Effects of cognitive behaviour therapy for worry on persecutory delusions in patients with psychosis (WIT): a parallel, single-blind, randomised controlled trial with a mediation analysis - PubMed
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Randomized Controlled Trial
Effects of cognitive behaviour therapy for worry on persecutory delusions in patients with psychosis (WIT): a parallel, single-blind, randomised controlled trial with a mediation analysis
Daniel Freeman et al. Lancet Psychiatry. 2015 Apr.
Abstract
Background: Worry might be a contributory causal factor in the occurrence of persecutory delusions in patients with psychotic disorders. Therefore we postulated that reducing worry with cognitive behaviour therapy (CBT) would reduce persecutory delusions.
Methods: For our two-arm, assessor-blinded, randomised controlled trial (Worry Intervention Trial [WIT]), we recruited patients aged 18-65 years with persistent persecutory delusions but non-affective psychosis from two centres: the Oxford Health National Health Service (NHS) Foundation Trust (Oxford, UK) and the Southern Health NHS Foundation Trust (Southampton, UK). The key inclusion criteria for participants were a score of at least 3 on the Psychotic Symptoms Rating Scale (PSYRATS) denoting a current persecutory delusion; that the delusion had persisted for at least 3 months; a clinical diagnosis of schizophrenia, schizoaffective disorder, or delusional disorder; and a clinically significant level of worry. We randomly assigned (1:1) eligible patients, using a randomly permuted block procedure with variable block sizes and division by four strata, to either six sessions of worry-reduction CBT intervention done over 8 weeks added to standard care (the CBT-intervention group), or to standard care alone (the control group). The assessors were masked to patient allocations and did their assessments at week 0 (baseline), 8 weeks (end of treatment), and 24 weeks, follow-up. The primary outcomes were worry measured by the Penn State Worry Questionnaire (PSWQ) and delusions measured by the PSYRATS-delusion scale; we did the analyses in the intention-to-treat population, and also did a planned mediation analysis. This trial is registered with the ISRCTN Registry (number ISRCTN23197625) and is closed to new participants.
Findings: From Nov 1, 2011, to Sept 9, 2013, we recruited 150 eligible participants and randomly assigned 73 to the CBT intervention group, and 77 to the control group. 143 patients (95%) provided primary outcome follow-up data. Compared with standard care alone, at 8 weeks the CBT intervention significantly reduced worry (mean difference 6·35 [SE 1·56] PSWQ units, 95% CI 3·30-9·40; p<0·001) and persecutory delusions (2·08 [SE 0·73] PSYRATS units, 95% CI 0·64-3·51; p=0·005). The reductions were maintained to 24 weeks follow-up. The mediation analysis suggested that the change in worry accounted for 66% of the change in delusion. No patients died or were admitted to secure units during our study. Six suicide attempts (two in the CBT intervention group, and four in the control group) and two serious violent incidents (one in each group) were noted, but no adverse events were deemed related to the treatments or the assessments.
Interpretation: To our knowledge, this is the first large trial focused on persecutory delusions. We have shown that long-standing delusions were significantly reduced by a brief intervention targeted on worry, although the limitations for our study include no determination of the key elements within the intervention. Our results suggest that worry might cause paranoia, and that worry intervention techniques might be a beneficial addition to the standard treatment of psychosis.
Funding: Efficacy and Mechanism Evaluation programme, which is a UK Medical Research Council and National Institute of Health Research partnership.
Copyright © 2015 Freeman et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.
Figures

Trial profile PSWQ=Penn State Worry Questionnaire. CBT=cognitive behavioural therapy.

Mediation analysis Rectangles or squares represent measured variables. Ellipses or circles represent latent variables (including random errors or residuals). Single headed arrows represent predisposing effects; bold arrows represent main ones of interest. Double-headed arrows represent correlations. W8=worry measures at 8 weeks. W24=worry measures at 24 weeks. D8=delusion measures at 8 weeks. D24=delusion measures at 24 weeks. e1 and e2=random residuals (worry). e3 and e4=random residuals (delusions).
Comment in
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New treatments for psychotic disorders.
Nieman DH. Nieman DH. Lancet Psychiatry. 2015 Apr;2(4):282-3. doi: 10.1016/S2215-0366(15)00093-0. Epub 2015 Mar 31. Lancet Psychiatry. 2015. PMID: 26360061 No abstract available.
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Steel C. Steel C. Evid Based Ment Health. 2016 Feb;19(1):27. doi: 10.1136/eb-2015-102175. Epub 2015 Dec 23. Evid Based Ment Health. 2016. PMID: 26701385 Free PMC article. No abstract available.
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