Previous studies investigating the effectiveness of augmentation therapy have been limited.

To evaluate the effectiveness of antipsychotic augmentation therapies among patients with treatment-resistant depression.

We included patients diagnosed with depression receiving two antidepressant courses within 1 year between 2009 and 2020 and used the clone-censor-weight approach to address time-lag bias. Participants were assigned to either an antipsychotic or a third-line antidepressant. Primary outcomes were suicide attempt and suicide death. Cardiovascular death and all-cause mortality were considered as safety outcomes. Weighted pooled logistic regression and non-parametric bootstrapping were used to estimate approximate hazard ratios and 95% confidence intervals.

The cohort included 39 949 patients receiving antipsychotics and the same number of matched antidepressant patients. The mean age was 51.2 (standard deviation 16.0) years, and 37.3% of participants were male. Compared with patients who received third-line antidepressants, those receiving antipsychotics had reduced risk of suicide attempt (sub-distribution hazard ratio 0.77; 95% CI 0.72–0.83) but not suicide death (adjusted hazard ratio 1.08; 95% CI 0.93–1.27). After applying the clone-censor-weight approach, there was no association between antipsychotic augmentation and reduced risk of suicide attempt (hazard ratio 1.06; 95% CI 0.89–1.29) or suicide death (hazard ratio 1.22; 95% CI 0.91–1.71). However, antipsychotic users had increased risk of all-cause mortality (hazard ratio 1.21; 95% CI 1.07–1.33).

Antipsychotic augmentation was not associated with reduced risk of suicide-related outcomes when time-lag bias was addressed; however, it was associated with increased all-cause mortality. These findings do not support the use of antipsychotic augmentation in patients with treatment-resistant depression.

Antidepressants are effective for depression, but most evidence excludes individuals with comorbid physical conditions.

To assess antidepressants’ efficacy and tolerability in individuals with depression and comorbid physical conditions.

Systematic review and network meta-analysis of randomised controlled trials (RCTs). Co-primary outcomes were efficacy on depressive symptoms and tolerability (participants dropping out because of adverse events). Bias was assessed with the Cochrane Risk-of-Bias 2 tool and certainty of estimates with the Confidence in Network Meta-Analysis approach. A study protocol was registered in advance (https://osf.io/9cjhe/).

Of the 115 included RCTs, 104 contributed to efficacy (7714 participants) and 82 to tolerability (6083 participants). The mean age was 55.7 years and 51.9% of participants were female. Neurological and cardiocirculatory conditions were the most represented (26.1% and 18.3% of RCTs, respectively). The following antidepressants were more effective than placebo: imipramine, nortriptyline, amitriptyline, desipramine, sertraline, paroxetine, citalopram, fluoxetine, escitalopram, mianserin, mirtazapine and agomelatine, with standardised mean differences ranging from −1.01 (imipramine) to −0.34 (escitalopram). Sertraline and paroxetine were effective for the largest number of ICD-11 disease subgroups (four out of seven). In terms of tolerability, sertraline, imipramine and nortriptyline were less tolerated than placebo, with relative risks ranging from 1.47 (sertraline) to 3.41 (nortriptyline). For both outcomes, certainty of evidence was ‘low’ or ‘very low’ for most comparisons.

Antidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit–risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo.

The methodology and impact of independent inquiries of homicides by people in care of mental health services have been questioned.

To analyse characteristics of patients who committed homicide, their victims and inquiries published in England between 2010 and 2023.

Documentary and thematic analysis of 162 mental health homicide inquiries. We compared characteristics of perpetrators with those from the National Confidential Inquiry into Suicide and Safety (2018), and characteristics of victims with those in the general population of England and Wales. We examined methodology used by inquiries and thematically analysed root causes, contributory factors, recommendations, action plans, predictability and preventability.

Fifty-two per cent of perpetrators had a diagnosis of schizophrenia and 52% had a history of non-adherence to medication and follow-up; 71% of victims in mental health homicides were family, friends or partners compared with 44% in the general population; 77% of inquiries used no clear methodology. The most frequent root causes and contributory factors related to deficits in assessment, treatment, follow-up or discharge, and risk assessment. There was no direct link between putative causes and resulting recommendations. The most frequent recommendations related to changing policy, improving clinical governance and training. Only 4% of inquiries deemed the homcide to be predictable and preventable.

