TOPUS - Testing an Implemented Intervention to Reduce Duration of Untreated Psychosis (TOPUS)

This study investigates whether a large-scale early-detection program for psychosis implemented in one Danish health region reduces the duration of untreated psychosis (DUP) and whether a shorter DUP leads to improved clinical and functional outcomes. The project takes advantage of an existing difference between two regions in Denmark: Region Zealand has, for more than a decade, operated campaign-supported early-detection teams, whereas the Capital Region provides standard detection pathways without additional outreach. Both regions deliver identical specialized treatment once patients enter the OPUS early-intervention services. This natural difference creates a unique opportunity to evaluate the real-world impact of early-detection efforts.

Scientific Rationale

DUP refers to the time between the onset of psychotic symptoms and the start of appropriate treatment. Prolonged DUP is consistently associated with worse outcomes, including more severe symptoms and poorer functioning. However, most existing evidence comes from observational studies that cannot rule out the possibility that long DUP is simply a marker of more severe or insidiously developing illness rather than a direct causal factor. The field therefore lacks strong evidence on whether active reduction of DUP improves outcomes.

Some early-detection initiatives-most prominently the TIPS study-have demonstrated that campaigns combined with rapid-access teams can significantly reduce DUP and may influence long-term functioning. However, not all attempts to reduce DUP have succeeded, and no consensus exists on the most effective strategy. It also remains uncertain how DUP should best be defined and operationalized, as several different definitions are used in the literature.

The present study is designed to help address these gaps. It examines whether an established early-detection strategy in Region Zealand has in fact shortened DUP compared with usual detection, whether any reduction has meaningful effects on two-year outcome trajectories, and which definitions of DUP provide the most reliable predictive value.

Study Design

The project uses a quasi-experimental design with two non-overlapping recruitment areas. Participants are adults with a first diagnosis of a schizophrenia-spectrum disorder who have entered OPUS treatment in either Region Zealand (early-detection region) or the Capital Region (comparison region). No experimental intervention is delivered by the research team. All participants receive routine clinical care as determined by their local OPUS center. The research activities consist of structured assessments conducted at baseline and during follow-up.

Because patients are recruited within established treatment programs and no treatment allocation is made, the study does not involve randomization or modification of clinical care. The design instead tests whether an existing system-level initiative-public awareness campaigns, stakeholder outreach, and a specialized early-detection team-has produced measurable differences in DUP and outcomes.

Study Objectives

The project is organized around three central objectives:

Effectiveness of Early Detection (WQ1):

Determine whether the early-detection initiatives in Region Zealand reduce DUP in first-episode schizophrenia compared with the Capital Region.

Impact of DUP on Outcomes (WQ2):

Evaluate whether variation in DUP predicts fifteen months functional and psychopathological outcomes within the cohort.

Operationalization of DUP (WQ3):

Compare different definitions and measurement approaches to identify how DUP is most reliably assessed and how different operationalizations affect its predictive power.

Assessments and Data Collection

At baseline, participants complete structured clinical interviews and psychometric assessments focusing on psychopathology, functioning, premorbid adjustment, cognition, and pathways to care. The measurement of DUP is central: the study uses the Nottingham Onset Schedule (NOS) as the primary tool, and definitions distinguishing between patient-level delay ("DUP Demand"), system-level delay ("DUP Supply"), and total DUP.

To examine trajectories after treatment begins, participants are contacted at 3 and 9 months for focused follow-up assessments, and they undergo a comprehensive fifteen months evaluation of functioning, symptoms, cognition, suicidality, and treatment factors. Register-based data on education, employment, hospitalization, and family formation supplement missing or incomplete follow-up information.

Analytical Approach

Because DUP is typically skewed, analyses will apply appropriate transformations or non-parametric approaches. Comparisons between regions will adjust for relevant confounders. Functional and symptom outcomes will be evaluated using regression models, and trajectories across the fifteen month period will be explored using latent class growth analysis to identify distinct functional subgroups. Multiple imputation will be used for handling missing follow-up data.

Expected Contributions

This study is among the few to evaluate early-detection efforts under real-world conditions in a public mental-health system. By comparing two regions with stable, well-defined differences in detection practices but identical treatment programs, the design provides an opportunity to examine both the system-level impact on DUP and the clinical implications of altered detection timing.

The results are expected to address three major uncertainties in the field:

whether early-detection campaigns and outreach teams meaningfully reduce the time patients remain untreated,

whether a reduced DUP improves functional and clinical outcomes, and

how DUP should be operationalized to provide the clearest and most clinically relevant information.

Establishing the effectiveness of an already-implemented early-detection model has the potential to inform service planning in Denmark and internationally. In addition, clarifying the causal role of DUP could support future health-care strategies aimed at minimizing untreated psychosis, and the project's methodological work may contribute to consensus definitions for DUP in both clinical and research settings.