Antidepressants for the prevention of depression following first-episode psychosis (ADEPP): study protocol for a multi-centre, double-blind, randomised controlled trial.

BACKGROUND: Depressive episodes are common after first-episode psychosis (FEP), affecting more than 40% of people, adding to individual burden, poor outcomes, and healthcare costs. If the risks of developing depression were lower, this could have a beneficial effect on morbidity and mortality, as well as improving outcomes. Sertraline is a selective serotonin reuptake inhibitor and a common first-line medication for the treatment of depression in adults. It has been shown to be safe when co-prescribed with antipsychotic medication, and there is evidence that it is an effective treatment for depression in established schizophrenia. We present a protocol for a multi-centre, double-blind, randomised, placebo-controlled clinical trial called ADEPP that aims to investigate the efficacy and cost-effectiveness of sertraline in preventing depression after FEP. METHODS: The recruitment target is 452 participants between the ages of 18 and 65 years who are within 12 months of treatment initiation for FEP. Having provided informed consent, participants will be randomised to receive either 50 mg of sertraline daily or matched placebo for 6 months, in addition to treatment as usual. The primary outcome measure will be a comparison of the number of new cases of depression between the treatment and placebo arms over the 6-month intervention phase. Secondary outcomes include suicidal behaviour, anxiety, rates of relapse, functional outcome, quality of life, and resource use. DISCUSSION: The ADEPP trial will test whether the addition of sertraline following FEP is a clinically useful, acceptable, and cost-effective way of improving outcomes following FEP. TRIAL REGISTRATION: ISRCTN12682719 registration date 24/11/2020.

Duration of untreated psychosis and clinical outcomes of first episode psychosis: An observational and an instrumental variables analysis.

AIM: Duration of untreated psychosis (DUP) is considered as a key prognostic variable in psychosis. Yet, it is unclear whether a longer DUP causes worse outcomes or whether reported associations have alternative explanations. METHODS: Data from 2 cohorts of patients with first episode psychosis were used (n = 2134). Measures of DUP were assessed at baseline and outcomes at 12 months. Regression models were used to investigate the associations between DUP and outcomes. We also investigated whether any associations were replicated using instrumental variables (IV) analysis to reduce the effect of residual confounding and measurement bias. RESULTS: There were associations between DUP per 1-year increase and positive psychotic symptoms (7.0% in symptom score increase 95% confidence interval (CI) 4.0%, 10.0%, P < .001), worse recovery (risk difference [RD] 0.78, 95%, CI 0.68, 0.83, P < .001) and worse global functioning (0.62 decrease in functioning score 95% CI -1.19, -0.04, P = .035). There was no evidence of an association with negative psychotic symptoms (1.0%, 95%, CI -2.0%, 5.0%, P = .455). The IV analysis showed weaker evidence of associations in the same direction between DUP per 1-year increase and positive psychotic symptoms, recovery and global functioning. However, there was evidence of an inverse association with negative psychotic symptoms (decrease of 15.0% in symptom score 95% CI -26.0%, -3.0%, P = .016). CONCLUSIONS: We have confirmed previous findings of a positive association between positive psychotic symptoms, global functioning and recovery and DUP using regression analysis. IV analysis shows some support for these findings. Future investigation using IV analysis should be repeated in large data sets.

Negative symptoms in first-episode psychosis: Clinical correlates and 1-year follow-up outcomes in London Early Intervention Services.

AIM: Negative symptoms (NS) have been associated with poor outcome and remain difficult to treat in patients with psychosis. This study examined the association of NS with clinical features at first presentation to mental health services for psychosis and with outcomes at 1-year follow-up. METHODS: Clinical data were utilized from five London Early Intervention Services (EIS) included in the MiData audit database. The sample comprised 484 first-episode psychosis patients with complete Positive and Negative Syndrome Scale data at baseline and 1-year follow-up. Multiple imputation (N = 50) was conducted to account for missing follow-up data. RESULTS: Baseline NS were associated with male gender (B = -1.63, P < .05), younger age at onset (B = -.15, P <. 05), a higher level of impairment on the Global Assessment of Functioning (disability) Scale at baseline (B = -.19, P <. 010), an absence of reported substance misuse prior to baseline assessment (B = -3.05, P <. 001) and unemployment at baseline (B = -.93, P <. 01). At 1-year follow-up, NS at presentation were associated with worse Global Assessment of Functioning Scale for symptom (B = -.28, P < .01) and disability (B = -.27, P <. 05) and with hospital admission (OR = 1.06, P < .01). CONCLUSIONS: Negative symptoms at presentation to EIS were associated with worse functioning at entry and poorer outcomes 1 year later. Future research is required to better understand the aetiology and trajectories of NS in early psychosis and propose novel targeted interventions.

Clinical and demographic differences between patients with manic, depressive and schizophrenia-spectrum psychoses presenting to Early Intervention Services in London.

