Karen P Hayhurst Date of Report: September 2007
Antipsychotic Prescribing Audit:
Measuring the impact of a prescribing intervention
Audit Co-ordinator/ Author of Report: Karen P Hayhurst
Supervisor: Professor Shôn W Lewis
Karen P Hayhurst Date of Report: September 2007
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Table of Contents
List of Tables................................................................................................... 3
List of Figures.................................................................................................. 4
Executive Summary ......................................................................................... 5
Recommendations............................................................................................ 8
Limitations ...................................................................................................... 9
Introduction ...................................................................................................10
Standards ......................................................................................................11
Definition .......................................................................................................13
Aim...............................................................................................................13
Method ..........................................................................................................13
Power calculation & sample size........................................................................14
Pre-Intervention Audit: Antipsychotic Prescribing Rates .......................................15
Antipsychotic monotherapy prescribing..............................................................17
Combination antipsychotic prescribing ...............................................................19
High Dose antipsychotic prescribing ..................................................................24
Summary: Pre-Intervention Prescribing Audit .....................................................30
Prescribing Intervention...................................................................................31
Post-Intervention Antipsychotic Prescribing Audit................................................32
Monotherapy prescribing..................................................................................33
Combination Antipsychotic Prescribing...............................................................35
High Dose antipsychotic prescribing ..................................................................40
Summary: Post-Intervention Antipsychotic Prescribing ........................................47
Effectiveness of Intervention ............................................................................48
Rates & Pattern of Combination Prescribing........................................................48
High Dose Prescribing (Chlorpromazine equivalents) ...........................................49
High Dose Prescribing (Percentage Maximum BNF Recommended Dose) ................50
Change in pattern of prescribing .......................................................................51
Pattern of antipsychotic monopharmacy.............................................................53
Clozapine Prescribing Rates..............................................................................54
Change in pattern of antipsychotic prescribing between the two time-points...........55
Acknowledgements .........................................................................................58
References .....................................................................................................59
Karen P Hayhurst Date of Report: September 2007
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List of Tables
Table Title Page
1 Pre-Intervention Audit: audit sample vs. overall population 15
2 Pre-Intervention Audit: characteristics of samples 16
3 Oldham (Intervention) Site: antipsychotic drugs prescribed to monotherapy group 17
4 Stockport (Control) Site: antipsychotics prescribed to monotherapy group 18
5 Oldham (Intervention) Site: antipsychotic drugs co-prescribed 21
6 Stockport (Control) Site: antipsychotic drugs co-prescribed 23
7 Oldham (Intervention) Site: high dose prescribing (CPZEq) 24
8 Stockport (Control) Site: high dose prescribing (CPZEq) 25
9 Pre-Intervention Prescribing Audit: CPZEq doses 26
10 Oldham (Intervention) Site: high doses (>100% Max BNF Dose) 27
11 Stockport (Control) Site: high doses (>100% Max BNF Dose) 28
12 Pre-Intervention Prescribing Audit: %MaxBNF doses 29
13 Oldham (Intervention) Site: antipsychotic drugs prescribed as monotherapy 33
14 Stockport (Control) Site: antipsychotic drugs prescribed as monotherapy 34
15 Oldham (Intervention) Site: antipsychotic drugs co-prescribed 37
16 Stockport (Control) Site: antipsychotic drugs co-prescribed 39
17 Oldham (Intervention) Site: high dose prescribing (CPZEq) 40
18 Stockport (Control) Site: high dose prescribing (CPZEq) 41
19 Post-Intervention Prescribing: CPZEq doses 42
20 Oldham (Intervention) Site: high doses (>100% Max BNF Dose) 44
21 Stockport (Control) Site: high doses (>100% Max BNF Dose) 45
22 Post-Intervention Prescribing Audit: %MaxBNF doses 46
23 Pattern of prescribing: Pre-Intervention to Post-Intervention 51
24 High Dose Rates: Pre-Intervention to Post-Intervention 52
25 High Dose Rates: Pre-Intervention to Post-Intervention 52
Karen P Hayhurst Date of Report: September 2007
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List of Figures
Fig. Title Page
1 Pre-Intervention pattern of co-prescribing: Oldham 20
2 Pre-Intervention pattern of co-prescribing: Stockport 22
3 Post-Intervention pattern of co-prescribing: Oldham 36
4 Post-Intervention pattern of co-prescribing: Stockport 38
Karen P Hayhurst Date of Report: September 2007
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Antipsychotic Prescribing Audit:
Measuring the impact of a prescribing intervention
Executive Summary
Design
A prescribing intervention was designed, informed by a comprehensive systematic
review and comprising an educational aspect involving an opinion leader and
individual, ‘outreach-type’ visits and a reminder system to alert clinicians to current
cases of combination and high dose antipsychotic prescribing.
