52 results found
Crawford M, Leeson V, Evans R, et 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
Deb S, Crawford M, Sharp D, et al., 2020, Risperidone versus placebo for aggression following traumatic brain injury: a feasibility randomised controlled trial, BMJ Open, Vol: 10, ISSN: 2044-6055
Objectives: To conduct a feasibility randomised controlled trial of risperidone for the treatment of aggression in adults with traumatic brain injury (TBI).Design: Multi-centre, parallel design, placebo controlled (1:1 ratio) double-blind feasibility trial with an embedded process evaluation. No statistical comparison was performed between the two study groups.Setting Four neuropsychiatric and neurology outpatient clinics in London and Kent, UK. Participants Our aim was to recruit 50 TBI patients over 18 months. Follow up participants at 12 weeks using a battery of assessment scales to measure changes in aggressive behaviour (MOAS-primary outcome, IRQ) as well as global functioning (GOS-E, CGI) and quality of life (EQ-5D-5L, SF-12), mental health (HADS) and medication adverse effects (UKU).Results: Six participants were randomised to the active arm of the trial and eight to the placebo arm over a 10-month period (28% of our target). Two participants withdrew because of adverse events. Twelve out of 14 (85.7%) patients completed a follow up assessment at 12 weeks. At follow up, the scores of all outcome measures improved in both groups. Placebo group showed numerically better score change according to the primary outcome MOAS. No severe adverse events were reported. The overall rate of adverse events remained low. Data from the process evaluation suggest that existence of specialised TBI Follow-up clinics, availability of a dedicated database of TBI patients’ clinical details, simple study procedures and regular support to participants would enhance recruitment and retention in the trial. Feedback from participants showed that once in the study, they did not find the trial procedure onerous.Conclusions: It was not feasible to conduct a successful randomised trial of risperidone versus placebo for post-TBI aggression using the methods we deployed in this study. It is not possible to draw any definitive conclusion about risperidone’s efficacy from such a s
Crawford MJ, Thana L, Evans R, et 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
Crawford MJ, Sanatinia R, Barrett B, et al., 2018, The clinical effectiveness and cost effectiveness of lamotrigine for people with borderline personality disorder: a randomized, placebo-controlled trial, American Journal of Psychiatry, Vol: 175, Pages: 756-764, ISSN: 0002-953X
Objectives:To examine whether lamotrigine is a clinically effective and cost-effective treatment for people with borderline personality disorder. Method:Multicentre, double-blind, placebo-controlled randomized trial. Between July 2013 to November 2016, we recruited 276 people aged 18 or over, who met diagnostic criteria for borderline personality disorder. We excluded those with co-existing bipolar affective disorder or psychosis, those already taking a mood stabiliser, and women at risk of pregnancy. We randomly allocated participants on a 1:1 ratio to up to 400mg of lamotrigine per day or an inert placebo using a remote web-based randomization service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. Secondary outcomes included depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Results:195 (70.6%) participants were followed up at 52 weeks, at which point 49 (36%) of those prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. Mean total ZAN-BPD score was 11.3 (SD = 6.6) among those randomized to lamotrigine and 11.5 (SD = 7.7) among those randomized to placebo (adjusted difference in means = 0.1, 95% C.I = -1.8 to 2.0, p=0.91). There was no evidence of any differences in secondary outcomes. Costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. Conclusions:Treating people with borderline personality disorder with lamotrigine is not a clinically effective or cost-effective use of resources.
