Cognitive behavioural therapy added to standard care for first-episode and recent-onset psychosis.

BACKGROUND: Cognitive behavioural therapy (CBT) can be effective in the general population of people with schizophrenia. It is still unclear whether CBT can be effectively used in the population of people with a first-episode or recent-onset psychosis. OBJECTIVES: To assess the effects of adding cognitive behavioural therapy to standard care for people with a first-episode or recent-onset psychosis. SEARCH METHODS: We conducted a systematic search on 6 March 2022 in the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, ISRCTN, and WHO ICTRP. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing CBT added to standard care vs standard care in first-episode or recent-onset psychosis, in patients of any age. DATA COLLECTION AND ANALYSIS: Two review authors (amongst SFM, CC, LK and IB) independently screened references for inclusion, extracted data from eligible studies and assessed the risk of bias using RoB2. Study authors were contacted for missing data and additional information. Our primary outcome was general mental state measured on a validated rating scale. Secondary outcomes included other specific measures of mental state, global state, relapse, admission to hospital, functioning, leaving the study early, cognition, quality of life, satisfaction with care, self-injurious or aggressive behaviour, adverse events, and mortality. MAIN RESULTS: We included 28 studies, of which 26 provided data on 2407 participants (average age 24 years). The mean sample size in the included studies was 92 participants (ranging from 19 to 444) and duration ranged between 26 and 52 weeks. When looking at the results at combined time points (mainly up to one year after start of the intervention), CBT added to standard care was associated with a greater reduction in overall symptoms of schizophrenia (standardised mean difference (SMD) -0.27, 95% confidence interval (CI) -0.47 to -0.08, 20 RCTs, n = 1508, I2 = 68%, substantial heterogeneity, low certainty of the evidence), and also with a greater reduction in positive (SMD -0.22, 95% CI -0.38 to -0.06, 22 RCTs, n = 1565, I² = 52%, moderate heterogeneity), negative (SMD -0.20, 95% CI -0.30 to -0.11, 22 RCTs, n = 1651, I² = 0%) and depressive symptoms (SMD -0.13, 95% CI -0.24 to -0.01, 18 RCTs, n = 1182, I² = 0%) than control. CBT added to standard care was also associated with a greater improvement in the global state (SMD -0.34, 95% CI -0.67 to -0.01, 4 RCTs, n = 329, I² = 47%, moderate heterogeneity) and in functioning (SMD -0.23, 95% CI -0.42 to -0.05, 18 RCTs, n = 1241, I² = 53%, moderate heterogeneity, moderate certainty of the evidence) than control. We did not find a difference between CBT added to standard care and control in terms of number of participants with relapse (relative risk (RR) 0.82, 95% CI 0.57 to 1.18, 7 RCTs, n = 693, I² = 48%, low certainty of the evidence), leaving the study early for any reason (RR 0.87, 95% CI 0.72 to 1.05, 25 RCTs, n = 2242, I² = 12%, moderate certainty of the evidence), adverse events (RR 1.29, 95% CI 0.85 to 1.97, 1 RCT, n = 43, very low certainty of the evidence) and the other investigated outcomes. AUTHORS' CONCLUSIONS: This review synthesised the latest evidence on CBT added to standard care for people with a first-episode or recent-onset psychosis. The evidence identified by this review suggests that people with a first-episode or recent-onset psychosis may benefit from CBT additionally to standard care for multiple outcomes (overall, positive, negative and depressive symptoms of schizophrenia, global state and functioning). Future studies should better define this population, for which often heterogeneous definitions are used.

Keyworker mediated enhancement of physical health in patients with first episode psychosis: A feasibility/acceptability study.