AIM: To investigate the relationship between the presenting clinical and demographic characteristics in first-episode psychosis (FEP) patients with their clinical diagnostic grouping 1 year later. METHODS: Data from 1014 first-presentation psychosis patients from seven London-based Early Intervention Services were extracted from the MiData audit database. Associations between clinical and demographic measures at presentation and clinical diagnosis made at 1 year were assessed with analysis of variance (ANOVA) and Chi-square tests. RESULTS: The sample comprised 76% of patients with schizophrenia-spectrum diagnoses, 9% with manic psychoses (MP) and 6% with depressive psychoses. Compared to the other 2 groups, patients who were diagnosed as having MP were younger, with higher education and shorter duration of untreated psychosis, and had higher Young Mania Rating Scale scores at presentation and lower Positive and Negative Syndrome Scale (PANSS) negative scores. Patients diagnosed at 1 year as having depressive psychosis were older and more likely to be white, with the lowest PANSS positive scores at baseline. Patients diagnosed at 1 year as having schizophrenia spectrum diagnoses were more likely to be males. Patients in the 3 diagnostic subgroups of psychosis differed on both clinical and demographic characteristics at presentation. CONCLUSIONS: There were significant clinical and demographic differences at presentation between FEP patients who received different clinical diagnoses at 1 year. Future work should determine the extent to which these differences can be used to guide clinical care.

Gender differences in one-year outcomes of first-presentation psychosis patients in inner-city UK Early Intervention Services.

AIM: Men and women have historically been shown to differ in their presentation and outcome of psychotic disorders and thus are likely to have different treatment needs. It is unclear whether Early Intervention Services (EIS) are able to provide equitable care for both men and women presenting for the first time with psychosis. The main aim of this study was to explore gender differences for first-presentation psychosis patients at the time of their referral to inner-city EIS and their outcomes 1 year later. METHODS: Audit data were utilized from 1098 first-presentation psychosis patients from seven EIS across London, UK, collected via the computerized MiData package. Binary logistic regression was employed to detect potential associations between gender and (i) initial clinical presentation (including duration of untreated psychosis, pathways to care, risk behaviours); and (ii) 1-year clinical and functional outcomes. RESULTS: At entry to EIS, male patients presented with more violent behaviour whereas female patients had more suicide attempts. Following 1 year of EIS care, men still presented as more violent towards others whereas women were more likely to have been admitted to a psychiatric ward. CONCLUSION: Gender differences in clinical outcome, service use and risk behaviours were apparent within the first year of specialist psychosis care. This may be partly due to the different pathways to care taken by men and women and differences in clinical presentation. Greater focus on the specific needs of each gender by EIS in detection and intervention is required to improve equality of outcome.

Schizophrenia in a Primary Care Setting.

In recent years, the focus of mental health care for people with schizophrenia has shifted from an expectation of lifelong disability to a 'recovery' approach in which patients and specialists anticipate discharge to management within primary care. Although the active symptoms of mental illness are generally well-managed with modern pharmacotherapy, primary care physicians often express concern about their lack of understanding and expertise in general management of schizophrenia. Moreover, the ability of patients to access care for their physical disorders in a timely fashion together with a higher prevalence of physical co-morbidities is likely to be responsible for the greater mortality and premature death of this already stigmatised and disadvantaged group. This paper focuses on new evidence over the past 5 years, considering the management of physical and mental health of schizophrenia patients in primary care, optimal processes and the reasons why these may not always be realised in practice.

Predictors of vocational activity over the first year in inner-city early intervention in psychosis services.

AIM: Work and educational activities are an important part of recovery for young people with psychosis, and improving vocational outcomes is a key target for early intervention services (EIS). This study evaluated predictors of vocational activity for first-episode psychosis (FEP) patients during the first year of EIS care. It was hypothesized that longer duration of untreated psychosis (DUP) and minority ethnic status would predict poorer vocational outcomes, whereas a history of good vocational functioning would predict better vocational functioning during follow up. METHODS: FEP patients aged 14-35 years, who presented to seven EIS in London, UK, between 2003 and 2010, were followed for 1 year. Sociodemographic, clinical and vocational information (qualifications obtained and paid employment) were collected using the MiData audit tool at entry to EIS and 1 year later. RESULTS: Approximately one-third of patients (n = 345/1013) were studying or employed at some point during the first year of EIS care. Baseline vocational activity was the strongest predictor of vocational functioning during 1 year of follow up. Moreover, employment prior to entry into EIS strongly predicted change in vocational activity during 1 year of follow up. Individuals with DUP <6 months or of Asian or black African origin were more likely to be studying than their white British counterparts. CONCLUSION: This study confirms that a significant proportion of FEP patients are able to engage in meaningful vocational activities even within the first year of EIS care. However, services need to focus more resources on getting patients with poor educational or employment histories into training programmes to improve their vocational outcomes.

Ethnic variations in compulsory detention and hospital admission for psychosis across four UK Early Intervention Services.

