4 results on '"Lewis, Shôn"'
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2. Minocycline for negative symptoms of schizophrenia and possible mechanistic actions: the BeneMin RCT
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Deakin, Bill, Suckling, John, Dazzan, Paola, Joyce, Eileen, Lawrie, Stephen M, Upthegrove, Rachel, Husain, Nusrat, Chaudhry, Imran B, Dunn, Graham, Jones, Peter B, Lisiecka-Ford, Danuta, Lewis, Shôn, Barnes, Thomas RE, Williams, Steven CR, Pariante, Carmine M, Knox, Emma, Drake, Richard J, Smallman, Richard, and Barnes, Nicholas M
- Abstract
BackgroundIn a previous trial we reported that the neuroprotective, anti-inflammatory antibiotic minocycline lessened the negative symptoms of schizophrenia compared with placebo over 1 year. The BeneMin study aimed to replicate this benefit and to determine whether or not there was associated preservation of grey matter, reduction in circulating inflammatory cytokines and enhancement of cognition.ObjectivesTo determine the efficacy of minocycline on the negative symptoms of schizophrenia and the mechanistic role of neuroprotective, anti-inflammatory and cognitive enhancing actions.MethodsTwo hundred and seven patients with a current research diagnosis of schizophrenia within 5 years of onset were randomised by a permuted blocks algorithm to minocycline (300 mg/day) or matching placebo as an adjunct to their continuing treatment. The primary efficacy outcome variable was the negative symptom subscale score from the Positive and Negative Syndrome Scales at 2, 6, 9 and 12 months. The primary mechanistic (biomarker) variables were (1) medial prefrontal grey matter volume (GMV), (2) circulating cytokine interleukin (IL) 6 concentration and (3) dorsolateral prefrontal cortex functional magnetic resonance imaging (fMRI) activations during performance of the N-back task. Movement disorder, side effects and treatment adherence were monitored throughout the study.ResultsCompared with placebo, the addition of minocycline had no effect on the severity of negative symptoms [treatment effect difference –0.186, 95% confidence interval (CI) –1.225 to 0.854] across the 2-, 6-, 9- and 12-month follow-up visits. None of the mechanistic biomarkers was influenced by minocycline: left GMV –91.2 (95% CI –303.8 to 121.4), IL-6 0.072 (95% CI –0.118 to 0.262) and N-back fMRI 0.66 (95% CI –1.53 to 0.20). There were no statistically significant treatment effects on any of the secondary outcomes and no group differences at baseline. Most measures were stable over the 12 months. Twenty-five out of the 29 serious adverse events were hospital admission for worsening psychiatric state, which affected 10 minocycline-treated participants and six placebo-treated participants.Main outcome measuresThe addition of minocycline to standard treatment had no benefit on the symptoms of schizophrenia in this early phase sample. There was no evidence of a progressive neuropathic or inflammatory process affecting GMV.LimitationsAlthough recruitment to target was achieved on time, only 43% (n = 89) of the 207 randomised patients completed 12 months of the study. However, 83% of those who started treatment remained on it and were assessed over 6 months. By contrast, no follow-up data were available for the cognitive and imaging markers in those who dropped out before the final 12-month assessments, and this reduced the power to detect treatment effects on these mechanistic variables. Patients were not selected for the presence of negative symptoms, and their initial overall psychopathology was, at most, moderate and, therefore, less likely to show treatment effects.ConclusionsThe results of the study do not support the use of adjunctive minocycline for the treatment of negative or other symptoms of schizophrenia within 2–5 years of onset. More secure evidence of central inflammation is needed before further trials are conducted at other stages of psychosis.Trial registrationCurrent Controlled Trials ISRCTN49141214.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research partnership. The study was sponsored by Greater Manchester Mental Health NHS Foundation Trust and supported by the UK Clinical Research Network.
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- 2019
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3. Digital methods to enhance the usefulness of patient experience data in services for long-term conditions: the DEPEND mixed-methods study
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Sanders C, Nahar P, Small N, Hodgson D, Ong BN, Dehghan A, Sharp CA, Dixon WG, Lewis S, Kontopantelis E, Daker-White G, Bower P, Davies L, Kayesh H, Spencer R, McAvoy A, Boaden R, Lovell K, Ainsworth J, Nowakowska M, Shepherd A, Cahoon P, Hopkins R, Allen D, Lewis A, and Nenadic G
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Background: Collecting NHS patient experience data is critical to ensure the delivery of high-quality services. Data are obtained from multiple sources, including service-specific surveys and widely used generic surveys. There are concerns about the timeliness of feedback, that some groups of patients and carers do not give feedback and that free-text feedback may be useful but is difficult to analyse., Objective: To understand how to improve the collection and usefulness of patient experience data in services for people with long-term conditions using digital data capture and improved analysis of comments., Design: The DEPEND study is a mixed-methods study with four parts: qualitative research to explore the perspectives of patients, carers and staff; use of computer science text-analytics methods to analyse comments; co-design of new tools to improve data collection and usefulness; and implementation and process evaluation to assess use of the tools and any impacts., Setting: Services for people with severe mental illness and musculoskeletal conditions at four sites as exemplars to reflect both mental health and physical long-terms conditions: an acute trust (site A), a mental health trust (site B) and two general practices (sites C1 and C2)., Participants: A total of 100 staff members with diverse roles in patient experience management, clinical practice and information technology; 59 patients and 21 carers participated in the qualitative research components., Interventions: The tools comprised a digital survey completed using a tablet device (kiosk) or a pen and paper/online version; guidance and information for patients, carers and staff; text-mining programs; reporting templates; and a process for eliciting and recording verbal feedback in community mental health services., Results: We found a lack of understanding and experience of the process of giving feedback. People wanted more meaningful and informal feedback to suit local contexts. Text mining enabled systematic analysis, although challenges remained, and qualitative analysis provided additional insights. All sites managed to collect feedback digitally; however, there was a perceived need for additional resources, and engagement varied. Observation indicated that patients were apprehensive about using kiosks but often would participate with support. The process for collecting and recording verbal feedback in mental health services made sense to participants, but was not successfully adopted, with staff workload and technical problems often highlighted as barriers. Staff thought that new methods were insightful, but observation did not reveal changes in services during the testing period., Conclusions: The use of digital methods can produce some improvements in the collection and usefulness of feedback. Context and flexibility are important, and digital methods need to be complemented with alternative methods. Text mining can provide useful analysis for reporting on large data sets within large organisations, but qualitative analysis may be more useful for small data sets and in small organisations., Limitations: New practices need time and support to be adopted and this study had limited resources and a limited testing time., Future Work: Further research is needed to improve text-analysis methods for routine use in services and to evaluate the impact of methods (digital and non-digital) on service improvement in varied contexts and among diverse patients and carers., Funding: This project was funded by the NIHR Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research ; Vol. 8, No. 28. See the NIHR Journals Library website for further project information., (Copyright © Queen’s Printer and Controller of HMSO 2020. This work was produced by Sanders et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.)
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- 2020
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4. Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.
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Barnes TR, Leeson VC, Paton C, Costelloe C, Simon J, Kiss N, Osborn D, Killaspy H, Craig TK, Lewis S, Keown P, Ismail S, Crawford M, Baldwin D, Lewis G, Geddes J, Kumar M, Pathak R, and Taylor S
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- Adult, Antidepressive Agents, Second-Generation administration & dosage, Antipsychotic Agents administration & dosage, Antipsychotic Agents therapeutic use, Citalopram administration & dosage, Cost-Benefit Analysis, Double-Blind Method, Drug Synergism, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Quality of Life, Schizophrenic Psychology, Treatment Outcome, Antidepressive Agents, Second-Generation therapeutic use, Citalopram therapeutic use, Schizophrenia drug therapy
- Abstract
Background: Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions., Objective: To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia., Design: A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up., Setting: Adult psychiatric services, treating people with schizophrenia., Participants: Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity., Interventions: Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study., Main Outcome Measures: The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale., Results: No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation., Limitations: The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited., Conclusion: Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies., Future Work: Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge., Trial Registration: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2009-009235-30 and Current Controlled Trials ISRCTN42305247., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 29. See the NIHR Journals Library website for further project information.
- Published
- 2016
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