Four-Year Follow-up of Cognitive Behavioral Therapy in Persons at Ultra-High Risk for Developing Psychosis: The Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial

Helga K. Ising, Tamar C. Kraan, Judith Rietdijk, Sara Dragt, Rianne M. C. Klaassen, Nynke Boonstra, Dorien H. Nieman, Monique Willebrands-Mendrik, David P. G. van den Berg, Don H. Linszen, Lex Wunderink, Wim Veling, Filip Smit, Mark van der Gaag, M. Willebrandts-Mendrik

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Previously, we demonstrated that cognitive behavior therapy for ultra-high risk (called CBTuhr) halved the incidence of psychosis over an 18-month period. Follow-up data from the same study are used to evaluate the longer-term effects at 4 years post-baseline. The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients comparing CBTuhr with treatment-as-usual (TAU) for comorbid disorders with TAU only. Of the original 196 patients, 113 consented to a 4-year follow-up (57.7%; CBTuhr = 56 vs TAU = 57). Over the study period, psychosis incidence, remission from UHR status, and the effects of transition to psychosis were evaluated. The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow-up to 12 at 4-year follow-up whereas it did not change in the TAU group (n = 22); this still represents a clinically important (incidence rate ratio [IRR] = 12/22 = 0.55) and significant effect (F(1,5) = 8.09, P = .03), favoring CBTuhr. The odds ratio of CBTuhr compared to TAU was 0.44 (95% CI: 0.24-0.82) and the number needed to treat was 8. Moreover, significantly more patients remitted from their UHR status in the CBTuhr group (76.3%) compared with the TAU group (58.7%) [t(120) = 2.08, P = .04]. Importantly, transition to psychosis was associated with more severe psychopathology and social functioning at 4-year follow-up. CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still effective at 4-year follow-up. Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and social outcomes compared with non-transitioned cases. The trial is registered at Current Controlled Trials as trial number ISRCTN21353122 (
Original languageEnglish
Pages (from-to)1243-1252
Number of pages10
JournalSchizophrenia Bulletin
Issue number5
Publication statusPublished - Sept 2016


  • at-risk mental state
  • cognitive behavior therapy
  • prevention
  • schizophrenia
  • ultra-high risk

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