AIM: Early intervention for people experiencing first episode psychosis is a priority, and keyworkers are vital to such services. However, keyworkers' roles in addressing first episode psychosis patients' physical health are under researched. This study addresses this knowledge gap by evaluating a keyworker-mediated intervention promoting physical health among first episode psychosis patients. METHODS: The study was informed by the Medical Research Council's Framework for Complex Interventions to Improve Health. First episode psychosis participants were recruited from three Irish mental health services. The intervention was evaluated in terms of its feasibility/acceptability. RESULTS: Feasibility outcomes were mixed (recruitment rate = 24/68 [35.3%]; retention rate = 18/24 [75%]). The baseline sample was predominantly male (M:F ratio = 13:6; Med age = 25 y; IQR = 23-42 y). Common health issues among participants included overweightness/obesity (n = 11) and substance use (smoking/alcohol consumption [n = 19]). Participants' initial health priorities included exercising more (n = 10), improving diet (n = 6), weight loss (n = 7) and using various health/healthcare services. The intervention's acceptability was evidenced by the appreciation participants had for physical health keyworkers' support, as well as the healthy lifestyle, which the intervention promoted. Acceptability was somewhat compromised by a low-recruitment rate, variable linkages between keyworkers and general practitioners (GPs) and COVID-19 restrictions. CONCLUSIONS: Physical health-oriented keyworker interventions for first episode psychosis patients show promise and further evaluation of such initiatives is warranted. Future interventions should be mindful of participant recruitment challenges, strategies to enhance relationships between keyworkers and GPs, and if necessary, they should mitigate COVID-19 restrictions' impacts on care.

The role of key workers in improving physical health in first episode psychosis: A scoping review.

AIM: Studies have demonstrated that a majority of the decline in health status and functioning emerges during the first few years following the onset of psychosis. This knowledge led to the development of specialized early intervention services (EIS) targeting patients experiencing their first episode of psychosis (FEP). The central component of EIS is often assertive case management delivered by a multidisciplinary team, where an appointed key worker is responsible for coordinating treatment and delivering various psychosocial interventions to service users. The aim of this scoping review was to examine how key workers can enhance the physical health outcomes in people with FEP by addressing the factors associated with increased mortality in this population. METHODS: The scoping review framework comprised a five-stage process developed by Arksey and O'Malley. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: A total of 27 studies conducted across 10 countries were analysed. These studies discussed the various ways in which key workers can mediate enhancements in the various factors contributing to the increased mortality rates in FEP patients. CONCLUSIONS: A broad range of key worker-mediated outcomes was identified, which were broadly classified into three themes: influences on lifestyle, influences on effects of psychosis and influences on organizational barriers. Our findings suggest that key workers primarily mediated the amelioration of psychosis-induced effects and the reduction of organizational barriers. Further trials of key worker interventions to enhance physical health outcomes in this cohort are warranted.

Key Worker-Mediated Enhancement of Physical Health in First Episode Psychosis: Protocol For a Feasibility Study in Primary Care.

BACKGROUND: Studies have demonstrated that, for patients with psychosis, a majority of the decline in health status and functioning emerges during the first few years after the onset of illness. This knowledge led to the development of specialized early intervention services (EISs) targeting patients experiencing their first episode of psychosis. The central component of EISs is often assertive case management delivered by a multidisciplinary team, where an appointed key worker is responsible for coordinating treatment and delivering various psychosocial interventions to service users. OBJECTIVE: This paper outlines the protocol for a feasibility study examining how key workers may enhance physical health by supporting integration between primary and secondary care. METHODS: Semistructured interviews were conducted with key stakeholder groups (General Practitioners and health care professionals working in mental health services). The interviews informed the development of the complex intervention involving a longitudinal pre-post intervention in 8 general practices in 2 regions in Ireland (one urban and one rural). Patients with first episode psychosis (FEP) will be identified from clinical records at general practices and mental health services. RESULTS: Baseline and follow-up data (at 6 months) will be collected, examining measures of feasibility, acceptability, and intervention effect size. CONCLUSIONS: Study findings will inform future practice by examining feasibility of key workers enhancing physical health through improved interaction between primary and secondary care. By identifying issues involved in enhancing recruitment and retention, as well as the likely effect size, the study will inform a future definitive intervention. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13115.

Two-year outcome of vagus nerve stimulation in treatment-resistant depression.

