Clinical Global Impression Research Articles

The effectiveness and safety of botulinum toxin injections for managing motor disorders of patients with Parkinson's disease: A meta-analysis of randomized controlled trials.

This study aimed to assess the effectiveness and safety of botulinum toxin (BTX) injections for managing motor disorders in patients with Parkinson's disease (PD). An electronic search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from available randomized controlled trials (RCTs) assessing BTX injections for motor disorders in PD patients were extracted for meta-analysis. Ultimately, 215 patients from eight RCTs were enrolled. Pooled analyses indicated that BTX was more effective than placebo in improving tremor (standardized mean difference [SMD] = 0.96, 95% CI [0.34, 1.58], p < 0.01), whereas no notable differences were observed between BTX and placebo regarding freezing of gait (SMD = 0.66, 95% CI [-0.26, 1.58], p = 0.162), United Parkinson's Disease Rate Scale (UPDRS) III score (SMD = -0.20, 95% CI [-1.17, 0.76], p = 0.68) and clinical global impression (CGI) score (SMD = 0.84, 95% CI [-0.74, 2.42], p = 0.298). Adverse events related to BTX injections were comparable to placebo (OR = 1.74, 95% CI [0.59, 5.14], p = 0.32). The current evidence suggests that BTX is effective and safe in treating PD tremor but fails to provide therapeutic benefits for freezing of gait and motor functional scores in PD patients. Furthermore, the limited number of included studies and heterogeneity in BTX intervention protocols suggest more research is needed, with additional standardized RCTs, to better understand and optimize BTX injections for motor disorders in PD.

Acculturation stress and mental health outcomes in a sample of migrant inpatients: Findings from a naturalistic study.

Migrants face numerous risk factors for mental disorders, including stressors and traumatic events during the pre-, peri-, and post-migratory phases. Acculturation stress, a significant post-migratory stressor, can adversely affect mental health during the cultural adaptation process. This study aims to assess the clinical implications of acculturation stress in migrants admitted to a psychiatric intensive care unit, with a focus on identifying predictors of acculturative stress and their impact on clinical outcomes. We conducted a retrospective study of 268 immigrant patients hospitalized between 2004 and 2019 at the psychiatric inpatient unit of the University of Foggia. We collected socio-demographic and clinical data using ad hoc schedules and validated assessment instruments, including the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning (GAF), and the Clinical Global Impression (CGI). Diagnoses were based on DSM-IV-TR/DSM-5 criteria. We analyzed associations between demographic and clinical characteristics of patients reporting acculturative stress and those not reporting it, using appropriate statistical methods. The majority of patients were diagnosed with affective (45.1%) or psychotic disorders (31.7%), with 57.1% experiencing their first psychiatric episode. Acculturation stress was reported by 51.9% of patients (N = 139), predominantly among males (71.9%), single individuals (80.9%), and those of Islamic faith (56.8%). Patients experiencing acculturation stress were more likely to be unemployed (57.6%) and without a residence permit (63.3%). This stress was particularly prevalent among patients with psychotic disorders (25.9%) and first-episode psychiatric cases (64.7%). At discharge, patients with acculturation stress showed less improvement on CGI, GAF, and BPRS scores compared to those without such stress. Acculturation stress is influenced by several socio-demographic factors and is crucial for the full symptomatic remission of migrant patients. Culturally-oriented mental health services, including language and cultural integration programs, are essential in reducing acculturative stress and improving the overall well-being of immigrants.

Taltirelin Hydrate in Patients with Ataxia Due to Spinocerebellar Degeneration.

