Relapse Prevention In Schizophrenia Research Articles

Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data

There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence. We conducted network meta-analyses using individual participant data from Swedish and Finnish national registries and aggregate data from RCTs. The target population was adults (age >18 and <65 years) with schizophrenia and schizoaffective disorder with stabilised symptoms. We analysed each registry separately to obtain hazard ratios (HRs) and 95% CIs for relapse within 6 months post-antipsychotic initiation as our main outcome. Interventions studied were antipsychotics, no antipsychotic use, and placebo. We compared HRs versus a reference drug (oral haloperidol) between registries, and between registry individuals who would be eligible and ineligible for RCTs, using the ratio of HRs. We synthesised evidence using network meta-analysis and compared results from our network meta-analysis of real-world data with our network meta-analysis of RCT data, including oral versus long-acting injectable (LAI) formulations. Finally, we conducted a joint real-world and RCT network meta-analysis. We included 90 469 individuals from the Swedish and Finnish registries (mean age 45·9 [SD 14·6] years; 43 025 [47·5%] women and 47 467 [52·5%] men, ethnicity data unavailable) and 10 091 individuals from 30 RCTs (mean age 39·6 years [SD 11·7]; 3724 [36·9%] women and 6367 [63·1%] men, 6022 White [59·7%]). We found good agreement in effectiveness of antipsychotics between Swedish and Finnish registries (HR ratio 0·97, 95% CI 0·88-1·08). Drug effectiveness versus no antipsychotic was larger in RCT-eligible than RCT-ineligible individuals (HR ratio 1·40 [1·24-1·59]). Efficacy versus placebo in RCTs was larger than effectiveness versus no antipsychotic in real-world (HR ratio 2·58 [2·02-3·30]). We found no evidence of differences between effectiveness and efficacy for between-drug comparisons (HR ratio vs oral haloperidol 1·17 [0·83-1·65], where HR ratio >1 means superior effectiveness in real-world to RCTs), except for LAI versus oral comparisons (HR ratio 0·73 [0·53-0·99], indicating superior effectiveness in real-world data relative to RCTs). The real-world network meta-analysis showed clozapine was most effective, followed by olanzapine LAI. The RCT network meta-analysis exhibited heterogeneity and inconsistency. The joint real-world and RCT network meta-analysis identified olanzapine as the most efficacious antipsychotic amongst those present in both RCTs and the real world registries. LAI antipsychotics perform slightly better in the real world than according to RCTs. Otherwise, RCT evidence was in line with real-world evidence for most between-drug comparisons, but RCTs might overestimate effectiveness of antipsychotics observed in routine care settings. Our results further the understanding of the generalisability of RCT findings to clinical practice and can inform preferential prescribing guidelines. None.

Psychosocial and psychological interventions for schizophrenia relapse prevention: A bibliometric analysis.

Various psychosocial and psychological interventions have been developed to reduce schizophrenia relapse prevention. A better understanding of these active interventions is important for clinical practice and for meaningful allocation of resources. However, no bibliometric analysis of this area has been conducted. Studies were retrieved from the Web of Science Core Collection database. The publication outputs and cooperation of institutions were visualized with Origin 2021. Global cooperation was visualized using ArcGIS Pro3.0. VOSviewer was used to generate visualizations of network of authors and keywords. The number of annual publications generally showed a fluctuating upward trend over the past 20years. Germany published the most relevant articles (361, 26.76%). The Technical University of Munich was the most productive institution (70, 9.86%). Leucht Stefan published the most articles (46, 6.48%) and had the highest number of citations (4,375 citations). Schizophrenia Research published the most studies (39, 5.49%). Keywords were roughly classified into three clusters: cognitive behavioral therapy (CBT), family interventions and family psychoeducation and other factors related to interventions. The findings provided the current status of research on psychosocial and psychological interventions for schizophrenia relapse prevention from a bibliometric perspective. Recent research has mainly focused on CBT, family interventions and family psychoeducation.

Does Slow and Steady Win the Race? Rates of Antipsychotic Discontinuation, Antipsychotic Dose, and Risk of Psychotic Relapse.