Barnes TRE, Leeson V, Paton C, et al., 2018, Amisulpride augmentation of clozapine for treatment-refractory schizophrenia: a double-blind, placebo-controlled trial, Therapeutic Advances in Psychopharmacology, Vol: 8, Pages: 185-197, ISSN: 2045-1253
Background:A second antipsychotic is commonly added to clozapine to treat refractory schizophrenia, notwithstanding the limited evidence to support such practice.Methods:The efficacy and adverse effects of this pharmacological strategy were examined in a double-blind, placebo-controlled, 12-week randomized trial of clozapine augmentation with amisulpride, involving 68 adults with treatment-resistant schizophrenia and persistent symptoms despite a predefined trial of clozapine.Results:There were no statistically significant differences between the amisulpride and placebo groups on the primary outcome measure (clinical response defined as a 20% reduction in total Positive and Negative Syndrome Scale score) or other mental state measures. However, the trial under recruited and was therefore underpowered to detect differences in the primary outcome, meaning that acceptance of the null hypothesis carries an increased risk of type II error. The findings suggested that amisulpride-treated participants were more likely to fulfil the clinical response criterion, odds ratio 1.17 (95% confidence interval 0.40–3.42) and have a greater reduction in negative symptoms, but these numerical differences were not statistically significant and only evident at 12 weeks. A significantly higher proportion of participants in the amisulpride group had at least one adverse event compared with the control group (p = 0.014), and these were more likely to be cardiac symptoms.Conclusions:Treatment for more than 6 weeks may be required for an adequate trial of clozapine augmentation with amisulpride. The greater side-effect burden associated with this treatment strategy highlights the need for safety and tolerability monitoring, including vigilance for indicators of cardiac abnormalities, when it is used in either a clinical or research setting.
Deb S, Leeson V, Aimola L, et al., 2018, Aggression following traumatic brain injury: effectiveness of Risperidone (AFTER): study protocol for a feasibility randomised controlled trial, Trials, Vol: 19, ISSN: 1745-6215
BackgroundTraumatic brain injury (TBI) is a major public health concern and many people develop long-lasting physical and neuropsychiatric consequences following a TBI. Despite the emphasis on physical rehabilitation, it is the emotional and behavioural consequences that have greater impact on people with TBI and their families. One such problem behaviour is aggression which can be directed towards others, towards property or towards the self. Aggression is reported to be common after TBI (37–71%) and causes major stress for patients and their families. Both drug and non-drug interventions are used to manage this challenging behaviour, but the evidence-base for these interventions is poor and no drugs are currently licensed for the treatment of aggression following TBI. The most commonly used drugs for this purpose are antipsychotics, particularly second-generation drugs such as risperidone. Despite this widespread use, randomised controlled trials (RCTs) of antipsychotic drugs, including risperidone, have not been conducted. We have, therefore, set out to test the feasibility of conducting an RCT of this drug for people who have aggressive behaviour following TBI.Methods/designWe will examine the feasibility of conducting a placebo-controlled, double-blind RCT of risperidone for the management of aggression in adults with TBI and also assess participants’ views about their experience of taking part in the study.We will randomise 50 TBI patients from secondary care services in four centres in London and Kent to up to 4 mg of risperidone orally or an inert placebo and follow them up 12 weeks later. Participants will be randomised to active or control treatment in a 1:1 ratio via an external and remote web-based randomisation service. Participants will be assessed at baseline and 12-week follow-up using a battery of assessment scales to measure changes in aggressive behaviour (MOAS, IRQ) as well as global functioning (GOS-E, CGI), quality of life (EQ-5D-5L
Crawford MJ, Sanatinia R, Barrett B, et al., 2018, Lamotrigine for people with borderline personality disorder: a RCT, HEALTH TECHNOLOGY ASSESSMENT, Vol: 22, Pages: 1-+, ISSN: 1366-5278
Background:No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD.Objective:To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD.Design:A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms.Setting:Secondary care NHS mental health services in six centres in England.Participants:Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant.Interventions:Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day.Main outcome measures:Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes.Results:Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52
