Cognitive–behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT

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; McLeod, Hamish J.; Griffiths, Helen; Barnes, Thomas R. E.; Davies, Linda; Shields, Gemma; Buck, Deborah; Tully, Sarah; Kingdon, David

doi:10.3310/hta23070

Cited by 20 publications

(23 citation statements)

References 175 publications

(306 reference statements)

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“…Two small unrandomised RCTs assessed the efficacy of CBT in clozapine non-responders, with benefits seen for total psychotic and general psychopathology symptoms compared to a befriending control intervention (total n=21) (Barretto et al, 2009), and improvements in positive symptoms compared to supportive therapy (total n=37) (Antonio Pinto et al, 1999). The recent Focusing On Clozapine Unresponsive Symptoms (FOCUS) randomised clinical trial is the largest and most rigorous trial of CBT for clozapine resistant psychosis, and failed to identify any significant differences in the primary outcome of Positive and Negative Syndrome Scale (PANSS) total score at 21 months (mean difference −0•89, 95% CI −3•32 to 1•55; p=0•48), between those treated with CBT and treatment as usual (Morrison et al, 2018). This is an important null study finding and fails to support widespread use of CBT for clozapine augmentation in clozapine resistant schizophrenia and other psychotic disorders.…”

Section: Clozapine Augmentation With Cognitive Behavioural Therapymentioning

confidence: 99%

Treatment resistant schizophrenia – review and a call to action

Lally

Gaughran

2018

Ir. j. psychol. Med.

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Recovery rates in schizophrenia remain suboptimal with up to one-third resistant to standard treatments, a population prevalence of 0.2%. Clozapine is the only evidenced-based treatment for treatment resistant schizophrenia (TRS), yet there are significant delays in its use or it may not be trialled, potentially impacting the chance of recovery. Better outcomes with earlier use of clozapine may be possible. There is emerging evidence that early treatment resistance is not uncommon from the earliest stages of psychosis. In this review, we provide an update on TRS, its epidemiology and its management, with a specific focus on the optimal use and timing of clozapine and augmentation strategies for the one-third of patients who do not respond to clozapine.

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Section: Clozapine Augmentation With Cognitive Behavioural Therapymentioning

confidence: 99%

Treatment resistant schizophrenia – review and a call to action

Lally

Gaughran

2018

Ir. j. psychol. Med.

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“…We collected data on adverse effects of medication and trial participation (described further under “Safety Monitoring”). We collected basic health economics data about services used by participants, using an economic patient questionnaire adapted from previous studies conducted by the authors [38, 39] and the EuroQol five dimension, five level scale (EQ-5D-5 L) health status questionnaire [40]. This information will inform the design of the economic component of a definitive trial.…”

Section: Methodsmentioning

confidence: 99%

Study protocol for a randomised controlled trial of CBT vs antipsychotics vs both in 14–18-year-olds: Managing Adolescent first episode Psychosis: a feasibility study (MAPS)

Pyle

Broome

Joyce

et al. 2019

Trials

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Background Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis. The National Institute for Clinical Excellence (NICE) recommend that adolescents with first episode psychosis (FEP) should be offered a combination of antipsychotic medication (APs), cognitive behavioural therapy (CBT) and family intervention (FI). The evidence for APs in treating psychosis is limited in adolescents compared to adults. Nevertheless, it indicates that APs can reduce overall symptoms in adolescents but may cause more severe side effects, including cardiovascular and metabolic effects, than in adults. CBT and FI can improve outcomes in adults, but there are no studies of psychological interventions (PI) in patients under 18 years old. Given this limited evidence base, NICE made a specific research recommendation for determining the clinical and cost effectiveness of APs versus PI versus both treatments for adolescent FEP. Methods/design The current study aimed to establish the feasibility and acceptability of conducting such a trial by recruiting 14–18-year-olds with a first episode of psychosis into a feasibility prospective randomised open blinded evaluation (PROBE) design, three-arm, randomised controlled trial of APs alone versus PI alone versus a combination of both treatments. We aimed to recruit 90 participants from Early Intervention and Child and Adolescent Mental Health Teams in seven UK sites. APs were prescribed by participants’ usual psychiatrists. PI comprised standardised cognitive behavioural therapy and family intervention sessions. Discussion This is the first study to compare APs to PI in an adolescent population with FEP. Recruitment finished on 31 October 2018. The study faced difficulties with recruitment across most sites due to factors including clinician and service-user treatment preferences. Trial registration Current controlled trial with ISRCTN, ISRCTN80567433 . Registered on 27 February 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3506-1) contains supplementary material, which is available to authorized users.

