Clinical Global Impression Research Articles

Are S100B and VILIP-1 Involved in a Common Mechanism of Neuroinflammation in Major Depressive Disorder?

This study aimed to evaluate the role of neuroinflammation in neuronal and glial cells in the pathophysiology of Major Depressive Disorder (MDD) through different biomarkers.S100-B and VILIP-1 levels of patients diagnosed with MDD were evaluated before and after antidepressant treatment. A total of 65 patients diagnosed with MDD and 69 healthy controls were included. Serum levels of S100B and VILIP-1 were measured at the time of diagnosis and after eight weeks antidepressant treatment and compared with healthy controls. Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression Scale (CGI) were applied to assess the severity of depression. In our study, although serum S100B levels were higher in patients before treatment compared to healthy controls, this difference was not statistically significant. Regarding VILIP-1 levels, there was no statistically significant difference between patients and healthy controls. A positive and statistically significant correlation was found between S100B and VILIP-1 levels in MDD group before the treatment. At the eighth week of treatment, a statistically significant positive correlation was also found between S100B and VILIP-1 levels. Our research is the first study to evaluate MDD through two separate biomarkers specific to glial and neuronal cells.The fact that S100B and VILIP-1 levels showed significant correlations in patients diagnosed with MDD both before and after treatment suggests that they may play a shared role in the pathophysiology of the disorder. The correlation between S100B and VILIP-1 may serve as a guide in understanding the pathophysiology of the disorder and in identifying new drug development targets.

High‐dose propranolol decreases aggression in young people with autism

As many as two‐thirds of individuals with autism spectrum disorder (ASD) experience challenging symptoms of irritability, including aggression and self‐injury. The antipsychotics risperidone and aripiprazole are approved for the treatment of irritability associated with ASD; however, their adverse effects can compromise long‐term use in many patients. Based on longstanding case reports showing promising results for the beta‐blocker propranolol in reducing challenging symptoms in ASD, investigators conducted a randomized, double‐blind, placebo‐controlled crossover trial to evaluate the feasibility of high‐dose propranolol for treating aggression in patients with ASD. The investigators recruited youths and young adults aged 12 to 30 with ASD and a history of severe and chronic aggression, self‐injury, and disruptive behaviors that interfere with daily activities. Participants were required to have had an inadequate trial of at least two psychotropic medications, including at least one antipsychotic. Dosing of propranolol started at 10 mg three times a day and could be increased until adequate therapeutic response was achieved, to a maximum dose of 200 mg three times a day. Most study visits were conducted via telehealth in order to minimize patient schedule disruption. The primary outcomes were change in scores on the Clinical Global Impression‐Improvement (CGI‐I) and Aberrant Behavior Checklist‐Community (ABC‐C) scales from baseline to study endpoint. Six participants with a mean age of 16 years were enrolled. The investigators found that propranolol resulted in mean reductions of 50% in scores on the CGI‐I and 37% in scores on the ABC‐C. Effect sizes were large for both measures: –0.74 for the CGI‐I and –0.64 for the ABC‐C. “As this was a feasibility pilot study, we had a small sample that limits the generalization of our results to a wider population, and therefore, until a placebo‐controlled, double‐blind study with an adequate number of subjects is conducted, the clinical value of this report is limited,” the study's authors wrote. [London, E., et al. (2024). J Clin Psychopharmacol. https://doi.org/10.1097/JCP.0000000000001895]

Therapeutic drug monitoring in children and adolescents with schizophrenia-spectrum, affective, behavioural, tic and other psychiatric disorders treated with aripiprazole: results of the TDM-VIGIL pharmacovigilance study.

