Befriending by volunteers has the potential to reduce the frequent social isolation of patients with schizophrenia and thus improve health outcomes. However, trial-based evidence for its effectiveness is limited.

To conduct a randomised controlled trial of befriending for patients with schizophrenia or related disorders.

Patients were randomised to a befriending programme for 1 year or to receive information about social activities only (trial registration: ISRCTN14021839). Outcomes were assessed masked to allocation at the end of the programme; at 12 months and at a 6-month follow-up. The primary outcome was daily time spent in activities (using the Time Use Survey (TUS)) with intention-to-treat analysis.

A total of 124 patients were randomised (63 intervention, 61 active control) and 92 (74%) were followed up at 1 year. In the intervention group, 49 (78%) met a volunteer at least once and 31 (49%) had more than 12 meetings. At 1 year, mean TUS scores were more than three times higher in both groups with no significant difference between them (adjusted difference 8.9, 95% CI −40.7 to 58.5, P = 0.72). There were no significant differences in quality of life, symptoms or self-esteem. However, patients in the intervention group had significantly more social contacts than those in the control group at the end of the 12-month period. This difference held true at the follow-up 6 months later.

Although no difference was found on the primary outcome, the findings suggest that befriending may have a lasting effect on increasing social contacts. It may be used more widely to reduce the social isolation of patients with schizophrenia.

Early intervention in psychosis is a complex intervention, usually delivered in a specialist stand-alone setting, which aims to improve outcomes for people with psychosis. Previous studies have been criticised because the control used did not accurately reflect actual practice.

To evaluate the cost-effectiveness of early intervention by estimating the incremental net benefit (INB) of an early-intervention programme, delivered in a real-world setting. INB measures the difference in monetary terms between alternative interventions.

Two contemporaneous incidence-based cohorts presenting with first-episode psychosis, aged 18–65 years, were compared. Costs and outcomes were measured over 1 year. The main outcome was avoidance of a relapse that required admission to hospital or home-based treatment.

From the health sector perspective, the probability that early intervention was cost-effective was 0.77. The INB was €2465 per person (95% CI − €4418 to €9347) when society placed a value of €6000, the cost of an in-patient relapse, on preventing a relapse requiring admission or home care. Following adjustment, the probability that early intervention was cost-effective was 1, and the INB to the health sector was €3105 per person (95% CI −€8453 to €14 663). From a societal perspective, the adjusted probability that early intervention was cost-effective was 1, and the INB was €19 928 per person (95% CI − €2075 to €41 931).

Early intervention has a modest INB from the health sector perspective and a large INB from the societal perspective. The perspective chosen is critical when presenting results of an economic evaluation of a complex intervention.

Little is known about long-term employment outcomes for patients with first-episode schizophrenia-spectrum (FES) disorders who received early intervention services.

We compared the 10-year employment trajectory of patients with FES who received early intervention services with those who received standard care. Factors differentiating the employment trajectories were explored.

Patients with FES (N = 145) who received early intervention services in Hong Kong between 1 July 2001 and 30 June 2002 were matched with those who entered standard care 1 year previously. We used hierarchical clustering analysis to explore the 10-year employment clusters for both groups. We used the mixed model test to compare cluster memberships and piecewise regression analysis to compare the employment trajectories of the two groups.

There were significantly more patients who received the early intervention service in the good employment cluster (early intervention: N = 98 [67.6%]; standard care: N = 76 [52.4%]; P = 0.009). In the poor employment cluster, there was a significant difference in the longitudinal pattern between early intervention and standard care for years 1–5 (P < 0.0001). The number of relapses during the first 3 years, months of full-time employment during the first year and years of education were significant in differentiating the clusters of the early intervention group.

Results suggest there was an overall long-term benefit of early intervention services on employment. However, the benefit was not sustained for all patients. Personalisation of the duration of the early intervention service with a focus on relapse prevention and early vocational reintegration should be considered for service enhancement.

Although clozapine is often discontinued, there is a paucity of guidelines and evidence on treatment options after clozapine discontinuation. Moreover, it is currently unknown whether reinstating clozapine in patients formerly using clozapine should be avoided.

To compare the real-world effectiveness of antipsychotics after clozapine cessation.

From Finnish registry data (1995–2017), we identified 2250 patients with schizophrenia who had been using clozapine for ≥1 year before treatment cessation. The primary analysis consisted of adjusted within-individual analyses of psychiatric ward readmission owing to psychosis and treatment failure. Secondary analyses concerned between-individual mortality differences.

Compared with no use of antipsychotics, risk of psychiatric ward readmission was lowest for reinitiation of clozapine (adjusted hazard ratio (aHR) 0.49; 95% CI 0.40–0.61; P < 0.0001), oral olanzapine (aHR 0.58; 95% CI 0.48–0.71; P < 0.0001) and antipsychotic polypharmacy (aHR 0.62; 95% CI 0.53–0.72; P < 0.0001). Risk of treatment failure was lowest for aripiprazole long acting injectable (aHR 0.42; 95% CI 0.27–0.65; P < 0.0001), reinitiation of clozapine (aHR 0.49; 95% CI 0.43–0.57; P < 0.0001) and oral olanzapine (aHR 0.69; 95% CI 0.61–0.77; P < 0.0001). Mortality risk was lowest for reinitiation of clozapine (aHR 0.18; 95% CI 0.09–0.36; P < 0.0001) and oral olanzapine (aHR 0.26; 95% CI 0.17–0.40; P < 0.0001).

Clozapine and olanzapine are the most effective and safest treatment options in those discontinuing clozapine for undefined reasons. Clozapine should therefore be reconsidered in patients with schizophrenia who previously discontinued this compound.

Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.

This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.

Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.

Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.

Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

Purported superior outcomes for treatment of psychosis in low- and middle-income (LMICs) compared with high-income (HICs) countries have not been examined in the context of early intervention services (EIS).

To compare 2-year clinical outcomes in first-episode psychosis (FEP) treated in EIS in Chennai (LMIC) and Montreal (HIC) using a similar EIS treatment protocol and to identify factors associated with any outcome differences.

Patients with FEP treated in EIS in Chennai (n = 168) and Montreal (n = 165) were compared on change in level of symptoms and rate and duration of positive and negative symptom remission over a 2-year period. Repeated-measures analysis of variance, and logistic and linear regression analyses were conducted.

Four patients died in Chennai compared with none in Montreal. Family support was higher for Chennai patients (F = 14.05, d.f. = 1, P < 0.001, ƞp2 = 0.061) and increased over time at both sites (F = 7.0, d.f. = 1.915, P < 0.001, ƞp2 = 0.03). Negative symptom outcomes were significantly better in Chennai for level of symptoms (time × site interaction F = 7.36, d.f. = 1.49, P = 0.002, ƞp2 = 0.03), duration of remission (mean 16.1 v. 9.78 months, t = −7.35, d.f. = 331, P < 0.001, Cohen's d = 0.80) and the proportion of patients in remission (81.5% v. 60.3%, χ2 = 16.12, d.f. = 1, P < 0.001). The site differences in outcome remained robust after adjusting for inter-site differences in other characteristics. Early remission and family support facilitated better outcome on negative symptoms. No significant differences were observed in positive symptom outcomes.

Patients with FEP treated in EIS in LMIC contexts are likely to show better outcome on negative symptoms compared with those in HIC contexts. Early remission and family support may benefit patients across both contexts.