The University of Southampton
University of Southampton Institutional Repository

Cognitive-behavioural therapy for clozapine-resistant schizophrenia: The FOCUS RCT

Cognitive-behavioural therapy for clozapine-resistant schizophrenia: The FOCUS RCT
Cognitive-behavioural therapy for clozapine-resistant schizophrenia: The FOCUS RCT

Background: Clozapine (clozaril, Mylan Products Ltd) is a first-choice treatment for people with schizophrenia who have a poor response to standard antipsychotic medication. However, a significant number of patients who trial clozapine have an inadequate response and experience persistent symptoms, called clozapine-resistant schizophrenia (CRS). There is little evidence regarding the clinical effectiveness of pharmacological or psychological interventions for this population. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of cognitive-behavioural therapy (CBT) for people with CRS and to identify factors predicting outcome. Design: The Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial was a parallel-group, randomised, outcome-blinded evaluation trial. Randomisation was undertaken using permuted blocks of random size via a web-based platform. Data were analysed on an intention-to-treat (ITT) basis, using random-effects regression adjusted for site, age, sex and baseline symptoms. Cost-effectiveness analyses were carried out to determine whether or not CBT was associated with a greater number of quality-adjusted life-years (QALYs) and higher costs than treatment as usual (TAU). Setting: Secondary care mental health services in five cities in the UK. Participants: People with CRS aged = 16 years, with an International Classification of Diseases, Tenth Revision (ICD-10) schizophrenia spectrum diagnoses and who are experiencing psychotic symptoms. Interventions: Individual CBT included up to 30 hours of therapy delivered over 9 months. The comparator was TAU, which included care co-ordination from secondary care mental health services. Main outcome measures: The primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months and the primary secondary outcome was PANSS total score at the end of treatment (9 months post randomisation). The health benefit measure for the economic evaluation was the QALY, estimated from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), health status measure. Service use was measured to estimate costs. Results: Participants were allocated to CBT (n = 242) or TAU (n = 245). There was no significant difference between groups on the prespecified primary outcome [PANSS total score at 21 months was 0.89 points lower in the CBT arm than in the TAU arm, 95% confidence interval (CI) -3.32 to 1.55 points; p = 0.475], although PANSS total score at the end of treatment (9 months) was significantly lower in the CBT arm (-2.40 points, 95% CI -4.79 to -0.02 points; p = 0.049). CBT was associated with a net cost of £5378 (95% CI -£13,010 to £23,766) and a net QALY gain of 0.052 (95% CI 0.003 to 0.103 QALYs) compared with TAU. The cost-effectiveness acceptability analysis indicated a low likelihood that CBT was cost-effective, in the primary and sensitivity analyses (probability < 50%). In the CBT arm, 107 participants reported at least one adverse event (AE), whereas 104 participants in the TAU arm reported at least one AE (odds ratio 1.09, 95% CI 0.81 to 1.46; p = 0.58). Conclusions: Cognitive-behavioural therapy for CRS was not superior to TAU on the primary outcome of total PANSS symptoms at 21 months, but was superior on total PANSS symptoms at 9 months (end of treatment). CBT was not found to be cost-effective in comparison with TAU. There was no suggestion that the addition of CBT to TAU caused adverse effects. Future work could investigate whether or not specific therapeutic techniques of CBT have value for some CRS individuals, how to identify those who may benefit and how to ensure that effects on symptoms can be sustained.

