Recent Submissions

  • Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records

    Morriss, Richard K.; Butler, Debbie; Hollis, Chris P. (2022)
    Background Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.Objectives To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments.Design and setting Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018.Participants 24 516 people diagnosed with depression, aged 18–99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine.Main outcome measures Hospitalisation or death due to deliberate self-harm. Age–sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates.Results Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose.Conclusions There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm.Clinical implications Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.No data are available. Data used in the study were provided under licence by CPRD ( and cannot be shared by the authors. All code lists and the statistical code (in the form of Stata do-files) used to prepare and analyse the data are available on (
  • An international adult guideline for making clozapine titration safer by using six ancestry-based personalized dosing titrations, CRP, and clozapine levels

    Rajkumar, Anto P. (2021)
    This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
  • Audit on clozapine dose and plasma level correlation for patients with chronic treatment-resistant psychosis

    Macnamara, Olivia; Lawton, John D.; Lankappa, Sudheer (2021)
    Aims Clozapine is associated with a risk of severe adverse events for which there are current monitoring systems are in place; however, there are no established regimens for monitoring of clozapine plasma levels. Recent Medicines and Healthcare products Regulatory Agency (MHRA) guidance advises clozapine levels should be monitored in certain clinical situations where toxicity may be suspected. This audit aimed to evaluate current practice of clozapine level monitoring within one Local Mental Health Team (LMHT). Method Electronic (RiO) records of 41 patients (33 male, 8 female; aged from 27 to 76 years; mean age 45 years) registered to the ZTAS system within the Nottingham City Central LMHT were reviewed. 46% had been on clozapine for over 16 years. 73.3% of patients were within clusters 12 and 13; 25.4% of patients were in cluster 11, with one patient in cluster 8. Dates of clozapine plasma level tests for each patient between 2006 and 2020 were found on the electronic NoTIS system, along with clozapine, norclozapine and total clozapine levels. Concurrent clozapine dose and regimens were obtained from pharmacy records from 2018 onwards. Result 273 clozapine plasma levels were conducted between 2006 and 2020. The average interval between levels taken was 10 months, 2 weeks but had a wide range, the shortest interval being 2 days, the longest being 13 years. 88 levels taken were >600 ug/L, suggesting increased toxicity risk. 108 levels were <350 ug/L, suggesting possible sub-optimal dosing or non-compliance. Statistical tests on correlation coefficient, although statistically non-significant (R = 0.37), showed a positive trend between total clozapine dose and the plasma level between all 3 parameters (i.e. clozapine, norclozapine and total clozapine). Conclusion There does not appear to be any routine plasma clozapine level monitoring throughout the LMHT with an average interval between tests of 10 months. There was a non-significant but positive trend between total daily dose of clozapine and clozapine level. 32% of clozapine levels returned were higher than the recommended level. We would recommend as suggested in the guidelines from MHRA, clozapine plasma levels should be monitored in certain clinical situations with increased toxicity risk. Trough levels should be taken with records of time of previous dose taken. Limitations of this study included a small sample size (41 patients) with data collection reliant on electronic systems. It was unclear if these results represent trough levels, making values difficult to interpret. Multifactorial impact on clozapine metabolism causes wide patient variability in plasma levels.
  • A clinical audit to investigate polypharmacy and interactions in inpatients in an old age psychiatric ward

    Mokashi, Nisha (2021)
    Aims To identify any problematic polypharmacy in the patient records of those staying in Cherry Ward, an old age psychiatric unit at Highbury Hospital, Nottingham in the calendar year 2018. Background Multi-morbidity is defined as more than one long-term medical condition in a single individual and is a factor that is closely associated with polypharmacy, the use of multiple medications concurrently. Appropriate and Problematic are the two classifications of polypharmacy outlined by the King's Fund report, the first describing optimised evidenced-based pharmacological management of comorbidities and the latter to label prescribed medications whose use is not in the best interests of the patient. The risk of drug interactions and adverse drug reactions is increased with polypharmacy, and frail elderly patients are particularly at risk of the side-effects of psychotropic medications used in the management of mental health disorders. Guidelines highlight this group as a key party to be identified when searching for at-risk people. Method The electronic records of those admitted and discharged from Cherry Ward in 2018 were reviewed in the period spanning January to May 2019, and the first forty-three patients were analysed in Microsoft Excel using criteria based on the King's fund report and the Medscape and BNF (British National Formulary) drug interaction tools. The Medscape drug interaction checker was used for initial screening; the complete medication list for each patient was entered into it and the number of interactions was displayed with advice on severity. If necessary, the individual interactions for each specific medication could also be cross-referenced in the BNF using the extensive lists provided for each drug. These are also graded from mild to severe. Result On discharge, 69.7% (thirty patients) met the criteria for being at higher risk of polypharmacy. One patient became at higher risk of polypharmacy during admission, and another two stepped down from meeting the criteria on admission but not on discharge. Thirty-one of the forty-three patients had at least one interaction recorded; 18.6% (eight patients) had at least one potentially severe interaction. Conclusion A substantial proportion of patients in Cherry ward in 2018 were at a higher risk of polypharmacy, reflecting current practice as outlined in the King's Fund report. Problematic polypharmacy is common among older patients hospitalised with psychiatric illness. Recommendations include use of an automated electronic system to investigate and flag up problematic polypharmacy and severe medication interactions.
  • Assessing the compliance of accurately documenting medication history in CAMHS - completion of the audit cycle