We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in spinocerebellar degeneration (SCD). Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was changes in the Korean version of Scale for the Assessment and Rating of Ataxia (K-SARA) scores at 24 weeks. The secondary endpoints include changes in the K-SARA scores at 4 and 12 weeks, the Clinical Global Impression, Five-level version of the EuroQol five-dimensional questionnaire, Tinetti balance test and gait analysis at 4, 12 and 24 weeks. A total of 149 patients (hereditary:non-hereditary = 86:63) were enrolled. There were significant differences in changes in K-SARA scores at 24 weeks from baseline between the taltirelin group and the control group (-0.51 ± 2.79 versus 0.36 ± 2.62, respectively; p = 0.0321). Of the K-SARA items, both 'Stance' and 'Speech disturbance' had significantly lower subscores in the taltirelin group as compared with the control group (-0.04 ± 0.89 versus 0.23 ± 0.79 and -0.07 ± 0.74 versus 0.18 ± 0.67; p = 0.0270 and 0.0130, respectively). But there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p > 0.05). Clinicians might consider using TH in the treatment of ataxia due to SCD.

Amyloid deposition and its association with depressive symptoms and cognitive functions in late-life depression: a longitudinal study using amyloid-β PET images and neuropsychological measurements

BackgroundAlthough depression is linked to an increased risk of dementia, the association between late-onset depression (LOD) and amyloid burden remains unclear. This study aimed to determine amyloid deposition in patients with LOD compared to healthy controls (HC) using amyloid-beta (Aβ) positron emission tomography (PET) images and neuropsychological assessments.MethodsForty patients first diagnosed with major depressive disorder after the age of 60 (LOD) and twenty-one healthy volunteers (HC) were enrolled. Depression and anxiety were evaluated using the 17-item Hamilton Depression Scale, Hamilton Anxiety Rating Scale, and Clinical Global Impression Scale. Cognitive function was assessed using the Korean versions of the Mini-Mental Status Examination, Montreal Cognitive Assessment, and Seoul Neuropsychological Screening Battery at baseline and 3-month follow-up. 18F-florbetapir PET images were co-registered with T1-weighted magnetic resonance images.ResultsThere was no significant difference in Aβ deposition between LOD and HC groups. No significant correlation between Aβ burden and depressive symptom severity was found in LOD patients. Higher somatic anxiety was correlated with lower Aβ burden in multiple brain regions, including the left inferior frontal lobe (p = 0.009), right anterior cingulate (p = 0.003), and right superior frontal lobe (p = 0.009). Despite cognitive recovery in areas such as attention (Digit Span Forward, p = 0.026), memory (Auditory Verbal Learning Test Recall Total, p = 0.010; Rey Complex Figure Test Delayed Recall, p = 0.039), and frontal executive function (Contrasting Program, p = 0.033) after three months of antidepressant treatment, cognitive improvement showed no association with amyloid deposition.ConclusionsThese findings suggest distinct mechanisms may underlie amyloid deposition in neurodegenerative changes associated with depression. While amyloid burden in specific brain regions negatively correlated with somatic anxiety, it showed no significant correlation with the severity of depression or overall cognitive function.

A Multicenter, Open-Label Study to Evaluate the Long-term Safety and Efficacy of Adjunctive Brexpiprazole 2 mg Daily in Japanese Patients with Major Depressive Disorder.

Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD. An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included treatment-emergent adverse events (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale(MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score. In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): - 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of - 0.8 (1.0), - 5.9 (6.3), and - 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment. This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks. ClinicalTrials.gov (NCT03737474; registered on 29 July 2018).

Extension and Further Replication of the Reliability, Criterion Validity, and Treatment Sensitivity of the PANSS10 and PANSS20 for Pediatric Trials.

