Therapeutic Advances in Psychopharmacology最新文献

{"title":"Lithium-induced blepharospasm in a middle-aged woman with recurrent depressive disorder: a case report.","authors":"Maria Del Rosario Arevalo Bazalar, Jayamal De Silva","doi":"10.1177/20451253261467607","DOIUrl":"10.1177/20451253261467607","url":null,"abstract":"<p><p>This case describes the presence of blepharospasm as a side effect after a short period of lithium treatment in a middle-aged woman with recurrent depressive disorder. Almost immediately after cessation of lithium carbonate, side effects subsided, indicating that the medication was the culprit for her symptoms. Switch to a different psychotropic as a mood-stabilising agent commenced. Four months later, side effects experienced remained absent and mental state appears to have improved, obtaining a remission of illness. There is a limited number of case reports which have reported blepharospasm as a side effect of lithium carbonate. Lithium is used worldwide for the management of mood disorders, although its use has declined over the years in certain parts of the world. In Australia, it is still considered the most effective mood stabilising agent and is recommended by the Royal Australian and New Zealand College of Psychiatry clinical practice guidelines for mood disorders.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261467607"},"PeriodicalIF":5.0,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685864","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":"Seizures associated with clozapine augmentation by other antipsychotics: a pharmacovigilance-pharmacodynamic analysis using VigiBase.","authors":"Masakazu Hatano, Hirofumi Hamano, Masaya Kanda, Takenao Koseki, Tsuyoshi Nakai, Rina Horii, Nozomi Yoshihara, Takeo Saito, Kenshi Takechi, Satoru Esumi, Yoshito Zamami, Shigeki Yamada","doi":"10.1177/20451253261472920","DOIUrl":"10.1177/20451253261472920","url":null,"abstract":"<p><strong>Background: </strong>Clozapine is associated with a high risk of central nervous system abnormalities. However, seizure risk related to interactions between clozapine and other antipsychotics remains poorly characterized, and the pharmacological mechanisms underlying these seizures are unclear.</p><p><strong>Objectives: </strong>We aimed to evaluate safety signals for seizures associated with clozapine augmentation by other antipsychotics and analyze the relationship between these signals and neurotransmitter receptor occupancy profiles.</p><p><strong>Design: </strong>A pharmacovigilance-pharmacodynamic analysis using a spontaneous reporting system.</p><p><strong>Methods: </strong>This pharmacovigilance study used VigiBase, an adverse drug reaction database maintained by the World Health Organization. Drug-drug interactions (DDIs) between clozapine and other antipsychotics were assessed using the Ω shrinkage measure model. The association between DDI signals and neurotransmitter receptor occupancy was evaluated using linear regression. Robustness was tested using four frequency statistical models: additive, multiplicative, combination risk ratio, and chi-square statistic models.</p><p><strong>Results: </strong>Of 38,758,077 reports in VigiBase between 1990 and 2024, 230,371 involved clozapine. Among antipsychotics classified under ATC code N05A, DDIs with clozapine were detected for amisulpride, chlorpromazine, haloperidol, lurasidone, olanzapine, penfluridol, risperidone, sulpiride, zotepine, and zuclopenthixol. A significant association between dopamine D₄ receptor occupancy and the point estimates of signal values was observed in the Ω shrinkage measure model (β = 0.295, 95% confidence interval: 0.119-0.471, <i>p</i> = 0.002) and replicated across all frequency statistical models.</p><p><strong>Conclusions: </strong>These findings suggest a potential role of dopamine D₄ receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261472920"},"PeriodicalIF":5.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654342","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":"Oestrogen modulators as augmentation to antipsychotics for the treatment of post- and perimenopausal psychosis: a systematic review.","authors":"Cassidy Keen, Athanasios Hassoulas, Jill Richardson","doi":"10.1177/20451253261460148","DOIUrl":"10.1177/20451253261460148","url":null,"abstract":"<p><strong>Background: </strong>It is theorised that oestrogen provides neuroprotection against psychosis. Oestrogen levels drop during post- and perimenopausal periods, creating a window for the onset of psychotic symptoms. Oestrogen treatment using hormonal therapy (HT) or selective oestrogen receptor modulators (SERMs) as an adjunct to antipsychotics could provide a new treatment option for post- and perimenopausal women.