    Guest, Laura; Lankappa, Sudheer (2021)
    Aims To assess the documentation of medication across all Child and Adolescent Mental Health Service (CAMHS) teams in the south region of Derbyshire Healthcare NHS Foundation Trust against a locally agreed protocol. The aim is to ensure accurate and timely documentation of medication history in a standardised way to reduce the risk of medication errors. Method We randomly selected 78 patients across seven teams within CAMHS that were currently prescribed medication as of November 2020. We reviewed each patient to see if medication history had been recorded in the specified section of the trust's patient database PARIS. We then cross referenced this information with the patient notes, clinic letters and prescriptions to review accuracy of information in terms of recording of drug name, dose, frequency, and whether the medication was regular or as required. We compared the data to the results of a previous audit in 2017 which used the same methods. Result Of the 78 patients, 74% (n = 58) had medication recorded in the correct section of PARIS compared to 13% in the 2017 audit. We found that compliance varied between different CAMHS teams ranging from 0% to 100%. Of those with medication history recorded, 86% had all drug names listed correctly, 79% had all drugs listed at the correct dose, 71% had the correct frequency recorded and 81% had whether the medication was regular, or PRN recorded. Conclusion Although we have seen improvement in standardised documentation of medication history since 2017, it remains difficult to rely on this information being up to date and reliable. There was a wide range of compliance in documentation of medication history across different teams, possibly reflecting how effectively the teaching following the previous 2017 audit had been delivered to each team. We have completed more teaching for medical and non-medical prescribers across all localities to highlight the importance of timely and standardised documentation. This is particularly important in CAMHS where the prescribing of medication often remains the responsibility of secondary care, with clinicians regularly prescribing on behalf of colleagues from other teams. Our findings support the move within the Trust towards a system where medication can be both documented and electronically prescribed in the same place (System One).
  • Compliance to completion of sodium valproate annual risk acknowledgement form among women of child-bearing age prescribed sodium valproate in the intellectual disability (ID) services of an NHS trust

    Ohize, Victor; Bagalkote, Deval (2021)
    Aims To determine the proportion of women of child-bearing age prescribed SV who have the SV ARF filled. Background In 2018, the Medicines and Healthcare products Regulatory Agency (MHRA) gave guidance regarding Sodium Valproate (SV) prescription. It acknowledged the significant risk of birth defects and developmental disorders in women of child-bearing age prescribed SV. Consequently, the MHRA recommendation is that SV must not be used in females of child-bearing age unless: conditions of pregnancy prevention programme are met; other treatments are ineffective or not tolerated; and evidence of discussion of risks with patient or carer and annual review of the risks are documented. The evidences of the above criteria are expected to be documented in an Annual Risk Acknowledgement Form (ARF). Method Retrospective study involving systematic search of Trust database to identify women with ID, aged 16–50 years prescribed SV from 2018 to 2019. Result 18 of 28 patients had ARF filled, a 64% compliance. The main indications for SV prescription were epilepsy; challenging behaviour; and mood stabilization. The distribution showed neurology and psychiatrist led prescription initiation equally distributed at 50%. The ARF compliance was higher in the neurology group (93%) compared to 36% in psychiatrist group. A review across the 5 ID teams (A,B,C,D and E) of the trust shows variable compliance to ARF compliance (17%,81%,100%,60%,0% respectively) with teams having higher proportion of neurology led SV prescription initiation also having higher proportion of ARF completion compliance (0%,55%,80%,80%,0% respectively). Conclusion Conclusion / Recommendation ARF compliance is below standard at 64%. Despite the SV prescription being equally distributed between neurology led and psychiatry led, patients whose prescription of SV is neurology led (prescription indication as epilepsy) had better ARF compliance outcome (93%) compared with patients whose prescription is psychiatry led (prescription indication as challenging behaviour or mood stabilization) with 36% ARF compliance. Organizational difference with dedicated epilepsy nurse in the ID service means patients with epilepsy had reviews of medication and compliance to MHRA guidance in completing the ARF. There is need to increase doctors’ awareness to review ARF status during patients’ appointment. Information Technology design to flag up out of date ARF may be helpful. The review of ARF may also flag up consideration of other alternatives: behavioural, psychological, functional and environmental interventions as well as alternative medications like Risperidone for challenging behaviours and other mood stabilizing options. This will minimize SV prescription, which is the original goal of the MHRA guidance.
  • Optimising medication management in children and young people with ADHD using a computerised test (QbTest): a feasibility randomised controlled trial