Introduction: The Positive and Negative Syndrome Scale (PANSS) is a widely accepted outcome measure for pediatric schizophrenia trials; however, it has notable limitations. Psychometric investigations have shown a multifactorial structure and some items have limited utility assessing symptom severity in children. To address these issues, we developed and evaluated optimized 10- and 20-item PANSS short-forms (PANSS10 and PANSS20) using patient-level clinical trial data. This study further assesses these optimized forms using independent clinical trial data. Methods: We examined patient-level data from a randomized pediatric schizophrenia trial comparing paliperidone ER to aripiprazole. Data were accessed through the Yale Open Data Access (YODA) secure platform. Analyses included confirmatory factor analyses, graded response models, ω score reliability, internal consistency, sensitivity to change, and criterion validity versus the Clinical Global Impressions of Severity (CGI-S). Bland-Altman analyses examined score calibration versus the 30-item PANSS and inclusion cut scores. Results: Participants (N = 288) were ages 12 to 17 years (M = 15.3, SD = 1.46; 66% male). Total scores for the PANSS10 and PANSS20 showed strong correlations with the 30-item PANSS (0.90 and 0.97, respectively). Average inter-item correlations were 0.10 and 0.14 and ωTotal reliabilities were 0.74 and 0.85. Both PANSS10 and PANSS20 scores showed reliability >0.80-2.3 to 4.5 SD and -3.0 to 6.0 SD about mean symptom severity, respectively. Sensitivity to treatment was also similar (partial eta squared 0.23 and 0.22), as was correlation with CGI-S at baseline (0.45 and 0.48; not significantly different). The mean item-average discrepancy with the 30-item PANSS was 0.095 for PANSS10 and 0.033 for PANSS20. Conclusions: The optimized PANSS forms continue to show impressive reliability, validity, and calibration compared with the 30-item PANSS. Researchers should consider replacing the 30-item PANSS with the PANSS10 as a clinical outcome and screening measure due to its length and psychometric performance.

Key mental health differences in conflict-related sexual violence and how sex, severity, and early intervention impact on improvement: a retrospective observational study

BackgroundConflict-related sexual violence (CRSV) is a significant health and human rights issue in humanitarian contexts, but there is a need of further research on differences between sexes in terms of severity of symptoms and improvement. Consequently, we explored the differences in severity and outcomes among male and female survivors of CRSV who received mental health and psychosocial support (MHPSS) in an armed conflict setting.MethodsWe retrospectively analysed medical records from 3442 CRSV survivors in a MHPSS programme in Borno State, Nigeria, between 2018 and 2019. Patient characteristics, severity (measured with Clinical Global Impression of Severity Scale [CGI-S scale]), and improvement (measured with Clinical Global Impression of improvement [CGI-I] scale) were assessed by an attending counsellor. We assessed predictors for severity and improvement using a multivariable logistic regression analysis and time to improvement by sex using Kaplan Meier (K–M) curves and Cox regression.ResultsWe included 3442 patients who had at least one CRSV event in this study (2955 [85.9%] female, 486 [14.1%] male, one unknown). The most prevalent categories of symptoms were depression (49.9%; n = 1716), post-traumatic (25.6%; n = 879), and anxiety (20.3%; n = 697) symptoms. Most patients had mild (59.0%; n = 1869/3170) or moderate (36.4%; n = 1153/3170) symptoms at baseline, with 4.7% having severe symptoms (n = 148/3170). The logistic regression analysis (n = 1106), showed male patients had a 59% higher odds of severe symptoms at baseline than female patients (aOR 1.59; 95% CI 1.04–2.45). Among males, those older than 55 years had three times higher odds of presenting severe symptoms than younger patients (aOR 3.65; 95% CI 1.43–9.34). Women aged 36–55 years were more likely to present improvement than younger female patients (aOR 1.32; 95% CI 1.11–1.58). For both sexes, prompt attention after a CRSV event (≤ 3 days) positively predicted improvement (aOR 13.9; 95% CI 1.48–130 males, aOR 2.11; 95% CI 1.22–3.64 females) compared to late attention. Time to improvement did not differ between sexes, with an average of at least three consultations needed to achieve improvement.ConclusionsOur study suggests that psychological attention of survivors within the first 72 h should be a priority. MHPSS programmes addressing CRSV should be inclusive to all patients, and gender-neutral approaches to ensure access, safety, confidentiality, and non-discrimination for all survivors should be developed.

