Abstract
Objective
Prescribers’ expectations of Zuclopethixol Acetate’s (ZA) efficacy and tolerability are shaped by clinical experience and organisational culture; however, these expectations may not be consistent with current evidence and best practice.
Methods
Quality improvement project (QIP) through a process audit of ZA prescribing, monitoring and patient outcomes (adverse events) in order to identify issues requiring intervention to align with service standards and practices.
Results
QIP interventions resulted in a statistically significant shift in psychiatrist oversight, identifying high dose ZA with adverse outcomes and cessation of prescribing/administration within the Emergency Department. Clinically significant changes in patterns of prescribing were observed between pre-post intervention audits.
Conclusion
Entrenching an evidence-based QIP approach to clinical practice can effect clinically significant patterns of practice change to improve safe prescribing and drug monitoring.
In clinical practice, prescribers’ expectations of a medication’s efficacy and tolerability are shaped by clinical experience and organisational culture; however, these expectations may not be consistent with current evidence and practice. In acute psychiatric settings, enthusiasm to use Zuclopenthixol Acetate (ZA) to treat acute psychotic disturbance based on its perceived ‘clinical effectiveness’, compared to standard treatment, and can be in contrast to the paucity of evidence in the literature. 1
A Cochrane review in 2012 highlighted that existing studies involving ZA were poorly reported and flawed methodologically. 1 It concluded that ZA did not appear to have a ‘rapid onset of action’ as initially believed or where rapid tranquilisation was required. The review recommended that ZA should only be used after an acutely psychotic patient who has required repeated multiple administration of injectable short-acting antipsychotics and/or hypnotics and that the response had been deemed ineffective, or when prolonged antipsychotic and sedative effect is required. 2
Within the Australian context, there is limited guidance in existing national guidelines on posology, which results in deference to clinical judgement, with dosage varying widely between 50 and 150 mg per administration. Newly uncovered evidence suggests lower doses (starting from 25 mg) may be as effective higher doses (100 mg). 3 A lack of clarity in dosing serves to reinforce prescribing patterns that are largely influenced by clinical experience, historical (or legacy) practices, organisational and professional culture, which can significantly impact fidelity to medication safety. 4
In response to acknowledged shortfalls in practice standards of ZA prescribing and monitoring, and following a number of clinical incidents in a regional health service, a quality improvement project (QIP) was implemented regarding ZA prescribing, administration, monitoring and safety evaluation. It comprised a process audit to assess current practices and benchmark against standards with an embedded plan-do-study-act (PDSA) cycle to test quality improvement interventions.
Methodology
This single-centre observational process audit was performed in a regional health service public teaching hospital. It was conducted retrospectively with an interrupted time series analysis of baseline audit data and post-intervention audit data of all patients prescribed ZA (n = 50) against defined clinical standards. Each epoch was for a period of 5 months. A plan-do-study-act (PDSA) cycle to test quality improvement was embedded within the process. Between each cohort, education interventions based off a literature review, baseline audit findings and revised governance arrangements for ZA prescribing were implemented (Figure 1). Quality improvement project: Clinical audit flow chart.
Zuclopenthixol acetate clinical audit tool
Note. ZA = Zuclopenthixol Acetate; IPU = in-patient unit.
Initially, two standards’ were identified during scoping the literature; however, the Western Australia Country Health Service (WACHS) – Zuclopenthixol Acetate (Clopixol Acuphase) Monitoring Guideline 5 was selected on the basis of more frequent observation and its practical application was similar to the service population demographics of our regional health service. Patient outcomes were assessed by audit of adverse side effects within the clinical file and adverse events on clinical incident management system. Ethics approval was obtained.
Baseline audit were completed between 1 Jan and 1 May 2020, with data deidentified. The intervention included adapting governance of prescribing, administration and monitoring of ZA within the services, with audit findings presented at medical education and training sessions regarding the safe provision of ZA across the service. Data was transcribed from Microsoft excel into Stata 14.2 for analysis. The analysis compared baseline audit and post-intervention audit across several prescribing variables.
Results
Cohort characteristics and descriptors
Note. ATSI = Aboriginal and Torres Strait Islander; FEP = First Episode Psychosis.
The gender distribution from each epoch was approximately two-thirds male (pre-intervention: 68% and post-intervention: 64%). Aboriginal and Torres Strait Islander (ATSI) ethnicity status was similar in each data epoch with an average of 62% of total cases (pre-intervention: 61% and post-intervention: 64%). The pre-intervention and post-intervention cohorts had a mean age of 29.8 years (SD = 9.6).
