Some trials have evaluated peer support for people with mental ill health in high-income, mainly English-speaking countries, but the quality of the evidence is weak.

To investigate the effectiveness of UPSIDES peer support in high-, middle- and low-income countries.

This pragmatic multicentre parallel-group wait-list randomised controlled trial (registration: ISRCTN26008944) with three measurement points (baseline and 4 and 8 months) took place at six study sites: two in Germany, and one each in Uganda, Tanzania, Israel and India. Participants were adults with long-standing severe mental health conditions. Outcomes were improvements in social inclusion (primary) and empowerment, hope, recovery, health and social functioning (secondary). Participants allocated to the intervention group were offered UPSIDES peer support.

Of the 615 participants (305 intervention group), 337 (54.8%) identified as women. The average age was 38.3 (s.d. = 11.2) years, and the mean illness duration was 14.9 (s.d. = 38.4) years. Those allocated to the intervention group received 6.9 (s.d. = 4.2) peer support sessions on average. Intention-to-treat analysis showed effects on two of the three subscales of the Social Inclusion Scale, Empowerment Scale and HOPE Scale. Per-protocol analysis with participants who had received three or more intervention sessions also showed an effect on the Social Inclusion Scale total score (β = 0.18, P = 0.031, 95% CI: 0.02–0.34).

Peer support has beneficial impacts on social inclusion, empowerment and hope among people with severe mental health conditions across diverse settings. As social isolation is a key driver of mental ill health, and empowerment and hope are both crucial for recovery, peer support can be recommended as an effective component of mental healthcare. Peer support has the potential to move global mental health closer towards a recovery- and rights-based orientation.

Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes.

The study used longitudinal data from the EU-GEI High Risk study. Data from 331 CHR participants were analyzed to examine the effects of SLEs on changes in functioning, positive and negative symptoms over a 2-year follow-up. We compared the prevalence of SLEs between CHR and HCs, and between CHR who did (CHR-T) and did not (CHR-NT) transition to psychosis.

CHR reported 1.44 more SLEs than HC (p < 0.001), but there was no difference in SLEs between CHR-T and CHR-NT at baseline. Recent SLEs were associated with poorer functioning and more severe positive and negative symptoms in CHR individuals (all p < 0.01) but did not reveal a significant interaction with time.

CHR individuals who had experienced recent SLEs exhibited poorer functioning and more severe symptoms. However, as the interaction between SLEs and time was not significant, this suggests SLEs did not contribute to a worsening of symptoms and functioning over the study period. SLEs could be a key risk factor to becoming CHR for psychosis, however further work is required to inform when early intervention strategies mitigating against the effects of stress are most effective.

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.

Depression is common in people with dementia, and negatively affects quality of life.

This paper aims to evaluate the cost-effectiveness of an intervention for depression in mild and moderate dementia caused by Alzheimer's disease over 12 months (PATHFINDER trial), from both the health and social care and societal perspectives.

A total of 336 participants were randomised to receive the adapted PATH intervention in addition to treatment as usual (TAU) (n = 168) or TAU alone (n = 168). Health and social care resource use were collected with the Client Service Receipt Inventory and health-related quality-of-life data with the EQ-5D-5L instrument at baseline and 3-, 6- and 12-month follow-up points. Principal analysis comprised quality-adjusted life-years (QALYs) calculated from the participant responses to the EQ-5D-5L instrument.

The mean cost of the adapted PATH intervention was estimated at £1141 per PATHFINDER participant. From a health and social care perspective, the mean difference in costs between the adapted PATH and control arm at 12 months was −£74 (95% CI −£1942 to £1793), and from the societal perspective was −£671 (95% CI −£9144 to £7801). The mean difference in QALYs was 0.027 (95% CI −0.004 to 0.059). At £20 000 per QALY gained threshold, there were 74 and 68% probabilities of adapted PATH being cost-effective from the health and social care and societal perspective, respectively.

The addition of the adapted PATH intervention to TAU for people with dementia and depression generated cost savings alongside a higher quality of life compared with TAU alone; however, the improvements in costs and QALYs were not statistically significant.

Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD).

The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148).

About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines.

Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

The frequent prescribing of psychotropics and high prevalence of polypharmacy among older adults with intellectual disabilities require close monitoring.