Sleep Awareness of Japanese Outpatients: A Survey at a Psychiatry Department of a University Hospital.

Background: Insomnia is common in patients with psychiatric disorders. However, patients' awareness of sleep has seldom been examined in detail. In this study, we investigated sleep awareness in outpatients at the psychiatry department of a university hospital. Methods: The participants (n = 241) were recruited at the psychiatry department of Ehime University Hospital between 11 October and 5 November 2021. The following questionnaires were used: Clinical Global Impression Scale of Severity (CGI-S), Global Assessment of Functioning (GAF), General Health Questionnaire (GHQ-30), Athens Insomnia Scale (AIS), and Epworth Sleepiness Scale (ESS). Psychiatric disorders were diagnosed by certified psychiatrists using the International Statistical Classification of Diseases and Related Health Problems 10. Participants with an AIS score of ≥6 were allocated to the insomnia group for statistical analysis. A logistic regression analysis was conducted to identify which items of sleep hygiene the patients with insomnia practiced using the Sleep Guidelines for Health Promotion. Results: Of 241 participants, 133 (55.2%) were allocated to the insomnia group. The mean scores for the CGI were significantly higher and the GAF scores were significantly lower in the insomnia group than in the healthy sleep group (p < 0.01). Of the 12 sleep guidelines proposed by the Japanese Government, "Do not go to bed until you are sleepful, do not delay getting up", was the item that maximally influenced insomnia. Conclusions: The insomnia group had worse scores on various medical assessment scales compared to the healthy sleep group. Based on a survey of outpatients at the psychiatry department of the university hospital, appropriate stimulus control techniques may help clinicians to treat outpatients with insomnia.

Help-seeking from traditional healers in patients with severe mental illness and its relationship with internalized stigma.

Help-seeking from traditional healers (TH) is common in patients with severe mental illness. However, the differences between patients with schizophrenia and bipolar disorder are not well-known. Although internalized stigma is also common in patients with severe mental illness, its impact on help-seeking from TH is not studied. To investigate help-seeking from TH and the relationship between help-seeking from TH and internalized stigma in patients with schizophrenia and bipolar disorder. In this cross-sectional study, we collected information about help-seeking from TH and clinical characteristics by using a semi-structured interview form from 310 patients with schizophrenia and bipolar disorder in two sites with different socio-cultural backgrounds. We measured internalized stigma by using The Internalized Stigma of Mental Illness (ISMI) scale. We found that 47% of the patients visited TH in any phase of their illness, and 46% of them sought help from TH before their first contact with a psychiatrist. Those who grew up in rural areas, were less educated, who attempted suicide before, with resistance to treatment, and with a family member who also admitted to TH were more frequent among the help-seekers from TH. This group also had more hospitalizations and higher Clinical Global Impression scores. Internalized stigma was found to be higher in the schizophrenia group, and it was related to help-seeking from TH and delay in admission to psychiatric facilities. Our findings suggest that help-seeking from TH is common both in patients with schizophrenia and bipolar disorder, and it has socio-cultural, illness-related, and stigma-related predictors.

Association of Cannabis Use Reduction With Improved Functional Outcomes: An Exploratory Aggregated Analysis From Seven Cannabis Use Disorder Treatment Trials to Extract Data-Driven Cannabis Reduction Metrics.

