Evidence map›Paper›PMID 40932600›Full record

Trial reportCNS drugs2026

Impact of Long-Acting Injectable Versus Oral Antipsychotic Treatment on All-Cause Discontinuation Risk in People with Early Phase Schizophrenia and Comorbid Substance Use Disorder: A Secondary Analysis of the EULAST Randomized Trial.

Matin Mortazavi, Zahra Aminifarsani, Inge Winter-van Rossum, René S Kahn, W Wolfgang Fleischhacker, Michael Davidson, Mark Weiser, Dan Siskind, Stefan Leucht, EULAST Study Group and 2 more

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter StudyComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in CNS drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02146547 (European Long-acting Antipsychotics in Schizophrenia Trial), which is not on this map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02146547 phase4completednot on this map

European Long-acting Antipsychotics in Schizophrenia Trial

TypeinterventionalSponsorUMC UtrechtRan2015 to 2020Enrolled536ConditionsSchizophreniaArmsAripiprazole, Aripiprazole depot, Paliperidone, Paliperidone palmitate
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
  2. Review
  3. Schizophrenia.Nature reviews. Disease primers · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Matin Mortazavi *Evidence-based Psychiatry and Psychotherapy, Faculty of Medicine, University of Augsburg, Augsburg, Germany. matinmortazavi3@gmail.com.ORCID 0000-0002-0826-7661
Zahra Aminifarsani *Evidence-based Psychiatry and Psychotherapy, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
Inge Winter-van RossumDepartment of Psychiatry, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University, Utrecht, Netherlands.
René S KahnDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
W Wolfgang FleischhackerDepartment of Psychiatry, Psychotherapy and Psychosomatic Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Michael DavidsonDepartment of Basic and Clinical Sciences, Psychiatry, University of Nicosia Medical School, 2414, Nicosia, Cyprus.
Mark WeiserPinchas and Drora Division of Psychiatry, Sheba Medical Center, Tel HaShomer, Israel.
Dan SiskindAddiction and Mental Health Service, Metro South Health, Brisbane, Australia.
Stefan LeuchtDepartment of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, 81675, Munich, Germany.
EULAST Study Group
Alkomiet Hasan *Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, BKH Augsburg, Augsburg, Germany.
Elias Wagner *Evidence-based Psychiatry and Psychotherapy, Faculty of Medicine, University of Augsburg, Augsburg, Germany.

Funding

German Center for Mental Health FKZ: 01EE2303C
6 · The paper itself

Abstract

backgroundIndividuals with schizophrenia and comorbid substance use disorder (SUD) often experience poor treatment adherence, leading to worse clinical outcomes. However, high-quality evidence from randomized trials on the preferred mode of antipsychotic treatment in this population remains limited.

aimsThe aim was to examine whether long-acting injectable (LAI) antipsychotic treatment reduces the risk of all-cause discontinuation (ACD) compared with oral antipsychotics in individuals with early phase schizophrenia and comorbid SUD.

methodsThis study was a secondary analysis of the European Long-Acting Antipsychotics in Schizophrenia Trial (EULAST), a multisite, randomized, open-label trial conducted across multiple European healthcare settings. A total of 471 individuals with early phase schizophrenia were included in this secondary analysis, stratified by presence (n = 143) or absence (n = 328) of comorbid SUD. The observation period lasted 18 months. Participants were randomly assigned to second-generation LAI or oral second-generation antipsychotic treatment. The primary outcome was ACD, an indirect measure of treatment efficacy, defined as discontinuation of the initially assigned treatment for any reason. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models, adjusted for relevant covariates.

resultsAmong 143 individuals with schizophrenia and SUD, LAI treatment was associated with a 36% lower risk of ACD compared with oral antipsychotics (adjusted HR = 0.641; 95% CI, 0.438-0.938; P = 0.022). Kaplan-Meier curves showed longer median time to ACD for LAI treatment (158 days) versus oral antipsychotics (97 days). By contrast, among the 328 individuals without SUD, LAI treatment did not significantly reduce ACD risk (P = 0.282). Crude HRs were also assessed, replicating the adjusted hazard findings.

conclusionsLAI antipsychotics significantly delayed treatment discontinuation compared with oral antipsychotics in participants with early phase schizophrenia and comorbid SUD but not in those without SUD. While these findings provide robust evidence supporting the use of LAIs in people with schizophrenia and comorbid SUD, future studies are needed to more precisely quantify the potential clinical benefits and tolerability of LAIs in this high-risk population. EULAST was registered at ClinicalTrials.gov (NCT02146547).

Indexed as

Antipsychotic AgentsSchizophreniaSubstance-Related DisordersAdministration, OralAdultDelayed-Action PreparationsFemaleHumansInjectionsMaleMiddle AgedTreatment OutcomeAntipsychotic AgentsDelayed-Action Preparations

Identifiers

PMID40932600
PMCPMC12769605

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.