Results
Antipsychotic co-prescribing
Post-intervention rates of co-prescribing in the Oldham (intervention) site (20%) did
not differ statistically from either those in the same site pre-intervention (22%) or
those in the Stockport (control) site post-intervention (14%) in a sufficiently powered
study. Samples from the two sites were reasonably comparable pre-intervention. The
most commonly-used antipsychotic combination in both sites before and after the
intervention was olanzapine together with flupenthixol depot.
High dose antipsychotic prescribing
The use of the percentage of maximum recommended BNF dose as the definition for
high dose prescribing gave a rate of about twice that seen with the use of a
chlorpromazine equivalents conversion. Post-intervention rates of high dose
prescribing in the Oldham (intervention) site (6% CPZEq/ 12% Max BNF dose) did
not differ statistically from either those in the same site pre-intervention (5% CPZEq/
9% Max BNF dose) or those in the Stockport (control) site post-intervention (6%
CPZEq/ 10% Max BNF dose). Treatment with combination therapy was associated
with significantly higher dose prescribing, in both sites, regardless of the definition
used.
Karen P Hayhurst Date of Report: September 2007
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New case rate
The number of new, or inception, cases of co-prescribing (patients switched from
monotherapy to combination therapy) were low in both sites. Similarly, a low number
of patients (less than four per cent in both sites, regardless of definition used) had
their treatment switched from standard dose therapy to high dose therapy.
Clozapine prescribing
Rates of clozapine prescribing were higher in the Stockport (control) site (22% pre-
and post-intervention) compared with the Oldham (intervention) site (16% pre- and
post-intervention) but rates did not differ statistically between the two locations.
Clozapine co-prescribing
Pre- and post-intervention samples in the two sites highlighted that the addition of a
second antipsychotic drug to clozapine therapy comprised between 6% and 16% of
combination-treated patients and between 1% and 3% of the sample overall. This
finding will be useful when auditing rates of combination prescribing as such co-
prescribing is permitted in widely-used clinical treatment guidelines such as NICE.
Antipsychotic switches
Although rates of combination and high dose prescribing were relatively consistent
throughout the timeperiod, across both sites 17% of patients (almost one in six)
experienced a switch in their antipsychotic drug over the period of the study.
Between 18% and 20% of patients in both sites were subject to antipsychotic dose
changes. In the Stockport (control) site there were a number of statistically significant
findings relating to antipsychotic drug switches, with patients most likely to switch
treatment between the two time-points being treated with antipsychotics in
combination rather than monotherapy; treated with a non-clozapine SGA rather than
clozapine; and on a higher dose (%Max BNF) than non-switchers at the baseline
audit.
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Conclusions
A multifaceted prescribing intervention failed to reduce rates of combination
antipsychotic prescribing post-intervention compared with rates seen pre-intervention
and rates seen in a site where the intervention did not take place. Baseline rates of
antipsychotic co-prescribing in both sites were substantially lower than those seen in
national prevalence data.
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Recommendations
A number of the recommendations made following the previous audit of antipsychotic
prescribing are repeated here as they remain important issues.
1. Clearer recording in patient casenotes, especially of current antipsychotic drug
treatment (drug and dose) is required.
2. A reduction in the rate of combination antipsychotic prescribing is required. One
in five patients in the Oldham site and around one in seven in the Stockport site
received treatment with a combination of antipsychotic drugs. A minority of
these were treated with three antipsychotic drugs concurrently. All current
treatment guidelines advise against such prescribing except for the addition of a
second antipsychotic drug to clozapine in treatment-resistant schizophrenia,
following an adequate trial of clozapine monotherapy. The definition of co-
prescribing used here of receipt of such treatment for more than one month
means that patients in the process of switching from one antipsychotic to
another will comprise a small proportion of this figure.
3. A reduction in the rate of high dose antipsychotic prescribing is required.
Depending on the definition employed, between five and twelve per cent of
patients received a high dose of antipsychotic drug treatment. More co-
prescribed patients were receiving high dose treatment compared with
monotherapy-treated patients, providing further evidence for the necessity of a
reduction in rates of combination antipsychotic treatment.
4. Rates of combination and high dose antipsychotic prescribing do not form
routinely collected prescribing data, despite the adverse events associated with
both of these practices. More accurate and straightforward methods of
collecting such important data require further exploration.
5. It is, as yet, unclear whether the new patient electronic records system (NCRS)
will ease data collection for antipsychotic prescribing audits.
