High-dose Antipsychotic Medication Research Articles

The HDAT Helper - Developing an Online Tool to Improve the Safety and Accuracy of Antipsychotic Prescribing

AimsHigh Dose Antipsychotic Therapy (HDAT) prescriptions and combinations of antipsychotic agents are not currently recommended as standard practice by the RCPsych. College guidance (RCPsych, CR 190) advises that there is “little convincing evidence that off-label prescription of doses of antipsychotic medication above the licensed dosage range has any therapeutic advantage in any clinical setting” and that “any prescription of high-dose antipsychotic medication should be seen as an explicit, time-limited individual trial with a distinct treatment target”. Despite this, both national and local data demonstrate that HDAT has continued to be used regularly across psychiatric inpatient settings, often out of hours and often secondary to the use of PRN Antipsychotics, without a clear treatment plan or rationale. My aim was to create a simple, accessible, online tool that would allow prescribers to quickly and efficiently calculate the BNF percentage of any antipsychotic prescription and that this will enable safer prescribing.MethodsWith the support of a web-developer, I developed an online tool quickly and easily calculate antipsychotic BNF percentages. The tool can be found here: www.hdat.co.ukResultsThe HDAT Helper has been well received at local presentations and I have recently gained the support of senior management at Southern Health NHS Foundation Trust to develop an education programme on HDAT and the HDAT Helper to expand use of the tool across Southern Health.ConclusionThe current expert guidance, clinical research and my own audit work demonstrates that there are ongoing issues with the prescription of high dose antipsychotics and that at times this occurs inadvertently when different agents are combined.I believe that the HDAT Helper can make prescribing of antipsychotic agents clearer and more efficient and as a result significantly improve patient safety.

Reducing the use of high dose antipsychotic medication in acute adult inpatient psychiatric units

AimsTo evaluate the use of antipsychotics, and high dose antipsychotic treatment (HDAT) in psychiatric inpatient unitsBackgroundThe Royal College of Psychiatrists published a consensus statement on high dose antipsychotic medication in October 1993. Such treatment carries an increased risk of adverse effects including towards ventricular tachycardia and sudden death.MethodA retrospective case note review of all male patients on acute adult inpatient units in a psychiatric hospital in South Birmingham on a date in June 2018 (n = 45) including review of electronic patient records and prescriptions. This was compared with the results of an earlier study, with identical methods, undertaken in June 2015.Result•In both 2015 and 2018, only a minority of patients (20% and 11% respectively) were informal.•In both 2015 and 2018, the majority of inpatients had a diagnosis of schizophrenia (54% and 67%)•In both 2015 and 2018, 93% inpatients were prescribed antipsychotic medication.•In 2015, 56% patients were prescribed HDAT. This reduced in 2018 to 16%.•This reduction in use of HDAT was almost entirely due to a reduction in the prescription of PRN antipsychotic medication.•In terms of regularly prescribed antipsychotic medication, in both years, the most commonly prescribed drug was flupentixol, with a range of other second generation oral and long acting medications being prescribed, usually at doses within BNF limits.Between the two years, there was a substantial change in the prescribing of PRN antipsychotics. In 2015, 59% individuals were prescribed at least one PRN antipsychotic (27% were prescribed two). In 2018, this reduced to 40% prescribed at least one, and only 2% being prescribed 2 PRN antipsychotics. In both years, oral quetiapine was a common choice (39% patients in 2015 prescribed oral quetiapine, and 34% in 2018). In 2015, 39% patients were prescribed oral or intramuscular aripiprazole, while this reduced to 7% in 2018.ConclusionThe vast majority of psychiatric inpatients were being prescribed antipsychotic medication. Prescription of high dose antipsychotic medication was common in 2015, and this was largely attributable to high levels of prescribing of PRN antipsychotics. Following an educational programme for junior doctors and ward nurses, and the introduction of electronic prescribing, we achieved a significant change in practice, particularly in the prescribing of PRN antipsychotics, which has reduced our patients’ risk of receiving high dose antipsychotic medication.

Physical health monitoring after rapid tranquillisation: clinical practice in UK mental health services.

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.

S69. A CASE STUDY OF CLOZAPINE AND COGNITION: FRIEND OR FOE?