    Williams, Laura; Hall, Charlotte L.; Brown, Susan S.; Guo, Boliang; James, Marilyn; Brown, Nikki; Sayal, Kapil; Hollis, Chris P.; Groom, Madeleine J. (2021)
    BACKGROUNDMedication for attention deficit hyperactivity disorder (ADHD) should be closely monitored to ensure optimisation. There is growing interest in using computerised assessments of ADHD symptoms to support medication monitoring. The aim of this study was to assess the feasibility and acceptability of a randomised controlled trial (RCT) to evaluate the efficacy of one such computerised assessment, the Quantified Behavior (Qb) Test, as part of medication management for ADHD.METHODSThis feasibility multi-site RCT conducted in child and adolescent mental health and community paediatric settings recruited participants aged 6-15 years diagnosed with ADHD starting stimulant medication. Participants were randomised into one of two arms: experimental (QbTest protocol) where participants completed a QbTest at baseline and two follow-up QbTests on medication (2-4 weeks and 8-10 weeks later) and control where participants received treatment as usual, including at least two follow-up consultations. Measures of parent, teacher, and clinician-rated symptoms and global functioning were completed at each time point. Clinicians recorded treatment decision-making and health economic measures were obtained. Data were analysed using multi-level modelling and participants (children and parents) and clinicians were interviewed about their experiences, resulting data were thematically analysed.RESULTSForty-four children and young people were randomised. Completion of study outcome measures by care-givers and teachers ranged from 52 to 78% at baseline to 47-65% at follow-up. Participants reported the questionnaires to be useful to complete. SNAP-IV inattention scores showed greater reduction in the intervention than the control group (- 5.85, 95% CI - 10.33, - 1.36,). Engagement with the intervention ranged from 100% at baseline, to 78% follow-up 1 and 57% follow-up 2. However, only 37% of QbTests were conducted in the correct time period. Interview data highlighted that the objectivity of the QbTest was appreciated by clinicians and parents. Clinicians commented that the additional time and resources required meant that it is not feasible to use QbTest for all cases.CONCLUSIONThe trial design and protocol appear to be feasible and acceptable but could be improved by modifying QbTest time periods and the method of data collection. With these changes, the protocol may be appropriate for a full trial. Adding QbTest may improve symptom outcome as measured by SNAP-IV.TRIAL, NCT03368573 , prospectively registered, 11th December 2017, and ISRCTN, ISRCTN69461593 , retrospectively registered, 10th April 2018.
  • Rapid tranquillisation in a psychiatric emergency hospital in Lebanon: TREC-Lebanon - a pragmatic randomised controlled trial of intramuscular haloperidol and promethazine v. intramuscular haloperidol, promethazine and chlorpromazine