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Limitations
It took longer than anticipated to collect prescribing data prior to and following the
use of the intervention package and to collect data on a sufficient number of patients
to satisfy the requirements of the power calculation. Data collection covered the
Christmas/ New Year period when attendance at outpatient clinics fell substantially at
both sites. Data collection therefore had to carry on well beyond the planned three-
month period.
Similarly, the time-consuming nature of the audit overall, particularly as it involved
collected the majority of data via patient casenotes, may well have led to
inaccuracies in data recording.
The cross-sectional nature of audit data means that caution must be attached in
inferring the direction of causality of any significant findings.
Karen P Hayhurst Date of Report: September 2007
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Introduction
Prescribing antipsychotic drugs in combination increases the incidence of adverse
drug effects and multiplies treatment costs, with no formal evidence for increased
efficacy (Hamann et al, 2003; Taylor et al, 2000; Yuzda, 2000). Receiving combined
high doses of antipsychotics may be an inadvertent consequence of co-prescribing
(Bingefors et al, 2003; Lelliott et al, 2002) with 20% of UK patients receiving
antipsychotics in doses exceeding BNF guidance (BNF, 2007; Harrington et al, 2002;
Hayhurst et al, 2007).
The previous audit of antipsychotic prescribing carried out in Pennine Care NHS
Trust, demonstrated that rates of combination antipsychotic prescribing and high
dose antipsychotic prescribing differed significantly from zero (for example, in
Oldham, 20% of patients received combination antipsychotic treatment and 15%
were treated with high dose antipsychotic treatment). The report of this previous audit
can be found using the following link:
www.burypct.nhs.uk/fileadmin/user_upload/health_promotion/test_page_2/Paul/sigma_05.pdf
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Standards
The main clinical treatment guidelines in force in the UK guard against the use of
antipsychotic polypharmacy, or combination prescribing.
National Institute for Health & Clinical Excellence (NICE, 2002a) guidance on the use
of newer (atypical) antipsychotic drugs for the treatment of schizophrenia states that,
“atypical and typical antipsychotic drugs should not be prescribed
concurrently, except for short periods to cover changeover of
medication”
This guidance was repeated in the NICE (2002b) ‘Core Interventions’ guidance,
although combination prescribing was permitted under certain circumstances,
“the addition of a second antipsychotic drug to clozapine may be
considered for people with treatment resistant schizophrenia for
whom clozapine has proved insufficiently effective”
The Royal College of Psychiatrists’ Consensus statement on high dose antipsychotic
prescribing was recently revised (May 2006) and states,
“the efficacy of combining two or more FGAs or adding a FGA to a
SGA (or vice versa) has not been established and there is
evidence for increased risk of adverse effects and pharmacokinetic
interactions”
Local (Greater Manchester) SiGMA guidelines state that,
“the co-prescribing of two or more antipsychotic drugs at the same
time, including atypical with typical drugs, apart from transitional
periods, has no proven advantages in general, with disadvantages
including increased side effects and difficulty in calculating the total
cumulative dose being taken”
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The British National Formulary (BNF, 2006) states,
“the prescribing of more than one antipsychotic at the same time is
not recommended as this may constitute a hazard”
The Maudsley prescribing guidelines (2005-2006) suggest that,
“antipsychotic monotherapy is desirable and should be the norm”
“polypharmacy should be undertaken only where response to a
single antipsychotic (including clozapine) has been clearly
demonstrated to be inadequate - in such cases, the effect of
polypharmacy should be carefully evaluated and documented -
where there is no clear benefit, treatment should revert to single
antipsychotic therapy”
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Definition: patients were classed as receiving combination antipsychotic treatment
based on an operational definition of the receipt of two or more antipsychotic drugs in
parallel for a period of more than one month.
Aim
Antipsychotic prescribing was audited in two sites of Pennine Care NHS Trust
(Oldham and Stockport) prior to the use of a prescribing intervention designed to
reduce levels of combination antipsychotic prescribing in one of the sites (Oldham).
Antipsychotic prescribing was then re-audited in both sites, with levels of combination
prescribing being compared to pre-intervention levels and post-intervention levels in
the site where the intervention did not take place (Stockport).
Method
Randomisation was carried out by an independent statistician, resulting in the Royal
Oldham Hospital, Pennine Care NHS Trust, being randomised to receive the
prescribing intervention and Stepping Hill Hospital, Stockport, also part of Pennine
Care NHS Trust, being randomised to be the control site.
The design of the prescribing intervention was informed by work on a systematic
review looking at previous studies which had attempted to change mental health
clinicians’ prescribing behaviour. This pointed to a multifaceted approach being more
effective in changing prescribing practices and that effective methods included a
combination of audit and feedback, the use of opinion leaders, educational outreach,
and the use of reminders.