Antipsychotics are recommended for prevention of relapse in schizophrenia. It is unclear whether increased risk of relapse following antipsychotic discontinuation is predominantly associated with an absolute magnitude of dose reduction or rate of antipsychotic reduction. Establishing the responsible mechanism is important because prolonged withdrawal schedules have been suggested to reduce risk of relapse. Individual patient data from antipsychotic discontinuation studies were obtained. We estimated the occupancy of receptors over time using half-lives and median effective dose ED50 values obtained from pharmacokinetic and receptor occupancy studies. Hazard ratios for relapse events were calculated using Cox proportional hazards models to assess the influence of formulation (oral, 1-monthly, and 3-monthly injections). The change in hazard ratio over time was estimated, and the effect of time-varying covariates was calculated, including rate of occupancy reduction and absolute receptor occupancy. Five studies including 1388 participants with schizophrenia were identified (k = 2: oral, k = 2: 1-monthly injection, k = 1: 3-monthly injection). Withdrawal of long-acting injectable medication did not lead to a lower hazard ratio compared with withdrawal of oral medication, and this included the period immediately following randomization. Hazard ratios were not associated with the rate of decline of receptor occupancy; however, they were associated with reduced absolute occupancy in trials of long-acting injections (P = .038). Antipsychotic discontinuation is associated with an increased risk of psychotic relapse, related to receptor occupancy. Although relapse does not appear to be related to the rate of discontinuation, gradual discontinuation strategies may allow for easier antipsychotic reinstatement in case of symptomatic worsening.

Treatment Journey From Diagnosis to the Successful Implementation of a Long-Acting Injectable Antipsychotic Agent in Young Adults With Schizophrenia.

Objective: Long-acting injectable antipsychotic agents (LAIs) are effective in schizophrenia relapse prevention but are often underutilized. This study aims to understand treatment patterns leading to a successful LAI implementation following schizophrenia diagnosis in a large dataset that included commercially insured patients in the United States.Methods: Patients aged 18-40 years with a first schizophrenia diagnosis (per ICD-9 or ICD-10 criteria), successful second-generation LAI implementation (defined a priori as ≥ 90 consecutive days of use), and ≥ 1 second-generation oral antipsychotic agent (OA) were identified from IBM MarketScan Commercial and Medicare Supplemental databases from January 1, 2012, to December 31, 2019. Outcomes were measured descriptively.Results: Of 41,391 patients with newly diagnosed schizophrenia, 1,836 (4%) received ≥ 1 LAI; 202 (< 1%) met eligibility criteria of successful LAI implementation following ≥ 1 second-generation OA. Median (range) time between diagnosis and first LAI was 289.5 (0-2,171) days, time between LAI initiation and successful implementation was 90.0 (90-1,061) days, and time to LAI discontinuation after successful implementation was 166.5 (91-799) days. Before LAI initiation, 58% received ≥ 2 OAs. For 86% with successful LAI implementation, the implementation was accomplished with the first LAI.Conclusions: In this dataset of mainly commercially insured patients, LAI use in early-phase schizophrenia was very low (4%). For the majority for whom a LAI was successfully implemented per a priori definition, the implementation was accomplished with the first LAI and in a short period of time (90 days). However, even when LAIs were used in early-phase schizophrenia, they were generally not the first therapy, as most patients had several prior OA treatments.

Crossroads of methodological choices in research synthesis: insights from two network meta-analyses on preventing relapse in schizophrenia

In recent years, network meta-analyses have been increasingly carried out to inform clinical guidelines and policy. This approach is under constant development, and a broad consensus on how to carry...

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia

Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

Digital aids for relapse prevention in schizophrenia

Psychosocial interventions are an important adjunct to pharmacotherapies in the maintenance treatment of people with schizophrenia. In the pharmacological maintenance trials, when patients are switched to placebo after responding to acute phase treatment, up to 60% relapse within a year; on maintenance antipsychotics, this proportion is 24%, without important differences among the drugs.1,2 In other words, one in four patients with schizophrenia might still relapse under well-supervised maintenance pharmacotherapy within a year.