Aripiprazole is approved for various severe mental disorders in adults and adolescents. However, off-label prescribing is common, especially in children and adolescents (youth) in whom aripiprazole therapeutic serum level reference ranges are lacking for any disorders. The aim of the study was to evaluate the relationship between aripiprazole dose and serum concentrations and provide further knowledge on the use of aripiprazole in order to improve drug safety and effectiveness in the treatment of minors. The clinical course of youth treated with aripiprazole in the multicentre pharmacovigilance study TDM-VIGIL was systematically followed and serum concentrations measured. Sex, age, weight and comedications were analysed to identify possible effect modifiers. A preliminary therapeutic reference range was estimated for youth with schizophrenia-spectrum disorders, affective disorders and behavioural/emotional/tic disorders coded as treatment responders based on a Clinical-Global Impressions-Improvement (CGI-I) score of much or very much improved. In 93 youth (mean age = 15.2 ± 2.6, range = 7.4-18.2 years, females = 53%, CGI-Severity = 4.4 ± 1.1, responders = 64%), a positive, moderate correlation between the weight-normalized daily dose (WNDD) and aripiprazole serum concentration (=0.791, p < 0.0001) was found. The WNDD and co-medications that interact with CYP2D6 and CYP3A4 affected aripiprazole serum levels, explaining 64% of the variance. In patients within the preliminary therapeutic ranges determined by interquartile ranges (IQRs), slightly better outcomes and fewer adverse drug reactions were found versus patients within preliminary therapeutic ranges determined by the mean ± SD. The preliminary reference range for paediatric patients with schizophrenia-spectrum disorders calculated by the IQR showed an identical lower threshold (100-230 ng/ml) compared to adult schizophrenia-spectrum disorders patients (100-350 ng/ml). The preliminary therapeutic ranges for patients with affective disorders was: 60-160 ng/ml and for patients with behavioural/tic disorders 60-140 ng/ml. The therapeutic reference ranges for aripiprazole in youth estimated via the 25th and 75th IQRs may result in more clinically relevant therapeutic windows. Further studies need to confirm these results, especially in patients with affective and behavioural/tic disorder diagnoses.

Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials

In the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials, xanomeline and trospium chloride (formerly known as KarXT) significantly improved symptoms of schizophrenia and was generally well tolerated. We pooled data from the EMERGENT trials to further characterize the efficacy of xanomeline/trospium and provide sufficient statistical power to analyze responses in participant subgroups. In pooled analyses, xanomeline/trospium significantly improved Positive and Negative Syndrome Scale (PANSS) total score at week 5 versus placebo (least squares mean difference, –9.9; 95% confidence interval, –12.4, –7.3; p < 0.0001; Cohen’s d effect size, 0.65). PANSS subscale and Clinical Global Impression–Severity scores also improved significantly with xanomeline/trospium versus placebo. Subgroup analyses consistently favored xanomeline/trospium over placebo regardless of differences in participant age, sex, race, body mass index, and baseline PANSS total score. These results add to existing evidence demonstrating robust and reliable improvements in symptoms with xanomeline/trospium across a broad spectrum of people with schizophrenia.

Efficacy and acceptability of lurasidone for bipolar depression: a systematic review and dose–response meta-analysis