    Dib, Joseph E.; Adams, Clive E. (2021)
    BACKGROUNDAgitated patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians differ in opinion and practice. In Lebanon, the use of the triple therapy haloperidol plus promethazine plus chlorpromazine (HPC) is frequently used but no studies involving this combination exists.METHODA pragmatic randomised open trial (September 2018-July 2019) in the Lebanese Psychiatric Hospital of the Cross in Beirut Lebanon involving 100 people requiring urgent intramuscular sedation due to aggressive behaviour were given intramuscular chlorpromazine 100 mg plus haloperidol 5 mg plus promethazine 25 mg (HPC) or intramuscular haloperidol 5 mg plus promethazine 25 mg.RESULTSPrimary outcome data were available for 94 (94%) people. People allocated to the haloperidol plus promethazine (HP) group showed no clear difference at 20 min compared with patients allocated to the HPC group [relative risk (RR) 0.84, 95% confidence interval (CI) 0.47-1.50].CONCLUSIONSNeither intervention consistently impacted the outcome of 'calm', or 'asleep' and had no discernible effect on the use of restraints, use of additional drugs or recurrence. If clinicians are faced with uncertainty on which of the two intervention combinations to use, the simpler HP is much more widely tested and the addition of chlorpromazine adds no clear benefit with a risk of additional adverse effects.
  • Antidepressants in children and adolescents: Meta-review of efficacy, tolerability and suicidality in acute treatment

    Cortese, Samuele (2020)
    Antidepressants are prescribed for the treatment of a number of psychiatric disorders in children and adolescents, however there is still controversy about whether they should be used in this population. This meta-review aimed to assess the effects of antidepressants for the acute treatment of attention-deficit/hyperactivity disorder (ADHD), anxiety disorders (ADs), autistic spectrum disorder (ASD), enuresis, major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) in children and adolescents. Efficacy was measured as response to treatment (either as mean overall change in symptoms or as a dichotomous outcome) and tolerability was measured as the proportion of patients discontinuing treatment due to adverse events. Suicidality was measured as suicidal ideation, behavior (including suicide attempts) and completed suicide. PubMed, EMBASE, and Web of Science were systematically searched (until 31 October 2019) for existing systematic reviews and/or meta-analyses of double-blind randomized controlled trials. The quality of the included reviews was appraised using AMSTAR-2. Our meta-review included nine systematic reviews/meta-analyses (2 on ADHD; 1 on AD; 2 on ASD; 1 on enuresis; 1 on MDD, 1 on OCD and 1 on PTSD). In terms of efficacy this review found that, compared to placebo: fluoxetine was more efficacious in the treatment of MDD, fluvoxamine and paroxetine were better in the treatment of AD; fluoxetine and sertraline were more efficacious in the treatment of OCD; bupropion and desipramine improved clinician and teacher-rated ADHD symptoms; clomipramine and tianeptine were superior on some of the core symptoms of ASD; and no antidepressant was more efficacious for PTSD and enuresis. With regard to tolerability: imipramine, venlafaxine, and duloxetine were less well tolerated in MDD; no differences were found for any of the antidepressants in the treatment of anxiety disorders (ADs), ADHD, and PTSD; tianeptine and citalopram, but not clomipramine, were less well tolerated in children and adolescents with ASD. For suicidal behavior/ideation, venlafaxine (in MDD) and paroxetine (in AD) were associated with a significantly increased risk; by contrast, sertraline (in AD) was associated with a reduced risk. The majority of included systematic reviews/meta-analyses were rated as being of high or moderate in quality by the AMSTAR-2 critical appraisal tool (one and five, respectively). One included study was of low quality and two were of critically low quality. Compared to placebo, selected antidepressants can be efficacious in the acute treatment of some common psychiatric disorders, although statistically significant differences do not always translate into clinically significant results. Little information was available about tolerability of antidepressants in RCTs of OCD and in the treatment of ADHD, ASD, MDD, and PTSD. There is a paucity of data on suicidal ideation/behavior, but paroxetine may increase the risk of suicidality in the treatment of AD and venlafaxine for MDD. Findings from this review must be considered in light of potential limitations, such as the lack of comparative information about many antidepressants, the short-term outcomes and the quality of the available evidence. © Copyright © 2020 Boaden, Tomlinson, Cortese and Cipriani.
  • Psychometric properties of the Brazilian version of the Nurses’ Knowledge of High-Alert Medications scale: A pilot study