</p><p><strong>Objective: </strong>This review investigated the effectiveness of oestrogen agents as adjunctive treatment to antipsychotic medications in post- and perimenopausal women with psychosis.</p><p><strong>Design: </strong>Systematic review.</p><p><strong>Data sources and methods: </strong>A systematic search of major databases identified trials examining oestrogen or SERMs as adjuncts to antipsychotics in women aged 40+ with psychosis. Studies were assessed for quality using the Cochrane Risk of Bias tool and the Joanna Briggs Institute (JBI) critical appraisal tools.</p><p><strong>Results: </strong>Ten studies met inclusion criteria: one using oestrogen HT and nine using raloxifene. Reductions in total Positive and Negative Syndrome Scale (PANSS) scores support evidence for the adjunctive use of raloxifene in improving psychotic symptoms. Of the nine included clinical trials, six reported statistically significant improvements with oestrogen-modulating agents: four in total PANSS reduction, and two in positive PANSS domain only. Quality assessments identified publication bias, inconsistent data reporting and variability in study design.</p><p><strong>Conclusion: </strong>Raloxifene shows potential as an adjunctive treatment in post- and perimenopausal psychosis, but further high-quality clinical trials are needed to inform practice and develop hormone-informed treatment protocols.</p><p><strong>Trial registration: </strong>Not registered.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261460148"},"PeriodicalIF":5.0,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654319","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":"Conceptual analysis of mechanisms and methods in psychedelic clinical trial design: a narrative review.","authors":"Martin Krsak, David Sparrow, Bernard Rosner, Deborah DeMolles, Scott Shannon","doi":"10.1177/20451253261470523","DOIUrl":"10.1177/20451253261470523","url":null,"abstract":"<p><p>Clinical trials with psychedelics face several challenges that are not present to such a degree with other pharmacotherapeutics. Psychedelic therapies often include a significant therapeutic container, including preparatory and integrative psychotherapy, along with supportive intervention during dosing sessions. All these are likely to have an effect on the outcomes. Additionally, the influence of the therapeutic relationship between study subjects and study therapists is often more pronounced and more impactful on the outcomes as it is in pharmacotherapies that do not require psychotherapy. Perhaps the most important challenge with psychedelic-assisted therapy trials is the inability to effectively conceal the assignment in placebo-controlled settings. Many different approaches have been tried, however, all have suffered from a complete or significant functional unblinding making it difficult to discern the true therapeutic effect of the psychedelic in conjunction with the psychotherapeutic modalities which accompany it from a positive expectancy effect (often in the subjects receiving active intervention), which is further compounded by an additional negative expectancy effect (often in the subjects receiving placebo). This can be particularly problematic if functional unblinding is not just a nuisance variable but is deeply connected with the mechanism of therapeutic action itself. In this manuscript, we discuss various advantages and disadvantages of currently available approaches utilized in psychedelic trials and propose conceptual and methodological perspectives on approaching these problems.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261470523"},"PeriodicalIF":5.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593409","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":"A qualitative exploration of perspectives on taking lithium supplements.","authors":"Madeleine Bloomfield, Lily Chebabo-Manning, Rebecca Strawbridge","doi":"10.1177/20451253261462260","DOIUrl":"10.1177/20451253261462260","url":null,"abstract":"<p><strong>Background: </strong>Lithium is widely recognized for its benefits as a medication to treat mood disorders. Low-dose lithium has been commercially available for decades as a nutritional supplement, but there is little research on its effects. Emerging evidence suggests that low-dose lithium may offer therapeutic benefits in mood disorders and cognition, with better tolerability and accessibility than higher doses.