The prescribing intervention comprised two main parts: firstly, a talk on evidence-
based antipsychotic prescribing by an opinion leader was followed by an individual
visit, which comprised an educational package and feedback of audit findings and
secondly, a reminder system was used to alert clinicians to current cases of
combination and high dose antipsychotic prescribing. Further details of the design of
the prescribing intervention are available on request.
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Power calculation & sample size
A power calculation indicated that, with significance set at 0.05, 210 patients in each
site would be sufficient to detect a reduction in rates of combination antipsychotic
prescribing from 20% to 10%, with 80% power. Inflating this figure by 10% in each
group to account for confounders meant that a minimum of 231 patients were
required in each group.
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Pre-Intervention Audit: Antipsychotic Prescribing Rates
The population covered by the Royal Oldham Hospital is approximately 250,000; that
covered by Stepping Hill Hospital, Stockport is approximately 350,000. Audit samples
for the two sites were derived from the CPA (Care Programme Approach) Register.
Following the removal of patients over the age of 65 years at the start of the
intervention period plus a number of duplicate listings, there were 436 patients on the
Oldham site register and 438 patients on the Stockport site register. The Oldham
audit sample comprised 244 patients and the Stockport audit sample 248 patients.
These two samples were comparable with the pool of available patients in each site
(and therefore a representative sample) in addition to being similar to each other in
terms of available demographic variables (see Table 1).
Table 1: Pre-Intervention Audit: audit sample vs. overall population
Oldham
(Intervention site)
Stockport
(Control site)
Sample
N=244
Overall pop.
N=436
Sample
N=248
Overall pop.
N=438
Age (years)
Mean (SD) 43.15 (11.54) 42.94 (11.82) 43.39 (11.08) 44.76 (11.23)
Median 42.47 42.28 42.38 43.91
Range 19.52 – 64.30 19.52 – 64.81 19.16 – 63.77 19.16 – 64.86
Gender
Male (%) 156 (64%) 275 (63%) 159 (64%) 288 (66%)
The pre-intervention audit measured antipsychotic prescribing prior to the start of the
intervention period (i.e. before June 2006).
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Table 2: Pre-Intervention Audit: characteristics of samples
Oldham
(Intervention site)
N=244
Stockport
(Control site)
N=248
Ethnicity
White 114 (47%) 157 (63%)
Pakistani 20 (8%) 3 (1%)
Bangladeshi 14 (6%) 1
Asian 7 (3%) 1
Afro-Caribbean 4 (2%) 0
Indian 2 2
Caribbean 2 0
Irish 0 2
Mixed Race 1 1
Chinese 1 2
Kenyan 1 0
Jamaican 1 0
Cambodian 1 0
Iraqi 0 1
NK 76 (31%) 78 (32%)
Length of illness (years)
Mean (SD) 13.6 (8.39) 12.1 (9.09)
Median/ Range 12/ 1 - 39 9/ 1 -39
Setting
Inpatient 14 (6%) 17 (7%)
Outpatient 230 (94%) 231 (93%)
The majority of the two audit samples were white, more so in the Stockport (control)
site and the majority were treated as outpatients. There was a wide range of lengths
of illness in both sites (see Table 2).
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Antipsychotic monotherapy prescribing
Oldham (Intervention) Site
Eight patients in the Oldham sample were not taking any antipsychotic drug
treatment at the time of the audit. Drugs prescribed to patients treated with
monotherapy in the Oldham site are listed in Table 3. Olanzapine was the oral drug
prescribed to most patients and flupenthixol the depot most often prescribed.
Table 3: Oldham (Intervention) Site: antipsychotic drugs prescribed to monotherapy group
Antipsychotic N Mean Dose Median Dose Dose Range
Amisulpride 4 463 mg 475 mg 200 – 700 mg
Aripiprazole 4 21 mg 20 mg 15 – 30 mg
Clozapine 34 417 mg 400 mg 200 – 650 mg
Olanzapine 38 12 mg 10 mg 5 – 30 mg
Quetiapine 8 244 mg 250 mg 50 – 400 mg
Risperidone oral 25 4 mg 3 mg 1 – 12 mg
Risperidone consta 13 37.5 2/52 37.5 2/52 25 2/52 – 50 2/52
Chlorpromazine 7 171 mg 100 mg 50 – 400 mg
Flupenthixol dec. 30 155 5/52 110 4/52 20 6/52 – 150 2/52
Fluphenazine dec. 12 80 5/52 25 2/52 12.5 4/52 – 100 2/52
Haloperidol dec. 2 140 4/52 140 4/52 75 4/52 – 200 4/52
Pipothiazine palm. 2 100 4/52 100 4/52 50 4/52 – 150 4/52
Sulpiride 2 650 mg 650 mg 500 – 800 mg
Trifluoperazine 1 10 mg -------- --------
Zuclopenthixol oral 1 100 mg -------- --------
Zuclopenthixol dec. 6 280 4/52 196 4/52 60 2/52 – 400 2/52
Karen P Hayhurst Date of Report: September 2007
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Stockport (Control) Site
Seven of the sample in the Stockport audit were not taking any antipsychotic drug
treatment. Drugs prescribed to patients treated with antipsychotic monotherapy are
listed in Table 4. Clozapine was the oral drug prescribed to most patients on
monotherapy in this site but flupenthixol was again the depot most often prescribed.