1366-5278
1-143
Morrison, Anthony P.
ca3dffe8-3954-451f-8145-db6655ad5105
Pyle, Melissa
56c6f458-fb7a-48e1-bb6b-f48a25eb8552
Gumley, Andrew
3aec63ea-08ee-436c-8c00-11e823376a07
Schwannauer, Matthias
82c7e321-d7c2-4001-bb86-42a90e7cc61e
Turkington, Douglas
3e0aca69-c932-4fb6-9145-6e19c7310700
MacLennan, Graeme
209593f8-0b7c-44fd-9abc-c1ea575b6c61
Norrie, John
d648d104-39a0-481f-af0f-9a7209d50fb5
Hudson, Jemma
3ca41223-889e-4d90-a89b-691bc2b296e0
Bowe, Samantha
2a3eb9f9-79c9-4e2b-b82d-d3e3c397ce8b
French, Paul
1a2a5667-f6a2-4d96-8f30-de1a972c1ead
Hutton, Paul
c45b42b0-125d-43c2-9386-c7a39986ccd4
Byrne, Rory
2bd48f2a-d944-46e5-a83b-9a39d9af20e4
Syrett, Suzy
19518036-62ce-4f18-8d00-d34f041a251a
Dudley, Robert
5e39f641-49de-4a27-bfe3-af34043ea120
Dudley, Robert
5e39f641-49de-4a27-bfe3-af34043ea120
Griffiths, Helen
5c1e2e63-87d1-4c85-be7b-d20a79466b86
Barnes, Thomas R.E.
3ae0ce78-0404-47dc-b54f-795ba8235e0e
Davies, Linda
5cb5a68e-ff0a-4519-a773-dafb313e2e70
Shields, Gemma
34afdb73-9cad-48c0-a7e1-16d3e6e044f8
Buck, Deborah
8670f928-bdd4-4049-a839-2574905fea0d
Tully, Sarah
304f0039-05ba-4424-9eaf-c9720603fea9
Kingdon, David
14cdc422-10b4-4b2d-88ec-24fde5f4329b
Morrison, Anthony P.
ca3dffe8-3954-451f-8145-db6655ad5105
Pyle, Melissa
56c6f458-fb7a-48e1-bb6b-f48a25eb8552
Gumley, Andrew
3aec63ea-08ee-436c-8c00-11e823376a07
Schwannauer, Matthias
82c7e321-d7c2-4001-bb86-42a90e7cc61e
Turkington, Douglas
3e0aca69-c932-4fb6-9145-6e19c7310700
MacLennan, Graeme
209593f8-0b7c-44fd-9abc-c1ea575b6c61
Norrie, John
d648d104-39a0-481f-af0f-9a7209d50fb5
Hudson, Jemma
3ca41223-889e-4d90-a89b-691bc2b296e0
Bowe, Samantha
2a3eb9f9-79c9-4e2b-b82d-d3e3c397ce8b
French, Paul
1a2a5667-f6a2-4d96-8f30-de1a972c1ead
Hutton, Paul
c45b42b0-125d-43c2-9386-c7a39986ccd4
Byrne, Rory
2bd48f2a-d944-46e5-a83b-9a39d9af20e4
Syrett, Suzy
19518036-62ce-4f18-8d00-d34f041a251a
Dudley, Robert
5e39f641-49de-4a27-bfe3-af34043ea120
Dudley, Robert
5e39f641-49de-4a27-bfe3-af34043ea120
Griffiths, Helen
5c1e2e63-87d1-4c85-be7b-d20a79466b86
Barnes, Thomas R.E.
3ae0ce78-0404-47dc-b54f-795ba8235e0e
Davies, Linda
5cb5a68e-ff0a-4519-a773-dafb313e2e70
Shields, Gemma
34afdb73-9cad-48c0-a7e1-16d3e6e044f8
Buck, Deborah
8670f928-bdd4-4049-a839-2574905fea0d
Tully, Sarah
304f0039-05ba-4424-9eaf-c9720603fea9
Kingdon, David
14cdc422-10b4-4b2d-88ec-24fde5f4329b

Morrison, Anthony P., Pyle, Melissa, Gumley, Andrew, Schwannauer, Matthias, Turkington, Douglas, MacLennan, Graeme, Norrie, John, Hudson, Jemma, Bowe, Samantha, French, Paul, Hutton, Paul, Byrne, Rory, Syrett, Suzy, Dudley, Robert, Dudley, Robert, Griffiths, Helen, Barnes, Thomas R.E., Davies, Linda, Shields, Gemma, Buck, Deborah, Tully, Sarah and Kingdon, David (2019) Cognitive-behavioural therapy for clozapine-resistant schizophrenia: The FOCUS RCT. Health Technology Assessment, 23 (7), 1-143. (doi:10.3310/hta23070).

Record type: Article

Abstract

Background: Clozapine (clozaril, Mylan Products Ltd) is a first-choice treatment for people with schizophrenia who have a poor response to standard antipsychotic medication. However, a significant number of patients who trial clozapine have an inadequate response and experience persistent symptoms, called clozapine-resistant schizophrenia (CRS). There is little evidence regarding the clinical effectiveness of pharmacological or psychological interventions for this population. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of cognitive-behavioural therapy (CBT) for people with CRS and to identify factors predicting outcome. Design: The Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial was a parallel-group, randomised, outcome-blinded evaluation trial. Randomisation was undertaken using permuted blocks of random size via a web-based platform. Data were analysed on an intention-to-treat (ITT) basis, using random-effects regression adjusted for site, age, sex and baseline symptoms. Cost-effectiveness analyses were carried out to determine whether or not CBT was associated with a greater number of quality-adjusted life-years (QALYs) and higher costs than treatment as usual (TAU). Setting: Secondary care mental health services in five cities in the UK. Participants: People with CRS aged = 16 years, with an International Classification of Diseases, Tenth Revision (ICD-10) schizophrenia spectrum diagnoses and who are experiencing psychotic symptoms. Interventions: Individual CBT included up to 30 hours of therapy delivered over 9 months. The comparator was TAU, which included care co-ordination from secondary care mental health services. Main outcome measures: The primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months and the primary secondary outcome was PANSS total score at the end of treatment (9 months post randomisation). The health benefit measure for the economic evaluation was the QALY, estimated from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), health status measure. Service use was measured to estimate costs. Results: Participants were allocated to CBT (n = 242) or TAU (n = 245). There was no significant difference between groups on the prespecified primary outcome [PANSS total score at 21 months was 0.89 points lower in the CBT arm than in the TAU arm, 95% confidence interval (CI) -3.32 to 1.55 points; p = 0.475], although PANSS total score at the end of treatment (9 months) was significantly lower in the CBT arm (-2.40 points, 95% CI -4.79 to -0.02 points; p = 0.049). CBT was associated with a net cost of £5378 (95% CI -£13,010 to £23,766) and a net QALY gain of 0.052 (95% CI 0.003 to 0.103 QALYs) compared with TAU. The cost-effectiveness acceptability analysis indicated a low likelihood that CBT was cost-effective, in the primary and sensitivity analyses (probability < 50%). In the CBT arm, 107 participants reported at least one adverse event (AE), whereas 104 participants in the TAU arm reported at least one AE (odds ratio 1.09, 95% CI 0.81 to 1.46; p = 0.58). Conclusions: Cognitive-behavioural therapy for CRS was not superior to TAU on the primary outcome of total PANSS symptoms at 21 months, but was superior on total PANSS symptoms at 9 months (end of treatment). CBT was not found to be cost-effective in comparison with TAU. There was no suggestion that the addition of CBT to TAU caused adverse effects. Future work could investigate whether or not specific therapeutic techniques of CBT have value for some CRS individuals, how to identify those who may benefit and how to ensure that effects on symptoms can be sustained.

Full text not available from this repository.

More information

Accepted/In Press date: 31 January 2019
Published date: February 2019

Identifiers

Local EPrints ID: 431684
URI: http://eprints.soton.ac.uk/id/eprint/431684
ISSN: 1366-5278
PURE UUID: a752d57a-17f9-49c9-bc76-4238748fe7ca

Catalogue record

Date deposited: 13 Jun 2019 16:30
Last modified: 07 Oct 2020 00:16

Export record

Altmetrics

Contributors

Author: Anthony P. Morrison
Author: Melissa Pyle
Author: Andrew Gumley
Author: Matthias Schwannauer
Author: Douglas Turkington
Author: Graeme MacLennan
Author: John Norrie
Author: Jemma Hudson
Author: Samantha Bowe
Author: Paul French
Author: Paul Hutton
Author: Rory Byrne
Author: Suzy Syrett
Author: Robert Dudley
Author: Robert Dudley
Author: Helen Griffiths
Author: Thomas R.E. Barnes
Author: Linda Davies
Author: Gemma Shields
Author: Deborah Buck
Author: Sarah Tully
Author: David Kingdon

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×