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Abstract

Objective: To examine antipsychotic usage in outpatients in three community mental health centres.

Method: A retrospective chart review was conducted for all outpatient files that were active in March 2000 at all community mental health services in Auckland (population 1.3 million). All patients prescribed an antipsychotic had information entered into a specifically designed computer software program. The antipsychotic, dose and route of administration were recorded. The diagnosis, number of hospitalizations, ethnicity and gender were also collected.

Results: 6558 community files were audited and 3254 people were prescribed antipsychotics; 3178 (97.6%) files had adequate information for study inclusion. The mean antipsychotic daily dose in chlorpromazine equivalents (CPZe) was 360 mg. Most of the population (76.6%) was prescribed an oral antipsychotic alone, 14.9% were prescribed depot antipsychotic only and 8.4% were on a depot and oral antipsychotic. The average daily dose prescribed for people on antipsychotic polypharmacy was 601 mg CPZe compared with 312 mg CPZe for those on a single antipsychotic. There were 2300 patients with schizophrenia (72.5% of cohort) and 585 patients with bipolar affective disorder (18.5%). The mean total daily dose in CPZe was significantly higher for schizophrenia than any other psychotic diagnoses. Regional analysis showed differences in the doses and type of antipsychotics prescribed; one health sector had significantly higher daily doses while another was significantly more likely to prescribe atypical antipsychotics and correspondingly fewer depot antipsychotics.

Conclusions: There is a significant variation in the prescribing of antipsychotics across the three Auckland health sectors. The variation relates to dosage used, type of antipsychotics prescribed and effect of multiple antipsychotic prescribing. Combination therapy of more than one oral antipsychotic or a combination of oral and depot antipsychotics leads to a significant trend of higher doses in excess of best practice guidelines.

Keywords

antipsychotic audit schizophrenia

The introduction of atypical antipsychotics has significantly changed the therapeutic options available for patients who require antipsychotic medication. Atypical antipsychotics share common features of a reduced likelihood of inducing extrapyramidal side effects and hyperprolactinaemia. Risperidone, although classified as an atypical, can have hyperprolactinaemia generally at higher doses. Clozapine remains the only antipsychotic with a clear therapeutic advantage for people with treatment-resistant schizophrenia [1]. Atypical antipsychotics have advantages in the treatment of cognitive deficits of schizophrenia [2] but the evidence for their effectiveness for the negative symptoms of schizophrenia is less certain [3].

Recent practice guidelines recommend choosing atypical antipsychotics as the initial treatment for schizophrenia [4], [5]. They also recommend switching from a standard antipsychotic to an atypical antipsychotic for patients who do not have a good treatment response. Other recommended prescribing trends for antipsychotics include using the lowest effective dose and limiting antipsychotic polypharmacy.

International research has demonstrated variance between prescribing guidelines and everyday practice. In a study of antipsychotic prescribing practice in the New York region of the Veteran's Healthcare Administration from 1998 to 2000, atypical antipsychotics were prescribed more commonly than typical antipsychotics [6]. However the results also showed low rates of clozapine use and a high rate of polypharmacy. There were clear inter-site variations in prescribing practice. The impact of prescribing guidelines for antipsychotics on clinicians was explored in a study of Thai psychiatrists. Passive dissemination of clinical guidelines for treatmentresistant schizophrenia did not impact on their attitude towards treatment [7].

A study performed in the UK analyzed 1441 inpatient and community prescriptions of antipsychotics [8]. A detailed chart review was performed for those patients prescribed an atypical and typical antipsychotic. They concluded that there was little to support the practice but there was clear evidence that it worsens adverse effect burden. Another study that compared prescribing practices between a psychiatric research ward and a general psychiatric ward in the same facility demonstrated greater antipsychotic polypharmacy in the general ward [9].

