Self-harm is widespread and often occurs in the community without resulting in hospital presentation. Individuals with depressive symptoms are at elevated risk. There are limited self-harm interventions designed for community and primary care settings. The Community Outpatient Psychological Engagement Service for Self-harm (COPESS) is a brief talking therapy intervention for self-harm based in community settings.

To assess the feasibility of evaluating the COPESS intervention in a community setting in relation to participant recruitment, retention, data collection and the acceptability of the intervention.

We used a mixed-method approach and a single-blind randomised controlled trial design with 1:1 allocation to either COPESS plus treatment as usual or treatment as usual alone. Adults with depressive symptoms and self-harm in the past 6 months were recruited from general practices. Secondary outcome measures were assessed at baseline and 1 month, 2 months and 3 months after randomisation. The trial was pre-registered on clinicaltrials.gov (NCT04191122) on 9 December 2019.

Fifty-five people were randomised (of an initial target of 60). Retention rates at follow-up assessments were high (>75%), as was attendance by all participants for all therapy sessions (93%). At 3 months, there were trends towards lower levels of self-harm urges, depressive symptoms and distress in the COPESS group compared with controls. Fidelity to the manualised COPESS therapy was moderate to high.

All progression criteria were met, supporting further evaluation of the intervention in a full-scale efficacy and/or cost-effectiveness trial. These findings add to the growing evidence base supporting the utility of brief psychological interventions for self-harm. COPESS has potential as a brief primary-care-based intervention for those struggling with self-harm.

Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

Cognitive decline and sleep concerns are significant health issues among older adults. Nonpharmacological treatments to address these concerns are needed, particularly for older adults who are more likely to be prescribed multiple medications and experience adverse effects of additional drugs. The aim of the current qualitative study was to understand and document the experiences of older adults with subjective memory decline participating in prolonged nightly fasting (PNF) intervention.

This single-group pilot study was conducted as a fully remote, 8-week, pre/postintervention. Postintervention, 16 participants (≥65 years) participated in semistructured qualitative exit interviews about their experiences with the PNF intervention. Interviews lasted approximately 20–30 minutes, were conducted by trained study staff, and then analyzed by the team to understand relevant themes.

Two major themes that emerged from the data were engagement with and perceived effects of the PNF intervention. Within these two themes, nine subthemes emerged: accountability; use of days off; feasibility; intervention tools; behavioral strategies; timing/routine; awareness; self-efficacy; and perceived health-related outcomes. Overall, interviews suggested strong engagement with the PNF intervention as well as a number of positive perceived effects of the intervention.

These findings contribute to a broad field of intermittent fasting by exploring and understanding the direct experiences of older adults participating in PNF. Some participants identified challenges of participation, yet this qualitative approach can guide future PNF implementation with older adults. Notably, responses support the quantitative data suggesting that PNF is a feasible and acceptable intervention for older adults.

Researchers acknowledge the need to share study results with the patients and their communities, but this is not done consistently due to a plethora of barriers, including a paucity of data to guide best practice approaches in different populations.

This study was nested within a large multi-center randomized controlled trial of antimalaria treatment. Data on dissemination preferences were collected at the third-month follow-up visit using a short questionnaire. Data were analyzed using descriptive statistics and subsequently fed into an iterative process with key stakeholders, to develop suitable strategies for result dissemination.

A total of 960 patients were enrolled in the trial, of whom 84.0% participated in the nested survey. A total of 601 (74.6%) participants indicated interest in receiving trial results. There was significant heterogeneity by study country, with 33.3% (58/174) of patients indicating being interested in Cambodia, 100% (334/334) in Ethiopia, 97.7% (209/214) in Pakistan, but none (0/85) in Indonesia. The preferred method of dissemination varied by site, with community meetings, favored in Ethiopia (79.0%, 264/334) and individualized communication such as a letter (27.6%, 16/58) or phone calls (37.9%, 22/58) in Cambodia. Dissemination strategies were designed with key stakeholders and based on patient preferences but required adaptation to accommodate local logistical challenges.