    de Oliveira, Deborah (2019)
    Background and Purpose: High-alert medication is considered to be a medication that presents a high risk of causing significant patient harm when used erroneously and its consequences can be fatal. The Nurses’ Knowledge of High- Alert Medication scale (NKHAM) is a tool available to evaluate the knowledge of nurses in practice about this issue. Aim: This pilot study aimed to measure the reliability and known-groups validity of the Brazilian version of the NKHAM. Methods: This pilot psychometric study was carried out at the Faculty of Nursing and University Hospital of the University of Campinas, São Paulo, Brazil. Forty nursing students and 44 registered nurses working in complex clinical or surgical settings completed a sociodemographic questionnaire and the Brazilian version of the NKHAM. The Kuder–Richardson 20 (KR-20) coefficient and Mann–Whitney test were used to establish reliability and known-groups validity. A significance level of ≤ 0.05 was adopted for all the analyses. Results: Analyses demonstrated preliminary acceptable reliability scores of 0.55 and 0.60 in domains A and B of NKHAM, respectively. A significant difference was found between the nursing students’ and the registered nurses’ knowledge of high-alert medications, demonstrating the scale’s ability to discriminate between the two groups. Implications for Practice: Although this is pilot study, results suggest that the Brazilian version of the NKHAM might be a reliable and valid tool to measure nurses’ knowledge of high-alert medications. (PsycInfo Database Record (c) 2020 APA, all rights reserved) (Source: journal abstract)
  • Secondary care specialist visits made by children and young people prescribed antidepressants in primary care: a descriptive study using the QResearch database

    Butler, Debbie; Hollis, Chris P.; Morriss, Richard K. (2020)
    BACKGROUNDAntidepressants may be used to manage a number of conditions in children and young people including depression, anxiety, and obsessive-compulsive disorder. UK guidelines for the treatment of depression in children and young people recommend that antidepressants should only be initiated following assessment and diagnosis by a child and adolescent psychiatrist. The aim of this study was to summarise visits to mental health specialists and indications recorded around the time of antidepressant initiation in children and young people in UK primary care.METHODSThe study used linked English primary care electronic health records and Hospital Episode Statistics secondary care data. The study included 5-17-year-olds first prescribed antidepressants between January 2006 and December 2017. Records of visits to paediatric or psychiatric specialists and potential indications (from a pre-specified list) were extracted. Events were counted if recorded less than 12 months before or 6 months after the first antidepressant prescription. Results were stratified by first antidepressant type (all, selective serotonin reuptake inhibitors (SSRIs), tricyclic and related antidepressants) and by age group (5-11 years, 12-17 years).RESULTSIn total, 33,031 5-17-year-olds were included. Of these, 12,149 (37%) had a record of visiting a paediatrician or a psychiatric specialist in the specified time window. The majority of recorded visits (7154, 22%) were to paediatricians. Of those prescribed SSRIs, 5463/22,130 (25%) had a record of visiting a child and adolescent psychiatrist. Overall, 17,972 (54%) patients had a record of at least one of the pre-specified indications. Depression was the most frequently recorded indication (12,501, 38%), followed by anxiety (4155, 13%).CONCLUSIONSThe results suggest many children and young people are being prescribed antidepressants without the recommended involvement of a relevant specialist. These findings may justify both greater training for GPs in child and adolescent mental health and greater access to specialist care and non-pharmacological treatments. Further research is needed to explore factors that influence how and why GPs prescribe antidepressants to children and young people and the real-world practice barriers to adherence to clinical guidelines.
  • Do clinical psychologists have a role in clients' use of psychotropic medication? A mixed methods investigation exploring current forms of involvement

    Aston, Amy; Smith, Sharron; Tickle, Anna C. (2020)
    Objectives: This study aimed to explore whether clinical psychologists in the United Kingdom (UK) have a role with their clients’ psychotropic medication by exploring forms of involvement undertaken, and decision‐making behind involvement. Design: A mixed methods design was employed; 147 clinical psychologists took part in an online survey, and 11 respondents were interviewed, selected using intensity sampling. Methods: Descriptive statistics and thematic analysis were used to analyse the quantitative and qualitative data, respectively. Results: All respondents reported having some role with their clients’ psychotropic medication. A thematic map diagram was created to capture the process of how clinical psychologists choose to become involved. Conclusions: Consensus was reached in that clinical psychologists do have a role with their clients’ psychotropic medication, although this varies by clinician and takes on many forms. In the light of the changing role, professional guidance would help to promote clarity and consistency.
  • Evaluation of the effectiveness and acceptability of intramuscular clozapine injection: illustrative case series

    Holmes, Nikki (2020)
    AIMS AND METHOD: A series of eleven patients prescribed intramuscular clozapine at five UK sites is presented. Using routinely collected clinical data, we describe the use, efficacy and safety of this treatment modality. RESULTS: We administered 188 doses of intramuscular clozapine to eight patients. The remaining three patients accepted oral medication. With the exception of minor injection site pain and nodules, side-effects were as expected with oral clozapine, and there were no serious untoward events. Nine patients were successfully established on oral clozapine with significant improvement in their clinical presentations. CLINICAL IMPLICATIONS: Although a novel formulation in the UK, we have shown that intramuscular clozapine can be used safely and effectively when the oral route is initially refused.
  • Exploring the impacts of organisational structure, policy and practice on the health inequalities of marginalised communities: Illustrative cases from the UK healthcare system