Question The optimal dose of lurasidone for bipolar depression is unclear. This study examined its dose–response relationship for efficacy, acceptability, and metabolic/endocrine profiles. Study selection and analysis Five databases and grey literature published until 1 August 2024, were systematically reviewed. The outcomes included efficacy (changes in depression, anxiety, clinical global impression, disability and quality of life), acceptability (dropout, manic switch, suicidality and side effects) and metabolic/endocrine profiles (changes in body weight, glucose, lipid and prolactin levels). Effect sizes were calculated using a one-step dose–response meta-analysis, expressed as standardised mean differences (SMDs), risk ratios (RRs) and mean differences (MDs) with 95% CIs. Findings Five randomised clinical trials (2032 patients, mean treatment duration 6 weeks) indicated that the optimal therapeutic dose of lurasidone (40–60 mg) improved depression (50 mg: SMD −0.60 (95% CI −0.30, –0.89)), anxiety (50 mg: −0.32 (95% CI −0.21, –0.42)), clinical global impression (50 mg: −0.67 (95% CI −0.30, –1.03)) and disability (50 mg: −0.38 (95% CI −0.08, –0.69)). Side effects increased with higher doses (50 mg: RR 1.15 (95% CI 1.05, 1.25); 100 mg: 1.18 (95% CI 1.02, 1.36)), but dropout, manic switch and suicidality did not show a dose–effect relationship. Weight increased at doses&lt;60 mg (40 mg: MD 0.38 (95% CI 0.16, 0.60) kg), while blood glucose levels rose at doses&gt;70 mg (100 mg: 3.16 (95% CI 0.76, 5.57) mg/dL). Prolactin levels increased in both males (50 mg: 3.21 (95% CI 1.59, 4.84) ng/mL; 100 mg: 5.61 (95% CI 2.42, 8.81)) and females (50 mg: 6.64 (95% CI 3.50, 9.78); 100 mg: 5.33 (95% CI 0.67, 10.00)). Conclusions A daily dose of 40–60 mg of lurasidone is a reasonable choice for bipolar depression treatment. Trial registration number INPLASY202430069.

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.

Defining treatment response in gambling disorder

BackgroundGambling disorder is a common mental health condition, and a growing cause of concern globally. Despite the availability of well-validated self-report and clinical instruments to measure symptom severity, there has been no study to establish optimal thresholds for determining treatment response based on these measures. MethodsData from 553 participants (aged 18-65 years) who had participated in previous pharmacological and psychotherapeutic clinical trials for gambling disorder were aggregated. Studies were included that collected Clinical Global Impression Improvement (CGI-I) at end-of-study (reference standard), as well as baseline and end-of-study symptom severity using the Gambling Symptom Assessment Scale (GSAS) and/or the Yale-Brown Obsessive-Compulsive Scale Modified for Pathological Gambling (PG-YBOCS). Receiver Operator Characteristic (ROC) analyses were conducted to identify optimal thresholds for determining treatment response. ResultsGreater than 50% improvement in PG-YBOCS and 35% improvement in GSAS were the optimal thresholds for defining treatment response. For the PG-YBOCS, the cutoff had acceptable sensitivity and specificity (85.0%, 83.0%) and area under the curve of 0.904. For the GSAS, the cutoff had acceptable sensitivity and specificity (81.2%, 73.4%), and area under the curve of 0.859. ConclusionsThis study provides useful thresholds on two widely used, valid outcome measures for gambling disorder, in terms of determining treatment response or absence thereof. These thresholds may be useful for clinical practice at the level of individual patients, but also for future clinical trials.

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.

A Prospective Nonrandomized Comparison of Wet Needling Versus Prolotherapy in Myofascial Pain.

The objective was to analyze the difference between prolotherapy and wet needling (WN) for myofascial trigger points (MTrPs) for the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Clinical Global Impression (CGI), and MTrPcount. Patients with myofascial pain for 1.5 years were included based on convenience sampling after a pilot study for sample size calculation. The WNgroup received an injection of bupivacaine 0.5% into the trigger points with WN. Participants in thedextrose prolotherapy (DPT) group received dextrose (25%) plus bupivacaine (0.5%) (1:1) into the same. Outcome measures were recorded at baseline immediatepost-injection, one month, three months, and 24 months. Among the 200 participants, there was no significant difference in the baseline VAS score between the two groups nor for immediate post-VAS. At three months of follow-up, the mean VAS was 6.34 ± 1.44 in the WN group and 1.99 ± 0.89 in the DPT group (p= 0.03). The mean VAS score significantly changed in both groups but favored the DPT group (p= 0.001)and again at 24 months (p= 0.001). The ODI showed a similar trend favoring the DPT group at all intervals. On correlating the VAS score with the ODI score, a statistically significant correlation was seen at one month, favoring the WN group, and at the end of the third month, favoring the DPT group. Both modalities are effective at one month. At three and 24 months, the DPT was significantly more effective in improving the VAS and ODI.

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