The Enhanced Trauma Pathway (ETP) at Berkshire Healthcare NHS Foundation Trust was established in 2018 to manage high demand on a highly specialist psychology team called the Berkshire Traumatic Stress Service (BTSS). The ETP is used to treat complicated cases of Post-Traumatic Stress Disorder (PTSD) within the IAPT service. However, because of the ETP there is now a cohort of Service Users (SUs) presenting to IAPT with a higher complexity than has been typical, presenting new challenges for the service. We aim to evaluate and redesign the ETP within IAPT to meet the needs of the changing population.

Clinically Led workforcE and Activity Redesign (CLEAR) is a workforce transformation methodology with four unique stages: i) Clinical Engagement: in-depth qualitative analysis of interview data from staff ii) Data Interrogation: cohort analysis using clinical and workforce data visualisations and analysis, iii) Innovation: developing novel solutions with insights from triangulated qualitative and quantitative data, iv) Recommendations: formulation of new models of care (NMOC) and smaller quick high impact service innovations. Thematic analysis was used for the qualitative data. Quantitative data analysis was conducted using the IAPT dataset.

27 semi-structured interviews were conducted with staff. SUs on the ETP had longer waiting times, their treatment took longer (18 sessions for ETP Vs 12 for core step 3) and they had lower recovery rates: 32.9% for ETP, 49.9% for core step 3 in IAPT and 57.3% for the whole IAPT service. SUs on the ETP presented with increased risk concerns, often not mitigated by stabilisation work offered. Thematic analysis also identified challenges with recruitment, a lack of qualified staff and inefficient use of skills across the pathway. Staff well-being was found to be paramount, however supporting staff was found to be challenging due to national constraints placed upon IAPT and the targets the service is asked to achieve. A series of recommendations were made including three options for a NMOC. The options suggested different ways to redesign the pathway including an option where there would be a trauma only team within IAPT working exclusively on the ETP.

This evaluation highlights the challenges for the ETP and identifies NMOC to reduce their impact on the service. Further work is required to assess the NMOC once it has been implemented and to further evaluate the needs of the SUs presenting to this service.

Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.

The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.

This was a naturalistic study of community patients recommended for clozapine treatment.

Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).

These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.

Evidence from genetics, post mortem and animal studies suggest that N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction has an important role in the pathophysiology of psychosis. However, it is not known if NMDAR activity is altered in the early stages of psychosis or if this links to symptom severity. Our aim was to investigate NMDAR availability in first-episode psychosis (FEP) and determine if it links to symptom severity. The NMDAR hypofunction hypothesis of schizophrenia was initially proposed in the 1990s on the basis of observations that ketamine and phencyclidine (PCP) induced the full range of schizophrenia-like symptoms (positive, negative and cognitive) when given to healthy participants and also that they worsen symptoms in patients with schizophrenia.

We recruited 40 volunteers, including 21 patients with schizophrenia from early intervention services in London (12 antipsychotic-free and 9 receiving antipsychotic medication) and 19 matched healthy controls. The uptake of an NMDAR selective ligand, [18F]GE179, was measured using positron emission tomography (PET) and indexed using the distribution volume ratio (DVR) and volume of distribution (VT, in millilitres per cubic centimetre) of [18F]GE179 in the hippocampus and additional exploratory regions (anterior cingulate cortex (ACC), thalamus, striatum and temporal lobe). Symptom severity was measured using the Positive and Negative Syndrome Scale (PANSS).

A total of 37 individuals were included in the analyses (mean [SD] age of controls, 26.7 [4.5] years; mean [SD] age of patients, 25.3 [4.9] years). There was a significant reduction in hippocampal DVR in the patients with schizophrenia relative to healthy controls (p = 0.02, Cohen's d = 0.81). Although the VT of [18F]GE179 was lower in absolute terms in patients, there was no significant effect of group on VT in the hippocampus (p = 0.15, Cohen's d = 0.49) or the exploratory brain regions. There was a negative association between hippocampal DVR and total PANSS symptoms (rho = –0.47, p = 0.04), depressive symptoms (rho = –0.67, p = 0.002), and general PANSS symptoms (rho = –0.74, p = 0.001).

These results indicate lower hippocampal NMDAR levels in schizophrenia relative to controls with a large effect size, and that lower NMDAR levels are associated with greater levels of symptom severity. These findings are consistent with the role of NMDAR hypofunction in the pathophysiology of schizophrenia; however, further work is required to test specificity and causal relationships.

To conduct a meta-analysis of the effect of ketamine on psychopathology in healthy volunteers and patients with schizophrenia, and the experimental factors affecting this.

Ketamine is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like symptoms. Despite this, the consistency and magnitude of symptoms induced by ketamine, or what factors influence the effects of ketamine on these remain unknown.