</p><p><strong>Objectives: </strong>To explore individuals' willingness to consider taking lithium supplements, and to explore the experiences of those currently taking lithium supplements.</p><p><strong>Design: </strong>Qualitative study.</p><p><strong>Methods: </strong>Two qualitative studies were undertaken. First, a focus group was conducted with those who had not taken lithium supplements before and were concerned about their own or another individual's cognitive health. Second, individual semi-structured interviews were undertaken with participants who were currently taking lithium supplements. Data from each study were analyzed separately using thematic analysis.</p><p><strong>Results: </strong>Four overall findings emerged. These relate to lithium supplement effects on mood stability, anxiety, and cognition, as well as distrust toward unfamiliar supplements. Participants taking lithium supplements perceived improvements in balancing and enhancing mood, reductions in anxiety and stress, and improved ability to cope with challenging situations. Three-quarters reported perceived improvement in cognition, particularly concentration and memory. Participants from both groups noted that, initially, lithium supplements elicited feelings of unease and wariness, partly due to association with lithium as a medication, as well as lack of information about its supplement form and an unawareness that lithium is a naturally occurring mineral.</p><p><strong>Conclusion: </strong>Results suggest that there may be benefits from lithium supplements. Participants reported a wide range of perceived benefits across mood, anxiety, and cognition, but also displayed skepticism toward lithium supplements. This research is limited by its size and likely lack of generalizability to the wider population; clinical trials are needed to clarify the safety and efficacy of lithium supplements.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261462260"},"PeriodicalIF":5.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585315","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 in the management of suicide: a formidable force in the fight against a fatal foe.","authors":"Gurubhaskar Shivakumar, Kinga Szymaniak, Erica Bell, Gin S Malhi","doi":"10.1177/20451253261467801","DOIUrl":"10.1177/20451253261467801","url":null,"abstract":"","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261467801"},"PeriodicalIF":5.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562931","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":"Patterns of antidepressant treatment changes among adults with major depressive disorder in Northwest Ethiopia: a hospital-based cross-sectional study.","authors":"Tilaye Arega Moges, Fasil Bayafers Tamene, Woretaw Sisay Zewdu, Getachew Yitayew Tarekegn, Asanti Dejen, Tigabu Eskeziya Zerihun, Abel Temeche Kassaw, Desalegn Addis Mussie, Samuel Agegnew Wondm, Abaynesh Fentahun Bekalu, Samuel Berihun Dagnew","doi":"10.1177/20451253261463711","DOIUrl":"10.1177/20451253261463711","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is a prominent cause of worldwide disability, severely affecting quality of life in Ethiopia. Despite a significant prevalence of treatment-resistant depression, challenges in treatment adherence, and a high prevalence of adverse drug reactions, the studies in Ethiopia have limited data on antidepressant treatment changes.</p><p><strong>Objectives: </strong>This research aims to identify patterns of antidepressant treatment changes, the reasons for treatment changes, and associated factors among patients with MDD in Ethiopia.</p><p><strong>Design: </strong>A hospital-based cross-sectional study.</p><p><strong>Methods: </strong>The present study was conducted at Debre Tabor Comprehensive Specialized Hospital, Northwest Ethiopia, from June 01, 2025, to August 30, 2025. The data was entered, cleaned, and analyzed by using SPSS Version 27. The antidepressant side-effect checklist was used to classify adverse effects as mild, moderate, or severe. The Naranjo adverse drug reactions (ADRs) probability scale assessed antidepressant-related adverse drug reactions; non-adherence was evaluated using a self-reported tablet count tool. A multivariable logistic regression model was utilized to identify factors associated with antidepressant treatment changes. The significance level was set at a <i>p</i>-value of 0.05, with a 95% confidence interval (CI).