This exploratory analysis sought to determine whether decreases in cannabis use are associated with improvements in cannabis-related problems and functional outcomes, and if so, what percentage decrease is associated with improvement. Data were aggregated from seven cannabis use disorder treatment trials conducted in the United States (N=920; ages 13 years and older; mean age, 25 years; 30% female, 7% Black, 11% Hispanic/Latinx). Outcome measures included the patient-reported Marijuana Problems Scale (MPS), Health-Related Quality of Life scale (HRQOL), and Pittsburgh Sleep Quality Index and the clinician-rated Clinical Global Impressions (CGI) severity and improvement scales (CGI-S and CGI-I). Generalized estimating equations tested the association between changes in 4-week cannabis use and improvements in functional outcomes. Classification and regression tree (CART) models were developed to determine what reductions in cannabis use could be used as classifiers of improvement. Decreases in the amount and frequency of cannabis use were significantly associated with improvements in MPS severity and total scores as well as improvements on the CGI-I and in sleep quality, but not improvements on the HRQOL. CART models performed best for CGI-I scores (72%-75% correct classification), while other outcome measures did not perform as well (40%-62% correct classification). CART models showed improvements on the CGI at 74% reduction in use amounts and 47% reduction in use days. Reductions in cannabis use (∼50% reduction in use days and ∼75% reduction in use amounts) were associated with clinician-assessed improvement, which suggests that cannabis use reduction may yield benefit among individuals with cannabis use disorder. These exploratory results extract a data-driven metric to inform future studies, clinicians, patients, and policy recommendations.

Efficacy of Cariprazine in the Psychosis Spectrum: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials in Schizophrenia and Bipolar Disorder.

Psychosis represents one of the most challenging clinical presentations in psychiatry. Schizophrenia and bipolar disorder may both present psychotic features, and cariprazine may offer improvement in the treatment and care of these conditions. Therefore, the objective of the current work was to synthesise results of efficacy for cariprazine in these disorders. In total, five electronic databases were searched for randomized controlled trials enrolling patients across the psychosis spectrum, using the search term 'Cariprazine' (PubMed, Embase, clinicaltrials.gov, EUDRACT, Cochrane-last search January 2024). No filter or limits were employed. Effect sizes were extracted, by the mean difference in psychometric variables before and after the intervention (Clinical Global Impression Scale, Positive and Negative Symptom Scale, Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, Hamilton Anxiety Rating Scale). In total, 12 studies enrolling either patients with schizophrenia or bipolar disorder were included (total n = 6477; n = 4814 patients treated with cariprazine, n = 1663 controls treated with placebo). Cariprazine was effective in reducing global clinical severity, and higher improvements were observed at increasing dosages (- 0.25 at ≤ 1.5 mg/day, - 0.45 at ≥ 3 mg/day). Cariprazine also effectively reduced psychotic total scores: - 6.74, [95% confidence interval (CI) - 8.31; - 5.17], depression: - 1.78, [95% CI - 2.54; - 1.02], mania: - 5.72, [95% CI - 6.95; - 4.49], and anxiety symptoms: - 1.24, [95% CI - 1.92; - 0.56]. Cariprazine was observed as efficacious across retrieved studies, offering a potential for tailored treatments across the psychosis spectrum. https://osf.io/pmyhq .

Pitolisant 40 mg for excessive daytime sleepiness in obstructive sleep apnea patients treated or not by CPAP: Randomised phase 3 study.

Obstructive sleep apnea (OSA) syndrome commonly leads to excessive daytime sleepiness (EDS). Pitolisant, a selective histamine-3 receptor antagonist, is efficacious at doses up to 20 mg once daily in OSA treated or not with continuous positive airway pressure (CPAP). We assessed the efficacy and safety of pitolisant at doses up to 40 mg once daily in patients with moderate to severe OSA treated or not with CPAP therapy. In this phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trial, patients with OSA were assigned 2:1 to receive pitolisant (according to an individual up-titration scheme, 10, 20 or 40 mg once daily) or placebo for 12 weeks. The primary endpoint was a change in the Epworth Sleepiness Scale (ESS) score from baseline to week 12. Secondary endpoints included a change in reaction time using the Oxford Sleep Resistance test (OSleR), Clinical Global Impression of Change (CGI-C), and Patient's Global Opinion of the Effect (PGOE) of study treatment. Overall, 361 patients (mean age 52.4 years, 77.3% male; mean apnea-hypopnea index [AHI] 27.0 events/h) were randomised to receive pitolisant (n = 242; 50% received CPAP) or placebo (n = 119; 48.7% CPAP). After the dose-adjustment phase (week 3), 88.8% of patients received pitolisant 40 mg. Compared with placebo, pitolisant produced a significant reduction in the ESS score at week 12 (least square mean difference -2.6 (95% CI: -3.4; -1.8; p < 0.001)) irrespective of CPAP use; and improved the reaction time on OSleR, CGI-C, and PGOE at week 12. Pitolisant was well tolerated; no new safety signals were identified. In conclusion, pitolisant up to 40 mg once daily was an effective treatment for EDS in patients with moderate to severe OSA irrespective of CPAP use.

