Background 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. Objectives To evaluate the efficacy and safety of ecopipam in patients with Tourette syndrome using updated randomized evidence. Design Systematic review and random-effects meta-analysis of randomized placebo-controlled trials. Data sources and methods 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. Results 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 2 =62.2%). Conclusion 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.
Background: 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. Objectives: The ELLIPSE study aimed to describe patient characteristics, treatment patterns, and 12-month outcomes of esketamine in routine clinical practice in France. Design: 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. Methods: 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. Results: 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%). Conclusion: 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.
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.
Background 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). Objective 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. Design A multicenter cross sectional study was conducted. Methods 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. Results 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. Conclusion 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.
Background Individuals with schizophrenia spectrum disorders are at increased risk of cardiometabolic complications, largely due to antipsychotic-associated metabolic effects. Effective management strategies remain limited. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown metabolic benefits in the general population, but its role in this population remains unclear. Objective To evaluate the efficacy and safety of semaglutide compared with placebo in individuals with schizophrenia spectrum disorders receiving antipsychotic therapy and experiencing metabolic abnormalities. Design Systematic review and meta-analysis of randomized controlled trials. Data Sources and Methods: A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Cochrane Library, Embase, and ScienceDirect were searched from inception to February 2026. Randomized controlled trials comparing semaglutide with placebo were included. The longest follow-up time point from each study was used for pooled analysis. Mean differences (MD) and odds ratios (OR) with 95% confidence intervals (CIs) were calculated using RevMan 5.4. The certainty of evidence for critical outcomes was assessed using the GRADE framework. Results Three randomized controlled trials (n = 258) were included. Semaglutide was associated with reductions in body weight (MD: -11.01 kg), BMI (MD: -3.63 kg/m 2 ), and waist circumference (MD: -6.33 cm). Improvements were also observed in body composition. No significant differences were found in lipid or glycemic parameters except HbA1c which showed a significant reduction. Psychiatric outcomes remained unchanged. Gastrointestinal adverse particularly nausea and vomiting events were more frequent with semaglutide. Conclusion Semaglutide appears to improve anthropometric outcomes without worsening psychiatric symptoms in individuals receiving antipsychotic therapy. However, evidence is limited, and larger, long-term trials are required. According to the GRADE framework, the certainty of evidence ranged from moderate for key anthropometric and safety outcomes to low or very low for several metabolic and psychiatric outcomes, highlighting the need for larger, long-term randomized trials.
Plain language summary The Ministry of Home Affairs, Nepal , “The National Master Plan on Prevention and Control of Narcotic Drugs 2012-2019″ 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.
Background 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. Objectives To assess the analytical accuracy and reproducibility of clozapine and norclozapine blood concentration measurements across four UK laboratories providing routine therapeutic drug monitoring. Design Laboratory-based analytical accuracy and repeatability study. Method 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. Results 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). Conclusion 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.
Introduction: 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. Objective: To assess the availability, cost, affordability, and geographic accessibility of psychotropic medicines across public and private sectors in all regions of Peru. Design: A secondary cross-sectional analytical study. Methods: 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. Results: 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. Conclusion: Psychotropic medication access in Peru is characterized by profound economic and geographic inequities. Trial registration: Not applicable.
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.
Background: 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. Objectives: 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. Design: A pharmacovigilance–pharmacodynamic analysis using a spontaneous reporting system. Methods: 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. Results: 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 D 4 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, p = 0.002) and replicated across all frequency statistical models. Conclusions: These findings suggest a potential role of dopamine D 4 receptor occupancy in seizures associated with clozapine augmentation by other antipsychotics. Further large-scale epidemiological studies are needed to validate these findings.
Background: 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. Objective: This review investigated the effectiveness of oestrogen agents as adjunctive treatment to antipsychotic medications in post- and perimenopausal women with psychosis. Design: Systematic review. Data sources and methods: 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. Results: 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. Conclusion: 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. Trial registration: Not registered.
