KEY FINDINGS: This study found that memantine treatment resulted in statistically significant reductions in hair pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on number needed to treat), and was well tolerated. The glutamate system may prove to be a beneficial target in the treatment of compulsive behaviors.
BACKGROUND: Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin, leading to noticeable hair loss or tissue damage. To date there is a severe paucity of evidence-based treatments for these conditions. In this study, the authors sought to determine whether memantine, a glutamate modulator, is more effective than placebo in reducing hair-pulling and skin-picking behavior.
DETAILS: One hundred adults with trichotillomania or skin-picking disorder (86 women; mean age, 31.4 years [SD=10.2]) were enrolled in a double-blind trial of memantine (dosing range, 10-20 mg/day) or placebo for 8 weeks. Participants were assessed with measures of pulling and picking severity. Outcomes were examined using a linear mixed-effects model. The prespecified primary outcome measure was treatment-related change on the NIMH Trichotillomania Symptom Severity Scale, modified to include skin picking. Compared with placebo, memantine treatment was associated with significant improvements in scores on the NIMH scale, Sheehan Disability Scale, and Clinical Global Impressions severity scale in terms of treatment-by-time interactions. At study endpoint, 60.5% of participants in the memantine group were "much or very much improved," compared with 8.3% in the placebo group (number needed to treat=1.9). Adverse events did not differ significantly between the treatment arms.
Copyright © American Psychiatric Association. All rights reserved.
Source: Grant, J. E., Chesivoir, E., Valle, S., et al. (2023). Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder. Am J Psychiatry. 2023; 180(5): 348-356. Published: May, 2023. DOI: 10.1176/appi.ajp.20220737.
Results From an Observational Cross-Sectional Multicenter European Study in 17 Countries
[Posted 22/Apr/2025]
AUDIENCE: Dermatology, Family Medicine
KEY FINDINGS: CPG patients have high levels of perceived stress, perceived stigmatization and body dysmorphic, which are partly related to sociodemographic factors like younger age or lower income as well as to other psychological and disease-related factors.
BACKGROUND: Anxiety, depression and suicidal ideation are frequent in patients with chronic prurigo (CPG). Purpose of the study is to analyze perceived stress, stigmatization, body dysmorphia, anxiety, depression and itch-related quality of life in CPG patients and compare them to controls, and then to identify variables/predictors of them. This study is part of a cross-sectional multicenter study in 17 European countries including 5487 consecutive patients and 2808 controls. CPG patients were older than controls and had significantly more comorbidities. However, multivariate analysis allowed controlling for these differences by including them as a covariate.
DETAILS: One hundred twenty-seven individuals with prurigo were included in the analyses. They reported higher levels of stress, stigmatization, and body dysmorphia than controls. In the patient group, stigmatization was associated with higher stress and having a severe disease, stress with younger age and lower income, depression and anxiety with lower income and higher itch intensity, body dysmorphia with younger age, and dissatisfaction with appearance.
Copyright © Published by Elsevier Inc. on behalf of the American Academy of Dermatology, Inc. All rights reserved.
Source: Ficheux, A., Brenaut, E., Schut, C., et al. (20245). Predictors of Perceived Stress, Perceived Stigmatization, and Body Dysmorphia in Patients With Chronic Prurigo/Prurigo Nodularis: Results From an Observational Cross-Sectional Multicenter European Study in 17 Countries. Journal of the American Academy of Dermatology. 2025; 92(5): 1056-1063. Published: May, 2025. DOI: 10.1016/j.jaad.2024.12.043.
A Systematic Review and Individual Patient Data Meta-Analysis
[Posted 7/Apr/2025]
AUDIENCE: Psychiatry, Family Medicine
KEY FINDINGS: This IPD meta-analysis found a small and uncertain advantage of other second-generation antipsychotics, mainly olanzapine and risperidone, and so did not provide evidence for superior efficacy of clozapine compared with other second-generation antipsychotics in treatment-resistant schizophrenia. It is limited by unavailability of IPD for some studies, uncaptured sources of variance, and uncertainty due to premature study discontinuation. Given the side-effects of clozapine, the observed uncertainty regarding clozapine's superiority warrants prudent use and further research.
BACKGROUND: Clozapine is recommended by national and international guidelines for people with treatment-resistant schizophrenia. However, available meta-analyses of randomised controlled trials have not shown superior efficacy of clozapine when compared with other second-generation antipsychotics, with heterogeneity identified between the original studies. Authors aimed to use individual patient data (IPD) to account for potential reasons of variability and to synthesise an adjusted estimate for the difference in efficacy between clozapine and other second-generation antipsychotics for treatment-resistant schizophrenia.
