Clinical Recovery and Long-Term Association of Specialized Early Intervention Services vs Treatment as Usual Among Individuals With First-Episode Schizophrenia Spectrum Disorder

Abstract

ImportanceThe OPUS 20-year follow-up is the longest follow-up of a randomized clinical trial testing early intervention services (EIS) among individuals with first-episode schizophrenia spectrum disorder.ObjectiveTo report on long-term associations of EIS compared with treatment as usual (TAU) for first-episode schizophrenia spectrum disorder.Design, Setting, and ParticipantsA total of 547 individuals were included in this Danish multicenter randomized clinical trial between January 1998 and December 2000 and allocated to early intervention program group (OPUS) or TAU. Raters who were blinded to the original treatment performed the 20-year follow-up. A population-based sample aged 18 to 45 years with first-episode schizophrenia spectrum disorder were included. Individuals were excluded if they were treated with antipsychotics (>12 weeks prior to randomization), had substance-induced psychosis, had mental disability, or had organic mental disorders. Analysis took place between December 2021 and August 2022.InterventionsEIS (OPUS) consisted of 2 years of assertive community treatment including social skill training, psychoeducation, and family involvement by a multidisciplinary team. TAU consisted of the available community mental health treatment.Main Outcomes and MeasuresPsychopathological and functional outcomes, mortality, days of psychiatric hospitalizations, number of psychiatric outpatient contacts, use of supported housing/homeless shelters, symptom remission, and clinical recovery.ResultsOf 547 participants, 164 (30%) were interviewed at 20-year follow-up (mean [SD] age, 45.9 [5.6] years; 85 [51.8%] female). No significant differences were found between the OPUS group compared with the TAU group on global functional levels (estimated mean difference, −3.72 [95% CI, −7.67 to 0.22]; P = .06), psychotic symptom dimensions (estimated mean difference, 0.14 [95% CI, −0.25 to 0.52]; P = .48), and negative symptom dimensions (estimated mean difference, 0.13 [95% CI, −0.18 to 0.44]; P = .41). The mortality rate was 13.1% (n = 36) in the OPUS group and 15.1% (n = 41) in the TAU group. Likewise, no differences were found 10 to 20 years after randomization between the OPUS and TAU groups on days of psychiatric hospitalizations (incidence rate ratio, 1.20 [95% CI, 0.73-1.20]; P = .46) or number of outpatient contacts (incidence rate ratio, 1.20 [95% CI, 0.89-1.61]; P = .24). Of the entire sample, 53 participants (40%) were in symptom remission and 23 (18%) were in clinical recovery.Conclusions and RelevanceIn this follow-up study of a randomized clinical trial, no differences between 2 years of EIS vs TAU among individuals with diagnosed schizophrenia spectrum disorders at 20 years were found. New initiatives are needed to maintain the positive outcomes achieved after 2 years of EIS and furthermore improve very long-term outcomes. While registry data was without attrition, interpretation of clinical assessments are limited by high attrition rate. However, this attrition bias most likely confirms the lack of an observed long-term association of OPUS with outcomes.Trial RegistrationClinicalTrials.gov Identifier: NCT00157313

20‐year trajectories of positive and negative symptoms after the first psychotic episode in patients with schizophrenia spectrum disorder: results from the OPUS study

“…Our analyses are based on a sample of patients originally included in a randomized controlled trial. We know that the interventions impacted differentially on symptom levels for the first two years after inclusion, but we also know that this effect was not seen at any following assessment 22,54,55 . The inclusion of the treat ment group in the analyses did not change the results, so we ruled out any significant impact of treatment on the trajectories.…”

Seven decades of antipsychotic drugs: Why is the life of Australians with schizophrenia still so suboptimal?

“…However, while at 2 years of follow-up, psychotic symptoms (mainly hallucinations) and negative symptoms were reduced in the intensive early intervention group compared with treatment as usual (TAU), these gains were not maintained in the longer term (Petersen et al, 2005). Thus, after 5, 10 and 20 years of follow-up, all the clinical outcomes favouring EIS had essentially dissipated (Bertelsen et al, 2008; Hansen et al, 2023; Secher et al, 2015). Closer to home, a recent large-scale RCT aiming to prevent psychosis in patients at high risk of psychosis found that a specialised intensive psychological intervention (cognitive behavioural case management (CBCM) and psychopharmacological intervention (CBCM and antidepressant medication) were not more effective than the control condition (McGorry et al, 2023).…”

Neuropsychiatric disorders, chronotype and sleep: A narrative review of GWAS findings and the application of Mendelian randomization to investigate causal relationships

“…Life‐long disability and the severity of neuropsychiatric disorders can be arguably reduced through early intervention 21 . However, there are currently few approaches available due to the complex and poorly understood neuropathology of neuropsychiatric disorders 22,23 .…”

“…20 Life-long disability and the severity of neuropsychiatric disorders can be arguably reduced through early intervention. 21 However, there are currently few approaches available due to the complex and poorly understood neuropathology of neuropsychiatric disorders. 22,23 Establishing a causal relationship between chronotype and neuropsychiatric disorders via MR could identify sleep-related phenotypes as modifiable risk factors for treating the disabling features of neuropsychiatric disorders.…”