Table 4: Stockport (Control) Site: antipsychotics prescribed to monotherapy group
Antipsychotic N Mean Dose Median Dose Dose Range
Amisulpride 12 683 mg 700 mg 400 – 1200 mg
Aripiprazole 13 15 mg 15 mg 10 – 30 mg
Clozapine 51 445 mg 450 mg 150 – 900 mg
Olanzapine 44 15 mg 15 mg 5 – 30 mg
Quetiapine 11 539 mg 600 mg 25 – 800 mg
Risperidone oral 21 6 mg 5 mg 1 – 12 mg
Risperidone consta 13 37.5 2/52 37.5 2/52 25 2/52 – 50 2/52
Chlorpromazine 1 50 mg -------- --------
Flupenthixol oral 1 3 mg -------- --------
Flupenthixol dec. 11 75 2/52 60 2/52 40 2/52 – 200 2/52
Fluphenazine dec. 5 155 5/52 50 2/52 50 3/52 – 125 2/52
Haloperidol oral 1 10 mg -------- --------
Haloperidol dec. 3 40 2/52 30 2/52 50 4/52 – 125 4/52
Pipothiazine palm. 4 30 2/52 25 2/52 25 4/52 – 50 2/52
Promazine 3 67 mg 50 mg 50 – 100 mg
Sulpiride 1 400 mg -------- --------
Trifluoperazine 2 3.5 mg 3.5 mg 2 – 5 mg
Zuclopenthixol oral 1 30 mg -------- --------
Zuclopenthixol dec 9 130 1/52 100 1/52 200 3/52 – 250 1/52
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Combination antipsychotic prescribing
Oldham (Intervention) Site
Patients receiving treatment with antipsychotic drugs in combination comprised 22%
of the Oldham sample (53 patients). Two patients had received such treatment for
less than one month and four patients were treated with oral risperidone and
injectable risperidone together; patients were not defined as receiving combination
therapy if they were treated with the same antipsychotic drug via different delivery
routes. .
Prescribed combinations are listed in Table 5. Four of the co-prescribed patients
were receiving three antipsychotic drugs together. The most common combination
was olanzapine together with flupenthixol depot. The majority of co-prescribed
patients (51%) were treated with an oral SGA (second generation antipsychotic, or
atypical) together with a depot FGA (first generation antipsychotic, or conventional).
Most of this group (85%) were treated with olanzapine together with an FGA depot.
A further 15% of co-prescribed patients were treated with an FGA depot (mostly
flupenthixol) together with an oral FGA; 11% with an oral SGA and an oral FGA; 11%
with two oral SGAs (three olanzapine with another SGA and three clozapine plus a
second SGA) and the four patients taking three antipsychotics were on olanzapine
taken together with an FGA depot and an oral FGA (see figure 1).
