Clinical Global Impressions-Improvement Scale Research Articles

Effects of Neurodevelopmental Disorders on the Clinical Presentations and Therapeutic Outcomes of Children and Adolescents with Severe Mood Disorders: A Multicenter Observational Study.

Individuals with neurodevelopmental disorders (NDDs) are more susceptible to developing severe or resistant mood disorders. However, they often face challenges in accessing specific treatments. To understand the barriers to treatment in this group, we conducted a secondary analysis of a multicenter observational study on 305 adolescents referred to specialized care (mean age 14.38 ± 0.13 years, 57% girls, 9% bipolar disorder, 91% depressive disorders). NDDs were categorized based on the number of co-occurring NDDs for each subject (none: 67%, one: 18%, two: 7%, three: 5%, four and more: 2%). We explored the predictive value of the number of NDDs on various clinical and therapeutic factors. The analysis revealed significant associations between the number of NDDs and the duration of mood symptoms, persistent irritability, associated disruptive behavioral disorders, lower scores on the Children's Global Assessment Scale (CGAS) at baseline, and polypharmacy. The number of NDDs did not correlate with the use of antidepressants, the Clinical Global Impression-Improvement scale (CGI-I) at discharge, or changes in the CGAS score during the stay. The challenges in distinguishing mood disorders from chronic emotional and behavioral difficulties may contribute to the difficulties in accessing specific care for mood disorders. These results suggest that treatments for mood disorders demonstrate comparable effectiveness when provided regardless of the associations with NDDs.

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).

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.

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...

High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study.

Despite the use of behavioral interventions and psychotropic medications, many individuals with autism spectrum disorder (ASD) who engage in severe aggression remain refractory to conventional treatment. Propranolol, a beta-blocker, has accumulated much anecdotal evidence as a promising option. However, well-designed studies are rare, and the apprehension about cardiovascular side effects from large doses continues to exist. The aims of this study were (1) to demonstrate the feasibility of treating aggression with high-dose propranolol using telehealth study visits and (2) to document cardiac safety. This study utilized a randomized, double-blind, placebo-controlled, crossover design. Dosing was titrated up in a flexible but stepwise fashion until therapeutic response was obtained or up to 200 mg tid. Following washout, those who were assigned propranolol were crossed over to placebo and vice versa. Six participants between the ages 12-19 participated. The primary outcome measures were the final Clinical Global Impression Improvement Scale (CGI-I) and the Aberrant Behavior Checklist-Community Irritability (ABC-C/I) scores at 200 mg tid. The CGI-I indicated a 50% reduction in symptoms in the propranolol phase, while the ABC-I indicated a 37% reduction in comparison to placebo. The effect sizes ( r ) for the CGI-I and the ABC-C/I were large, -0.74 and -0.64, respectively. The average blood pressure was 122/68 during the placebo phase and 109/72 during the propranolol phase. All Holter monitor exams were unremarkable. These results suggest that propranolol is an effective option in decreasing aggression in individuals with ASD. As this was a small study, a larger clinical trial is needed.

Defining a clinically meaningful within-patient change threshold for the Cohen-Mansfield Agitation Inventory in Alzheimer's dementia.

The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This post hoc analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer's disease. Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease (ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584). Change in CMAI Total score (range 29-203; higher scores indicate higher frequency of agitation behaviors) from baseline to Week 12 was the primary endpoint in each trial. MWPC thresholds were estimated from anchor-based mean change analyses and receiver operating characteristic (ROC) curves. The Clinical Global Impression-Severity of illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales, both as related to agitation, were used as anchors. Empirical cumulative distribution functions (eCDFs) and probability density functions (PDFs) were plotted as supportive evidence. Distribution-based methods were also employed. Data from 898 patients were analyzed (mean age, 73.7 years; mean baseline CMAI Total score, 73.8). The mean CMAI Total score change corresponding to a difference of small improvement vs. stable (CGI-S one-point decrease vs. no change), or minimally improved vs. no change (CGI-I rating of 3 vs. 4), ranged from -10.6 to -13.5 points. The mean CMAI Total score change corresponding to a difference of moderate improvement vs. stable (CGI-S two-point decrease vs. no change), or much improved vs. no change (CGI-I rating of 2 vs. 4), ranged from -20.2 to -25.7 points. ROC curve analyses generally produced smaller estimates of meaningful change. eCDFs and PDFs showed good distribution and separation of CMAI Total score change between CGI-S/CGI-I categories. In distribution-based analyses, the minimal detectable change for CMAI Total score (10.5-11.8 points) was generally lower than anchor-suggested thresholds. Triangulation of evidence from anchor- and distribution-based analyses supports an MWPC threshold for CMAI Total score of -20 points, with a threshold range of -15 to -25 points, in patients with agitation associated with dementia due to Alzheimer's disease.

Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials

BackgroundRett syndrome (RTT) is a rare, life-threatening, genetic neurodevelopmental disorder. Treatment in RTT encounters many challenges. Trofinetide, a modified amino-terminal tripeptide of insulin-like growth factor 1, has demonstrated clinically promising results in RTT. In this study, trofinetide efficacy and safety in RTT are systematically reviewed and meta-analyzed.MethodsA systematic search of five electronic databases was conducted until January 2024. Review Manager 5.4 software was used for the analysis. The analysis was based on a weighted mean difference and standard error with a confidence interval (CI) of 95%, and a statistically significant P-value was considered if it was < 0.05. The study was registered on PROSPERO with registration number CRD42024499849. Quality of evidence was assessed using GRADE.ResultsThree randomized controlled trials (RCTs) with 276 patients were included in the analysis. Trofinetide improved both caregiver outcomes and clinical scales by improving the Rett Syndrome Behavior Questionnaire (RSBQ) (mean difference (MD): − 3.46 points, 95% CI: − 5.63 to − 1.27, P = 0.0002) and Clinical Global Impression Scale–Improvement (CGI-I) (MD: − 0.35, 95% CI: − 0.51 to − 0.18, P < 0.0001), respectively. However, trofinetide neither improved the Caregiver Top 3 Concerns Visual Analog Scale nor the Rett Motor Behavioral Assessment. Regarding safety, trofinetide was significantly associated with vomiting compared to placebo (odds ratio (OR): 3.17, 95% CI: 1.57 to 6.43, P = 0.001). After solving heterogeneity, results showed a statistically significant incidence of diarrhea in the trofinetide (200 mg) group compared to placebo (OR: 18.51, 95% CI: 9.30 to 36.84, P ≤ 0.00001).ConclusionsTrofinetide demonstrated statistically significant improvements in CGI-I and RSBQ in pediatrics and adult patients with Rett. Side effects are limited to vomiting and diarrhea. Although diarrhea yielded an insignificant result in our analysis, it emerged as a cause for treatment discontinuation in the participating trials, and a statistically significant risk for diarrhea emerged when excluding the study using a lower dose of the drug, hence causing heterogeneity, in the meta-analysis. Given the diverse genetic landscape of RTT, future RCTs investigating correlations between RTT genotype and phenotypic improvements by trofinetide will be beneficial. RCTs encompassing male patients with larger and longer cohorts are recommended.Graphical

Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder

BackgroundThe understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI).Methods67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[−]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance).ResultsMDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia.ConclusionIR appears to be linked to depressive symptoms characteristic of the “metabolic” MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI.

Integrated model of care for functional movement disorder: targeting brain, mind and body

Purpose To describe the therapy approaches and clinical outcomes of an integrated care model for patients with functional movement disorder (FMD). Materials and Methods A retrospective chart review was conducted for all treated individuals with a primary diagnosis of FMD between January 2020 and July 2022. Patients received time-limited integrated therapy (n = 21) (i.e., simultaneous therapy delivered by psychiatry, neurology and physiotherapy), physiotherapy (n = 18) or virtual physiotherapy alone (n = 9). Primary outcomes included the Simplified-Functional Movement Disorders Rating Scale (S-FMDRS) and Clinical Global Impression-Improvement scale (CGI-I) collected at baseline and post-intervention. Results Forty-eight patients completed treatment (42% male; mean age, 48.5 ± 16.6 years, median symptom duration 30 months). The most common presentations were gait disorder, tremor and mixed hyperkinetic FMD. Common comorbidities included pain and fatigue. Three-quarters of patients had a comorbid psychiatric diagnosis. There was a significant reduction in S-FMDRS score following therapy (71%, p < 0.0001) and 69% had “much” or “very much” improved on the CGI-I. There was no difference between therapy groups. Attendance rates were high for both in-person (94%) and virtual (97%) visits. Conclusions These findings support that a time-limited integrated model of care is feasible and effective in treating patients with FMD.