This is the first audit of antipsychotic drug usage in Auckland (population 1.3 million). There was little known about the variation of antipsychotic use in the three different health sectors of Auckland (Auckland Healthcare, South Auckland Health and Waitemata Health) or whether any particular patient factors such as ethnicity or diagnosis would be relevant to the way antipsychotics would be used in the community setting. The New Zealand Mental Health Commission's ‘Blueprint for Mental Health Services’ documents a target atypical antipsychotic use of 225 per 100 000 population [10]. Figures from their progress report in 1999 suggested national under-prescribing [11]. In New Zealand, clozapine has been available since 1990, risperidone from 1994, olanzapine from 1997 and quetiapine from 2001. The information presented in this paper is from the first phase of this audit. The second data collection phase occurred in October 2001. Ethnicity data and concomitant psychotropic medication from the first audit will be presented in subsequent papers.

Method

Prior to the data collection process active consultation took place with the management and senior clinicians of the three health sectors involved. This dialogue included the scope of the research and mechanisms for sharing results with the community teams involved. Cultural consultation addressed the impact of this audit for Maori and mechanisms for sharing the results with Maori services. Pacific Island clinical leaders in mental health also supported this audit.

All active outpatient files for the month of March 2000 in the three mental health sectors in Auckland were audited (n = 6558). Current client lists were provided by the community mental health centres and a manual review of files performed. Those patients prescribed an antipsychotic were included in the dataset for Time Point 1 (n = 3254). The data was collected by research nurses and entered into specifically designed software by clerical assistants. The data collected included age, gender, ethnicity, diagnosis and number of hospitalizations. The type of antipsychotic prescribed, the dose and route of administration were recorded. Prescribed daily dose (mg/day) for all antipsychotics was converted to a standard, chlorpromazine equivalent (CPZe) for comparison (Table 1). The concept of chlorpromazine equivalence is controversial but useful where aggregated data is represented to show broad trends across patient groups. Although the CPZe derivation differs by up to 500% in the literature [12], for the typical antipsychotics conversion data related to dopamine (D2) affinity and therapeutic response is commonly available. The introduction of the atypical antipsychotics required new equivalence estimates. Woods in a recent review explored the range of published atypical CPZe estimations and proposed a set of equivalences based on a proxy method of calculation in the absence of studies designed to estimate atypical therapeutic dose equivalence [13]. Equivalency estimates in research studies such as this are a useful tool to compare overall antipsychotic practice and burden across health sectors but are not intended to reflect therapeutic efficacy for issues such as negative and cognitive symptoms, and quality of life. The conversions used in this study lie within the range of published estimates and were chosen after consulting a number of widely quoted references [14–20].

Table 1.

Chlorpromazine equivalence ratios

Data omissions and vagaries were clarified initially with members of the community mental health team and when this was not possible a psychiatrist reviewed the files and spoke to the treating team involved.

Data analyses were conducted using SPSS (Version 10). Continuous variables were compared between groups using independent t-tests or analysis of variance. Post-hoc analyses of group main effects were conducted using Scheffe test. Discrete variables were analyzed using χ². In order to minimize type I error associated with multiple comparisons, the error rate required to demonstrate significance was set at 0.01.

Results

Of the 3254 people prescribed an antipsychotic 3178 (97.6%) had meaningful data for analysis. The mean daily dose of antipsychotic prescribed in the dataset was 360 ± 253 mg/day CPZe and the median was 300 mg/day (range 10–1800 mg/day). Overall 50% of community mental health centre patients were prescribed an antipsychotic. This challenges the popular belief that all public mental health outpatient settings are psychosis services. There was variation in the percentages of outpatients on an antipsychotic by region with South Auckland Health having 58% of their outpatients on an antipsychotic compared with 44% for Auckland Healthcare.

There were 2300 patients with a diagnosis of schizophrenia in the sample (72.5%), this included people diagnosed with schizoaffective disorder. Patients with a diagnosis of bipolar affective disorder comprised 18.5% of the sample (n = 585) and other diagnoses (predominantly personality disorder, anxiety disorder or depression) were 8.8%. People with a diagnosis of developmental disorder or dementia/neurological disorder contributed a very small number of the sample (n < 100). For 10 patients it was impossible to clarify their clinical diagnosis. The diagnostic distribution was even throughout the three health sectors. The mean total daily dose was higher for schizophrenia (407 ± 246 mg/day) than any other psychotic diagnoses. This was apparent regardless of the route of antipsychotic delivery. The sample had unbalanced genders (M = 59%, F = 41%) and when total daily doses were analyzed independent of diagnosis the dose for men (387 ± 254 mg/day) was significantly higher (t₍₃₁₇₂₎ = −7.280, p < 0.001) than that for females (320 ± 245 mg/day).