7519 Withdrawal of DCCR (Diazoxide Choline) Extended-Release Tablets Worsens Hyperphagia and Increases Weight and BMI in a 16-week Double-blind, Placebo-controlled, Randomized Withdrawal Period in Patients with Prader Willi Syndrome

Abstract Disclosure: E.F. Gevers: Advisory Board Member; Self; Pfizer, Inc., Soleno. Research Investigator; Self; Soleno Therapeutics, Inc.. Speaker; Self; Pfizer, Inc., Novo Nordisk, Soleno Therapeutics, Inc. J.L. Miller: Research Investigator; Self; Soleno Therapeutics, Inc. N.A. Bridges: Research Investigator; Self; Soleno Therapeutics, Inc. E.I. Felner: Research Investigator; Self; Soleno Therapeutics, Inc. P. Salehi: Research Investigator; Self; Soleno Therapeutics, Inc. D. Stevenson: Research Investigator; Self; Soleno Therapeutics, Inc. J. Yanovski: Research Investigator; Self; Soleno Therapeutics, Inc. L. Bird: Research Investigator; Self; Soleno Therapeutics, Inc. V. Kimonis: Research Investigator; Self; Soleno Therapeutics, Inc. A.H. Shoemaker: Research Investigator; Self; Soleno Therapeutics, Inc. K.S. Obrynba: Research Investigator; Self; Soleno Therapeutics, Inc. M. Lah: Research Investigator; Self; Soleno Therapeutics, Inc. E. Littlejohn: Research Investigator; Self; Soleno Therapeutics, Inc. N. Cowen: Employee; Self; Soleno Therapeutics, Inc.. Stock Owner; Self; Soleno Therapeutics, Inc. N. Cowen: Employee; Self; Soleno Therapeutics, Inc.. Stock Owner; Self; Soleno Therapeutics, Inc. K. Yen: Employee; Self; Soleno Therapeutics, Inc.. Stock Owner; Self; Soleno Therapeutics, Inc. S. Ballal: Employee; Self; Soleno Therapeutics, Inc.. Stock Owner; Self; Soleno Therapeutics, Inc. P. Hirano: Employee; Self; Soleno Therapeutics, Inc.. Stock Owner; Self; Soleno Therapeutics, Inc. M. Huang: Employee; Self; Soleno Therapeutics, Inc.. Stock Owner; Self; Soleno Therapeutics, Inc. A. Bhatnagar: Employee; Self; Soleno Therapeutics, Inc.. Stock Owner; Self; Soleno Therapeutics, Inc.. Background: Prader-Willi syndrome (PWS) is a rare genetic neurobehavioral-metabolic disease characterized by hyperphagia, endocrinopathies, weight gain, hypotonia, behavioral problems, and an increased risk of mortality and reduced life expectancy. There are currently no approved treatments for hyperphagia in PWS. Diazoxide choline extended-release (DCCR) is a novel, once daily oral therapy being developed for the treatment of PWS. Herein, we present results of the Randomized Withdrawal Period (RWP) of Clinical Study C602, a long-term treatment study of DCCR in people with PWS. Objectives and Methods: This was a 16-week multi-center, double-blind, placebo-controlled RWP that enrolled participants ≥4 years of age who were actively enrolled in the open label period of Clinical Study C602 and had received 2-4 years of DCCR treatment (target dose: ≥3.3 mg/kg; optimal range: 4.2-5.8 mg/kg) at the time of RWP entry. RWP-eligible participants were randomized 1:1 to continue DCCR or withdraw from DCCR and receive Placebo. The primary objective was to evaluate the effect of continued DCCR administration versus Placebo on hyperphagia based on the change in Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score from Baseline to Week 16. Additional endpoints included: the Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) at Week 16; changes in body composition (weight, BMI, and BMI z-scores) at Week 16; and the safety profile of DCCR. Results: DCCR (n=38) and Placebo (n=39) groups were generally balanced for demographic and baseline characteristics. At Week 16, a statistically significant difference in change from baseline in HQ-CT Total Score was observed between DCCR and Placebo groups with HQ-CT Total Scores increasing markedly (indicating worsening hyperphagia) in the Placebo group compared to the DCCR group (LSMean difference [SE] -5.0 [1.57], p=0.002). CGI-S and CGI-I showed trends towards worsening in the Placebo group versus the DCCR group (p=0.079 and 0.092, respectively). The Placebo group also experienced significantly greater increases in weight, BMI, and BMI z-scores (p=0.035, 0.034, and 0.023, respectively) than the DCCR group. DCCR was well-tolerated, with no new or unexpected safety signals, and no serious adverse events or discontinuations due to adverse events in the DCCR group. Conclusions: In this 16-week RWP, the Placebo group experienced significant worsening in hyperphagia and increases in body weight, BMI, and BMI z-scores, along with worsening trends for the CGI-S and CGI-I, compared to the DCCR group. DCCR was well tolerated, with a safety profile that was consistent with prior experience. These data suggest treatment with DCCR may lead to clinical benefits in people with PWS by reducing hyperphagia and improving body composition. Presentation: 6/2/2024