</p><p><strong>Results: </strong>Out of 220 respondents, 127 (57.7%) did not respond to their antidepressants, which impacted their ability to carry out daily responsibilities. Approximately one-third of participants (80, or 36.4%) had switched medications. More than half of the patients with MDD (114, or 51.82%) experienced ADRs related to antidepressants. The prevalence of non-adherence to medication was 54.6%; 95% CI: 48.6, 60.9. Antidepressant treatment change was significantly associated with having a history of relapse (AOR = 2.52, 95% CI: 1.28, 5.42) and a history of hospital admission (AOR = 2.35, 95% CI: 1.25, 7.59).</p><p><strong>Conclusion: </strong>The management of MDD in Ethiopia faces challenges such as high non-adherence rates, significant ADRs, and limited access to alternative treatments. About 36.4% of patients underwent antidepressant treatment changes. A history of relapse and admission history were associated with antidepressant treatment changes. Future research should investigate longitudinal research to understand non-response and its impact on patient outcomes.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261463711"},"PeriodicalIF":5.0,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472809","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":"Identifying patients at risk of supratherapeutic amisulpride exposure in routine psychiatric practice: a real-world therapeutic drug monitoring study.","authors":"Keyu Yan, Gehang Ju, Aowei Li, Ruomei Gao, Na Wang, Qing Shao","doi":"10.1177/20451253261460142","DOIUrl":"10.1177/20451253261460142","url":null,"abstract":"<p><strong>Background: </strong>Amisulpride is an important antipsychotic used in the treatment of schizophrenia, yet its exposure shows inter-individual variability. Although therapeutic drug monitoring (TDM) is recommended, supratherapeutic concentrations (>600 ng/mL) still occur in routine practice and may increase the risk of adverse effects. However, practical risk prediction studies of supratherapeutic amisulpride exposure based on routine clinical variables remain limited.</p><p><strong>Objectives: </strong>To identify patients at increased risk of supratherapeutic amisulpride exposure in routine psychiatric care and to develop a clinically interpretable risk prediction approach based on routinely available clinical variables.</p><p><strong>Design: </strong>This was a retrospective observational study using real-world TDM data from psychiatric inpatients.</p><p><strong>Methods: </strong>Therapeutic drug monitoring data were retrospectively analyzed. Patients were split at the patient level into training (70%) and validation (30%) cohorts. To identify the optimal representation of renal function and drug elimination, predictors were organized into three candidate pools: (i) apparent clearance (CL/F) calculated from the final covariate equation of a previously published population pharmacokinetic model, (ii) estimated creatinine clearance (eCLcr), and (iii) the original clinical variables used to calculate eCLcr. Within each candidate predictor pool, predictors were screened using LASSO-penalized logistic regression and then entered into multivariable logistic regression. The most clinically practical model was selected for nomogram construction. Model performance was assessed by discrimination, calibration, and decision curve analysis.</p><p><strong>Results: </strong>A total of 413 steady-state trough samples from 299 patients were analyzed, of which 19.6% exceeded a steady-state trough plasma concentration of 600 ng/mL. Reduced renal function and higher daily doses were consistently associated with an increased risk of supratherapeutic exposure. Among the three candidate strategies, the Key Covariate-based strategy achieved acceptable discrimination in both the training (area under the receiver operating characteristic curve (AUC) 0.738) and validation (AUC 0.720) cohorts, with good calibration. Decision curve analysis suggested potential clinical utility across a range of lower to moderate threshold probabilities.</p><p><strong>Conclusion: </strong>A simple risk stratification approach based on eCLcr and daily dose may offer a reference for individualized risk assessment. This model may provide preliminary support for identifying patients at risk of supratherapeutic exposure in routine psychiatric practice.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261460142"},"PeriodicalIF":5.