[Posted 2/Jun/2023]

AUDIENCE: Psychiatry, Family Medicine

DETAILS: Today, the U.S. Food and Drug Administration approved Brixadi (buprenorphine) extended-release injection for subcutaneous use (under the skin) to treat moderate to severe opioid use disorder (OUD). Brixadi is available in two formulations, a weekly injection that can be used in patients who have started treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine, and a monthly version for patients already being treated with buprenorphine.

“Buprenorphine is an important treatment option for opioid use disorder. Today’s approval expands dosing options and provides people with opioid use disorder a greater opportunity to sustain long-term recovery,” said FDA Commissioner Robert M. Califf, M.D. “The FDA will continue to take the critical steps necessary to pursue efforts that advance evidence-based treatments for substance use disorders, which is a strategic priority under the FDA’s Overdose Prevention Framework.”

Buprenorphine is a safe and effective medication for the treatment of OUD. According to the Substance Abuse and Mental Health Services Administration (SAMHSA), patients receiving medication for their OUD cut their risk of death from all causes in half.

The FDA continues to implement a comprehensive approach to increase options to treat OUD. Earlier this month, the agency issued a joint letter with SAMHSA to clarify the importance of counseling and other services as part of a comprehensive treatment plan for OUD, and to also reiterate that supplying buprenorphine should not be made contingent upon participation in such services. The agency also held a virtual public workshop that highlighted the need for additional strengths and dosing regimens for extended-release formulations.

Brixadi is approved in both weekly and monthly subcutaneous injectable formulations at varying doses, including lower doses that may be appropriate for those who do not tolerate higher doses of extended-release buprenorphine that are currently available. The weekly doses are 8 milligrams (mg), 16 mg, 24 mg, 32 mg; and the monthly doses are 64 mg, 96 mg, 128 mg. The approved weekly formulation in various lower strengths offers a new option for people in recovery who may benefit from a weekly injection to maintain treatment adherence. Brixadi will be available through a Risk Evaluation and Mitigation Strategy (REMS) program and administered only by health care providers in a health care setting.

The most common adverse reactions (occurring in >=5% of patients) with Brixadi include injection-site pain, headache, constipation, nausea, injection-site erythema, itchy skin at the injection site (injection-site pruritus), insomnia and urinary tract infections.

The safety and efficacy of Brixadi were evaluated in a behavioral pharmacology study assessing the ability of two weekly doses of Brixadi to block the subjective effects of opioids, and one randomized, double-blind, active-controlled clinical trial in 428 adults with a diagnosis of moderate-to-severe OUD. After an initial test dose of transmucosal buprenorphine, patients were randomized to treatment with Brixadi plus a sublingual placebo, or active sublingual buprenorphine plus placebo injections. After titration over the first week, patients were treated with weekly injections over 12 weeks and then transitioned to monthly injections for an additional 12 weeks. A response to treatment was measured by urine drug screening and self-reporting of illicit opioid use during the treatment period. Patients were considered responders if they had negative opioid assessments at the end of each of the two treatment phases. The proportion of patients meeting the responder definition was 16.9% in the Brixadi group and 14.0% in the sublingual buprenorphine group.

The FDA granted approval of Brixadi to Braeburn Inc.

The agency remains focused on responding to all facets of substance use, misuse, substance use disorders, overdose and death in the U.S. through its FDA Overdose Prevention Framework. The framework’s priorities include: supporting primary prevention by eliminating unnecessary initial prescription drug exposure and inappropriate prolonged prescribing; encouraging harm reduction through innovation and education; advancing development of evidence-based treatments for substance use disorders; and protecting the public from unapproved, diverted or counterfeit drugs presenting overdose risks.

Copyright © FDA. All rights reserved.

Source: FDA Approves New Buprenorphine Treatment Option for Opioid Use Disorder. FDA. Published: May 23, 2023.

[Posted 1/Jul/2025]

AUDIENCE: Neurology, Internal Medicine, Ob/Gyn

KEY FINDINGS: This population-based study on dementia biomarkers found that P-tau181 was dependent on age and APOEe4; NfL on age and sex; and GFAP on age, sex, APOEe4, and menopause status. GFAP levels and rate of increase were higher in women, especially in premenopausal participants. Future research should confirm these findings and further explore the role of menopause in dementia pathogenesis among women.