There is considerable variation in the methodology of mental health homicide inquiries, with little use of human factors and systems theory. Inquiries repeatedly identify the same themes, and most mental health homicides are found to be neither predictable nor preventable. We make recommendations for improving consistency and usefulness.

Involuntary treatment for patients with anorexia nervosa is common and lifesaving, but also highly intrusive. Understanding how morbidity patterns relate to involuntary treatment can help minimise its use.

We estimate the relative risk of involuntary treatment according to morbidity profiles in patients with anorexia nervosa.

This register-based cohort study included all individuals diagnosed with anorexia nervosa (ICD-10: F50.0, F50.1) between 1 January 2000 and 31 December 2016 in Denmark. Individuals were grouped by prior morbidities using latent class analysis (LCA). Cox proportional hazards regression estimated the relative risk of first involuntary treatment (e.g. involuntary admission, detention, locked wards) after a diagnosis with anorexia nervosa, regardless of the associated diagnosis. The relative risk of involuntary treatment was estimated with latent classes and the number of morbidities as exposure.

A total of 9892 individuals with anorexia nervosa were included (93.3% female), of which 821 (8.3%) individuals experienced at least one involuntary treatment event. The LCA produced six classes, with distinct morbidity profiles. The highest hazard ratio was observed for a group characterised by personality disorders, self-harm and substance misuse (hazard ratio 4.46, 95% CI: 3.43–5.79) followed by a high burden group with somatic and psychiatric disorders (hazard ratio 3.96, 95% CI: 2.81–5.59) and a group with developmental and behavioural disorders (hazard ratio 3.61, 95% CI: 2.54–5.11). The relative risk of involuntary treatment increased primarily with the number of psychiatric morbidities.

Specific morbidity groups are associated with highly elevated risk of involuntary treatment among patients with anorexia nervosa. Targeting preventive interventions to high-risk groups may help reduce the need for involuntary treatment.

Evidence suggests the crucial role of dysfunctional default mode (DMN), salience and frontoparietal (FPN) networks, collectively termed the triple network model, in the pathophysiology of treatment-resistant depression (TRD).

Using the graph theory- and seed-based functional connectivity analyses, we attempted to elucidate the role of low-dose ketamine in the triple networks, namely the DMN, salience and FPN.

Resting-state functional connectivity magnetic resonance imaging (rs–fcMRI) data derived from two previous clinical trials of a single, low-dose ketamine infusion were analysed. In clinical trial 1 (Trial 1), patients with TRD were randomised to either a ketamine or normal saline group, while in clinical trial 2 (Trial 2) those patients with TRD and pronounced suicidal symptoms received a single infusion of either 0.05 mg/kg ketamine or 0.045 mg/kg midazolam. All participants underwent rs–fcMRI pre and post infusion at Day 3. Both graph theory- and seed-based functional connectivity analyses were performed independently.

Trial 1 demonstrated significant group-by-time effects on the degree centrality and cluster coefficient in the right posterior cingulate cortex (PCC) cortex ventral 23a and b (DMN) and the cluster coefficient in the right supramarginal gyrus perisylvian language (salience). Trial 2 found a significant group-by-time effect on the characteristic path length in the left PCC 7Am (DMN). In addition, both ketamine and normal saline infusions exerted a time effect on the cluster coefficient in the right dorsolateral prefrontal cortex a9-46v (FPN) in Trial 1.

These findings may support the utility of the triple-network model in elucidating ketamine’s antidepressant effect. Alterations in DMN, salience and FPN function may underlie this effect.

People with dementia (PwD) and their carers often consider maintaining good quality of life (QoL) more important than improvements in cognition or other symptoms of dementia. There is a clinical need for identifying interventions that can improve QoL of PwD. There are currently no evidence-based guidelines to help clinicians, patients and policy makers to make informed decisions regarding QoL in dementia.

To conduct the first comprehensive systematic review of all studies that investigated efficacy of any pharmacological or non-pharmacological intervention for improving QoL of PwD.

Our review team identified eligible studies by comprehensively searching nine databases. We completed quality assessment, extracted relevant data and performed GRADE assessment of eligible studies. We conducted meta-analyses when three or more studies investigated an intervention for improving QoL of PwD.