There were significant statistical differences between the pre-intervention and post-intervention cohorts’ diagnoses. A diagnosis of schizophrenia was reported in 40% (n = 11/28) of the pre-intervention cohort compared to 86% (n = 19/22) in post-intervention cohort (p = .001; odds ratio 9.79, 95% CI: 2:33–41.09). A statistically significant higher proportion of First Episode Psychosis/Drug Induced Psychosis were prescribed ZA (39%) in the baseline epoch compared to (4.5%) in the post-intervention epoch (p = .005).
Sub-analysis of baseline audit
Note. ZA = Zuclopenthixol Acetate; WACHS = Western Australia Country Health Service; IPU = in-patient unit.
Pre-intervention audit results
Adverse events occurred in 46.7% of cases prescribed ZA in the ED. There were no adverse events reported in the IPU. These results were statistically significant (p = .007, RR = 1.87, 95% CI: 1.16–3.04). Two ‘Code Blue’ (critical adverse) events occurred in the ED, which required intensive care admission. Both were prescribed maximum doses of ZA (150 mg). These events were recorded on the Clinical Incident Management System.
ZA administration in ED occurred in high-risk patients at a rate of 46.7% (n = 7/15). There were zero instances of high-risk patients receiving ZA on the IPU. These results were statistically significant (p = .007, RR = 1.87, 95% CI: 1.16–3.04). Documented consultant psychiatrist approval of prescribing ZA occurred at approximately twice the rate in the IPU compared to ED but did not reach statistical significance (p = .024, OR = 8.25, 95% CI:1.32–51.26). All doses of ZA were administered within the recommended dosage range with a minimum period of 36 h between doses in line with existing service standard.
No post-ZA monitoring was completed in either location in the baseline audit. It was noted that one patient was discharged within 24 h of ZA administration.
Post-intervention audit results
Pre-intervention (baseline audit) versus post-intervention prescribing variables
aFrequency of major events was too low to model separately. Note. ZA = Zuclopenthixol Acetate.
All post-intervention prescribing occurred within the accepted current standard dosing range with appropriate timing between doses (>36 h). A number of trends were identified: increase in clinical justification for ZA prescription being documented; reduction in reported side effects (adverse events); reduction in high-risk groups being exposed to ZA; and reduced concomitant psychotropic prescription.
Monitoring after ZA administration occurred in 67% (15/22) of cases post-intervention.
Discussion
This quality improvement project identified significant systemic issues associated with prescribing, administration and monitoring practices of ZA within the regional health service. These issues required mitigation by implementing interventions aimed at improving medication safety and governance of a high-risk medication. Post-intervention audit revealed an overall shift towards more robust and safer prescribing practices, however, on-going deficiencies in monitoring practices according to benchmark standards.
There were significant differences between overall pre-intervention and post-intervention cohort diagnoses. The impact of mandating consultant psychiatrist review resulted in a 40% increase in senior clinician oversight reflected in a shift away from ZA prescription in First Episode Psychosis (FEP) and Drug Induced Psychosis, which in the pre-intervention setting was approximately 40%, whereas in the post-intervention audit was just 4.5%. The corollary of this intervention was that ZA prescribing was almost exclusively used in patients with schizophrenia (86%) in the post-intervention cohort. This effect reinforces the notion that ZA may have been too widely and possibly inappropriately used in clinical practice prior to the QIP. 6
The finding that higher doses of ZA (in excess of 100 mg) were over 7 times more likely to result in side effects (and adverse events) reinforced the need to develop a local prescribing and monitoring procedure. Combined with findings in the literature and practice in other jurisdictions, this result underpinned the decision to recommend a maximal ZA single dose of 100 mg rather than 150 mg.2,7
This quality improvement audit process identified clear shortcomings with existing clinical practice standards with ZA use in the service. Following a post-intervention analysis of results, further recommendations were developed to address prescribing and monitoring deficits. These included: updating and removal of the Rapid Tranquilisation Procedure; Implementation of a service-wide ZA prescribing and monitoring procedure; clinical education sessions regarding the safe use of ZA; and, a further clinical governance audit of ZA to be conducted in 12 months’ time.
However, there were a number of limitations of the project, including but not limited to the small sample size, limited statistical analysis of the data and single setting. Nonetheless, the clinical significance of the original audit and quality enhancement of clinical practice with ZA following the intervention were significant.
Conclusion
This QIP identified significant shortfalls in the clinical prescribing, administration and monitoring of ZA use within a regional health service. Entrenching an evidence-based approach to clinical practice through audit can effect clinically significant patterns of incremental change to improve safe prescribing and monitoring practice.
Footnotes
Authors’ note
The paper was prepared from a submitted scholarly project for the RANZCP.
Disclosure
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical approval
This Quality Improvement Project obtained ethics approval from the Human Research Ethics Committee of the NT Department of Health and Menzies School of Health and Research (2020-3754).
Informed consent
Informed consent was waivered within the ethics approval and patient information deidentified.