Effective family interventions for people with schizophrenia

It is encouraging to read a research paper with findings ready for immediate translation to clinical practice. In The Lancet Psychiatry, Alessandro Rodolico, Irene Bighelli and colleagues 1 Rodolico A Bighelli I Avanzato C et al. Family interventions for relapse prevention in schizophrenia: a systematic review and network meta-analysis. Lancet Psychiatry. 2022; (published online Jan 27.)https://doi.org/10.1016/S2215-0366(21)00437-5 Google Scholar report the findings of a thorough systematic review and network meta-analysis of family interventions for relapse prevention in schizophrenia. The authors evaluated 90 randomised controlled trials, with more than 10 000 participants, and identified 11 different models of family therapy. Sometimes simple is best. Family psychoeducation alone reduced the relapse rate significantly when compared with treatment as usual, and to a larger extent than more complex interventions. The findings showed that informing the family about the illness, symptoms, and treatment options had a protective role in the prevention of relapse: about 10% of patients involved in family psychoeducation relapsed compared with 37% among patients who received treatment as usual. Family interventions for relapse prevention in schizophrenia: a systematic review and network meta-analysisAlmost all family intervention models were efficacious in preventing relapse in schizophrenia. Family psychoeducation alone, without behavioural or skills training, was superior to the more complex models. Our results suggest that in contexts where there are financial constraints, family psychoeducation alone should be implemented. Full-Text PDF

Family interventions for relapse prevention in schizophrenia: a systematic review and network meta-analysis

Family interventions are efficacious for relapse prevention in schizophrenia. Multiple different models have been developed. We aimed to compare the efficacy, acceptability, and tolerability of family interventions for relapse prevention in schizophrenia. In this systematic review and network meta-analysis, we searched for randomised controlled trials that investigated family intervention models aimed at preventing relapse in patients with schizophrenia. We searched EMBASE, MEDLINE, PsycINFO, BIOSIS, CENTRAL, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform up to Jan 20, 2020 and PubMed up to July 15, 2021. We included blinded and open-label randomised controlled trials in which at least 80% of patients had schizophrenia spectrum disorders. We excluded studies in which all patients were acutely ill, had a concurrent medical or psychiatric disorder, or were prodromal or "at risk of psychosis". Study selection and data extraction were done by two independent reviewers. Data were extracted about overall, positive, negative, and depressive symptoms of schizophrenia, quality of life, adherence, overall functioning, family burden, expressed emotion, and discontinuations due to inefficacy. The primary outcome was relapse, measured with operationalised criteria, psychiatric hospital admissions, or clinical judgement. We did a frequentist, random-effects, network meta-analysis to calculate odds ratios ([ORs]; dichotomous outcomes) or standardised mean differences (continuous outcomes) with 95% CIs. The study protocol was registered with PROSPERO, CRD42020169951. We identified 28 395 studies through the database search and 334 from references of previous studies. We compared 11 family intervention models tested on a total of 90 randomised controlled trials with 10 340 participants (3579 females and 5632 males with sex indicated; median age 31 years [range 14-65]) in the network meta-analysis. Ethnicity data were not available. All interventions, with the exception of crisis-oriented interventions and family psychoeducation with two sessions or fewer, reduced the relapse rate significantly when compared with treatment as usual at the primary timepoint of 12 months. ORs compared with treatment as usual ranged from 0·18 (95% CI 0·12-0·27) for family psychoeducation alone to 0·63 (0·42-0·94) for community-based interventions involving family members. The results were robust in various sensitivity and subgroup analyses. The confidence in the estimates ranged from moderate to very low for different comparisons. Almost all family intervention models were efficacious in preventing relapse in schizophrenia. Family psychoeducation alone, without behavioural or skills training, was superior to the more complex models. Our results suggest that in contexts where there are financial constraints, family psychoeducation alone should be implemented. German Ministry for Education and Research.

Real-life effectiveness of transitioning from paliperidone palmitate 1-monthly to paliperidone palmitate 3-monthly long-acting injectable formulation.