BackgroundCognitive dysfunction is as a hallmark feature of schizophrenia. Antipsychotic medication is effective for treating the positive symptoms of psychosis, but their potential for therapeutic effects on cognition continues to divide researchers.Improvements in clinical symptoms can occur independently of cognitive functioning, whereby typical antipsychotics improve different clinical domains, but have little or no efficacy for improving primary cognitive functions. However, it has been suggested that the second-generation antipsychotic clozapine can improve cognition in schizophrenia. Unusual cases, such as remitted patients who decide to stop taking clozapine, thus represent a unique opportunity to understand the effect of antipsychotic medication on cognition, as described in the case study below.MethodsA 38-year old man suffered severe psychotic episodes at age 19, leading to a diagnosis of treatment-resistant schizophrenia. Clozapine was initiated at age 21, with excellent treatment response and complete remission of positive, negative and depressive symptoms. For the following 16 years, he had a full-time paid job, lived independently and had an ample social circle. For the last five years, he was stable and compliant taking 175 mg of clozapine, with clozapine levels in sub-therapeutic range (between 0.17 and 0.26 mg/L). He had no metabolic syndrome and no oversedation, but complained of hypersalivation and persistent memory problems. He decided, against advice, that medication was no longer needed and requested support for waning off clozapine.A five-month program was subsequently implemented, with 25 mg reductions of clozapine every six weeks. Four enhanced assessments were scheduled after two weeks on stable doses of 125, 75, 25 and 0 mg, respectively, which included the Brief Assessment of Cognition in Schizophrenia (BACS) and the Clinical Global Impression-Schizophrenia scale (CGI-SCH).ResultsAt each level of clozapine dose, the patient continued to be stable. However, the patient showed impaired cognitive performance at the highest dose of clozapine titration (see T-scores from Table and figure), with improvements then shown at each level of dose reduction (75 and 25 mg). The final assessment was done after 6 weeks of not taking medication. At this time, he was admitted to hospital for psychotic relapse. Unfortunately, the patient refused to re-initiate clozapine and has remained floridly psychotic for 18 months.Our case suggests that cognitive impairment is dose-dependent with clozapine. As presented, the t-score of the patient at 125 mg was worse than normative data reported for healthy controls (z-score=0.50) and patients with schizophrenia treated with other first-or second generation antipsychotics (z-score=-1.42). However, cognitive performance of the patient was most notably impaired when medication-free.DiscussionThe longterm effects of high-dose antipsychotic medication on cognition in patients with schizophrenia are largely unknown. It is also possible that changes in cognitive states are either domain-specific with clozapine. Nonetheless, daily antipsychotic dose and polypharmacy have been shown to predict poor cognitive functioning.The present case is also a reminder that the appropriate long-term maintenance dose of clozapine is poorly understood. As this case suggests, the current recommended therapeutic levels of clozapine (0.35 to 0.50 mg/L) might be unnecessarily high for patients in full remission. Controlled studies are therefore needed to evaluate the potential for cognitive improvements in schizophrenia as a function of reduced clozapine dose, to ensure the optimal delivery needed not just for good clinical but also good cognitive outcome.

Metabolic syndrome in patients with severe mental illness undergoing psychiatric rehabilitation receiving high dose antipsychotic medication.

Background:To review evidence of chronic antipsychotic medication and the association with metabolic syndrome in mentally ill patients. This evidence was used to analyse a cohort of patients with severe mental illness and to deduce a correlation between the prevalence of metabolic syndrome and their dose regimens.Materials and Methods:Twenty-four male patients undergoing Psychiatric rehabilitation underwent a review of current medication and assessment of risk factors for metabolic syndrome. Assessment criteria was based upon National Cholesterol Education Programme expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III) (NCEP ATP III) criteria, incorporating waist circumference, raised triglycerides, reduced high density lipoprotein, raised blood pressure and fasting blood glucose. PubMed, Nature and Science Direct databases have been used to compile the medical and scientific background on metabolic syndrome and antipsychotic medication and the effect on patients particularly on high dose.Results:Out of 24 patients, 10 patients (41.7%) were receiving high dose antipsychotics (HDA) and four were on maximum dosage limits of 100%. 8.3% (2/24) patients were receiving only one first generation antipsychotics (FGA), 37.5% (9/24) patients were receiving only one second generation antipsychotic (SGA), 45.8% patients (11/24) were receiving two or more SGA only, and only one patient was receiving two or more FGA. One patient was receiving a combination of FGA and SGA. PRN (“as needed”) therapy was not included in this study as their usage was limited. Clozapine was mostly prescribed in these patients (10/24, 41.6%). Four out of the 24 patients refused blood tests therefore were excluded from the following results. In the patients evaluated, 55% (11/20) had confirmed metabolic syndrome. In these patients with metabolic syndrome, 45.4% (5/11) were on HDA and 27.3% (3/11) were on maximum British National Formulary (BNF) limits of 100% of dosage. Four out of the nine remaining patients not diagnosed with metabolic syndrome were on HDA.Conclusions:Evidence supports the association between antipsychotic medication and metabolic syndrome. The data extrapolated from this cohort of mentally ill patients demonstrates that there is an increase in risk factors for metabolic syndrome and weight gain in the majority of patients on antipsychotic medication. The data however does not support any further predisposition to metabolic syndrome in these patients taking HDA. It also cannot be assumed antipsychotic medication is independently associated with the prevalence of these abnormalities.