Background: 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. Objectives: To explore individuals’ willingness to consider taking lithium supplements, and to explore the experiences of those currently taking lithium supplements. Design: Qualitative study. Methods: 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. Results: 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. Conclusion: 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.
Background: 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. Objectives: This research aims to identify patterns of antidepressant treatment changes, the reasons for treatment changes, and associated factors among patients with MDD in Ethiopia. Design: A hospital-based cross-sectional study. Methods: 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 p -value of 0.05, with a 95% confidence interval (CI). Results: 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). Conclusion: 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.
Background: 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. Objectives: 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. Design: Human volunteer study. Methods: 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). Results: 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). Conclusion: 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.
Background:Ketamine has emerged as a promising rapid-acting antidepressant for treatment-resistant depression (TRD), yet its mechanisms of action and reliable biomarkers of treatment response remain poorly understood. Recent evidence suggests that the aperiodic exponent (1/f slope) of electroencephalography (EEG) power spectra reflects cortical excitation-inhibition balance (EIB), offering a potential non-invasive marker of treatment outcomes. Objective:Our study investigated whether subanesthetic ketamine modulates the EEG aperiodic exponent in patients with major depressive disorder (MDD), most of whom met criteria for TRD. We also examined whether pretreatment aperiodic exponent predicts antidepressant response. Design:A placebo-controlled, single-blind, one-arm, fixed-sequence design without randomization trial of intravenous ketamine infusion in patients with MDD. Method:Twenty-four MDD patients underwent both placebo and ketamine (0.54 mg/kg over 30 min) infusions. Resting-state EEG was recorded pre-, start-, end-, and 24 h post-infusion. Aperiodic exponent (1-40 Hz) was extracted using spectral parameterization. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale, with responders defined as ⩾33% symptom reduction 24 h post-infusion. Result:Meta-analysis revealed substantial heterogeneity in ketamine's effect on aperiodic exponents. In our cohort, ketamine significantly reduced the aperiodic exponent across the scalp. Notably, responders exhibited higher pretreatment occipital aperiodic exponents than non-responders. A steeper pretreatment 1/f slope in the occipital region predicted better treatment outcomes. Conclusion:Subanesthetic ketamine alters cortical aperiodic dynamics in MDD, potentially reflecting EIB modulation. The EEG aperiodic exponent, particularly in occipital regions, may serve as a useful biomarker for predicting antidepressant response to ketamine. However, our meta-analysis underscores the complexity and variability of the EEG aperiodic exponent. Future large-scale, multimodal studies are needed to validate and expand on these findings. Trial registration:EudraCT Number: 2013-000952-17 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000952-17/CZ).
Treatment-resistant depression (TRD) and bipolar depression (TRBD) are severe, heterogeneous mood disorders associated with substantial functional impairment, elevated suicide risk and persistent unmet treatment needs. While pharmacological and psychological interventions continue to advance, many patients experience delayed, partial or unsustained benefit, underscoring the need for therapies with novel mechanisms and rapid onset of action. Ketamine and esketamine have emerged as distinctive treatments in this context, demonstrating rapid antidepressant and anti-suicidal effects, yet differing fundamentally from conventional antidepressants in their acute subjective effects, physiological profile, delivery models and misuse potential. This narrative review synthesizes evidence from regulatory guidance, clinical trials, observational studies and qualitative research to identify key patient information needs and propose practical psychoeducational strategies. Core elements include explanations of indications, mechanisms and treatment algorithms; guidance on visit preparation, scheduling and monitoring; management of acute adverse effects; counselling on suicidality and substance misuse; and tailored considerations for special populations, including older adults, women of reproductive potential and medically complex patients. Drawing on this synthesis, the review proposes a patient-centred framework for ketamine and esketamine psychoeducation, outlining key informational domains and practical tools that can be embedded within clinical services, and identifies priorities for future research aimed at optimizing patient experience and supporting the responsible integration of ketamine-based therapies into mood disorder care.