Watson AJ, Joyce EM, Fugard AJB, et al., 2017, More haste less speed: A meta-analysis of thinking latencies during planning in people with psychosis, PSYCHIATRY RESEARCH, Vol: 258, Pages: 576-582, ISSN: 0165-1781
Barnes TRE, Leeson VC, Paton C, et al., 2017, Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness, HEALTH TECHNOLOGY ASSESSMENT, Vol: 21, Pages: 1-+, ISSN: 1366-5278
Barnes T, Leeson V, Paton C, et al., 2017, LONG-TERM ANTIDEPRESSANT TREATMENT FOR NEGATIVE SYMPTOMS IN SCHIZOPHRENIA: THE ACTIONS STUDY, 16th International Congress on Schizophrenia Research (ICOSR), Publisher: OXFORD UNIV PRESS, Pages: S214-S215, ISSN: 0586-7614
Barnes T, Leeson V, Paton C, et al., 2017, AMISULPRIDE AUGMENTATION OF CLOZAPINE FOR TREATMENT-REFRACTORY SCHIZOPHRENIA: THE AMICUS STUDY, 16th International Congress on Schizophrenia Research (ICOSR), Publisher: OXFORD UNIV PRESS, Pages: S164-S165, ISSN: 0586-7614
Barnes TR, Leeson VC, Paton C, et al., 2016, Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial, Health Technology Assessment, Vol: 20, ISSN: 1366-5278
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 inter
Crawford MJ, Sanatinia R, Barrett B, et al., 2015, Lamotrigine versus inert placebo in the treatment of borderline personality disorder: study protocol for a randomized controlled trial and economic evaluation, TRIALS, Vol: 16, ISSN: 1745-6215
Gutierrez-Galve L, Chu EM, Leeson VC, et al., 2015, A longitudinal study of cortical changes and their cognitive correlates in patients followed up after first-episode psychosis, PSYCHOLOGICAL MEDICINE, Vol: 45, Pages: 205-216, ISSN: 0033-2917
Ananthavarathan P, Leeson V, Barnes T, 2014, A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EFFICACY AND SAFETY OF SODIUM VALPROATE FOR "OFF-LABEL" INDICATIONS IN MENTAL HEALTH, 27th Annual General Meeting of the British-Neuropsychiatry-Association (BNPA), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
Leeson VC, Tyrer P, 2013, The advance of research governance in psychiatry: one step forward, two steps back, EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES, Vol: 22, Pages: 313-320, ISSN: 2045-7960
Galve LBG, Wheeler-Kingshott CAM, Altmann DR, et al., 2012, CORTICAL THINNING OVER TWO YEARS FOLLOWING THE FIRST EPISODE OF PSYCHOSIS: RELATIONSHIP TO TREATMENT DURATION AND COGNITIVE IMPAIRMENT, SCHIZOPHRENIA RESEARCH, Vol: 136, Pages: S205-S205, ISSN: 0920-9964
Leeson V, Barnes TRE, Harrison I, et al., 2011, DO PEOPLE DEVELOPING PSYCHOSIS IN THE CONTEXT OF CANNABIS USE HAVE BETTER COGNITIVE FUNCTION BECAUSE THEY HAVE FEWER NEURODEVELOPMENTAL RISK FACTORS?, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A76-A76, ISSN: 0269-8811
Leeson VC, Sharma P, Harrison M, et al., 2011, IQ Trajectory, Cognitive Reserve, and Clinical Outcome Following a First Episode of Psychosis: A 3-Year Longitudinal Study, SCHIZOPHRENIA BULLETIN, Vol: 37, Pages: 768-777, ISSN: 0586-7614
Leeson VC, Harrison I, Ron MA, et al., 2011, The Effect of Cannabis Use and Cognitive Reserve on Age at Onset and Psychosis Outcomes in First-Episode Schizophrenia, Schizophrenia Bulletin
Objective: Cannabis use is associated with a younger age at onset of psychosis, an indicator of poor prognosis, but better cognitive function, a positive prognostic indicator. We aimed to clarify the role of age at onset and cognition on outcomes in cannabis users with first-episode schizophrenia as well as the effect of cannabis dose and cessation of use. Methods: Ninety-nine patients without alcohol or substance abuse other than cannabis were divided into lifetime users and never-users of cannabis and compared on measures of premorbid function, cognition, and clinical outcome. Results: Cannabis users demonstrated better cognition at psychosis onset, which was explained by higher premorbid IQ. They also showed better social function and neither measure changed over the subsequent 15 months. Cannabis users had an earlier age at onset of psychosis, and there was a strong linear relationship between age at first cannabis use and age at onset of both prodromal and psychotic symptoms. Cannabis use spontaneously declined over time with 3-quarters of users giving up altogether. Later age at first cannabis use predicted earlier cessation of use and this in turn was linked to fewer positive psychotic symptoms and days in hospital during the first 2 years. Conclusions: Cannabis use brings forward the onset of psychosis in people who otherwise have good prognostic features indicating that an early age at onset can be due to a toxic action of cannabis rather than an intrinsically more severe illness. Many patients abstain over time, but in those who persist, psychosis is more difficult to treat.