Persistent Psychosis After a Single Ingestion of “Ecstasy” (MDMA)

Persistent Psychosis After a Single Ingestion of “Ecstasy” (MDMA)

A simple clinical audit of antipsychotic medication prescribing on Hollywell Psychiatric Intensive Care Unit (PICU)

Aim and method: To review antipsychotic prescribing practice using selected recommendations from the 2006 Royal College of Psychiatrists’ (RCPsych) consensus statement on the use of high dose antipsychotic medication. A clinical audit of antipsychotic prescribing for patients from two periods, February to October 2005 and February to October 2006, who were discharged from Hollywell PICU at Hillcrest and had received one or more antipsychotic medications whilst an inpatient there.Results: The proportion of patients receiving a single antipsychotic increased from 9 (31%) in 2005 to 22 (55%) in 2006 and the proportion prescribed high dosages of antipsychotics declined, 10 (33%) in 2005 vs. 3 (8%) in 2006. The number of high dose combination prescriptions also declined, 4 (13%) in 2005 vs. 1 (3%) in 2006.Clinical implications: The audit illustrates the potential for individual variation in prescribing practice in the PICU environment. It suggests that the Royal College of Psychiatrists’ 2006 consensus statements on antipsychotic prescribing can be used to both benchmark clinical practice and promote evidence based prescribing.

High-Dose Antipsychotic Medication; A Practical Pocket Checklist

High-dose antipsychotic medication; a practical pocket checklist There is evidence that a significant number of patients with schizophrenia and other chronic psychotic psychosis are prescribed high-dose antipsychotic drugs despite the fact that clinical guidelines recommend the routine use of a single antipsychotic drug in a standard dose. The prescriptions for high-dose and combined antipsychotic drugs are relatively common in clinical practice. This occurs despite the fact that results of published trials of high-dose antipsychotic drug treatment for schizophrenia provide little evidence to support effectiveness of using high-dose antipsychotic treatment and most importantly such strategy is not recommended. Moreover, there is mounting evidence of higher incidence of side effects and mortality associated with high dose antipsychotic treatment. Therefore we are presenting a practical pocket checklist which is aimed at minimizing predicted and unpredicted side effects during such treatments.

Use of psychotropic medication in seven English psychiatric intensive care units

Aims and methodTo describe the psychotropic medication given to 332 patients admitted consecutively to seven English psychiatric intensive care units (PICUs) by prospective, multicentre case-note analysis.ResultsOverall, 104 (32%) patients received rapid tranquillisation or zuclopenthixol acetate by intramuscular injection; 72 (23%) received more than one regular antipsychotic drug simultaneously. It was reported that 20 patients received high-dose antipsychotic medication, which was probably an underestimate. The use of these interventions varied significantly between different units.Clinical implicationsPotentially risky treatments such as forcible intramuscular medication are a standard part of PICU activity. Further work is needed to clarify the reasons behind the differences in prescribing practices between different PICUs.

High-dose antipsychotic prescribing: comparison survey

In May 2006, the Royal College of Psychiatrists published the consensus statement on high-dose antipsychotic medication, highlighting that up to a quarter of psychiatric in-patients are prescribed a high dose of antipsychotic medication ([Royal College of Psychiatrists, 2006][1]). I carried out a

QTc‐interval abnormalities in a forensic population

Antipsychotic drugs have been linked to sudden death among psychiatric patients, with a suggestion that prolongation of the QT-interval detectable on a standard electrocardiogram may be linked to fatal cardiac arrhythmias in these circumstances. Patients in secure forensic psychiatric facilities may be particularly likely to be on high-dose antipsychotic medication, and yet, as far as the authors are aware, no study of QT-intervals among such patients has been reported. To investigate the prevalence of QT-interval abnormalities and associated known risk factors for fatal cardiac arrhythmias in a sample of forensic patients. Participants had a 12-lead electrocardiogram taken at 50 mm/s. Information was collected on their age, gender, psychiatric diagnosis, history of cardiovascular, liver and kidney diseases, and smoking, on all medications and on history of seclusion over the previous 12 months. Analysis was carried out using binary logistic regression. Lower rates of QT-interval abnormalities than might be expected for this population were found. It was also found that a high dose of antipsychotics was associated with QTc prolongation (Adjusted OR = 9.5, 95% CI 2.6-34.2), a result consistent with previous literature. Forensic patients need not be at increased risk of QTc abnormality provided risk factors are properly managed. A high dose of antipsychotic medication increases the risk of QTc prolongation.

Audit on High Dose Antipsychotic Medication in Three Tertiary Services for People with Learning Disability

(2003). Audit on High Dose Antipsychotic Medication in Three Tertiary Services for People with Learning Disability. The British Journal of Development Disabilities: Vol. 49, No. 97, pp. 117-124.