BACKGROUND: Dementia-related blood biomarkers are the future of large-scale dementia risk stratification; however, the extent to which phosphorylated tau (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are associated with nonmodifiable risk factors has yet to be confirmed in the community, and the role of menopause has yet to be investigated. Therefore, the aim of this study was to examine the association of age, sex, APOEe4 status, and menopause, with dementia-related blood biomarker levels (P-tau181, NfL, and GFAP) and rate of change over 11 years in longitudinal biomarker measurements in community-dwelling adults.

DETAILS: Within this German population-based Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung cohort study (n = 9,940), a nested case-control study of 1,026 participants (1:1, without dementia during follow-up: incident dementia during follow-up) aged 50-75 years at baseline followed over 17 years was conducted. Blood biomarker measurements (P-tau181, NfL, and GFAP) were completed in blood from baseline, 8-year, and 11-year follow-ups, and cross-sectional and longitudinal regression analyses were used to assess the association with age, sex, APOEe4, and menopause. The mean age of participants was 64 years, and women accounted for slightly over half (54%) of the sample. Age was cross-sectionally and longitudinally significantly associated with all dementia-related biomarkers (p < 0.001). NfL and GFAP levels more strongly correlated (Spearman R = 0.55 and 0.49) with age at baseline than P-tau181 levels (Spearman R = 0.21). Women experienced significantly higher levels and rates of increase in GFAP (p < 0.001) while men experienced higher levels of NfL after adjusting for age and APOEe4 (p < 0.01). APOEe4 status was significantly associated with baseline and longitudinal levels of P-tau181 (baseline β = 0.30, p < 0.05) and GFAP (baseline β = 15.84, p < 0.001). Of interest, premenopausal status was significantly associated with higher GFAP levels after adjusting for age, sex, and APOEe4 (β = 19.09, p < 0.05).

Copyright © American Academy of Neurology. All Rights Reserved.

Source: Stocker, H., Beyer, L., Trares, K., et al. Association of Nonmodifiable Risk Factors With Alzheimer Disease Blood Biomarkers in Community-Dwelling Adults in the ESTHER Study. American Academy of Neurology. 2025; 104(9): 213500. Published: May 27, 2025. DOI: 10.1212/WNL.000000000021350.

A Cross-Sectional Study

[Posted 15/May/2025]

AUDIENCE: Nursing, Neurology

KEY FINDINGS: FOP and resilience parallelly mediated the effect of PSF on PSD, which may provide a novel perspective for healthcare professionals in preventing PSD. Targeted interventions aiming at reducing PSF, lowering FOP levels and enhancing resilience may be possible ways to alleviate PSD.

BACKGROUND: Purpose of the study is to explore the effect of post-stroke fatigue (PSF) on post-stroke depression (PSD) and examine the mediating effects of fear of disease progression (FOP) and resilience between PSF and PSD. This study enriched the literature by exploring the effect of PSF on PSD and further examining the mediating effects of FOP and resilience between PSF and PSD. Findings emphasized the important effects of PSF, FOP and resilience on PSD.

DETAILS: A total of 315 stroke patients participated in the questionnaire survey between November 2022 and June 2023. Data were collected using the General Information Questionnaire, Fatigue Severity Scale, Fear of Disease Progression Questionnaire-Short Form, Connor-Davidson Resilience Scale-10 Item and Hospital Anxiety and Depression Scale-Depression Subscale. Data were analysed by descriptive analysis, Mann-Whitney U-test, Kruskal-Wallis H-test, Pearson or Spearman correlation, hierarchical regression analysis and mediation analysis. PSF had a significant positive total effect on PSD (ß = .354, 95% CI: .251, .454). Additionally, FOP and resilience played a partial parallel-mediating role in the relationship between PSF and PSD (ß = .202, 95% CI: .140, .265), and the total indirect effect accounted for 57.06% of the total effect.

Copyright © John Wiley & Sons Ltd. All rights reserved.

Source: Ning, L., Fu, Y., Wang, Y., et al. (20245). Fear of Disease Progression and Resilience Parallelly Mediated the Effect of Post-Stroke Fatigue on Post-Stroke Depression: A Cross-Sectional Study. J Clin Nurs. 2025; 34(5): 1753-1764. Published: May, 2025. DOI: 10.1111/jocn.17323.

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.