BackgroundSubstantial ethnic variations have been found in incidence, pathways to care and outcomes in psychosis. It is unknown whether these remain as marked in the presence of specialist Early Intervention Services (EIS) for psychosis. We present the first UK study exploring ethnic differences in compulsory detention and hospitalization rates for EIS patients. We investigated whether the excess rates of compulsory admission for people from Black groups have persisted following nationwide introduction of EIS. We also explored variations in compulsory admission for other ethnic groups, and differences by gender and diagnosis.MethodsFour inner-city London EIS teams gathered data from first-presentation psychosis patients between 2004¿2009 using the MiData audit tool. Clinical, sociodemographic and pathways to care data were recorded regarding adult patients from eight different ethnic groups at entry to EIS and one year later.ResultsBlack African EIS service users had odds of being detained and of being hospitalised three times greater than White British patients, even after adjustment for confounders. This was most marked in Black African women (seven to eight times greater odds than White British women). A post-hoc analysis showed that pathways to care and help-seeking behaviour partially explained these differences.ConclusionThese findings suggest EIS input in its current form has little impact on higher admission and detention rates in certain Black and minority groups. There is a need to tackle these differences and engage patients earlier, focusing on the needs of men and women from the most persistently affected groups.

Duration of untreated psychosis in adolescents: ethnic differences and clinical profiles.

BACKGROUND: Duration of Untreated Psychosis (DUP) is an important measure associated with outcome of psychosis. This first study in the UK compared DUP between adolescent and adult-onset individuals and explored whether the adolescent-onset group showed variations in DUP that could be accounted for by sociodemographic and selected risk factors. METHODS: This naturalistic cohort study included 940 new first-episode psychosis cases aged 14-35years (136 adolescent-onset versus 804 adult-onset psychotic individuals) referred to nine Early Intervention Services for Psychosis in London (2003-2009). Sociodemographic characteristics, age of onset, family history of mental illness, duration of untreated psychosis, suicidality and substance use information were collected at entry to the services. RESULTS: Adolescents presented with significantly greater median DUP (179days) than adults (81days, p=0.005). Large differences in DUP were found amongst adolescent ethnic groups (median DUP: White: 454days; Black: 103days; Asian and mixed: 28.5days). In addition, younger age of onset and higher lifetime cannabis use were associated with longer treatment delay amongst adolescents. CONCLUSIONS: This study of DUP in adolescent-onset psychosis found it to be approximately twice the length of DUP amongst adults. For the adolescent White sub-group, DUP was far greater than the UK Department of Health target (<3months). Both the high rates of lifetime cannabis use and the lower age of onset might explain the long DUP in this ethnic group. Physicians need to be particularly vigilant about identifying and managing early psychosis in adolescents.

Ethnic variations in pathways into early intervention services for psychosis.

BACKGROUND: Ethnic variations have previously been identified in the duration of untreated psychosis (DUP) and pathways into psychiatric services. These have not been examined in the context of early intervention services, which may alter these trajectories. AIMS: To explore ethnic differences in the nature and duration of pathways into early intervention services. METHOD: In a naturalistic cohort study, data were collected for 1024 individuals with psychotic disorders accepted for case management by eight London early intervention services. RESULTS: Duration of untreated psychosis was prolonged in the White British group compared with most other ethnic groups. White British individuals were more likely to make contact with their general practitioner and less likely to be seen within emergency medical services. All Black patient groups were more likely than their White British counterparts to experience involvement of criminal justice agencies. CONCLUSIONS: Variations continue to exist in how and when individuals from different ethnic groups access early intervention services. These may account for disparities in DUP.

Evidence of the effectiveness of a specialist vocational intervention following first episode psychosis: a naturalistic prospective cohort study.

BACKGROUND: Employment rates among people with severe mental illness are low and work has beneficial effects on mental health. There is now good evidence of the effectiveness of a specialist vocational intervention (supported employment) in people with schizophrenia. However, the potential benefits of modifying this model for use in first episode psychosis cohorts remain relatively untested. METHODS: The aim of our study was to evaluate the effectiveness of a specialist vocational intervention in aiding vocational recovery following the onset of first episode psychosis. In a naturalistic prospective cohort study, 114 first episode psychosis service users were followed up during 12 months of engagement with an early intervention service; 44 resident in an area where a vocational intervention was available and 70 in an area where it was not. RESULTS: The main finding in our study was that having access to the specialist vocational intervention was a statistically significant independent predictor of vocational recovery during 12 months of follow-up (after adjusting for confounders). Service users who had access to the intervention had odds of achieving vocational recovery 3.53 times greater than those who did not (OR = 3.53, 95% CI = 1.25-10.00). CONCLUSION: This study provides further preliminary evidence of the effectiveness of a specialist vocational intervention following first episode psychosis. This is an important outcome from the perspective of service users and clinicians alike (as well as having wider societal value). Other important predictors of vocational recovery cannot be modified by the time a first episode psychosis emerges.