The Effectiveness and Safety Analysis of Duloxetine in Treating Comorbid Depression in Parkinson's Disease: A Retrospective Study.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms, including depression, which significantly impacts the quality of life of affected individuals. This study aims to investigate the real-world effectiveness and safety of duloxetine in treating comorbid depression in patients with Parkinson's disease and to compare its outcomes with traditional treatment approaches. This study included adult patients diagnosed with Parkinson's disease combined with depression from December 2020 to December 2023. Based on the use of duloxetine, the cohort was divided into a traditional treatment group and a duloxetine group (traditional treatment combined with duloxetine). Patients with incomplete medical records, concurrent antidepressant therapy, or major psychiatric or neurological disorders were excluded. Retrospective data, including demographic information, treatment adherence, and various assessment scores, were collected from medical records by trained research staff. In total, 106 patients were analyzed, with 50 patients receiving traditional treatment and 56 patients receiving duloxetine. The duloxetine group exhibited significantly lower scores than the traditional treatment group in the Unified PD Rating Scale (p = 0.015), Hamilton Depression Rating Scale (p = 0.013), Beck Depression Inventory (p = 0.031), Parkinson's disease Questionnaire-39 (p = 0.006), and Clinical Global Impression-Improvement (p < 0.001) scores. In motor function assessment, the duloxetine group demonstrated improvements in kinetic tremor scores (p = 0.017), gait speed (p < 0.001), Timed Up and Go Test performance (p < 0.001), dyskinesia severity (p = 0.017), and rigidity (p = 0.019) compared to the traditional treatment group. Additionally, the duloxetine group exhibited better cognitive function across various assessments, including the Symbol Digit Modalities Test (p = 0.024), Stroop Color-Word Test (p = 0.048), and Montreal Cognitive Assessment (p = 0.024). Duloxetine is associated with superior efficacy in improving motor and non-motor symptoms, overall clinical status, and cognitive function. These findings support the potential utility of duloxetine as a comprehensive treatment option for comorbid depression in Parkinson's disease.