Non-adherence to antipsychotics in schizophrenia is associated with an increased risk of psychotic relapse and hospitalization, a risk that is reduced with the use of long-acting injectable (LAI) antipsychotics. Randomized clinical trials (RCTs) have demonstrated the efficacy of paliperidone palmitate 3-monthly (PP3M) for psychotic relapse prevention in schizophrenia, but it remains poorly documented among individuals treated in real-life settings who can benefit the most out of LAIs. The objective of this study was to evaluate the effectiveness of PP3M in relapse prevention among patients with schizophrenia. This is a multicentre retrospective study conducted in four outpatients' clinics across Canada. All consecutive patients with a main diagnosis of schizophrenia who initiated PP3M between June 2016 and March 2020 were included. The primary outcome was psychotic relapse, defined using broad and clinically relevant criteria. Among 178 consecutive patients who were switched to PP3M, the 12-month relapse rate was 18.5% and the relapse-free survival probability was 0.788 (95% confidence interval [CI] = 0.725-0.856). Comorbid diagnoses of personality disorders and substance use disorders were associated with hazard rates (HRs) of 3.6 (95% CI = 1.8-7.3, p < 0.001) and 3.1 (95% CI = 1.6-6.2), respectively. Increased psychopathology severity was associated with an increased likelihood of relapse, while having a job or being in school was protective. These findings reinforce the necessity of conducting research in patients with comorbid psychiatric disorders who are typically underrepresented in RCTs, yet overrepresented in real-life settings, in order to better inform and guide clinical practice.

Contingency planning and risk mitigation strategies for a schizophrenia relapse prevention trial during the COVID-19 pandemic

Contingency planning and risk mitigation strategies for a schizophrenia relapse prevention trial during the COVID-19 pandemic

Time course of adverse events – descriptive data analysis of a schizophrenia relapse prevention trial of cariprazine

Time course of adverse events – descriptive data analysis of a schizophrenia relapse prevention trial of cariprazine

Psychosocial interventions for relapse prevention in schizophrenia: New evidence

The Sri Lanka Journal of Psychiatry (SLJP) is a peer-reviewed, open access journal published bi annually by the Sri Lanka College of Psychiatrists.The Journal publishes original papers, brief reports including case reports and commentaries relevant to psychiatry and allied sciences. The Sri Lanka Journal of Psychiatry is committed to maintaining and conforming to the editorial and ethical standards recommended by the International Committee of Medical Journal Editors.Cover“Perseverance”. These tenacious fishermen in Mannar continue their livelihood despite numerous difficulties. L. N. P. Samarasinghe, Acting Consultant Psychiatrist, Base Hospital Nikaweratiya, Sri Lanka.

Effective psychological interventions for relapse prevention in schizophrenia

In a network meta-analysis, Irene Bighelli and colleagues1 report the most comprehensive and precise evaluation to date of psychological and psychosocial interventions for relapse prevention in schizophrenia. The authors specifically targeted trials with a primary outcome of relapse, assessed either by operationalised criteria or as rehospitalisation, at minimum 12 weeks post-randomisation. Trials targeting patients in the acute or prodromal phase of schizophrenia, “at-risk” for psychosis, or with comorbidities were excluded.

Psychosocial and psychological interventions for relapse prevention in schizophrenia: a systematic review and network meta-analysis