Antipsychotic prescribing

The mean daily dose for each antipsychotic prescribed in the audit is depicted in Table 2 expressed in both its native form and in CPZe.

Table 2.

Mean daily antipsychotic dose

Analysis of the route of administration of the antipsychotic medication showed that 76.6% were prescribed an oral antipsychotic only, 14.9% were prescribed their antipsychotic in depot form and 8.4% were prescribed a combination of an oral and depot antipsychotic. The daily overall antipsychotic dose was significantly different for combination antipsychotic treatment compared to monotherapy (t₍₆₁₁₎ = −20.03, p < 0.001). The mean daily dose for those prescribed a single antipsychotic was 312 ± 207 mg CPZe (oral 316 mg and depot 294 mg, respectively). Of importance was that for those patients prescribed a combination of antipsychotics their mean daily dose was 601 ± 315 mg CPZe.

Multiple antipsychotic prescribing was present in 16.4% of the sample (n = 521). Of those prescribed oral therapies alone, 242 were prescribed two antipsychotics and 12 were prescribed three different oral antipsychotics. For those on a combination of oral and depot preparations, 244 received a depot and one oral antipsychotic and 23 were prescribed a depot and two oral antipsychotics.

Of the 23.4% of the sample on a depot antipsychotic (n = 742), flupenthixol decanoate was the most commonly prescribed (40.4%) and zuclopenthixol the least commonly prescribed (4.4%). Table 3 summarizes the sector differences in mean depot doses. There were regional differences in frequency of depot prescription and the doses used. Waitemata Health had a significantly lower chance of prescribing a depot as opposed to oral therapy (χ² (2) = 61.71, p < 0.001). South Auckland's depot doses were significantly higher than the other two sectors for overall depot administration and this was largely determined by the prescription of depots in combination with oral antipsychotics. When depot antipsychotics were prescribed as monotherapy Waitemata Health used significantly lower doses of depot than South Auckland Health (pairwise comparison, p < 0.001).

Table 3.

Mean daily depot antipsychotic dose by sector

Table 4 shows the proportion of people (n = 1869) prescribed atypical antipsychotics (risperidone, olanzapine, clozapine and quetiapine). The percentage of people on atypical versus typical oral antipsychotics was 58.9%: 20%, a 3: 1 ratio. Co-prescribing of atypical and oral typical antipsychotics occurred in 162 cases and with depot antipsychotics in 53 cases. In 12 cases patients were prescribed combinations of atypical antipsychotic medication.

Table 4.

Regional percentage distribution of atypical antipsychotics

There were clear regional differences in atypical antipsychotic prescribing. Waitemata Health used more atypicals in general largely determined by clozapine. Waitemata and South Auckland Health used significantly more risperidone than Auckland Healthcare. The average daily dose of each of the atypical agents is shown in Table 2. The only significant difference was in the use of risperidone where South Auckland prescribed higher doses. As only a small number of people were prescribed quetiapine, no comments can be made on the low doses.

Discussion

Antipsychotic polypharmacy

This audit described the practice of outpatient antipsychotic use that can be compared with clinical guidelines. One major finding was the extent of antipsychotic polypharmacy. In this study 16.4% of the sample was prescribed more than one form of antipsychotic despite there being little supporting evidence to justify this. It is possible that on this cross-sectional analysis some of the consumers were being gradually changed from one antipsychotic medication to another. This is unlikely to explain all cases.

Interestingly this rate of antipsychotic polypharmacy is consistent with other research documenting antipsychotic prescribing in non-research settings. Weissman examined outpatient prescribing for people with schizophrenia in five New York Veteran's Healthcare Administration services [6]. Prescription data over a two-month period showed antipsychotic polypharmacy at a rate of 15–17% with significant inter-site variation between 11–29%.

A further study of outpatient prescribing for a random sample of people with schizophrenia treated in Connecticut reviewed prescription records from July 1996 to June 1998 [21]. Cross-sectional analysis on a random day demonstrated an antipsychotic polypharmacy rate of 11%. Wang et al. found 17% of 154 patients with schizophrenia or other psychotic disorders were taking more than one antipsychotic. This study used random sampling from the patients of 417 American psychiatrists [22].