MEDLINE, EMBASE and PsychINFO databases were searched for within-subject placebo controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or people with schizophrenia. Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive and negative BPRS and PANSS scores were extracted. Sub-group analyses were conducted examining the effect of: blinding status, ketamine preparation, infusion method and time between ketamine and placebo condition. Standardized mean change scores were used as effect sizes for individual studies. Standardized mean changes between ketamine and placebo for total, positive and negative BPRS and PANSS were calculated.

Of 7819 citations retrieved, 36 studies involving healthy participants were included. The overall sample included 725 healthy volunteers exposed to both the ketamine and placebo condition. Ketamine induced a significant increase in transient psychopathology in healthy participants, for total (Standardized mean change (SMC) = 1.50 (95% CI = 1.23 to 1.77), p < 0.0001), positive (SMC = 1.55 (95% CI = 1.29 to 1.81), p < 0.0001) and negative (SMC = 1.16, (95% CI = 0.96 to 1.35), p < 0.0001) symptom ratings, relative to the placebo condition. This effect was significantly greater for positive symptoms than negative symptoms (p = 0.004). Bolus followed by constant infusion increased ketamine's effect on positive symptoms relative to infusion alone (p = 0.006). Single-day study design increased ketamine's effect on total symptoms (p = 0.007), but age and gender did not moderate effects. There were insufficient studies for meta-analysis of studies in schizophrenia. Of these studies, two found a significant increase in symptoms with ketamine administration in total and positive symptoms. Only one study found an increase in negative symptom severity with ketamine.

These findings show that acute ketamine administration induces schizophrenia-like symptomatology with large effect sizes but there is a greater increase in positive than negative symptoms, and when a bolus is used. These findings suggest bolus doses should be avoided in its therapeutic use to minimize the risk of inducing transient positive psychotic symptoms.

The mental and physical health of individuals with a psychotic illness are typically poor. Access to psychosocial interventions is important but currently limited. Telephone-delivered interventions may assist. In the current systematic review, we aim to summarise and critically analyse evidence for telephone-delivered psychosocial interventions targeting key health priorities in adults with a psychotic disorder, including (i) relapse, (ii) adherence to psychiatric medication and/or (iii) modifiable cardiovascular disease risk behaviours.

Ten peer-reviewed and four grey literature databases were searched for English-language studies examining psychosocial telephone-delivered interventions targeting relapse, medication adherence and/or health behaviours in adults with a psychotic disorder. Study heterogeneity precluded meta-analyses.

Twenty trials [13 randomised controlled trials (RCTs)] were included, involving 2473 participants (relapse prevention = 867; medication adherence = 1273; and health behaviour = 333). Five of eight RCTs targeting relapse prevention and one of three targeting medication adherence reported at least 50% of outcomes in favour of the telephone-delivered intervention. The two health-behaviour RCTs found comparable levels of improvement across treatment conditions.

Although most interventions combined telephone and face-to-face delivery, there was evidence to support the benefit of entirely telephone-delivered interventions. Telephone interventions represent a potentially feasible and effective option for improving key health priorities among people with psychotic disorders. Further methodologically rigorous evaluations are warranted.

The extent of metabolic and lipid changes in first-episode psychosis (FEP) is unclear.

To investigate whether individuals with FEP and no or minimal antipsychotic exposure show lipid and adipocytokine abnormalities compared with healthy controls.

We conducted a meta-analysis of studies examining lipid and adipocytokine parameters in individuals with FEP and no or minimal antipsychotic exposure v. a healthy control group. Studies reported fasting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and leptin levels.

Of 2070 citations retrieved, 20 case–control studies met inclusion criteria including 1167 patients and 1184 controls. Total cholesterol and LDL cholesterol levels were significantly decreased in patients v. controls, corresponding to an absolute reduction of 0.26mmol/L and 0.15mmol/L respectively. Triglyceride levels were significantly increased in the patient group, corresponding to an absolute increase of 0.08 mmol/L However, HDL cholesterol and leptin levels were not altered in patients v. controls.

Total and LDL cholesterol levels are reduced in FEP, indicating that hypercholesterolaemia in patients with chronic disorder is secondary and potentially modifiable. In contrast, triglycerides are elevated in FEP. Hypertriglyceridaemia is a feature of type 2 diabetes mellitus, therefore this finding adds to the evidence for glucose dysregulation in this cohort. These findings support early intervention targeting nutrition, physical activity and appropriate antipsychotic prescription.

There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP).

Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study. We conducted a case–control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex. Leucine-rich glioma inactiviated-1 (LGI1) and contactin-associated protein (CASPR) antibodies were also measured. Notably, patients with suspicion of organic disease were excluded.

VGKC-complex antibodies were found in both cases (n = 3) and controls (n = 2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls.

This case–control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context.