To describe change in prevalence, predictors and health outcomes of psychotropic use during the four waves (2009/2010, 2013/2014, 2016/2017, 2019/2020) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA).

Eligible participants were adults (≥40 years) with intellectual disabilities who participated in all four waves of IDS-TILDA and who reported medication use for the entire period. Differences between groups were tested using Cochran's Q test for binary variables and the McNemar–Bowker test for variables with more than two categories. Generalised estimating equation models were used to assess associations between psychotropic use, participants’ characteristics and health outcomes.

Across waves (433 participants) there were no significant differences in prevalence of psychotropic use (61.2–64.2%) and psychotropic polypharmacy (42.7–38.3%). Antipsychotics were the most used subgroup, without significant change in prevalence between waves (47.6–44.6%). A significant decrease was observed for anxiolytics (26.8–17.6%; P < 0.001) and hypnotics/sedatives (14.1–9.0%; P < 0.05). A significant increase was recorded for antidepressants (28.6–35.8%; P < 0.001) and mood-stabilising agents (11.5–14.6%; P < 0.05). Psychotropic polypharmacy (≥2 psychotropics) was significantly associated with moderate to total dependence in performing activities of daily living over the 10-year period (OR = 1.80, 95% CI 1.21–2.69; P < 0.05).

The study indicates an increase in usage of some classes of psychotropic, a reduction in others and no change in the relatively high rate of antipsychotic use over 10 years in a cohort of older adults with intellectual disabilities and consequent risk of psychotropic polypharmacy and medication-related harm.

Excellence is that quality that drives continuously improving outcomes for patients. Excellence must be measurable. We set out to measure excellence in forensic mental health services according to four levels of organisation and complexity (basic, standard, progressive and excellent) across seven domains: values and rights; clinical organisation; consistency; timescale; specialisation; routine outcome measures; research and development.

To validate the psychometric properties of a measurement scale to test which objective features of forensic services might relate to excellence: for example, university linkages, service size and integrated patient pathways across levels of therapeutic security.

A survey instrument was devised by a modified Delphi process. Forensic leads, either clinical or academic, in 48 forensic services across 5 jurisdictions completed the questionnaire.

Regression analysis found that the number of security levels, linked patient pathways, number of in-patient teams and joint university appointments predicted total excellence score.

Larger services organised according to stratified therapeutic security and with strong university and research links scored higher on this measure of excellence. A weakness is that these were self-ratings. Reliability could be improved with peer review and with objective measures such as quality and quantity of research output. For the future, studies are needed of the determinants of other objective measures of better outcomes for patients, including shorter lengths of stay, reduced recidivism and readmission, and improved physical and mental health and quality of life.

Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis.

To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole.

Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method.

A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml).

The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

People with post-traumatic stress disorder (PTSD) exhibit negative cognitions, predictive of PTSD severity. The Post-Traumatic Cognitions Inventory (PTCI) is a widely used instrument measuring trauma-related cognitions and beliefs with three subscales: negative thoughts of self (SELF), negative cognitions about the world (WORLD), and self-blame (BLAME).

The current study attempted to validate the use of the PTCI in people with serious mental illness (SMI), who have greater exposure to trauma and elevated rates of PTSD, using confirmatory factor analysis (CFA) and examining convergent and divergent correlations with relevant constructs.

Participants were 432 individuals with SMI and co-occurring PTSD diagnosis based on the Clinician Administered PTSD Scale, who completed PTCI and other clinical ratings.

CFAs provided adequate support for Foa’s three-factor model (SELF, WORLD, BLAME), and adequate support for Sexton’s four-factor model that also included a COPE subscale. Both models achieved measurement invariance at configural, metric and scalar levels for three diagnostic groups: schizophrenia, bipolar and major depression, as well as for ethnicity (White vs Black), and gender (male vs female). Validity of both models was supported by significant correlations between PTCI subscales, and self-reported and clinician assessed PTSD symptoms and associated symptoms.

Findings provide support for the psychometric properties of the PTCI and the conceptualization of Sexton’s four-factor and Foa’s three-factor models of PTCI among individuals diagnosed with SMI (Foa et al., 1999).

Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR).

In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview.

At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment.

ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.