    Hui, Ada (2020)
    This paper explores how organisational structure, policies and practices in healthcare can inadvertently disadvantage marginalised populations (e.g. individuals from ethnic minority backgrounds) and reinforce health inequalities. We draw upon three diverse UK healthcare settings (long term care institutions, high security hospitals and community pharmacies) to illustrate how systemic injustices negatively impact on access to care, treatment and health outcomes. The first case study considers the care of older people within nursing homes; specifically the disempowering effects of this service structure and impacts of choice reduction upon health and their access to health provision. The second case study explores the impact of security restrictions upon patients within high security hospitals, focusing particularly on the maintenance of relationships and support networks outside of the hospital. The third and final case study, draws upon a national community pharmacy medicine management service to illustrate ways in which policies and guidelines inadvertently obstruct patients' engagement with the service within a community setting. We draw upon these settings to highlight inequalities within different contexts and to illustrate the ways in which well intended services can inadvertently disadvantage marginalised communities in multiple ways.
  • Do Asian patients require only half of the clozapine dose prescribed for caucasians? A critical overview

    Rajkumar, Anto P. (2020)
    Since 1997, studies have found that Asians need lower clozapine doses than Caucasians. Caucasians with average clozapine metabolism may need from 300 to 600 mg/day to reach the therapeutic range (350 ng/ml). Thus, serum clozapine concentration-to-dose (C/D) ratios typically range between 0.60 (male smokers) and 1.20 (female non-smokers). A 2019 systematic review of clozapine levels demonstrated weighted mean C/D ratios of 1.57 in 876 East Asians and 1.07 in 1147 Caucasians (<i>P</i> <.001). In Asian countries, average clozapine doses are lower than 300 mg/day. After sex and smoking stratification in 5 Asian samples with clozapine concentrations, the clozapine dose required to reach 350 ng/ml in female non-smokers ranged from 145 to 189 mg/day and in male smokers, from 259 to 294 mg/day. Thus, in Asian patients with average metabolism (with no inducers other than smoking, with no inhibitors, and in the absence of extreme obesity), the dose needed for clinical response may range between 150 mg/day for female non-smokers to 300 mg/day for male smokers. Clozapine levels may help personalize dosing in clozapine poor metabolizers (PMs) and ultrarapid metabolizers (UMs). Asian PMs may need very low doses (50-150 mg/day) to obtain therapeutic concentrations. About 10&#37; (range 2-13&#37;) of Asians are genetic PM cases. Other PMs are patients taking CYP1A2 inhibitors such as fluvoxamine, oral contraceptives, and valproate. Temporary clozapine PM status may occur during severe systemic infections/inflammations with fever and C-reactive protein (CRP) elevations. Asian UMs include patients taking potent inducers such as phenytoin, and rarely, valproate.
  • 'New Medicine Service': supporting adherence in people starting a new medication for a long-term condition: 26-week follow-up of a pragmatic randomised controlled trial

    Craig, Chris (2019)
    OBJECTIVE: To examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks. METHODS: Pragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged >/=14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective). RESULTS: Unadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: - pound104 (95% CI - pound37 to pound257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI -0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of - pound113.9 (-1159.4, 683.7). The incremental cost-effectiveness ratio was - pound2758/QALY (2.5% and 97.5%: -38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of pound20 000 per QALY. CONCLUSIONS: At 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high. TRIAL REGISTRATION NUMBER: NCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494.
  • Physical health monitoring after rapid tranquillisation: clinical practice in UK mental health services

    Adams, Clive E. (2019)
    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, determining nursing observation schedules and detecting acute deterioration in physical health. The effectiveness and clinical utility of such an approach would be worth testing.
  • A retrospective audit to assess the utilisation of clozapine in a high secure forensic hospital

    Huang, Li-Ying; Holmes, Nikki (2019)
    Poster from the Trent Study Day 2019
  • Evaluation of the use of intramuscular clozapine

    Holmes, Nikki (2019)
    Poster from the Trent Study Day 2019
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    Poster from the Trent Study Day 2019

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