We screened 14 389 abstracts and included 324 eligible studies. Our meta-analysis confirmed level 1 evidence supporting the use of group cognitive stimulation therapy for improving QoL (standardised mean difference 0.25; P = 0.003) of PwD. Our narrative data synthesis revealed level 2 evidence supporting 42 non-pharmacological interventions, including those based on cognitive rehabilitation, reminiscence, occupational therapy, robots, exercise or music therapy. Current evidence supporting the use of any pharmacological intervention for improving QoL in dementia is limited.

Current evidence highlights the importance of non-pharmacological interventions and multidisciplinary care for supporting QoL of PwD. QoL should be prioritised when agreeing care plans. Further research focusing on QoL outcomes and investigating combined pharmacological and non-pharmacological interventions is urgently needed.

Late-life affective disorders (LLADs) are common and are projected to increase by 2050. There have been several studies linking late-life depression to an increased risk of dementia, but it is unclear if bipolar affective disorder or anxiety disorders pose a similar risk.

We aimed to compare the risk of LLADs progressing to all-cause dementia, and the demographic and clinical variables mediating the risk.

We used the South London and Maudsley National Health Service Foundation Trust Clinical Records Interactive Search system to identify patients aged 60 years or older with a diagnosis of any affective disorder. Cox proportional hazard models were used to determine differences in dementia risk between late-life anxiety disorders versus late-life depression, and late-life bipolar disorder versus late-life depression. Demographic and clinical characteristics associated with the risk of dementia were investigated.

Some 5695 patients were identified and included in the final analysis. Of these, 388 had a diagnosis of bipolar affective disorder, 1365 had a diagnosis of an anxiety disorder and 3942 had a diagnosis of a depressive disorder. Bipolar affective disorder was associated with a lower hazard of developing dementia compared to depression (adjusted model including demographics and baseline cognition, hazard ratio: 0.60; 95% CI: 0.41–0.87). Anxiety disorders had a similar hazard of developing dementia (adjusted hazard ratio: 1.05; 95% CI: 0.90–1.22). A prior history of a depressive disorder reduced the risk of late-life depression progressing to dementia – suggesting the new onset of a depressive disorder in later life is associated with higher risk – but a prior history of anxiety disorders or bipolar affective disorder did not alter risk.

LLADs have a differential risk of developing all-cause dementia, with demographic- and illness-related factors influencing the risk. Further prospective cohort studies are needed to explore the link between LLADs and dementia development, and mediators of the lower risk of dementia associated with late-life bipolar disorder compared to late-life depression.

Self-harm, self-poisoning or self-injury, irrespective of the motivation, is a central risk factor for suicide. Still, there is limited knowledge of self-harm among patients with substance use disorders (SUDs) who die by suicide.

We aimed to describe the prevalence of a history of self-harm and identify the factors associated with self-harm, comparing individuals who died by suicide with and without SUDs.

We used data from the Norwegian Surveillance System for Suicide in Mental Health and Substance Use Services, which is based on a national linkage between the Norwegian Cause of Death Registry and the Norwegian Patient Registry, to identify individuals who died by suicide within 1 year after last contact with mental health or substance use services (n = 1140). A questionnaire was retrieved for 1041 (91.3%) of these individuals. We used least absolute shrinkage and selection operator (LASSO) regression to select variables and compared patients with and without SUDs. Conditional selective inference was used to improve 90% confidence intervals and p-values.

The prevalence of self-harm was 55% in patients with SUDs and 52.6% in patients without SUDs. Suicidal ideation (odds ratio 2.98 (95% CI 1.74–5.10)) emerged as a factor shared with patients without SUDs, while personality disorders (odds ratio 1.96 (1.12–3.40)) and a history of violence (odds ratio 1.86 (1.20–2.87)) were unique factors for patients with SUDs.

A history of self-harm is prevalent in patients with SUDs who die by suicide and is associated with suicidal ideation, a history of violence and personality disorders in patients with SUDs.

While cognitive impairment is a core feature of psychosis, significant heterogeneity in cognitive and clinical outcomes is observed.

The aim of this study was to identify cognitive and clinical subgroups in first-episode psychosis (FEP) and determine if these profiles were linked to functional outcomes over time.

A total of 323 individuals with FEP were included. Two-step hierarchical and k-means cluster analyses were performed using baseline cognitive and clinical variables. General linear mixed models were used to investigate whether baseline cognitive and clinical clusters were associated with functioning at follow-up time points (6–9, 12 and 15 months).