Early symptom improvement and other clinical predictors of response to repetitive transcranial magnetic stimulation for depression

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a rapidly emerging treatment for depression, but outcome prediction is still a challenge. This study aimed to identify predictors of response to rTMS among baseline clinical factors and early symptomatic improvements. MethodsThis cohort study comprised 136 patients with a unipolar or bipolar depressive episode referred for clinical intermittent theta-burst stimulation or right-sided 1 Hz rTMS at the Uppsala Brain Stimulation Unit. The co-primary outcomes used for logistic regression were response, defined as ≥50 % reduction of Montgomery and Åsberg Depression Rating Scale Self-assessment (MADRS-S) total score, and 1–2 points on the Clinical Global Impression Improvement (CGI-I) scale. Early improvement was defined as ≥20 % reduction in the MADRS-S total score, or ≥ 1 point reduction in each MADRS-S item, after two weeks of treatment. ResultsThe response rates were 21 % for MADRS-S and 45 % for CGI-I. A depressive episode >24 months had lower odds for MADRS-S response compared to ≤12 months. Early improvement of the MADRS-S total score predicted CGI-I response (95 % CI = 1.35–9.47, p = 0.011), Initiative6 predicted MADRS-S response (95 % CI = 1.08–9.05, p = 0.035), and Emotional involvement7 predicted CGI-I response (95 % CI = 1.03–8.66, p = 0.044). LimitationsNo adjustment for concurrent medication. ConclusionsA depressive episode ≤12 months and early improvement in overall depressive symptoms, as well as the individual items, Initiative6 and Emotional involvement7, predicted subsequent rTMS response in a naturalistic sample of depressed patients. This could facilitate the early identification of patients who will benefit from further rTMS sessions.

Safety and Efficacy of Paliperidone Palmitate in Pediatric Patients with Autism and Intellectual Disability.

This retrospective chart review examines the safety, tolerability and effectiveness of long acting injectable paliperidone palmitate (P-LAI) targeting irritability in twenty-six youth and transition-aged individuals with autism spectrum disorder (ASD) and/or intellectual disability (ID) over a 3-year window. Clinical response was evaluated via prospectively assigned Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales as well as number of hospital presentations. P-LAI was well tolerated with only 3 patients stopping P-LAI due to side effects. The average duration of P-LAI treatment was 21.1months. Difficulty with medication compliance was the most common reason for initiating P-LAI. There was a statistically significant improvement in CGI-I, CGI-S and hospital visits and no change in BMI noted. Given the potential difficulty of medication administration in this population, this evidence of safety, tolerability as well as preliminary data supporting effectiveness is an important addition to the literature regarding psychopharmacologic management of irritability in youth with ASD and ID.

Neurocognitive functioning in adults with trichotillomania: Predictors of treatment response and symptom severity in a randomized control trial

Trichotillomania (TTM) is associated with impairments in response inhibition and cognitive flexibility, but it is unclear how such impairments relate to treatment outcome. The present study examined pre-treatment response inhibition and cognitive flexibility as predictors of treatment outcome, change in these domains from pre-to post-treatment, and associations with TTM severity. Participants were drawn from a randomized controlled trial comparing acceptance-enhanced behavior therapy (AEBT) to psychoeducation and supportive therapy (PST) for TTM. Adults completed assessments at pre-treatment (n = 88) and following 12 weeks of treatment (n = 68). Response inhibition and cognitive flexibility were assessed using the Stop Signal Task and Object Alternation Task, respectively. Participants completed the MGH-Hairpulling Scale. Independent evaluators administered the NIMH-Trichotillomania Severity Scale and Clinical Global Impressions-Improvement Scale. Higher pre-treatment TTM severity was associated with poorer pre-treatment cognitive flexibility, but not response inhibition. Better pre-treatment response inhibition performance predicted positive treatment response and lower post-treatment TTM symptom severity, irrespective of treatment assignment. Cognitive flexibility did not predict treatment response. After controlling for age, neither neurocognitive variable changed during treatment. Response inhibition and cognitive flexibility appear uniquely related to hair pulling severity and treatment response in adults with TTM. Implications for treatment delivery and development are discussed.

Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome

Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. ClinicalTrials.gov Identifier: NCT03916055.

Long-Term Effectiveness of Off-Label Risperidone Treatment in Children and Adolescents: A Randomized, Placebo-Controlled Discontinuation Study.

Objectives: Risperidone is commonly prescribed off-label in children and adolescents to manage disruptive behavior. This study aimed to investigate continued benefits of risperidone after at least 1 year of treatment and effects of discontinuation on physical health. Methods: Thirty-five youths (aged 6-18 years, intelligence quotient [IQ] >70) who were treated with risperidone for at least 1 year in regular clinical practice receiving outpatient care were randomly assigned to double-blind continuation of risperidone during 16 weeks or continuation for 2 weeks, gradual dose lowering over 6 weeks, and placebo for 8 weeks. Primary outcome was the total Disruptive Behavior (D-total) score of the parent-reported Nisonger Child Behavior Rating Form-Typical IQ (NCBRF-TIQ). Secondary outcome measures were the clinician-rated Clinical Global Impressions-Improvement scale (CGI-I), the parent, child, and teacher-rated Strengths and Difficulties Questionnaire (SDQ), the parent-rated Retrospective Modified Overt Aggression Scale (R-MOAS), and several health parameters (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale [UKU-SERS], dyskinesia, akathisia, parkinsonism, body mass index (BMI), waist circumference, and laboratory outcomes). Mixed models for repeated measures were conducted for continuous outcomes and a chi-square test for the CGI-I. Results: Discontinuation of risperidone, as compared with continuation, was not associated with significant changes in parent-reported disruptive behaviors. However, discontinuation was related to significant deterioration in parent-rated verbal aggression, teacher-rated behavioral functioning, clinician-rated general functioning, and significant improvements in weight, BMI, waist circumference, and glucose, insulin, and prolactin levels. Although 56% of participants in the discontinuation group experienced relapse, causing premature withdrawal from the study, 44% was able to successfully discontinue risperidone. Conclusion: Discontinuation of risperidone was associated with deterioration on some, but not all behavioral measures according to this explorative study. Discontinuation was associated with important health gains. Despite long-term benefits of risperidone, attempts to withdraw risperidone should be undertaken in individual children. This is a crucial step in preventing harm and fostering health.

Digital Therapeutic (Mika) Targeting Distress in Patients With Cancer: Results From a Nationwide Waitlist Randomized Controlled Trial.

Distress is highly prevalent among patients with cancer, but supportive care needs often go unmet. Digital therapeutics hold the potential to overcome barriers in cancer care and improve health outcomes. This study conducted a randomized controlled trial to investigate the efficacy of Mika, an app-based digital therapeutic designed to reduce distress across the cancer trajectory. This nationwide waitlist randomized controlled trial in Germany enrolled patients with cancer across all tumor entities diagnosed within the last 5 years. Participants were randomized into the intervention (Mika plus usual care) and control (usual care alone) groups. The participants completed web-based assessments at baseline and at 2, 6, and 12 weeks. The primary outcome was the change in distress from baseline to week 12, as measured by the National Comprehensive Cancer Network Distress Thermometer. Secondary outcomes included depression, anxiety (Hospital Anxiety and Depression Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and quality of life (Clinical Global Impression-Improvement Scale). Intention-to-treat and per-protocol analyses were performed. Analyses of covariance were used to test for outcome changes over time between the groups, controlling for baseline. A total of 218 patients (intervention: n=99 and control: n=119) were included in the intention-to-treat analysis. Compared with the control group, the intervention group reported greater reductions in distress (P=.03; ηp²=0.02), depression (P<.001; ηp²=0.07), anxiety (P=.03; ηp²=0.02), and fatigue (P=.04; ηp²=0.02). Per-protocol analyses revealed more pronounced treatment effects, with the exception of fatigue. No group difference was found for quality of life. Mika effectively diminished distress in patients with cancer. As a digital therapeutic solution, Mika offers accessible, tailored psychosocial and self-management support to address the unmet needs in cancer care. German Clinical Trials Register (DRKS) DRKS00026038; https://drks.de/search/en/trial/DRKS00026038.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis

IntroductionExpert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. MethodsWe conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. ResultsIndividual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. ConclusionWhile the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Treatment-resistant obsessive-compulsive disorders

Obsessive-compulsive disorders (OCD) are mainly treated with disorder-specific cognitive behavioral therapy using exposure and response management and/or selective serotonin reuptake inhibitors; however, asignificant subgroup of patients does not sufficiently benefit from this approach. This article provides an overview of treatment-resistant OCD. In this narrative review the definition, causes, diagnostic and therapeutic approaches to treatment-resistant OCD are addressed. Treatment resistance can be assumed in the absence of clinically relevant improvement under therapy, in the sense of areduction of < 25% on the Yale-Brown obsessive-compulsive scale and ascore of 4(no change) on the clinical global impression-improvement scale. The number of unsuccessful treatment attempts required to establish treatment resistance is defined differently. Causative factors include misdiagnosis, a high severity, comorbid disorders, substance use, specific symptom constellations, organic causes, environmental factors, and aggravating factors in psychotherapy and pharmacotherapy. Suggestions for diagnostic and therapeutic approaches based on the GermanS3 guideline on OCD are presented. For patients with treatment resistance to first-line therapy, useful diagnostic and therapeutic recommendations are available (psychotherapeutic, psychopharmacological and neurostimulation procedures).

Time is ticking for TikTok tics: A retrospective follow-up study in the post-COVID-19 isolation era.

During the COVID-19 pandemic, an influx of adolescents presented worldwide with acute onset of functional tic-like behaviors (FTLBs). Our goal was to evaluate psychosocial factors around onset, to elucidate outcomes after pandemic isolation protocols were lifted, and to examine therapy and medication management. A retrospective review was performed of 56 patients ages 10-18 years with new-onset FTLBs seen at Boston Children's Hospital beginning in March 2020. Demographic factors, medical history, and treatment were evaluated. Patient outcomes were determined retrospectively based on the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales from follow-up visits. CGI-I scores assessed the progression of FTLBs; CGI-S assessed overall function. Ninety-six percent of patients were female-assigned at birth with high rates of comorbid anxiety (93%) and depression (71%). Forty-five percent were gender-diverse. Based on scales that assessed FTLBs (CGI-I) and overall functioning (CGI-S), up to 79% of patients improved independent of comorbid diagnosis or treatment. Evidence-based tic-specific treatments were not more effective than other treatments. A subset of patients had improvement in their FTLBs but not in their general functioning and continued to have other psychosomatic presentations. While many patients' FTLBs improved, it is critical to remain alert to patients' overall function and to assess for other functional neurological disorders and mental health concerns. The tendency of FTLBs to improve in this population, independent of treatment, highlights the unique pathophysiology of FTLBs. Future research on contributing psychosocial factors and specific treatment protocols will allow optimal support for these patients.

Use of ECT for Children With and Without Catatonia: A Single-Site Retrospective Analysis.

The objective study was to investigate the safety and efficacy of electroconvulsive therapy (ECT) in a retrospective cohort of pediatric patients. A single-site retrospective analysis was conducted of patients aged younger than 18 years who received ECT in a private university hospital from January 28, 2012 to April 8, 2023. Treatment efficacy and adverse events were determined retrospectively through review of the medical record. A total of 36 pediatric patients met the inclusion criteria. Catatonia was the most common presenting indication for ECT, followed by psychosis and suicidal ideation. For all patients, Clinical Global Impressions-Improvement scale scores indicated that it was very likely for a subject to experience at least "much improvement" with the estimated probability of receiving a Clinical Global Impressions-Improvement scale score better than 3 of 0.852 (t.s. = 16.3; P < 0.001; 95% confidence interval, 0.711-0.931). All patients with catatonia demonstrated a positive clinical response and experienced a statistically significant reduction in total Bush-Francis Catatonia Rating Scale scores observed ( t = 11.9; df = 20; SD = 6.3; P < 0.001; 95% confidence interval, 12.6-17.9). No significant adverse events were reported for any patient in the cohort. However, 14 (38.9%) patients experienced prolonged seizures, all of which were terminated with propofol (mean, 49.7 mg). This study provides further data supporting the safe and effective use of pediatric ECT in the treatment of various psychiatric conditions. However, more research is needed to determine the risk factors associated with prolonged seizures and the optimal seizure parameters in young people.