The varying preferences observed across different sites underscore that a one-size-fits-all approach is inadequate. Strategies can be tailored to patient preference but require adaptation to accommodate logistical challenges.

Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.

To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.

The Ketamine for Adult Depression Study was a multisite 4-week randomised, double-blind, active (midazolam)-controlled trial. The study initially used fixed low dose ketamine (0.5 mg/kg, cohort 1), before protocol revision to flexible, response-guided dosing (0.5–0.9 mg/kg, cohort 2). This secondary analysis assessed anxiety using the Hamilton Anxiety (HAM-A) scale (primary measure) and ‘inner tension’ item 3 of the Montgomery–Åsberg Depression Rating Scale (MADRS), at baseline, 4 weeks (end treatment) and 4 weeks after treatment end. Analyses of change in anxiety between ketamine and midazolam groups included all participants who received at least one treatment (n = 174), with a mixed effects repeated measures model used to assess the primary anxiety measure. The trial was registered at www.anzctr.org.au (ACTRN12616001096448).

In cohort 1 (n = 68) the reduction in HAM-A score was not statistically significant: −1.4 (95% CI [−8.6, 3.2], P = 0.37), whereas a significant reduction was seen for cohort 2 (n = 106) of −4.0 (95% CI [−10.6, −1.9], P = 0.0058), favouring ketamine over midazolam. These effects were mediated by total MADRS and were not maintained at 4 weeks after treatment end. MADRS item 3 was also significantly reduced in cohort 2 (P = 0.026) but not cohort 1 (P = 0.96).

Ketamine reduces anxiety in people with TRD when administered subcutaneously in adequate doses.

Individuals who play video games on computers and cellphones may have better psychomotor skills. It is unknown whether simulated driving performance varies between individuals who play video games more per week compared to individuals who play less. This study investigates whether initial simulated driving performance differs between high and low gamers during a brief (e.g., 10 minutes) driving simulation.

Data for this study were collected at baseline during enrollment for a randomized clinical trial (n = 40). Participants playing video games for > 10 hours/week were categorized as the high gaming group; others were in the low gaming group. Each participant drove the same simulation on the STISIM M1000 simulator, which recorded various driving performance metrics (e.g., driving out of lane and time to initial collision). Data between the groups were compared using Cox proportional hazards and analysis of covariance regression models.

The average age of participants was 21 ± 2.7 years and 48% were male. After adjusting for age, sex, and miles driven per week, the high gaming group spent a mean 4% less time driving out of lane compared to the low gaming group (β = –4.03, SD = 1.32, p ≤ 0.05). No other differences were observed between groups for any other outcome.

With the exception of percentage time driving out of lane, the number of hours gaming per week does not seem to impact an individual’s initial driving performance on a driving simulator. These findings may inform future driving simulation research methodology.

No drugs are currently approved for the treatment of borderline personality disorder (BPD). These studies (a randomised study and its open-label extension) aimed to evaluate the efficacy, safety and tolerability of brexpiprazole for the treatment of BPD.

The Phase 2, multicentre, randomised, double-blind, placebo-controlled, parallel-group study enrolled adult outpatients with BPD. After a 1-week placebo run-in, patients were randomised 1:1 to brexpiprazole 2–3 mg/day (flexible dose) or placebo for 11 weeks. The primary endpoint was change in Zanarini Rating Scale for BPD total score from randomisation (Week 1) to Week 10 (timing of randomisation and endpoint blinded to investigators and patients). The Phase 2/3, multicentre, open-label extension study enrolled patients who completed the randomised study; all patients received brexpiprazole 2–3 mg/day (flexible dose) for 12 weeks. Safety assessments included treatment-emergent adverse events (TEAEs).

Brexpiprazole was not statistically significantly different from placebo on the primary endpoint of the randomised study (N = 324 randomised; N = 110 analysed per treatment group; least squares mean difference −1.02; 95% confidence limits −2.75, 0.70; p = 0.24). Numerical efficacy advantages for brexpiprazole were observed at other time points. The most common TEAE in the randomised study was akathisia (brexpiprazole, 14.0%; placebo, 1.2%); data from the open-label study (N = 199 analysed) suggested that TEAEs were transient.