DETAILS: In this systematic review and IPD meta-analysis, authors searched the Cochrane Schizophrenia Group's Study-Based Register from inception to Jan 24, 2024, and previous reviews for blinded randomised controlled trials comparing clozapine with other second-generation antipsychotics in participants with treatment-resistant schizophrenia. Trials were eligible if they included patients with treatment-resistant schizophrenia and had a duration of at least 6 weeks. IPD were requested from trial investigators. The primary outcome was change in overall schizophrenia symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) between clozapine and other second-generation antipsychotics after 6-8 weeks of treatment. The effect size measure for the primary outcome was mean difference with 95% credible interval (CrI). Authors fitted a Bayesian random-effects IPD meta-regression model that included duration of illness, baseline severity, and sex as potential prognostic factors or treatment effect modifiers. Confidence in the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). People with lived experience of mental illness were involved in this study. Authors screened 13 876 references and included 19 studies with data for 1599 participants; IPD were available for 12 of 19 trials (n=1052; mean age 37.67 years [SD 11.24; range 10-66]; 348 [33.08%] women and 704 [66.92%] men). Data on ethnicity were not available. The estimated mean difference in change from baseline PANSS total score was -0.64 points (95% CrI -3.97 to 2.63; τ=2.68) in favour of other second-generation antipsychotics. Shorter duration of illness and higher baseline severity were prognostic factors associated with a larger reduction in symptoms, but neither those factors nor sex were found to modify the relative effect between clozapine and other second-generation antipsychotics. The confidence in the evidence was graded as very low.
Copyright © The Author(s). Published by Elsevier Ltd. All rights reserved.
Source: Schneider-Thoma, J., Hamza, T., Chalkoi, K., et al. (2025). Efficacy of Clozapine Versus Second-Generation Antipsychotics in People With Treatment-Resistant Schizophrenia: A Systematic Review and Individual Patient Data Meta-Analysis. The Lancet Psychiatry. 2025; 12(4): 254-265. Published: April, 2025. DOI: 10.1016/S2215-0366(25)00001-X.
A Phase 3 Randomized Clinical Trial
[Posted 11/Mar/2025]
AUDIENCE: Psychiatry, Family Medicine, Nursing
KEY FINDINGS: Results of this randomized clinical trial show that brexpiprazole + sertraline combination treatment statistically significantly improved PTSD symptoms vs sertraline + placebo, indicating its potential as a new efficacious treatment for PTSD. Brexpiprazole + sertraline was tolerated by most participants, with a safety profile consistent with that of brexpiprazole in approved indications.
BACKGROUND: New pharmacotherapy options are needed for posttraumatic stress disorder (PTSD). Purpose of this study is to investigate the efficacy, safety, and tolerability of brexpiprazole and sertraline combination treatment (brexpiprazole + sertraline) compared with sertraline + placebo for PTSD.
DETAILS: This was a parallel-design, double-blind, randomized clinical trial conducted from October 2019 to August 2023. The study had a 1-week, placebo run-in period followed by an 11-week, double-blind, randomized, active-controlled, parallel-arm period (with 21-day follow-up) and took place at 86 clinical trial sites in the US. Adult outpatients with PTSD were enrolled (volunteer sample). The primary end point was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score (which measures the severity of 20 PTSD symptoms) from randomization (week 1) to week 10 for brexpiprazole + sertraline vs sertraline + placebo. Safety assessments included adverse events. A total of 1327 individuals were assessed for eligibility. After 878 screen failures, 416 participants (mean [SD] age, 37.4 [11.9] years; 310 female [74.5%]) were randomized. Completion rates were 137 of 214 participants (64.0%) for brexpiprazole + sertraline and 113 of 202 participants (55.9%) for sertraline + placebo. At week 10, brexpiprazole + sertraline demonstrated statistically significant greater improvement in CAPS-5 total score (mean [SD] at randomization, 38.4 [7.2]; LS mean [SE] change, -19.2 [1.2]; n = 148) than sertraline + placebo (randomization, 38.7 [7.8]; change, -13.6 [1.2]; n = 134), with LS mean difference, -5.59 (95% CI, -8.79 to -2.38; P .001). All key secondary and other efficacy end points were also met. Treatment-emergent adverse events with incidence of 5% or greater for brexpiprazole + sertraline (and corresponding incidences for sertraline + placebo) were nausea (25 of 205 [12.2%] and 23 of 196 [11.7%]), fatigue (14 of 205 [6.8%] and 8 of 196 [4.1%]), weight increase (12 of 205 [5.9%] and 3 of 196 [1.5%]), and somnolence (11 of 205 [5.4%] and 5 of 196 [2.6%]). Discontinuation rates due to adverse events were 8 of 205 participants (3.9%) for brexpiprazole + sertraline and 20 of 196 participants (10.2%) for sertraline + placebo.
Copyright © American Medical Association. All Rights Reserved.