The disadvantages of antipsychotic polypharmacy are multiple. There is an increased risk of adverse effects, drug interactions and medication error. It is also clear that the more complex a medication regimen the higher the likelihood of non-adherence. In this audit combinations of oral and intramuscular antipsychotics were associated with a combined daily dose of antipsychotic in excess of standard practice. An Italian study of outpatients prescribed three or more antipsychotics showed that the average daily dose was twice that of those prescribed a single agent [23].

Regional variation

The population of Auckland during this study period was estimated to be 1 233 290. West and north Auckland are within the catchment area of Waitemata Health (450 820); Auckland Healthcare provides care for central and part of east Auckland (394 150); and South Auckland Health provides care for south Auckland and some eastern suburbs (388 320). The three regions have differences in their socio-economic composition. South Auckland has the highest number of people living in the most deprived circumstances as assessed by the Jarmen Index [24]. It also has a higher number of Maori and Pacific Island Nations people living in its catchment zone. South Auckland Health was also the last sector of Auckland to close its large psychiatric hospital as part of deinstitutionalization.

Clear differences were found in prescribing of antipsychotics between the regions related to both dose and type of antipsychotic used. South Auckland Health used higher doses of antipsychotics overall. The relative use of atypical antipsychotic medication and depot antipsychotics also showed regional variation. Waitemata Health had only 14.5% of those on antipsychotics being prescribed a depot; this was approximately half that of the other two sectors. Waitemata Health had the highest number of pharmacists employed in mental health and a research and training centre that actively promoted the use of atypical antipsychotic medication.

A large Australian database (n = 7500) of antipsychotic prescribing has 42% of their sample prescribed an intramuscular antipsychotic [25]. This is a significantly greater number than the Auckland sample and in excess of the Connecticut audit which had 23% of their outpatient sample prescribed a depot [21].

The results of the audit available at this stage do not allow any comparison of rates of hospitalization between the sectors, which is the only clinical marker of severity that was recorded. The audit does not allow for breakdown according to individual prescribing practice or changes of staff that may be relevant to dosing variation.

Covell et al. recorded prescribing by individual doctors and found this was an important factor in accounting for type of antipsychotic prescribed and the rate of polypharmacy [21]. They suggested that ‘doctor’ prescribing style could be influenced by factors associated with their caseloads, such as numbers of patients, crisis visits, comorbid substance abuse and the model of service delivery. Non-patient related factors such as price, ease of use, idiosyncratic beliefs and the impact of marketing have also been suggested as relevant in understanding prescribing patterns [26].

Atypical antipsychotics

Much has been written about the exponential increase in atypical prescribing. Psychiatrists internationally have differences in their ability to prescribe atypical antipsychotics often related to cost. Even within the same country different groups of patients are more or less likely to be prescribed atypical antipsychotics relating to such factors as service delivery or ethnicity [27].

Within this study 58.9% of the sample were prescribed an atypical antipsychotic. This is a similar rate to Keks et al. who audited an inner urban community psychiatric service in Australia and found 53% of the prescriptions of antipsychotics to be atypical [28]. By contrast a study of prescribing for people with diagnosis of schizophrenia in a south London service demonstrated atypical antipsychotics being used in 26% of the cases and an inconsistent definition of treatment-resistant schizophrenia [29].

Conclusion

This audit has described the ways that antipsychotics are prescribed throughout the three sectors of Auckland. It has provided a basis for education for the different community services in terms of the doses used and modes of delivery as compared with best practice guidelines. While the finding that antipsychotic polypharmacy is encouragingly low, the prescribing differences between sectors is of concern. It stimulates questions for future research relating to whether antipsychotics are prescribed differently in the three sectors because of internal service characteristics or patient population characteristics or both. It also provides a baseline to compare change in patterns in prescribing that will be established in phase II of the audit.

Footnotes

Acknowledgements

This work was supported by an unconditional research grant from Eli Lilly NZ Ltd and the three District Health Boards. We also thank the Mental Health Services and staff from each DHB.

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