Many psychosocial and psychological interventions are used in patients with schizophrenia, but their comparative efficacy in the prevention of relapse is not known. We aimed to evaluate the efficacy, acceptability, and tolerability of psychosocial and psychological interventions for relapse prevention in schizophrenia. To conduct this systematic review and network meta-analysis we searched for published and unpublished randomised controlled trials that investigated psychosocial or psychological interventions aimed at preventing relapse in patients with schizophrenia. We searched EMBASE, MEDLINE, PsycINFO, BIOSIS, Cochrane Library, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to Jan 20, 2020, and searched PubMed up to April 14, 2020. We included open and masked studies done in adults with schizophrenia or related disorders. We excluded studies in which all patients were acutely ill, had a concomitant medical or psychiatric disorder, or were prodromal or "at risk of psychosis". Study selection and data extraction were done by two reviewers independently based on published and unpublished reports, and by contacting study authors. Data were extracted about efficacy, tolerability, and acceptability of the interventions; potential effect moderators; and study quality and characteristics. The primary outcome was relapse measured with operationalised criteria or psychiatric hospital admissions. We did random-effects network meta-analysis to calculate odds ratios (ORs) or standardised mean differences (SMDs) with 95% CIs. The study protocol was registered with PROSPERO, CRD42019147884. We identified 27 765 studies through the database search and 330 through references of previous reviews and studies. We screened 28 000 records after duplicates were removed. 24 406 records were excluded by title and abstract screening and 3594 full-text articles were assessed for eligibility. 3350 articles were then excluded for a variety of reasons, and 244 full-text articles corresponding to 85 studies were included in the qualitative synthesis. Of these, 72 studies with 10 364 participants (3939 females and 5716 males with sex indicated) were included in the network meta-analysis. The randomised controlled trials included compared 20 psychological interventions given mainly as add-on to antipsychotics. Ethnicity data were not available. Family interventions (OR 0·35, 95% CI 0·24-0·52), relapse prevention programmes (OR 0·33, 0·14-0·79), cognitive behavioural therapy (OR 0·45, 0·27-0·75), family psychoeducation (OR 0·56, 0·39-0·82), integrated interventions (OR 0·62, 0·44-0·87), and patient psychoeducation (OR 0·63, 0·42-0·94) reduced relapse more than treatment as usual at 1 year. The confidence in the estimates ranged from moderate to very low. We found no indication of publication bias. We found robust benefits in reducing the risk of relapse for family interventions, family psychoeducation, and cognitive behavioral therapy. These treatments should be the first psychosocial interventions to be considered in the long-term treatment for patients with schizophrenia. German Ministry for Education and Research.

Relapse prevention in schizophrenia: expectations and reality

Aim. The aim of the paper was to evaluate the practical prospects for preventing from relapsing or worsening in schizophrenia patients. Selected literature review. Some of the recent publications deal with the prospects for preventing from relapsing or worsening symptoms in patients suffering from schizophrenia. This paper reviews publications highlighting the effectiveness of such prevention measures. Conclusions. The review revealed that both pharmacological and non-pharmacological methods of treatment may be useful in the clinical improvement of schizophrenia.

Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia

The doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue. To examine dose-response findings in a meta-analysis of randomized clinical trials. Studies were identified through the Cochrane Schizophrenia Group's Study-Based Register of Trials (March 9, 2020), PubMed (January 1, 2021), and previous reviews. First authors and/or pharmaceutical companies were contacted for additional information. Two reviewers independently selected randomized clinical trials that compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention in patients with stable schizophrenia. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, all parameters in duplicate were extracted and frequentist dose-response random-effects meta-analyses were conducted. Study-defined relapse (primary outcome), rehospitalization, Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale total score reduction from baseline, all-cause discontinuation, and dropouts due to adverse events. Evidence from 72 dose arms from 26 studies with 4776 participants was analyzed. The efficacy-related dose-response curves had a hyperbolic shape meaning that the probability to relapse decreased rapidly with doses of up to 5-mg/d risperidone equivalent (relative relapse risk, 0.43; 95% CI, 0.31-0.57; standardized mean difference for Positive and Negative Syndrome Scale total score reduction, -0.55; 95% CI, -0.68 to -0.41), but flattened thereafter. In contrast, dropouts due to adverse events continued to increase beyond this dose (relative risk at 5 mg/d, 1.38; 95% CI, 0.87-2.55; relative risk at 15 mg/d, 2.68; 95% CI, 1.49-4.62). In a subgroup analysis of patients in remission, a plateau was reached earlier, at approximately 2.5-mg/d risperidone equivalent. The findings of this meta-analysis suggest that doses higher than approximately 5-mg/d risperidone equivalent may provide limited additional benefit for relapse prevention but more adverse events. For patients in remission or who are receiving high-potency first-generation antipsychotics, doses as low as 2.5-mg/d risperidone equivalent may be sufficient. However, caution is needed at this low dose end when further decreases of dose may be accompanied by a disproportionally higher relapse risk. Moreover, the observations are averages, and factors such as slow or rapid metabolism, age, illness stage, comorbidities, and drug-drug interactions suggest that individual patients will often need higher or lower doses.