Exploring correlations between Conners' Continuous Performance Test and subjective measures of attention deficit hyperactivity disorder symptoms in a paediatric clinical sample.

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental condition characterised by inattention and/or hyperactivity-impulsivity. The ADHD symptoms are often evaluated and quantified using various assessment tools, such as the Conners' Continuous Performance Test II (CCPT-II), ADHD Rating Scale (ADHD-RS), Child Behaviour Checklist (CBCL), Clinical Global Assessment Scale (CGAS) and Clinical Global Impression Scale (CGIS). This study sought to compare CCPT-II with parent- and clinician-rated rating scales (ADHD-RS, CBCL, CGAS and CGIS) in measuring the core ADHD symptoms within the paediatric ADHD population. The data, gathered from a large-scale randomised controlled trial involving 172 children aged 6-12 years with ADHD, was pooled, and a Pearson correlation analysis was conducted. No significant correlations were observed between CCPT-II and ADHD-RS, as well as the various subscales of CBCL, CGAS and CGIS. While CCPT-II may offer insights into ADHD symptomatology, its relationship with parent- and clinician-rated rating scales such as ADHD-RS, CBCL, CGAS and CGIS appears limited. Further research is warranted to elucidate the nuances of these assessment tools and their roles in evaluating ADHD.

Development and Validation of SCACOMS, a Composite Scale for Assessing Disease Progression and Treatment Effects in Spinocerebellar Ataxia.

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.

Single-blinded, randomised, parallel-group, controlled trial comparing the efficacy and cost-effectiveness of therapist- and self-guided internet-delivered behavioural activation versus treatment as usual for adolescents with mild to moderate depression: study protocol

IntroductionThe number of adolescents seeking professional help for depression is increasing and, despite advances in treatment, large unmet treatment needs remain. In the current protocol, we describe the design and...

Impact of air pollution exposure on the severity of major depressive disorder: Results from the DeprAir study.

Major depressive disorder (MDD) is one of the most prevalent medical conditions worldwide. Different factors were found to play a role in its etiology, including environmental ones (e.g., air pollution). The aim of this study was to evaluate the association between air pollution exposure and MDD severity. Four hundred sixteen MDD subjects were recruited. Severity of MDD and functioning were evaluated through five rating scales: Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Sheehan Disability Scale (SDS). Daily mean estimates of particulate matter with diameter ≤10 (PM10) and 2.5 μm (PM2.5), nitrogen dioxide (NO2), and apparent temperature (AT) were estimated based on subjects' residential addresses. Daily estimates of the 2 weeks preceding recruitment were averaged to obtain cumulative exposure. Multivariate linear and ordinal regression models were applied to assess the associations between air pollutants and MDD severity, overall and stratifying by hypersusceptibility and AT. Two-thirds of subjects were women and one-third had a family history of depression. Most women had depression with symptoms of anxiety, while men had predominantly melancholic depression. NO2 exposure was associated with worsening of MDD severity (HAMD: β = 1.94, 95% confidence interval [CI], [0.41-3.47]; GAF: β = -1.93, 95% CI [-3.89 to 0.02]), especially when temperatures were low or among hypersusceptible subjects. PM exposure showed an association with MDD severity only in these subgroups. Exposure to air pollution worsens MDD severity, with hypersusceptibility and lower temperatures being exacerbating factors.

The minimal important difference in obsessive-compulsive disorder: An analysis of double-blind SSRI trials in adults.

The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID). We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as "minimal improvement"). We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4-5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms. By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.

Measuring clinically relevant change in apathy symptoms in ADMET and ADMET 2.

Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales. Retrospective anchor- and distribution-based analyses of change in apathy symptom scores. Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively. Two hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer's disease. The Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory - Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics. Among the MCID was a decrease of four points (95% CI: -4.0 to -4.8) on the NPI-A, 0.56 points (95% CI: -0.47 to -0.65) on the DAIR, and three points on the AES-I (95% CI: -0.9 to -5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID. MCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales.