Imperial College London

ProfessorThomasBarnes

Faculty of MedicineDepartment of Brain Sciences

Emeritus Professor of Clinical Psychiatry
 
 
 
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Contact

 

t.r.barnes

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

381 results found

Herniman SE, Wood SJ, Khandaker G, Dazzan P, Pariante CM, Barnes NM, Krynicki CR, Nikkheslat N, Vincent RC, Roberts A, Giordano A, Watson A, Suckling J, Barnes TRE, Husain N, Jones PB, Joyce E, Lawrie SM, Lewis S, Deakin B, Upthegrove R, BeneMin Study Teamet al., 2023, Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial., Transl Psychiatry, Vol: 13

Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Network analysis was applied to baseline and 6-month data from the large multi-center BeneMin trial of minocycline (N = 207) in schizophrenia. Pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at baseline. At 6 months, the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed.

Journal article

Wagner E, Siskind D, Falkai P, Howes O, Correll C, Lee J, Honer WG, Kane JM, Fernandez-Egea E, Barnes TRE, Hasan A, TRRIP Working Groupet al., 2023, Clozapine Optimization: A Delphi Consensus Guideline From the Treatment Response and Resistance in Psychosis Working Group., Schizophr Bull, Vol: 49, Pages: 962-972

BACKGROUND AND HYPOTHESIS: There is limited evidence to guide the approaches to clozapine treatment. Accordingly, an international initiative was undertaken with the aim of developing consensus recommendations for the optimization of clozapine monotherapy. STUDY DESIGN: We conducted an online Delphi survey among members of the Treatment Response and Resistance in Psychosis (TRRIP) working group comprising experts from twenty-nine countries. The threshold criterion for a consensus recommendation was ≥ 75% agreement ("agree" and "strongly agree" responses) on a question. Agreement of ≥ 50% but < 75% in a second or third Delphi round was deemed to provide guidance. STUDY RESULTS: Forty-nine (first round), 32 (second round), and 48 (third round) of the 91 current TRRIP members participated. Expert recommendations at ≥ 75% comprised second-line treatment with clozapine in cases of persistent positive symptoms with co-occurring extrapyramidal symptoms, tardive dyskinesia, or suicidality/aggression. There was considerable disagreement on myocarditis screening parameters. The management of somatic and neuropsychiatric adverse drug reactions warrants further research for more evidence-based recommendations. Rechallenge with clozapine was recommended for eosinophilia, sinus tachycardia and fever and guidance (agreement ≥ 50%) was reached for pneumonia and thrombocytopenia. CONCLUSIONS: Given the limited evidence available, this consensus-based series of recommendations and guidance statements supports clinical decision-making to optimize clozapine monotherapy and provides guidance for future research in treatment-resistant schizophrenia.

Journal article

Millgate E, Smart SE, Pardiñas AF, Kravariti E, Ajnakina O, Kępińska AP, Andreassen OA, Barnes TRE, Berardi D, Crespo-Facorro B, D'Andrea G, Demjaha A, Di Forti M, Doody GA, Kassoumeri L, Ferchiou A, Guidi L, Joyce EM, Lastrina O, Melle I, Pignon B, Richard J-R, Simonsen C, Szöke A, Tarricone I, Tortelli A, Vázquez-Bourgon J, Murray RM, Walters JTR, MacCabe JH, STRATA Consortiumet al., 2023, Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study., Schizophr Res, Vol: 255, Pages: 173-181

BACKGROUND: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases. METHODS: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases. Cognitive measures were grouped into seven cognitive domains based on the pre-existing literature. We ran multiple imputation for missing data and used logistic regression to test for associations between cognitive performance at FEP and treatment resistant status at follow-up. RESULTS: On average patients who were future classified as treatment resistant reported poorer performance across most cognitive domains at baseline. Univariate logistic regressions showed that antipsychotic treatment resistance cases had significantly poorer IQ/general cognitive functioning at FEP (OR = 0.70, p = .003). These findings remained significant after adjusting for additional variables in multivariable analyses (OR = 0.76, p = .049). CONCLUSIONS: Although replication in larger studies is required, it appears that deficits in IQ/general cognitive functioning at first episode are associated with future treatment resistance. Cognitive variables may be able to provide further insight into neurodevelopmental factors associated with treatment resistance or act as early predictors of treatment resistance, which could allow prompt identification of refractory illness and timely interventions.

Journal article

Sinclair J, Barnes TRE, Lingford-Hughes A, Drummond C, Loubser I, Rendora O, Paton Cet al., 2023, Management of medically assisted withdrawal from alcohol in acute adult mental health and specialist addictions in-patient services: UK clinical audit findings, BJPsych Open, Vol: 9, Pages: 1-8, ISSN: 2056-4724

BackgroundMedically assisted alcohol withdrawal (MAAW) is increasingly undertaken on acute adult psychiatric wards.AimsComparison of the quality of MAAW between acute adult wards and specialist addictions units in mental health services.MethodClinical audit conducted by the Prescribing Observatory for Mental Health (POMH). Information on MAAW was collected from clinical records using a bespoke data collection tool.ResultsForty-five National Health Service (NHS) mental health trusts/healthcare organisations submitted data relating to the treatment of 908 patients undergoing MAAW on an acute adult ward or psychiatric intensive care unit (PICU) and 347 admitted to a specialist NHS addictions unit. MAAW had been overseen by an addiction specialist in 33 (4%) of the patients on an acute adult ward/PICU. A comprehensive alcohol history, measurement of breath alcohol, full screening for Wernicke's encephalopathy, use of parenteral thiamine, prescription of medications for relapse prevention (such as acamprosate) and referral for specialist continuing care of alcohol-related problems following discharge were all more commonly documented when care was provided on a specialist unit or when there was specialist addictions management on an acute ward.ConclusionsThe findings suggest that the quality of care provided for medically assisted withdrawal from alcohol, including the use of evidence-based interventions, is better when clinicians with specialist addictions training are involved. This has implications for future quality improvement in the provision of MAAW in acute adult mental health settings.

Journal article

Winter-van Rossum I, Weiser M, Galderisi S, Leucht S, Bitter I, Glenthøj B, Hasan A, Luykx J, Kupchik M, Psota G, Rocca P, Stefanis N, Teitelbaum A, Bar Haim M, Leucht C, Kemmler G, Schurr T, EULAST Study Group, Davidson M, Kahn RS, Fleischhacker WWet al., 2023, Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomised trial (EULAST)., Lancet Psychiatry, Vol: 10, Pages: 197-208

BACKGROUND: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. METHODS: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. FINDINGS: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 24

Journal article

Smart SE, Agbedjro D, Pardinas AF, Ajnakina O, Alameda L, Andreassen OA, Barnes TRE, Berardi D, Camporesi S, Cleusix M, Conus P, Crespo-Facorro B, D'Andrea G, Demjaha A, Di Forti M, Do K, Doody G, Eap CB, Ferchiou A, Guidi L, Homman L, Jenni R, Joyce E, Kassoumeri L, Lastrina O, Melle I, Morgan C, O'Neill FA, Pignon B, Restellini R, Richard J-R, Simonsen C, Spaniel F, Szoke A, Tarricone I, Tortelli A, Ucok A, Vazquez-Bourgon J, Murray RM, Walters JTR, Stahl D, MacCabe JHet al., 2022, Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium, SCHIZOPHRENIA RESEARCH, Vol: 250, Pages: 1-9, ISSN: 0920-9964

Journal article

Howes OD, Barnes TRE, Lennox BR, Markham S, Natesan Set al., 2022, Time to re-evaluate the risks and benefits of valproate and a call for action, BRITISH JOURNAL OF PSYCHIATRY, Vol: 221, Pages: 711-713, ISSN: 0007-1250

Journal article

Paton C, Citrome L, Fernandez-Egea E, Rendora O, Barnes TREet al., 2022, Who is prescribed valproate and how carefully is this treatment reviewed in UK mental health services? Data from a clinical audit, THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY, Vol: 12, ISSN: 2045-1253

Journal article

Barnes TRE, MacCabe JH, Kane JM, Delgado O, Khan M, Paton Cet al., 2022, Prescribing clozapine in the UK: Quality improvement issues identified by clinical audit, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 1036-1040, ISSN: 0269-8811

Journal article

Crawford M, Leeson V, Evans R, Barrett B, McQuaid A, Cheshire J, Sanatina R, Lamph G, Sen P, Anagnostakis K, Millard L, Qurashi I, Larkin F, Husain N, Moran P, Barnes T, Paton C, Hoare Z, Picchioni M, Gibbon Set al., 2022, The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): A randomised placebo-controlled trial., Therapeutic Advances in Psychopharmacology, Vol: 12, Pages: 1-14, ISSN: 2045-1253

Background:Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted. Methods:Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at six months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at six months adjusted for baseline score, allocation group and site. Results:The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at six months, of whom 21 (72%) were included in the mITT analysis. At six months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at six months was -3.86 (95% Confidence Intervals = -10.04 to 2.32, p=0.22). There were 14 serious adverse events; six in the clozapine arm and eight in the placebo arm of the trial. There was little difference in the cost of care between groups. Interpretation:We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units.Trial registrationISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058

Journal article

Pardiñas AF, Smart SE, Willcocks IR, Holmans PA, Dennison CA, Lynham AJ, Legge SE, Baune BT, Bigdeli TB, Cairns MJ, Corvin A, Fanous AH, Frank J, Kelly B, McQuillin A, Melle I, Mortensen PB, Mowry BJ, Pato CN, Periyasamy S, Rietschel M, Rujescu D, Simonsen C, St Clair D, Tooney P, Wu JQ, Andreassen OA, Kowalec K, Sullivan PF, Murray RM, Owen MJ, MacCabe JH, O'Donovan MC, Walters JTR, Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances STRATA Consortium and the Schizophrenia Working Group of the Psychiatric Genomics Consortium PGC, Ajnakina O, Alameda L, Barnes TRE, Berardi D, Bonora E, Camporesi S, Cleusix M, Conus P, Crespo-Facorro B, D'Andrea G, Demjaha A, Do KQ, Doody GA, Eap CB, Ferchiou A, Di Forti M, Guidi L, Homman L, Jenni R, Joyce EM, Kassoumeri L, Khadimallah I, Lastrina O, Muratori R, Noyan H, O'Neill FA, Pignon B, Restellini R, Richard J-R, Schürhoff F, Španiel F, Szöke A, Tarricone I, Tortelli A, Üçok A, Vázquez-Bourgon Jet al., 2022, Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia., JAMA Psychiatry, Vol: 79, Pages: 260-269

IMPORTANCE: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. OBJECTIVE: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. DESIGN, SETTING, AND PARTICIPANTS: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). MAIN OUTCOMES AND MEASURES: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. RESULTS: The study included a total of 85 490 participants (48 635 [56.9%] male

Journal article

Watson AJ, Giordano A, Suckling J, Barnes TRE, Husain N, Jones PB, Krynicki CR, Lawrie SM, Lewis S, Nikkheslat N, Pariante CM, Upthegrove R, Deakin B, Dazzan P, Joyce EMet al., 2022, Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers, PSYCHOLOGICAL MEDICINE, ISSN: 0033-2917

Journal article

Cousins DA, Barnes TRE, Young AH, Delgado O, Paton Cet al., 2022, Plus ca change? Switching lithium preparations, BJPSYCH BULLETIN, ISSN: 2056-4694

Journal article

Paton C, Roy A, Purandare K, Rendora O, Barnes TREet al., 2021, Prescribing antipsychotic medication for adults with intellectual disability: shared responsibilities between mental health services and primary care, BJPSYCH BULLETIN, Vol: 46, Pages: 311-315, ISSN: 2056-4694

Journal article

Paton C, Craig TKJ, McConnell B, Barnes TREet al., 2021, Side-effect monitoring of continuing LAI antipsychotic medication in UK adult mental health services, THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY, Vol: 11, ISSN: 2045-1253

Journal article

Krynicki CR, Dazzan P, Pariante CM, Barnes NM, Vincent RC, Roberts A, Giordano A, Watson A, Suckling J, Barnes TRE, Husain N, Jones PB, Joyce E, Lawrie SM, Lewis S, Deakin B, Upthegrove R, BeneMin Study teamet al., 2021, Deconstructing depression and negative symptoms of schizophrenia; differential and longitudinal immune correlates, and response to minocycline treatment, Brain, Behavior, and Immunity, Vol: 91, Pages: 498-504, ISSN: 0889-1591

BACKGROUND: Immune dysfunction has been implicated in negative symptoms of schizophrenia and also in depression. These disorders are frequently co-morbid, with some symptoms such as anhedonia and apathy common to both. The anti-inflammatory agent minocycline may be ineffective in schizophrenia, but more positive effects have been seen in depression. Our aim was to investigate the role of immune dysfunction in depression and sub-domains of negative symptoms in schizophrenia by investigating their intercorrelation and the influence of treatment with minocycline. METHODS: We analysed longitudinal data from 207 patients within 5 years of onset of schizophrenia, from the randomised double-blind, placebo-controlled trial of minocycline (BeneMin). Symptom ratings and circulating IL-6, C-reactive protein (CRP) and TNF-α concentrations were collected at baseline and repeated over twelve months. The sample was not stratified by CRP prior to randomisation. Positive and Negative Syndrome Scale composite ratings of avolition-apathy and diminished expression, Calgary Depression Scale total scores, and immune markers were examined cross-sectionally using Spearman's rank, and longitudinally by linear mixed effect models that included body mass index and minocycline. Additionally, post hoc analysis of the sample stratified by elevated CRP (>1 mg/l and <10 mg/l at baseline) was carried out to assess whether minocycline had any effect on specific symptoms in an immune active sub-group of patients. RESULTS: Depression and avolition-apathy were significantly positively related, and depression correlated weakly with IL-6 at baseline. Diminished expression was associated with increased TNF-α both cross-sectionally and longitudinally. CRP was unrelated to any symptom domain. Minocycline did not affect any individual symptom or sub-domain in the full sample or in the immune active sub-group. DISCUSSION: IL-6 may have some specificity to depression in early schizo

Journal article

Crawford MJ, Thana L, Evans R, Carne A, O'Connell L, Claringbold A, Saravanamuthu A, Case R, Munjiza J, Jayacodi S, Reilly JG, Hughes E, Hoare Z, Barrett B, Leeson VC, Paton C, Keown P, Pappa S, Green C, Barnes TREet al., 2020, Switching antipsychotic medication to reduce sexual dysfunction in people with psychosis: the REMEDY RCT, HEALTH TECHNOLOGY ASSESSMENT, Vol: 24, Pages: 1-+, ISSN: 1366-5278

Journal article

Barnes TRE, MacCabe JH, Kane JM, Delgado O, Paton Cet al., 2020, The physical health and side-effect monitoring of patients prescribed clozapine: data from a clinical audit conducted in UK mental health services, THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY, Vol: 10, ISSN: 2045-1253

Journal article

Paton C, Anderson IM, Cowen PJ, Delgado O, Barnes TREet al., 2020, Prescribing for moderate or severe unipolar depression in patients under the long-term care of UK adult mental health services, Therapeutic Advances in Psychopharmacology, Vol: 10, ISSN: 2045-1253

Background: A quality improvement programme addressing prescribing practice for depression was initiated by the Prescribing Observatory for Mental Health. Methods: A baseline clinical audit against evidence-based practice standards was conducted in UK adult mental health services. Results: 55 mental health services submitted data for 2082 patients, under the care of a community psychiatric team (CMHT) for at least a year, with a diagnosis of moderate or severe unipolar depression, 54% of whom had a comorbid psychiatric diagnosis. SSRIs were prescribed for 35% of the patients, other newer generation antidepressants for 60%, tricyclic antidepressants for 6% and MAOIs for <1%. The most commonly prescribed individual antidepressants were mirtazapine (33%, usually in combination with another antidepressant), venlafaxine (25%), and sertraline (21%). Patients with severe depression were more likely (p<0.001) to be co-prescribed an antipsychotic medication, lithium, or to have received ECT. There was a documented clinical review in the last year in 85%, with a symptom rating scale used in 11%. A documented comprehensive treatment history was accessible for 50% of those prescribed antidepressant medication. Conclusions: Patients with moderate or severe depression remaining under the care of a CMHT for longer than a year are clinically complex. The failure to achieve a level of wellness allowing discharge from mental health services may be partly related to the finding that not all patients had the benefit of a systematic approach to clinical assessment and sequential testing of available evidence-based pharmacological interventions. KeywordsDepression; antidepressant; quality improvement; mental health services; prescribing practice

Journal article

Haddad PM, Barnes TRE, 2020, Good Clinical Practice in Psychopharmacology, SEMINARS IN CLINICAL PSYCHOPHARMACOLOGY, 3RD EDITION, Editors: Haddad, Nutt, Publisher: CAMBRIDGE UNIV PRESS, Pages: 203-226

Book chapter

Paton C, Adams CE, Dye S, Delgado O, Okocha C, Barnes TREet al., 2019, Physical health monitoring after rapid tranquillisation: clinical practice in UK mental health services, Therapeutic Advances in Psychopharmacology, Vol: 9, ISSN: 2045-1253

Background:We aimed to assess the quality of physical health monitoring following rapid tranquillisation (RT) for acute behavioural disturbance in UK mental health services.Methods:The Prescribing Observatory for Mental Health (POMH-UK) initiated an audit-based quality improvement programme addressing the pharmacological treatment of acute behavioural disturbance in mental health services in the UK.Results:Data relating to a total of 2454 episodes of RT were submitted by 66 mental health services. Post-RT physical health monitoring did not reach the minimum recommended level in 1933 (79%) episodes. Patients were more likely to be monitored (OR 1.78, 95% CI 1.39–2.29, p < 0.001) if there was actual or threatened self-harm, and less likely to be monitored if the episode occurred in the evening (OR 0.79, 95% CI 0.62–1.0, p < 0.001) or overnight (OR 0.57, 95% CI 0.44–0.75, p < 0.001). Risk factors such as recent substance use, RT resulting in the patient falling asleep, or receiving high-dose antipsychotic medication on the day of the episode, did not predict whether or not the minimum recommended level of post-RT monitoring was documented.Conclusions:The minimum recommended level of physical health monitoring was reported for only one in five RT episodes. The findings also suggest a lack of targeting of at-risk patients for post-RT monitoring. Possible explanations are that clinicians consider such monitoring too demanding to implement in routine clinical practice or not appropriate in every clinical situation. For example, physical health measures requiring direct contact with a patient may be difficult to undertake, or counter-productive, if RT has failed. These findings prompt speculation that post-RT monitoring practice would be improved by the implementation of guidance that integrated and refined the currently separate systems for undertaking and recording physical health observations post-RT, d

Journal article

Barnes TR, Schizophrenia Consensus Group, 2019, Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology., Journal of Clinical Psychopharmacology, Vol: 25, Pages: 567-620, ISSN: 0271-0749

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.

Journal article

Moncrieff J, Lewis G, Freemantle N, Johnson S, Barnes TRE, Morant N, Pinfold V, Hunter R, Kent LJ, Smith R, Darton K, Horne R, Crellin NE, Cooper RE, Priebe Set al., 2019, Randomised controlled trial of gradual antipsychotic reduction and discontinuation in people with schizophrenia and related disorders: the RADAR trial (Research into Antipsychotic Discontinuation and Reduction), BMJ OPEN, Vol: 9, ISSN: 2044-6055

Journal article

Tibber MS, Kirkbride JB, Mutsatsa S, Harrison I, Barnes TRE, Joyce EM, Huddy Vet al., 2019, Are socioenvironmental factors associated with psychotic symptoms in people with first-episode psychosis? A cross-sectional study of a West London clinical sample, BMJ OPEN, Vol: 9, ISSN: 2044-6055

Journal article

Lennox B, Yeeles K, Jones PB, Zandi M, Joyce E, Yu L-M, Tomei G, Pollard R, Vincent S-A, Shimazaki M, Cairns I, Dowling F, Kabir T, Barnes TRE, Hughes AL, Hosseini AA, Harrower T, Buckley C, Coles Aet al., 2019, Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2), Trials, Vol: 20, ISSN: 1745-6215

BackgroundEvidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care.MethodsWe will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group.Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2–4 consecutive days no later than 7 days from baseline. It will continue 4–5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2–3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12

Journal article

Ricciardi L, Pringsheim T, Barnes TRE, Martino D, Gardner D, Remington G, Addington D, Morgante F, Poole N, Carson A, Edwards Met al., 2019, Treatment Recommendations for Tardive Dyskinesia, CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE, Vol: 64, Pages: 388-399, ISSN: 0706-7437

Journal article

Paton C, Adams CE, Dye S, Fagan E, Okocha C, Barnes TREet al., 2019, The pharmacological management of acute behavioural disturbance: Data from a clinical audit conducted in UK mental health services, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 33, Pages: 472-481, ISSN: 0269-8811

Journal article

Morrison AP, Pyle M, Gumley A, Schwannauer M, Turkington D, MacLennan G, Norrie J, Hudson J, Bowe S, French P, Hutton P, Byrne R, Syrett S, Dudley R, McLeod HJ, Griffiths H, Barnes TRE, Davies L, Shields G, Buck D, Tully S, Kingdon Det al., 2019, Cognitive-behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT, HEALTH TECHNOLOGY ASSESSMENT, Vol: 23, Pages: 1-+, ISSN: 1366-5278

Journal article

Osborn D, Burton A, Walters K, Atkins L, Barnes T, Blackburn R, Craig T, Gilbert H, Gray B, Hardoon S, Heinkel S, Holt R, Hunter R, Johnston C, King M, Leibowitz J, Marston L, Michie S, Morris R, Morris S, Nazareth I, Omar R, Petersen I, Peveler R, Pinfold V, Stevenson F, Zomer Eet al., 2019, Primary care management of cardiovascular risk for people with severe mental illnesses: the Primrose research programme including cluster RCT

<h4>Background</h4>Effective interventions are needed to prevent cardiovascular disease (CVD) in people with severe mental illnesses (SMI) because their risk of CVD is higher than that of the general population.<h4>Objectives</h4>(1) Develop and validate risk models for predicting CVD events in people with SMI and evaluate their cost-effectiveness, (2) develop an intervention to reduce levels of cholesterol and CVD risk in SMI and (3) test the clinical effectiveness and cost-effectiveness of this new intervention in primary care.<h4>Design</h4>Mixed methods with patient and public involvement throughout. The mixed methods were (1) a prospective cohort and risk score validation study and cost-effectiveness modelling, (2) development work (focus groups, updated systematic review of interventions, primary care database studies investigating statin prescribing and effectiveness) and (3) cluster randomised controlled trial (RCT) assessing the clinical effectiveness and cost-effectiveness of a new practitioner-led intervention, and fidelity assessment of audio-recorded appointments.<h4>Setting</h4>General practices across England.<h4>Participants</h4>All studies included adults with SMI (schizophrenia, bipolar disorder or other non-organic psychosis). The RCT included adults with SMI and two or more CVD risk factors.<h4>Interventions</h4>The intervention consisted of 8–12 appointments with a practice nurse/health-care assistant over 6 months, involving collaborative behavioural approaches to CVD risk factors. The intervention was compared with routine practice with a general practitioner (GP).<h4>Main outcome measures</h4>The primary outcome for the risk score work was CVD events, in the cost-effectiveness modelling it was quality-adjusted life-years (QALYs) and in the RCT it was level of total cholesterol.<h4>Data sources</h4>Databases studies used The Health Improvement

Journal article

Deakin B, Suckling J, Dazzan P, Joyce E, Lawrie SM, Upthegrove R, Husain N, Chaudhry IB, Dunn G, Jones PB, Lisiecka-Ford D, Lewis S, Barnes TRE, Williams SCR, Pariante CM, Knox E, Drake RJ, Smallman R, Barnes NMet al., 2019, Minocycline for negative symptoms of schizophrenia and possible mechanistic actions: the BeneMin RCT

<h4>Background</h4>In 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.<h4>Objectives</h4>To determine the efficacy of minocycline on the negative symptoms of schizophrenia and the mechanistic role of neuroprotective, anti-inflammatory and cognitive enhancing actions.<h4>Methods</h4>Two 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.<h4>Results</h4>Compared 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 an

Journal article

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