One of the major goals of antidepressant treatment is a sustained response and remission of depressive symptoms. Some of the previous studies of vagus nerve stimulation (VNS) have suggested antidepressant effects. Our naturalistic study assessed the efficacy and the safety of VNS in 74 European patients with therapy-resistant major depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS. Mixed-model repeated-measures analysis of variance revealed a significant reduction (P < or = 0.05) at all the 3 time points in the 28-item Hamilton Rating Scale for Depression (HRSD28) score, the primary outcome measure. After 2 years, 53.1% (26/49) of the patients fulfilled the response criteria (> or =50% reduction in the HRSD28 scores from baseline) and 38.9% (19/49) fulfilled the remission criteria (HRSD28 scores < or = 10). The proportion of patients who fulfilled the remission criteria remained constant as the duration of VNS treatment increased. Voice alteration, cough, and pain were the most frequently reported adverse effects. Two patients committed suicide during the study; no other deaths were reported. No statistically significant differences were seen in the number of concomitant antidepressant medications. The results of this 2-year open-label trial suggest a clinical response and a comparatively benign adverse effect profile among patients with treatment-resistant depression.

Effect of aspirin on hypothalamic-pituitary-adrenal function and on neuropsychological performance in healthy adults: a pilot study.

RATIONALE: Hypothalamic-pituitary-adrenal axis dysregulation predicts poor clinical and biochemical response to antidepressants. Antiglucocorticoids have therapeutic benefits but most have a troublesome adverse event profile. Aspects of neuropsychological performance, notably working memory, are susceptible to corticosteroid modulation and are impaired in depression. Aspirin has been shown to attenuate the adrenocorticotropic hormone (ACTH) and cortisol response to physiological challenge suggesting its potential to act as an augmenting agent in depression. OBJECTIVES: To examine the effect of sub-acute (300 mg daily for 7 days) aspirin pre-treatment on the cortisol awakening response and the effect of acute (600 mg) and sub-acute aspirin on the neuroendocrine and neuropsychological response to the arginine vasopressin analogue, desmopressin. RESULTS: We demonstrated that aspirin pre-treatment did not attenuate the cortisol or ACTH response to desmopressin but, as hypothesised, significantly reduced the cortisol awakening response and improved working memory. CONCLUSIONS: Further studies to examine the impact of aspirin on neuropsychological performance and HPA axis function are warranted.

Implication of rates of referral to a specialised inpatient neuropsychiatry team.

OBJECTIVES: This study examined and compared the number and pattern of referrals from neurosurgery and neurology specialist services to the inpatient liaison neuropsychiatry service in the years 2002 and 2005. We estimated the prevalence of psychiatric illness and evaluated the results of subsequent psychiatric assessment and follow-up of all patients reviewed by the neuropsychiatry service. METHODS: The medical notes of those patients referred to the neuropsychiatry team were retrospectively examined to obtain appropriate information on assessment and management of these cases. RESULTS: There were 544 referrals over the two years selected for study. Rates of referral to the inpatient neuropsychiatry service increased overall by 35% between 2002 and 2005. Overall, referrals from neurology comprised 85%, neurosurgery 15%. Patients with epilepsy comprised the majority of referrals (36%). A total of 378 (73%) had an acute psychiatric disorder and this group had a significantly higher rate (p = 0.01) of past psychiatric disorder (40%) than that in those with no acute mental illness (33%). Depressive episode was the most frequent acute psychiatric diagnosis (38%), followed by anxiety and organic psychiatric disorder (both 15%). Overall, 21% of patients diagnosed with acute mental illness were referred on discharge to the neuropsychiatry outpatient clinic for specialist follow up and the remainder followed-up by either local mental health teams or their GP. CONCLUSIONS: These findings provide clear evidence that further resources should be allocated to expanding neuropsychiatry mental health services to improve detection and management of mental illness in this vulnerable patient group.

Maximizing treatment outcomes in the depressed patient.

Depression is a serious illness associated with morbidity and mortality, but it is treatable. However, outcomes are often far from ideal with patients left with residual symptoms of depression. These are associated with poor social functioning and an increased risk of relapse.

Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study.

We evaluated the efficacy and safety of vagus nerve stimulation therapy in the treatment of 11 patients with chronic treatment-resistant depression. Mood was evaluated at frequent intervals over the year following implantation. All measures of depression, including the Hamilton Rating Scale for Depression reduced significantly. The response and remission rates were 55% and 27% respectively at 1 year. Side-effects were common, and some were severe.

The effects of vagus nerve stimulation on pro- and anti-inflammatory cytokines in humans: a preliminary report.