Source: Davis, L. L., Behl, S., Lee, D., et al. (2024). Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial. JAMA Psychiatry. 2025; 82(3): 218-227. Published: March, 2025. DOI: 10.1001/jamapsychiatry.2024.3996.
The YAWNS NB Randomized Clinical Trial
[Posted 30/Dec/2024]
AUDIENCE: Psychiatry, Family Medicine
KEY FINDINGS: Results of the YAWNS NB randomized clinical trial show that, as a simple, scalable, direct-to-patient intervention, YAWNS-1 substantially reduced BZRA use and improved sleep outcomes. It could be implemented to transform insomnia care for older adults at the population level.
BACKGROUND: Direct-to-patient interventions enabling transitions from long-term benzodiazepine receptor agonist (BZRA) use to cognitive behavioral therapy for insomnia (CBTI) by older adults has the potential to reduce BZRA use and related harms while improving sleep outcomes without requiring prearranged clinician involvement. Aim of this study was to compare 2 direct-to-patient behavior change interventions with treatment as usual (TAU) on BZRA use, sleep, and other health outcomes, and uptake of CBTI techniques.
DETAILS: The Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study was a 3-arm, pragmatic, open-label, minimum-contact, randomized clinical trial. The study began November 2020 and ended June 2022. Participants were randomly allocated to 1 of 3 groups, including 2 different mailed behavior change interventions or no intervention (TAU). Participants were from communities across the province of New Brunswick, Canada, and included adults 65 years and older living independently with long-term use of BZRAs and current or past insomnia. The Sleepwell package (YAWNS-1) consisted of a cover letter and 2 booklets (“How to Stop Sleeping Pills” and “How to Get Your Sleep Back”). The other package (YAWNS-2) included updated versions of the 2 booklets (“You May Be at Risk” and “How to Get a Good Night’s Sleep Without Medication”) used in the Eliminating Medications Through Patient Ownership of End Results (EMPOWER) study. Main outcomes and measures: BZRA use at 6 months was the primary measure. Secondary measures included CBTI use, sleep, insomnia, daytime sleepiness, safety, anxiety, frailty, and quality of life.
A total of 1295 individuals expressed interest in the study, and 565 (43.6%) completed a baseline assessment. Participants had a mean (SD) age of 72.1 (5.7) years, a mean (SD) BZRA use duration of 11.4 (9.1) years, and 362 (64.1%) were female. Discontinuations and dose reductions of 25% or greater were highest with YAWNS-1 (50 of 191 [26.2%]; 39 of 191 [20.4%]; total, 46.6%) compared with YAWNS-2 (38 of 187 [20.3%]; 27 of 187 [14.4%]; total, 34.8%, P = .02) and TAU (14 of 187 [7.5%]; 24 of 187 [12.8%]; total, 20.3%, P < .001). YAWNS-1 also demonstrated better uptake of CBTI techniques and sleep outcomes compared with YAWNS-2 (new CBTI techniques: 3.1 vs 2.4; P =.03; sleep efficiency change: 4.1% vs -1.7%; P =.001) and reduced insomnia severity and daytime sleepiness compared with TAU (insomnia severity index change: -2.0 vs 0.3; P <.001; Epworth Sleepiness Scale change: -0.8 vs 0.3; P =.001).
Copyright © American Medical Association. All Rights Reserved.
Source: Gardner, D. M., Turner, J. P., Magalhaes, S., et al. (2024). Patient Self-Guided Interventions to Reduce Sedative Use and Improve Sleep: The YAWNS NB Randomized Clinical Trial. JAMA Psychiatry. 2024; 81(12): 1187-1197. Published: December, 2024. DOI: 10.1001/jamapsychiatry.2024.2731.
KEY FINDINGS: The study reveals that the SIS can predict status anxiety. The SIS can contribute to research regarding important phenomena such as the detrimental psychological effects of income inequality.
BACKGROUND: Although substantial research indicates that considerations about status can lead to anxiety and other negative outcomes, a valid measure of the importance individuals attribute to status is lacking.
DETAILS: The study introduces the Status Importance Scale (SIS), a mono-factorial 10-item self-report questionnaire that quantifies how important a person deems status to be. Five studies validate the scale showing that it has excellent internal reliability and acceptable test–retest reliability, it correlates with several related measures (supporting convergent validity), it shows little correlation with theoretically unrelated constructs (supporting discriminant validity), it is the best predictor of conspicuous consumption compared with other potential candidates (supporting concurrent validity), and it can help predicting which activities one gives importance to (further supporting concurrent validity).
Copyright © The British Psychological Society. All rights reserved.
Source: Rigoli, F. and Mirolli, M. (2024). The Status Importance Scale: Development and Validation of a Self-Report Questionnaire for Measuring How Much People Care About Status. British Journal of Psychology. 2024; 115(4): 683-705. Published: November, 2024. DOI: 10.1111/bjop.12716.
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