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Figure 1: Pre-Intervention pattern of co-prescribing: Oldham
0
5
10
15
20
25
30
SGA o
ral &
FGA d
epot
FGA d
epot &
FGA o
ral
SGA o
ral &
SG
A ora
l
SGA o
ral &
FGA o
ral
FGA o
ral &
FGA o
ral
3 AP d
rugs
pa
tie
nts
(N
)
Karen P Hayhurst Date of Report: September 2007
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Table 5: Oldham (Intervention) Site: antipsychotic drugs co-prescribed
SGA oral + FGA Depot FGA Depot + FGA Oral
Olanzapine 30 + flupenthixol 30 2/52 Flupenthixol 80 1/52 + chlorpromazine 300
Olanzapine 25 + flupenthixol 40 2/52 Flupenthixol 150 2/52 + chlorpromazine 100
Olanzapine 20 + flupenthixol 150 2/52 Flupenthixol 100 2/52 + chlorpromazine 100
Olanzapine 20 + flupenthixol 100 2/52 Flupenthixol 50 2/52 + promazine 100
Olanzapine 20 + flupenthixol 60 2/52 Flupenthixol 50 2/52 + promazine 50
Olanzapine 20 + flupenthixol 20 2/52 Flupenthixol 30 2/52 + sulpiride 400
Olanzapine 15 + flupenthixol 100 2/52 Flupenthixol 37.5 2/52 + haloperidol 5
Olanzapine 10 + flupenthixol 200 1/52 Fluphenazine 25 3/52 + chlorpromazine 150
Olanzapine 10 + flupenthixol 100 2/52 SGA oral + SGA oral
Olanzapine 10 + flupenthixol 60 2/52 Olanzapine 20 + amisulpride 400
Olanzapine 10 + flupenthixol 40 2/52 Olanzapine 20 + amisulpride 200
Olanzapine 10 + flupenthixol 20 2/52 Olanzapine 20 + aripiprazole 10
Olanzapine 5 + flupenthixol 160 2/52 Clozapine 600 + risperidone 2
Olanzapine 5 + flupenthixol 80 1/52 Clozapine 750 + risperidone 4
Olanzapine 5 + flupenthixol 40 2/52 Clozapine 400 + amisulpride 200
Olanzapine 5 + flupenthixol 50 4/52 SGA oral + FGA oral
Olanzapine 20 + fluphenazine 40 4/52 Clozapine 900 + sulpiride 800
Olanzapine 15 + fluphenazine 100 4/52 Clozapine 600 + sulpiride 600
Olanzapine 40 + zuclopenthixol 100 2/52 Clozapine 400 + promazine 200
Olanzapine 15 + zuclopenthixol 300 2/52 Olanzapine 20 + chlorpromazine 150
Olanzapine 10 + zuclopenthixol 600 2/52 Olanzapine 15 + chlorpromazine 250
Olanzapine 5 + zuclopenthixol 200 2/52 Amisulpride 400 + promazine 75
Olanzapine 15 + pipothiazine palm. 60 2/52 Risperidone 2 + chlorpromazine 100
Risperidone 6 + fluphenazine 100 1/52 FGA oral + FGA oral
Risperidone 2 + fluphenazine 50 4/52 Sulpiride 1000 + chlorpromazine 200
Quetiapine 600 + flupenthixol 100 2/52 3 antipsychotic drugs
Quetiapine 250 + flupenthixol 30 2/52 Olanzapine 35 + flupenthixol 100 2/52 + chlorpromazine 250
Olanzapine 20 + flupenthixol 60 2/52 + haloperidol 30
Olanzapine 20 + flupenthixol 80 1/52 + chlorpromazine 50
Olanzapine 10 + fluphenazine 37.5 2/52 + chlorpromazine 50
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Stockport (Control) Site
In the Stockport site, patients receiving combination treatment comprised 16% of the
sample (39 patients). Two patients were taking a second antipsychotic drug listed as
‘prn’, one patient had received combination treatment for less than one month and
two patients were treated with oral risperidone and injectable risperidone together:
these patients were not defined as receiving combination treatment.
Combinations of drugs in this sample are listed in Table 6. One patient was taking
three antipsychotics concurrently. The most common combination was olanzapine
and flupenthixol depot in this site also. The majority of patients receiving combination
treatment were receiving an oral SGA drug together with a depot FGA (49% of co-
prescribed patients). The majority (58%) of this group were treated with olanzapine
together with an FGA depot.
A further 23% of those co-prescribed were treated with an FGA depot together with
an oral FGA; 15% received two oral SGAs (four clozapine with a second SGA and
two olanzapine plus a second SGA); 10% were taking an oral SGA together with an
oral FGA and the patient on three antipsychotics was taking an FGA depot and two
oral FGAs combined (see figure 2).