OBJECTIVE: Vagus nerve stimulation (VNS) is a novel therapy in resistant epilepsy, and is undergoing clinical trials in resistant depression. The mechanism of action of VNS is assumed to be due to modulation of deep brain structures via its afferent connections. As the vagus nerve has potentially important immunological actions that may have relevance to its therapeutic effects, we hypothesised that an additional mechanism may occur via vagally mediated actions on cytokine synthesis. METHODS: Patients (n=10) with resistant depression were studied in the weeks prior to, and 3 months following, implantation of a vagus nerve stimulator. No medication changes were made during the course of the study. High-sensitivity ELISA kits were used to measure plasma IL-1 beta, IL-6, TNF-alpha, IL-10 and TGF-beta concentrations. C-reactive protein (CRP) was measured using a high sensitivity immunonephelometry assay. RESULTS: There were highly significant increases in the plasma levels of IL-6, TNF-alpha and TGF-beta. Increases seen with IL-10 and IL-1 beta were not significant. Plasma CRP levels were unchanged. CONCLUSION: VNS is associated with marked peripheral increases in pro- and anti-inflammatory circulating cytokines. Such changes are unlikely to be non-specific inflammatory reactions, reflected by CRP levels. In view of gathering evidence supporting a role for the immune system in modulating affect, as well as seizure activity, these effects of VNS may be therapeutically relevant.

Changes in hypothalamic-pituitary-adrenal axis measures after vagus nerve stimulation therapy in chronic depression.

BACKGROUND: Little is known about the hypothalamic-pituitary-adrenal (HPA) axis stress system in chronic depression. This study examined the corticotropin-releasing hormone (CRH) challenge test in a group of patients with chronic depression, before and after 3 months of treatment with vagus nerve stimulation (VNS) therapy, and a matched group of healthy control subjects. METHODS: Key inclusion criteria were DSM-IV-defined major depressive disorder, a history of a current episode lasting for at least 2 years, and unresponsiveness to at least two classes of antidepressant medications. Eleven test subjects and 11 matched control subjects underwent a CRH challenge. RESULTS: There were significant reductions in depression scores over the study period. The CRH/ACTH (adrenocorticotropic hormone) responses in the depressed group before VNS implantation were significantly higher than in the healthy group and were reduced to normal values after VNS treatment. Some measures of cortisol response were elevated before treatment and were reduced to normal over the study period. The only clinical measure correlated with HPA axis alterations was reduction in atypical depressive symptom scores. CONCLUSIONS: These preliminary results suggest that chronic depression, in contrast to acute melancholic depression, might be characterized by increased ACTH response to CRH challenge. Short-term treatment with VNS therapy was associated with normalization of this response.

Long-stay forensic psychiatric inpatients in the Republic of Ireland: aggregated needs assessment.

OBJECTIVES: To profile the current cohort of forensic psychiatric inpatients in the Republic of Ireland, comparing psychiatric healthcare and placement needs of long-stay patients with those more recently admitted. METHOD: All forensic psychiatric inpatients in the Central Mental Hospital, Dundrum on a census date were included in the study. Patients and key worker were interviewed using a standardised schedule and validated research instruments. Static and dynamic risk factors for violence including demographic, diagnostic and legal characteristics were supplemented by detailed chart review. Standardised anonymised case vignettes were presented to panels of forensic and community psychiatric multidisciplinary teams who assessed current and future treatment and placement requirements for the cohort. RESULTS: There were 88 forensic psychiatric inpatients on the census date. Forty-three had lengths of stay over two years (17 over 20 years). Both patient groups were predominantly males with severe mental illness and histories of violent offending. The majority of the long-stay group were receiving regular parole and this group had lower levels of positive symptoms and comorbid substance misuse disorders. Significant gaps in existing rehabilitation inputs were identified. Almost half the long-stay patients were inappropriately placed. Thirty per cent of long-stay patients could be safely transferred to lower levels of security within six months and 63% within three years. CONCLUSIONS: Holding patients in conditions of excessive security impedes rehabilitation and has considerable human rights implications. Almost half of long-stay forensic psychiatric patients in Ireland are inappropriately placed. Barriers to discharge include legislative inadequacies, lack of local low-secure facilities and under-resourcing of community psychiatric services. Such barriers lead to inappropriate utilisation of limited resources and limit access to secure facilities for higher-risk mentally disordered offenders. These findings are of particular relevance in the context of proposed new insanity legislation.