blood concentrations is central to safe and effective treatment and is commonly assumed to be accurate and reproducible across providers. Chromatographic assays require batch-specific setup and are performed using different equipment and techniques, which may introduce error or variability. However, systematic evaluation of inter-provider consistency is limited.</p><p><strong>Objectives: </strong>To assess the analytical accuracy and reproducibility of clozapine and norclozapine blood concentration measurements across four UK laboratories providing routine therapeutic drug monitoring.</p><p><strong>Design: </strong>Laboratory-based analytical accuracy and repeatability study.</p><p><strong>Method: </strong>A panel of 15 spiked plasma samples covering a clinically relevant concentration range for clozapine and norclozapine (74-1443 ng/mL) was distributed to four UK laboratories providing routine therapeutic drug monitoring. Each laboratory analysed the same samples on two separate occasions. Analytical accuracy relative to known values and intra-laboratory consistency were assessed using regression and agreement analyses.</p><p><strong>Results: </strong>All laboratories demonstrated strong linearity between measured and known concentrations (r = 0.932-0.999). Laboratories A and C showed slopes close to unity (0.94-0.99), minimal mean bias (-28 to +22 ng/mL), and narrow limits of agreement for clozapine (-89 to +51 ng/mL) and norclozapine (-71 to +71 ng/mL) across both rounds. In contrast, laboratories B and D showed reduced agreement on repeat testing, with increased slopes, positive bias, and widened limits of agreement in the second round. For laboratory B, the clozapine slope increased from 0.99 to 1.33, with limits of agreement widening to -320 to +673 ng/mL. Laboratory D showed greater deviation, with the clozapine slope increasing from 1.18 to 1.59 and mean bias rising to +349 ng/mL, with very wide limits of agreement (-354 to +1053 ng/mL).</p><p><strong>Conclusion: </strong>Laboratory assays of clozapine using LC-MS and HPLC are not always accurate or reproducible over time. Some laboratories show a significant bias, reporting measured concentrations much higher than the true value.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261473111"},"PeriodicalIF":5.0,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798166","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}
Javier A Flores-Cohaila, Luis Arturo Vílchez Salcedo, Carlos Alexis Salgado Valenzuela, Cesar Li Amenero, Jose Carlos Bojórquez-De la Torre, Ana Maria Zamalloa-Torres, Brayan Miranda-Chavez, Jeff Huarcaya-Victoria, Cesar Copaja-Corzo
{"title":"Therapeutic apartheid: a cross-sectional assessment of estimated cost, accessibility, affordability, and availability among psychotropic medications across 25 regions.","authors":"Javier A Flores-Cohaila, Luis Arturo Vílchez Salcedo, Carlos Alexis Salgado Valenzuela, Cesar Li Amenero, Jose Carlos Bojórquez-De la Torre, Ana Maria Zamalloa-Torres, Brayan Miranda-Chavez, Jeff Huarcaya-Victoria, Cesar Copaja-Corzo","doi":"10.1177/20451253261440374","DOIUrl":"https://doi.org/10.1177/20451253261440374","url":null,"abstract":"<p><strong>Introduction: </strong>Mental disorders affect approximately 20% of the global population and remain a leading cause of disability and premature mortality. Despite pharmacotherapy being central to treatment, access to psychotropic medicines is highly unequal, particularly in low- and middle-income countries. In South America, comprehensive national evaluations integrating availability, price, affordability, and geographic accessibility are scarce.</p><p><strong>Objective: </strong>To assess the availability, cost, affordability, and geographic accessibility of psychotropic medicines across public and private sectors in all regions of Peru.</p><p><strong>Design: </strong>A secondary cross-sectional analytical study.</p><p><strong>Methods: </strong>We use open-access data from the Peruvian Observatory of Pharmaceutical Products between May 20 and 25, 2025. A total of 54 psychotropic medicines were included based on the WHO and national essential medicine lists and expert consensus. Outcomes included median unit cost (interquartile range), availability (% of facilities), affordability (days of minimum wage for a 30-day treatment), and regional accessibility. Public-private cost differences were assessed using Wilcoxon rank-sum tests and Cliff's Delta.</p><p><strong>Results: </strong>Only 22.2% of psychotropics were classified as essential by both WHO and national criteria. Median costs were substantially higher in the private sector, with price differences ranging from 2- to 140-fold (e.g., risperidone 2 mg: $1.41 private vs $0.01 public; Cliff's Delta = 0.99). While essential medicines were generally affordable in the public sector (<1 day of minimum wage), newer and long-acting formulations required up to 276 days of labor. Public-sector availability was limited, and geographic accessibility showed marked centralization: several Amazonian and highland regions lacked access to key psychotropics, whereas private-sector availability was near-universal.</p><p><strong>Conclusion: </strong>Psychotropic medication access in Peru is characterized by profound economic and geographic inequities.</p><p><strong>Trial registration: </strong>Not applicable.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261440374"},"PeriodicalIF":5.0,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798188","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}