Figure. 2: Pre-Intervention pattern of co-prescribing: Stockport
02468
101214161820
SGA o
ral &
FGA d
epot
FGA d
epot &
FGA o
ral
SGA o
ral &
SG
A ora
l
SGA o
ral &
FGA o
ral
3 AP d
rugs
pa
tie
nts
(N
)
Karen P Hayhurst Date of Report: September 2007
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Table 6: Stockport (Control) Site: antipsychotic drugs co-prescribed
SGA oral + FGA Depot FGA Depot + FGA Oral
Olanzapine 20 + flupenthixol 70 2/52 Flupenthixol 100 2/52 + chlorpromazine 50
Olanzapine 20 + flupenthixol 80 3/52 Flupenthixol 40 3/52 + chlorpromazine 350
Olanzapine 20 + flupenthixol 20 2/52 Flupenthixol 100 1/52 + trifluoperazine 5
Olanzapine 20 + flupenthixol 25 3/52 Flupenthixol 50 2/52 + trifluoperazine 15
Olanzapine 10 + flupenthixol 30 2/52 Fluphenazine 75 1/52 + trifluoperazine 15
Olanzapine 5 + flupenthixol 40 2/52 Fluphenazine 25 2/52 + haloperidol 5
Olanzapine 5 + flupenthixol 20 2/52 Pipo palm. 150 2/52 + chlorpromazine 300
Olanzapine 20 + fluphenazine 50 4/52 Pipo palm. 75 4/52 + promazine 150
Olanzapine 10 + fluphenazine 37.5 6/52 Zuclopenthixol 500 2/52 + chlorpromazine 300
Olanzapine 5 + fluphenazine 25 1/52 SGA oral + SGA oral
Olanzapine 15 + zuclopenthixol 200 2/52 Clozapine 475 + amisulpride 800
Risperidone 6 + flupenthixol 60 4/52 Clozapine 450 + amisulpride 400
Risperidone 8 + fluphenazine 12.5 3/52 Clozapine 700 + quetiapine 400
Risperidone 3 + fluphenazine 50 1/52 Clozapine 600 + quetiapine 400
Risperidone 8 + zuclopenthixol 200 2/52 Olanzapine 20 + aripiprazole 5
Quetiapine 700 + flupenthixol 50 2/52 Olanzapine 10 + amisulpride 800
Quetiapine 600 + flupenthixol 250 3/52 SGA oral + FGA oral
Amisulpride 200 + flupenthixol 100 3/52 Olanzapine 20 + flupenthixol 12
Aripiprazole 10 + zuclopenthixol 300 2/52 Olanzapine 5 + haloperidol 45
3 antipsychotic drugs Olanzapine 2.5 + fluphenazine 10
Flupenthixol 40 2/52 + Trifluoperazine 15 + Thioridazine 50
Risperidone 6 + promazine 75
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High Dose antipsychotic prescribing
Oldham (Intervention) Site
Eleven of the Oldham sample (5%) were treated with a high dose of over 1000 mg
chlorpromazine equivalents (CPZEq). All but one of these were receiving
combination treatment and three patients were taking three antipsychotic drugs
concurrently (see Table 7).
Table 7: Oldham (Intervention) Site: high dose prescribing (CPZEq)
Drug 1 Drug 2 Drug 3 poly
1 Olanzapine 20 mg Flupenthixol 150 2/52 √
2 Olanzapine 10 mg Flupenthixol 200 1/52 √
3 Clozapine 750 mg Risperidone 4 mg √
4 Clozapine 900 mg Sulpiride 800 mg √
5 Risperidone 6 mg Fluphenazine 100 1/52 √
6 Quetiapine 600 mg Flupenthixol 100 2/52 √
7 Flupenthixol 80 1/52 Chlorpromazine 300 mg √
8 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg √
9 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg √
10 Olanzapine 20 mg Flupenthixol 60 2/52 Haloperidol 30 mg √
11 Risperidone 12 mg Risperidone 50 2/52 X
Karen P Hayhurst Date of Report: September 2007
25
Stockport (Control) Site
Thirteen of the Stockport sample (5%) were treated with a high dose (>1000 mg
CPZEq). Two-thirds of these (nine patients) received combination treatment (see
Table 8).
Table 8: Stockport (Control) Site: high dose prescribing (CPZEq)
Drug 1 Drug 2 poly
1 Amisulpride 1200 mg X
2 Quetiapine 800 mg X
3 Quetiapine 800 mg X
4 Quetiapine 800 mg X
5 Clozapine 700 mg Quetiapine 400 mg √
6 Clozapine 600 mg Quetiapine 400 mg √
7 Clozapine 475 mg Amisulpride 800 mg √
8 Quetiapine 700 mg Flupenthixol 50 2/52 √
9 Quetiapine 600 mg Flupenthixol 250 3/52 √
10 Olanzapine 5 mg Haloperidol 45 mg √
11 Flupenthixol 100 1/52 Trifluoperazine 5 mg √
12 Fluphenazine 75 1/52 Trifluoperazine 15 mg √
13 Pipothiazine palm. 150 2/52 Chlorpromazine 300 mg √
Karen P Hayhurst Date of Report: September 2007
26
Table 9 shows chlorpromazine equivalent (CPZEq) doses for patients receiving
combination treatment or monotherapy. CPZEq doses of co-prescribed patients were
higher than those treated with a single antipsychotic drug in both sites (p<0.001). In
the Oldham (intervention site) 91% of patients receiving a high dose were on
combination treatment; in the Stockport (control) site this figure was 69%.