Joyce EM, Leeson VC, Ron MA, et al., 2011, THE IMPACT OF COGNITIVE RESERVE ON SCHIZOPHRENIA: NEURAL UNDERPINNINGS AND CLINICAL OUTCOMES, 13th International Congress on Schizophrenia Research (ICSR), Publisher: OXFORD UNIV PRESS, Pages: 245-245, ISSN: 0586-7614
Barnett JH, Robbins TW, Leeson VC, et al., 2010, Assessing cognitive function in clinical trials of schizophrenia, NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, Vol: 34, Pages: 1161-1177, ISSN: 0149-7634
Gutierrez-Galve L, Wheeler-Kingshott CAM, Altmann DR, et al., 2010, Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis, BIOLOGICAL PSYCHIATRY, Vol: 68, Pages: 51-60, ISSN: 0006-3223
Leeson V, Joyce EM, Harrison I, et al., 2010, DOES THE EARLY COURSE OF COGNITIVE FUNCTION IN FIRST-EPISODE SCHIZOPHRENIA PREDICT FUNCTIONAL OUTCOME?, 2nd Conference of the Schizophrenia-International-Research-Society (SIRS), Publisher: ELSEVIER SCIENCE BV, Pages: 280-280, ISSN: 0920-9964
Joyce EM, Leeson VC, Sharma P, et al., 2010, WORKING MEMORY NOT PROCESSING SPEED IS THE BASIS OF HIGHER-ORDER PLANNING DEFICITS IN FIRST EPISODE SCHIZOPHRENIA, 2nd Conference of the Schizophrenia-International-Research-Society (SIRS), Publisher: ELSEVIER SCIENCE BV, Pages: 175-175, ISSN: 0920-9964
Leeson VC, Barnes TR, Harrison M, et al., 2010, The relationship between IQ, memory, executive function, and processing speed in recent-onset psychosis: 1-year stability and clinical outcome., Schizophr Bull, Vol: 36, Pages: 400-409, ISSN: 1745-1701
Studies commonly report poor performance in psychotic patients compared with controls on tasks testing a range of cognitive functions, but, because current IQ is often not matched between these groups, it is difficult to determine whether this represents a generalized deficit or specific abnormalities. Fifty-three first-episode psychosis patients and 53 healthy controls, one-to-one matched for sex, age, and full-scale current IQ, were compared on Wechsler Adult Intelligence Scale (WAIS) subtests representing indices of perceptual organization, verbal comprehension, processing speed, and working memory as well as other tests of executive function and episodic memory. The groups showed an equivalent pattern of performance on all WAIS subtests except digit symbol processing speed, on which the patients were significantly worse. Patients were also worse on measures where performance correlated with digit symbol score, namely working and verbal memory tasks. Standardized residual scores for each subtest were calculated for each patient using the difference between their actual subtest score and a predicted subtest score based on their full-scale IQ and the performance of controls. Scaled scores and residual scores were examined for relationships with clinical measures. Digit symbol-scaled score was significantly correlated with concurrent negative syndrome score at baseline, and digit symbol residual score significantly predicted residual negative symptoms at 1-year follow-up. In summary, our comparison of patients and controls precisely matched for IQ revealed that processing speed was attenuated in recent-onset schizophrenia, contributed significantly to working and episodic memory deficits, and was a prognostic factor for poor outcome at 1 year.
Leeson VC, Robbins TW, Franklin C, et al., 2009, Dissociation of long-term verbal memory and fronto-executive impairment in first-episode psychosis, PSYCHOLOGICAL MEDICINE, Vol: 39, Pages: 1799-1808, ISSN: 0033-2917
Leeson VC, Joyce EM, 2009, Cognitive Impairment in Schizophrenia, Research Progress in Alzheimer's Disease and Dementia, Editors: Sun, ISBN: 9781608761524
Leeson VC, Robbins TW, Matheson E, et al., 2009, Discrimination Learning, Reversal, and Set-Shifting in First-Episode Schizophrenia: Stability Over Six Years and Specific Associations with Medication Type and Disorganization Syndrome, BIOLOGICAL PSYCHIATRY, Vol: 66, Pages: 586-593, ISSN: 0006-3223
Harrison I, Barnes TR, Leeson V, et al., 2009, THE IMPACT OF CANNABIS USE ON ILLNESS COURSE IN FIRST EPISODE PSYCHOSIS, 12th International Congress on Schizophrenia Research, Publisher: OXFORD UNIV PRESS, Pages: 319-320, ISSN: 0586-7614
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.