Background: Ensuring participants understand informed consent forms (ICFs) is a core ethical requirement of clinical research, particularly in psychiatry, where cognitive and affective symptoms can compromise decisional capacity. As ketamine-based interventions are increasingly studied for mental health conditions, the readability of consent materials in these trials warrants systematic evaluation. Objectives: To assess the readability and linguistic complexity of ICFs from ClinicalTrials.gov used in ketamine clinical trials for mental health conditions. Design: Cross-sectional analysis. Methods: We conducted a cross-sectional analysis of English-language ICFs posted on ClinicalTrials.gov for interventional ketamine clinical trials involving mental health conditions. All documents were converted to plain text and standardised for text-based analysis. Readability and linguistic complexity were assessed using established indices, including the Flesch–Kincaid Grade Level, Gunning Fog Index, Flesch Reading Ease Score, and Fry Readability Graph. Document length and estimated silent reading time were also calculated. Descriptive statistics summarised the findings. Results: Fourteen ketamine clinical trials met the inclusion criteria. ICFs ranged from 1681 to 8637 words (mean: 5031; median: 4622), with sentence counts from 129 to 503. Estimated silent reading times ranged from 7.0 to 36.0 min (mean: 21.4; median: 19.5). Flesch–Kincaid Grade Level scores ranged from 5.7 to 11.5 (mean: 9.8), with 13 of 14 documents above grade 8. Gunning Fog Index values ranged from 7.7 to 13.8 (mean: 11.7). Flesch Reading Ease Scores ranged from 41.3 to 73.9 (mean: 52.8). Fry Readability scores ranged from grade 6 to grade 13. Conclusion: Thirteen of fourteen ketamine mental health trial consent forms on ClinicalTrials.gov exceeded recommended readability thresholds. Sponsors and ethics committees should require consent materials to meet an eighth-grade reading level, verified by a documented readability assessment before approval, to support informed participation in psychiatric research.
Background:Benzodiazepine receptor agonists (BZRA) are frequently tapered because of risk of dependence and hazards of use in ageing. Standard tapering protocols may fail or result in harm from improper utilization of pharmacologic principles, lack of recognition of withdrawal and/or failures in shared decision-making. Objective:The aim of this work was to derive principles from experts to optimize deprescribing success while minimizing withdrawal among patients who use BZRA medication long-term. Design:Modified Delphi consensus study among experts from two not-for-profit organizations dedicated to BZRA use issues. Methods:Three stages of anonymized voting were conducted among clinical experts and patient representatives. An 80% agreement ('agree' or 'strongly agree' on a five item Likert-type scale) was required for consensus. Recommendations which failed to reach initial consensus, were modified from feedback and downgraded to 'moderate' (>80% agreement) or 'weak' consensus (50%-80% agreement) in the subsequent rounds. Results:A total of 35 of 48 invitees participated (73% response rate) which included seven family physicians, nine psychiatrists, five pharmacists, six patient advocates, two nurse practitioners, two licensed clinical social workers, two health service policy researchers, a physician assistant and a psychotherapist. A total of 31 of 35 participants were from the United States, with the remaining representatives from Canada, the UK and Ireland. Strong consensus was achieved for attaining informed consent prior to deprescribing (recommendation 1), using a flexible and gradual tapering approach (recommendation 2) characterized by shared decision-making (recommendation 3) with hyperbolic dose reductions (recommendation 4) facilitated via novel preparation techniques or compounded pharmaceutical formulations (recommendation 7). Reversion to previous doses may occur if necessary to reduce the incidence of withdrawal (recommendation 6). Strong consensus was also reached for adjunctive psychosocial interventions (recommendation 8) and/or peer-support resources (recommendation 9). Moderate and weak consensus was achieved, respectively, for step-wise conversion to a longer-acting BZRA (recommendation 5) and the avoidance of adjunctive non-BZRA pharmacotherapy (recommendation 10). Conclusion:This consensus guidance document for primary care providers, mental health clinicians and long-term users of BZRA outlines ten principles/recommendations intended for improving deprescribing outcomes with an emphasis on minimizing withdrawal risk.