Three distinct cognitive clusters were identified: a cognitively intact group (N = 59), a moderately impaired group (N= 77) and a more severely impaired group (N= 122). Three distinct clinical clusters were identified: a subgroup characterised by predominant mood symptoms (N = 76), a subgroup characterised by predominant negative symptoms (N= 19) and a subgroup characterised by overall mild symptom severity (N = 94). The subgroup with more severely impaired cognition also had more severe negative symptoms at baseline. Cognitive clusters were significantly associated with later social and occupational function, and associated with changes over time. Clinical clusters were associated with later social functioning but not occupational functioning, and were not associated with changes over time.

Baseline cognitive impairments are predictive of both later social and occupational function and change over time. This suggests that cognitive profiles offer valuable information in terms of prognosis and treatment needs.

We rely heavily on cut-off points of brief measures of psychological distress in research and clinical practice to identify those at risk of mental health conditions; however, few studies have compared the performance of different scales.

To determine the extent to which the child- and parent-report Strength and Difficulty Questionnaire (SDQ), Revised Children’s Anxiety and Depression Scale (RCADS), short Mood and Feeling Questionnaire (sMFQ) and child-report KIDSCREEN correlated and identified the same respondents above cut-off points and at risk of mental health conditions.

A cross-sectional survey was conducted among 231 children aged 11–16 years and 289 parents who completed all the above measures administered via a mobile app, MyJournE, including the SDQ, RCADS and sMFQ.

The psychopathology measures identified similar proportions of young people as above the cut-off point and at risk of depression (child report 14.7% RCADS, 19.9% sMFQ, parent report 8.7% RCADS, 12.1% sMFQ), anxiety (child report 24.7% RCADS, 26.0% SDQ-Emotional subscale, parent report 20.1% RCADS, 26% SDQ-Emotional subscale) and child-report internalising problems (26.8% RCADS, 29.9% SDQ). Despite strong correlations between measures (child report 0.77–0.84 and parent report 0.70–0.80 between the SDQ, sMFQ and RCADS) and expected directions of correlation with KIDSCREEN and SDQ subscales, kappa values indicate moderate to substantial agreement between measures. Measures did not consistently identify the same children; half (n = 36, 46%) of those on child report and a third (n = 30, 37%) on parent report, scoring above the cut-off point for the SDQ-Emotional subscale, RCADS total or sMFQ, scored above the cut-off point on all of them. Only half (n = 46, 54%) of the children scored above the cut-off point on child report by the SDQ-Internalising and RCADS total scales.

This study highlights the risk of using a screening test to ‘rule out’ potential psychopathology. Screening tests should not be used diagnostically and are best used together with broad assessment.

Within the medical model, ‘impairment’ is required for a diagnosis of autism. However, the diagnostic manuals provide limited guidance as to how to interpret impairment, which can impact diagnostic rates and the provision of support. Impairment is discussed within the context of the medical model and current sociocultural landscape.

Researchers explore the biology of painful experiences not primarily felt in the body (‘non-physical pain’), sometimes referred to as mental, social or emotional pain. A critical challenge lies in how to operationalise this subjective experience for biological research, a crucial process for translating findings into clinical practice.

To map studies investigating biological features of non-physical pain, focusing on their conceptual features (i.e. terms and definitions of non-physical pain) and methodological characteristics (e.g. experimental paradigms and measures).

This methodological systematic review searched reports of primary research on the biological features of non-physical pain across Embase, MEDLINE and Web of Science. Using a meta-research approach, we synthetised results on terms, definitions, populations, experimental paradigms, confounders, measures of non-physical pain and investigation methods (e.g. functional magnetic resonance imaging).

We identified 92 human studies, involving 7778 participants. Overall, 59.1% of the studies did not report any definition of non-physical pain, and 82% of studies did not use a specific measure. Regarding the possibility of translating results to clinical settings, most of the human studies involved only healthy participants (71.7%) and the seven different experimental paradigms used to induce non-physical pain had unknown external validity. Confounders were not considered by 32.4% of the experimental studies. Animal studies were rare, with only four rodent studies.

Biomedical studies of non-physical pain use heterogeneous concepts with unclear overlaps and methods with unknown external validity. As has been done for physical pain, priority actions include establishing an agreed definition and measurement of non-physical pain and developing experimental paradigms with good external validity.