High-dose antipsychotic medication in maximum security

This study compares patients in an English Special Hospital treated on high doses of neuroleptics with a matched group of patients on standard doses. High-dose patients had significantly more psychiatric morbidity and side-effects than controls. They were also rated as more aggressive, but psychosis rather than aggression best predicted antipsychotic dose. This study adds support to the case that there is little benefit from the use of high-dose antipsychotics.

Hidden high-dose antipsychotic prescribing: effects of p.r.n. doses

Aims and methodThe Royal College of Psychiatrists' Consensus Statement on “The use of high-dose antipsychotic medication’ suggests only fully qualified psychiatrists (MRCPsych) should recommend the prescribing of high-dose antipsychotic treatment. We observed changes in anti-psychotic prescribing in two surveys of psychiatric in-patients conducted eight and 32 months after publication of the Consensus Statement.ResultsOverall mean chlorpromazine equivalent doses of antipsychotic drugs reduced between the surveys. When p.r.n. (as required) prescribing (usually done by junior doctors) is included, mean potential doses and numbers of patients who might receive ‘high-doses' increases substantially, although the reduction between surveys in total mean dose and proportion of patients on high-dose antipsychotic medication is preserved, and the actual use of p.r.n. medication was low (4–5% of p.r.n. prescriptions).Clinical implicationsWe recommend the development of local guidelines for junior staff concerning antipsychotic drug prescribing, regular monitoring of p.r.n. medication by consultants, and pharmacists' involvement in reviews of patients prescribed high-dose antipsychotic medication.

Monitoring patients on high-dose antipsychotics

Aims and methodFollowing the publication of the 1994 Consensus Statement on the use of high-dose antipsychotic medication, we identified our high-dose patients and undertook an audit of the recommended physical investigations. The patients were identified by scrutiny of prescription records. Data were collected retrospectively at six-monthly intervals for four audit cycles. Results were fed back to clinicians at the hospital journal club.ResultsThe percentage of patients identified in the high-dose category fell from 35 to 23% over 18 months. Electrocardiograph monitoring of the group increased from 5 to 63%. Other tests showed a similar improvement. A very small number of abnormal results was shown. There were no untoward cardiac events.Clinical implicationsIntroduction of the standards of physical monitoring advised in the Consensus Statement has implications of cost to the NHS to be balanced against risk avoidance for patients. The number of abnormalities detected in our population was low. Changing prescribing behaviour in response to reported abnormal findings proved unexpectedly slow and a new system was required.

Monitoring of patients on high dose antipsychotic medication

In the light of recently published Royal College of Psychiatrists' guidelines on the use of high dose antipsychotic medication, electrocardiographic and blood investigations were performed on 11 patients with learning disabilities receiving such treatment. All patients had normal electrocardiograms (ECGs). Four patients had asymptomatic low white cell counts and mild anaemia was detected in three individuals. Three patients were hyponatraemic; liver function tests were essentially normal. Issues around routine monitoring of such patients are discussed.

A survey of the use of the electrocardiogram in psychiatry

A survey was undertaken to ascertain if doctors working in psychiatry knew when to perform electrocardiograms (ECGs) prior to and during psychiatric treatments where indicated, and to investigate the training, confidence and ability of doctors in ECG interpretation. Half had received no training in the indications for performing an ECG. Opinion differed widely as to when to perform an ECG, with 54% stating an ECG was required before treatment with pimozide and only 19% and 11% stating ECGs were required during the course of treatment with pimozide and high dose antipsychotic medication respectively.Ability in ECG interpretation correlated negatively with time spent in psychiatry but no correlation existed between grade and ability to identify an ECG as normal or abnormal.

How well do psychiatric trainees interpret electrocardiographs

The consensus statement by the Royal College of Psychiatrists recommended that patients on high dose antipsychotic medication receive regular electro-cardiographic monitoring to identify prolongation of the QT interval. A survey of trainee psychiatrists in three hospitals investigated the accuracy with which trainees could identify this abnormality and found only 20% could do so.

Neuroleptic prescribing in an adolescent psychiatric in-patient unit

The Royal College of Psychiatrists' consensus statement suggests that prescribing high dose antipsychotic medication in children and adolescents should rarely be necessary. Our objective was to study the prescribing of antipsychotic medication in a regional adolescent unit during a three-year period. We found that antipsychotic prescribing on this unit is common in psychotic disorders and often high closes are required. This is not in keeping with the recommendations of the consensus statement. Review of clinical practice on other adolescent units is needed, together with a more comprehensive evaluation of the outcome of psychotic disorders in this age group.

High dose antipsychotic medication: The impact of the royal college consensus statement on prescribing practice

High dose antipsychotic medication: The impact of the royal college consensus statement on prescribing practice