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“…We used an economic patient questionnaire that was adapted from previous studies conducted by the authors 111,112 to gather information about the types of health and social care services used by participants and the frequency of their contact with these services. We also used the EuroQol-Dimensions, five-level version (EQ-5D-5L), health status questionnaire, a valid measure of health outcomes in people with a schizophrenia diagnosis.…”

Section: Health Economic Datamentioning

confidence: 99%

“…We assessed this using a measure developed in our HTA FOCUS (Focusing on Clozapine Unresponsive Symptoms) trial. 111,119 The optional self-report measure was given to participants at point of exit from the trial or at point of withdrawal for those who left the trial. The measure contains 27 items (including 'taking part involved too much hard work' and 'I did not feel listened to or believed by MAPS staff'), which participants responded to on a five-point scale from 'not at all' to 'very much'.…”

Section: Potential Adverse Effects Of Trial Participationmentioning

confidence: 99%

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Psychological intervention, antipsychotic medication or a combined treatment for adolescents with a first episode of psychosis: the MAPS feasibility three-arm RCT

Morrison

Pyle

Byrne

et al. 2021

Health Technol Assess

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Background When psychosis emerges in young people there is a risk of poorer outcomes, and access to evidence-based treatments is paramount. The current evidence base is limited. Antipsychotic medications show only a small benefit over placebo, but young people experience more side effects than adults. There is sparse evidence for psychological intervention. Research is needed to determine the clinical effectiveness and cost-effectiveness of psychological intervention versus antipsychotic medication versus a combined treatment for adolescents with psychosis. Objectives The objective of Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS) was to determine the feasibility of conducting a definitive trial to answer the question of clinical effectiveness and cost-effectiveness of these three treatment options. Design This was a prospective, randomised, open-blinded, evaluation feasibility trial with a single blind. Participants were allocated 1 : 1 : 1 to receive antipsychotic medication, psychological intervention or a combination of both. A thematic qualitative study explored the acceptability and feasibility of the trial. Setting Early intervention in psychosis services and child and adolescent mental health services in Manchester, Oxford, Lancashire, Sussex, Birmingham, Norfolk and Suffolk, and Northumberland, Tyne and Wear. Participants People aged 14–18 years experiencing a first episode of psychosis either with an International Classification of Diseases, Tenth Revision, schizophrenia spectrum diagnosis or meeting the entry criteria for early intervention in psychosis who had not received antipsychotic medication or psychological intervention within the last 3 months. Interventions Psychological intervention involved up to 26 hours of cognitive–behavioural therapy and six family intervention sessions over 6 months, with up to four booster sessions. Antipsychotic medication was prescribed by the participant’s psychiatrist in line with usual practice. Combined treatment was a combination of psychological intervention and antipsychotic medication. Main outcome measures The primary outcome was feasibility (recruitment, treatment adherence and retention). We used a three-stage progression criterion to determine feasibility. Secondary outcomes were psychosis symptoms, recovery, anxiety and depression, social and educational/occupational functioning, drug and alcohol use, health economics, adverse/metabolic side effects and adverse/serious adverse events. Results We recruited 61 out of 90 (67.8%; amber zone) potential participants (psychological intervention, n = 18; antipsychotic medication, n = 22; combined treatment, n = 21). Retention to follow-up was 51 out of 61 participants (83.6%; green zone). In the psychological intervention arm and the combined treatment arm, 32 out of 39 (82.1%) participants received six or more sessions of cognitive–behavioural therapy (green zone). In the combined treatment arm and the antipsychotic medication arm, 28 out of 43 (65.1%) participants received antipsychotic medication for 6 consecutive weeks (amber zone). There were no serious adverse events related to the trial and one related adverse event. Overall, the number of completed secondary outcome measures, including health economics, was small. Limitations Medication adherence was determined by clinician report, which can be biased. The response to secondary outcomes was low, including health economics. The small sample size obtained means that the study lacked statistical power and there will be considerable uncertainty regarding estimates of treatment effects. Conclusions It is feasible to conduct a trial comparing psychological intervention with antipsychotic medication and a combination treatment in young people with psychosis with some adaptations to the design, including adaptations to collection of health economic data to determine cost-effectiveness. Future work An adequately powered definitive trial is required to provide robust evidence. Trial registration Current Controlled Trials ISRCTN80567433. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 4. See the NIHR Journals Library website for further project information.

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Cognitive–behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT

Cited by 20 publications

References 175 publications

Treatment resistant schizophrenia – review and a call to action

Treatment resistant schizophrenia – review and a call to action

Study protocol for a randomised controlled trial of CBT vs antipsychotics vs both in 14–18-year-olds: Managing Adolescent first episode Psychosis: a feasibility study (MAPS)

Psychological intervention, antipsychotic medication or a combined treatment for adolescents with a first episode of psychosis: the MAPS feasibility three-arm RCT

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