The primary endpoint of the randomised study was not met. Further research on brexpiprazole in BPD is warranted based on possible efficacy signals at other time points and its safety profile.

ClinicalTrials.gov identifiers: NCT04100096, NCT04186403. Funding: Otsuka, Lundbeck.

To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).

This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints.

1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole n = 240; ADT + placebo n = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; p = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C.

Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.

ClinicalTrials.gov identifier: NCT03538691. Funding: Otsuka, Lundbeck.

The COVID-19 pandemic amplified known challenges associated with the conduct of inpatient clinical trials, while also introducing new ones that needed to be addressed.

Stakeholders based in the United States who participated in the conduct of inpatient therapeutic trials for the treatment of COVID-19 as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program identified challenges experienced in the conduct of these trials through a series of meeting to discuss and identify common themes. In addition, innovations developed to address these challenges and other potential solutions that may be utilized in future pandemics were highlighted.

Six thematic challenges including infection control considerations, the interplay between provision of clinical care and research, competing clinical trials, arduous consenting procedures, onerous procedural requirements, and participant recruitment including achieving representation of diverse populations were identified and are discussed here.

Consideration of the lessons learned and recommendation outlined here may allow for more efficient conduct of inpatient clinical trials in future pandemics.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.

The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).

Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.

ClinicalTrials.gov Identifier: NCT02458690

Nasal septoplasty is one of the most performed procedures within ENT. Nasal obstruction secondary to a deviated nasal septum is the primary indication for functional septoplasty. Since the coronavirus disease 2019 pandemic, waiting lists have increased and are now long. This study assessed patients on the waiting list for septoplasty and/or inferior turbinate reduction surgery using the Nasal Obstruction Symptom Evaluation instrument.

Patients on our waiting list for septoplasty and/or inferior turbinate reduction surgery were reviewed using a validated patient-reported outcome measure tool to assess symptom severity.

Eighty-six out of a total of 88 patients (98 per cent) had Nasal Obstruction Symptom Evaluation scores of 30 or more. In addition, 78 (89 per cent) and 50 (57 per cent) patients were classified as having ‘severe’ or ‘extreme’ nasal obstruction, respectively. Two patients scored less than 30 and were classified as having non-significant nasal obstruction.

The Nasal Obstruction Symptom Evaluation instrument is a quick and easy way to validate septoplasty waiting lists. In this study, two patients were identified who no longer required surgery.

To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075).

We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin.

Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm.

Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.

Lewy body dementia (LBD) is a prevalent yet frequently underdiagnosed form of dementia, accounting for up to 15% of all dementia cases.

This study aims to increase awareness and advocacy for LBD by gathering and critically assessing the economic evidence, including the cost of illness and cost-effectiveness of interventions for managing LBD.

A systematic literature review was undertaken with EMBASE, Medline, CINAHL, PsycINFO, NHS Economic Evaluation Database and EconLit. This search was supplemented by grey literature on Google Scholar and reviewing the reference lists of identified studies. The papers included in the review were published between 2008 and 2023, and involved participants with LBD (dementia with Lewy bodies or Parkinson's disease dementia), which either addressed the cost of illness or conducted an economic evaluation.

Thirteen papers were included, comprising ten cost-of-illness studies and three economic evaluations. The cost of LBD tends to be higher than that of other forms of dementia, such as Alzheimer's disease, and these costs escalate more steeply as the disease progresses. These cost differences may not be solely influenced by the subtype of dementia, but possibly also by patient characteristics like physical and cognitive abilities. Cost-effectiveness of potential interventions for LBD is limited.

Despite numerous drug trials and other interventions for dementia, very few have targeted LBD, let alone explored the cost-effectiveness of such therapies for LBD. This disparity highlights the urgent need for cost-effective strategies and interventions targeting LBD. We propose the establishment of universally accepted standards for LBD research.