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412949","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":"Making a case for using MDMA-assisted psychotherapy for borderline personality disorder and complex PTSD: a descriptive systematic review of the literature.","authors":"Karthika Kasiviswanathan, Dinuli Nilaweera, Melissa Morando, Sathya Rao, Jessica Lee, Joseph Fettling, Jillian H Broadbear","doi":"10.1177/20451253251408626","DOIUrl":"10.1177/20451253251408626","url":null,"abstract":"<p><strong>Background: </strong>3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has demonstrated considerable efficacy in treating post-traumatic stress disorder (PTSD). PTSD and complex PTSD (CPTSD) frequently co-occur with borderline personality disorder (BPD), a complex disorder marked by emotional dysregulation, interpersonal difficulties and abandonment fears - often accompanied by suicidal and non-suicidal self-injury. While MDMA-AP is beneficial for PTSD and hypothesised to be effective for BPD, its application to CPTSD and BPD has not been systematically reviewed.</p><p><strong>Objectives: </strong>To systematically evaluate primary evidence on the use of MDMA-AP in treating PTSD, CPTSD, and BPD.</p><p><strong>Design: </strong>Descriptive systematic review.</p><p><strong>Data sources and methods: </strong>A systematic search of four databases (Ovid Medline, Embase, APA PsycINFO and CENTRAL) identified 24 eligible peer-reviewed studies published before 17 February 2025. Risk of bias and data extraction were conducted independently using standardised methods.</p><p><strong>Results: </strong>Of the 24 studies involving 335 participants, 15 reported outcomes from seven clinical trials, four were case reports, and five were non-randomised interventions. Four studies included participants with multiple forms of trauma, and three included those with dissociative PTSD. Most reported reduced PTSD symptoms post-intervention; some noted decreased dissociative symptoms at higher MDMA doses. Six studies did not exclude participants with BPD. Although none directly assessed MDMA-AP for CPTSD or BPD, improvements in emotional regulation, interpersonal functioning, identity coherence and abandonment concerns were reported. Adverse drug reactions were mild to moderate, although specific safety concerns remain.</p><p><strong>Conclusion: </strong>Findings from this review suggest that MDMA-AP may have applicability beyond PTSD, with potential benefits for CPTSD and BPD, offering preliminary insights to inform future research and clinical considerations.</p><p><strong>Protocol registration: </strong>PROSPERO ID: CRD42025594896.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253251408626"},"PeriodicalIF":5.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412971","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":"Assessment of clozapine taste in healthy volunteers: evidence for non-aversive sensory profile.","authors":"Laura Modica de Mohac, Alex Keeley, David Taylor, Catherine Tuleu","doi":"10.1177/20451253261458524","DOIUrl":"10.1177/20451253261458524","url":null,"abstract":"<p><strong>Background: </strong>Acceptability is crucial for treatment efficacy, and the World Health Organization emphasizes its impact on patient compliance. Taste plays a significant role in acceptability, with bitter taste often leading to treatment discontinuation. Clozapine, an effective drug for treatment-resistant schizophrenia, faces acceptability challenges that have been connected to its poor taste.</p><p><strong>Objectives: </strong>The aim of this study was to conduct, for the first time, a human taste assessment of clozapine to directly measure its level of aversiveness.</p><p><strong>Design: </strong>Human volunteer study.</p><p><strong>Methods: </strong>Employing a \"swirl and spit\" method, 23 young healthy adults rated the taste of four clozapine solutions (0.0011-0.018 mg/mL) on a visual analog scale (VAS) ranging from 0 (not aversive) to 100 mm (extremely aversive).</p><p><strong>Results: </strong>Clozapine was not aversive at any concentrations, even at saturation: mean VAS scores ranged from 5.6 to 10.3/100 (median scores ranged between 2 and 4).</p><p><strong>Conclusion: </strong>Reported barriers to compliance linked to taste aversiveness of marketed or extemporaneous dosage forms of clozapine may be linked to factors such as the dosage form itself, other negative formulation or excipients' organoleptic characteristics, packaging, and user instructions linked to dosing frequency and duration, and of course, patient and disease-related factors, which require further investigations.</p>","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"16 ","pages":"20451253261458524"},"PeriodicalIF":5.0,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391635","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}