The Effectiveness of Relapse Prevention Intervention on the Ability of Patients and Their Families to Prevent Psychotic symptoms of Relapse among Patients with Schizophrenia: Systematic Literature Review

Background: Most patients with schizophrenia have family support. The role of a family as a carepartner has the capability of expanding the patient’s recovery and solving the family’s need for awareness,encouragement, and improves skills. Objective: Assessing the effectiveness of relapse preventionintervention on the ability of patients and their families that are reported to prevent psychotic symptomsof relapse among patients with schizophrenia. Method: A systematic review was conducted followingPreferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for the studiespublished between 2010 and 2020. Results: Twelve retrieved studies were shown the relapse preventionintervention increases the ability of patients and their families to minimize and prevent psychotic symptoms.The relapse prevention interventions in this review including; optimal case management, multifamily grouppsycho-education, integrated psychological intervention, psychosocial treatment, Information TechnologyAided Schizophrenia Relapse Prevention, family-focused therapy, and Family psycho-education programs.Conclusion: Various relapse prevention interventions have been reported to reduce the risk of relapse rate,prevent psychotic symptoms, and sustain remission by incorporating and emphasize the importance ofeffective cooperation families with patients with psychotic relapse.

Effect of Long-Acting Injectable Antipsychotics vs Usual Care on Time to First Hospitalization in Early-Phase Schizophrenia

Long-acting injectable antipsychotics (LAIs) can potentially reduce hospitalization risk by enhancing medication adherence but are rarely considered for early-phase schizophrenia treatment. To determine whether encouraging use of a LAI compared with usual care delays the time to first hospitalization with patients with early-phase illness. The Prevention of Relapse in Schizophrenia (PRELAPSE) trial was cluster randomized with a follow-up duration of 2 years. The study began in December 2014, was completed in March 2019, and was conducted in 39 mental health centers in 19 US states. Site randomization assigned 19 clinics to encourage treatment with long-acting aripiprazole monohydrate (aripiprazole once monthly [AOM] condition) and 20 to provide treatment as usual (clinician's choice [CC] condition). Participant eligibility criteria included (1) schizophrenia diagnosis confirmed by a structured clinical interview, (2) fewer than 5 years of lifetime antipsychotic use, and (3) age 18 to 35 years. The AOM sites identified 576 potentially eligible participants, of whom 234 (40.6%) enrolled; CC sites identified 685 potentially eligible participants, of whom 255 (37.2%) enrolled. There were no restrictions on treatment at CC sites (including using LAIs) or at AOM sites with the exception that aripiprazole monohydrate had to be prescribed within US Food and Drug Administration-approved guidelines. The primary outcome was time to first psychiatric hospitalization based on participant interviews every 2 months, the service use resource form administered every 4 months, and other sources (eg, health records) as available. Potential events were adjudicated by an independent committee masked to treatment assignment. The 489 participants (368 men [75.3%]) had a mean (SD) age of 25.2 (4.2) years and 225 (46.0%) had 1 year or less lifetime antipsychotic use. Fifty-two AOM (22%) and 91 CC participants (36%) had at least 1 hospitalization. The mean survival time until first hospitalization was 613.7 days (95% CI, 582.3-645.1 days) for AOM participants and 530.6 days (95% CI, 497.3-563.9 days) for CC participants. For time to first hospitalization, the hazard ratio was 0.56 (95% CI, 0.34- 0.92; P = .02), favoring AOM. Survival probabilities were 0.73 (95% CI, 0.65-0.83) for AOM participants and 0.58 (95% CI, 0.50-0.67) for CC participants. The number needed to treat to prevent 1 additional hospitalization was 7 participants treated with AOM compared with CC. Long-acting injectable antipsychotic use by patients with early-phase schizophrenia can significantly delay time to hospitalization, a personally and economically important outcome. Clinicians should more broadly consider LAI treatment for patients with early-phase illness. ClinicalTrials.gov Identifier: NCT02360319.

Psychosocial treatments for relapse prevention in schizophrenia: study protocol for a systematic review and network meta-analysis of randomised evidence

IntroductionThere is evidence that different psychosocial interventions could reduce the risk of relapse in schizophrenia, but a comprehensive evidence based on their relative efficacy is lacking. We will conduct a...