Table 9: Pre-Intervention Prescribing Audit: CPZEq doses
Oldham
(Intervention) site
Stockport
(Control) site
Monotherapy
Group
N=191
Co-prescribed
Group
N=53
Monotherapy
Group
N=209
Co-prescribed
Group
N=39
CPZEq
Dose
Mean (SD) 311.01 (188.06) 720.08 (416.68) 386 (238.13) 707 (374.65)
Median 300.00 600.00 341.5 550
Range 20 – 1400 200 – 2200 33 - 1200 200 - 1633
As there is a debate as to which method to best use to convert drug doses, these
were also converted into percentage of maximum recommended dose for each
antipsychotic drug (%MaxBNF Dose) listed in the British National Formulary (BNF,
2006).
Karen P Hayhurst Date of Report: September 2007
27
Oldham (Intervention) Site
The use of this definition led to 22 patients (9%) being defined as receiving a high
dose in the Oldham site. As can be seen in Table 10 this was mainly because of the
inclusion of patients receiving a daily dose of over 20 mg of olanzapine in the high
dose group. The majority of the high dose group were, again receiving combination
treatment and three of the group were prescribed more than two antipsychotics
concurrently.
Table 10: Oldham (Intervention) Site: high doses (>100% Max BNF Dose)
Drug 1 Drug 2 Drug 3 poly
1 Olanzapine 30 mg X
2 Risperidone 3 mg Risperidone 50 2/52 X
3 Risperidone 12 mg Risperidone 50 2/52 X
4 Olanzapine 30 mg Flupenthixol 30 2/52 √
5 Olanzapine 25 mg Flupenthixol 40 2/52 √
6 Olanzapine 20 mg Flupenthixol 20 2/52 √
7 Olanzapine 20 mg Flupenthixol 100 2/52 √
8 Olanzapine 20 mg Flupenthixol 60 2/52 √
9 Olanzapine 20 mg Flupenthixol 150 2/52 √
10 Olanzapine 20 mg Amisulpride 400 mg √
11 Olanzapine 20 mg Amisulpride 200 mg √
12 Olanzapine 20 mg Aripiprazole 10 mg √
13 Olanzapine 20 mg Fluphenazine 40 4/52 √
14 Olanzapine 40 mg Zuclopenthixol 100 2/52 √
15 Olanzapine 15 mg Pipothiazine palm. 60 2/52 √
16 Olanzapine 20 mg Chlorpromazine 150 mg √
17 Clozapine 750 mg Risperidone 4 mg √
18 Clozapine 900 mg Sulpiride 800 mg √
19 Risperidone 6 mg Fluphenazine 100 1/52 √
20 Olanzapine 20 mg Flupenthixol 60 2/52 Haloperidol 30 mg √
21 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg √
22 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg √
Karen P Hayhurst Date of Report: September 2007
28
Stockport (Control) Site
The use of the percentage of maximum recommended BNF dose (%MaxBNF) dose
conversion led to 26 patients (10%) in the Stockport site being categorised as
receiving high dose treatment (see Table 11).
Table 11: Stockport (Control) Site: high doses (>100% Max BNF Dose)
Drug 1 Drug 2 poly
1 Olanzapine 30 mg X
2 Olanzapine 25 mg X
3 Olanzapine 25 mg X
4 Olanzapine 25 mg X
5 Quetiapine 800 mg X
6 Quetiapine 800 mg X
7 Quetiapine 800 mg X
8 Risperidone 50 2/52 Risperidone 1 mg X
9 Risperidone 50 2/52 Promazine 50 mg prn X
10 Fluphenazine 125 2/52 Chlorpromazine 50 mg prn X
11 Olanzapine 20 mg Flupenthixol 70 2/52 √
12 Olanzapine 20 mg Flupenthixol 80 3/52 √
13 Olanzapine 20 mg Flupenthixol 20 2/52 √
14 Olanzapine 20 mg Flupenthixol 25 3/52 √
15 Olanzapine 20 mg Fluphenazine 50 4/52 √
16 Olanzapine 10 mg Amisulpride 800 mg √
17 Olanzapine 20 mg Aripiprazole 5 mg √
18 Clozapine 700 mg Quetiapine 400 mg √
19 Clozapine 600 mg Quetiapine 400 mg √
20 Clozapine 475 mg Amisulpride 800 mg √
21 Quetiapine 600 mg Flupenthixol 250 3/52 √
22 Risperidone 3 mg Fluphenazine 50 1/52 √
23 Olanzapine 20 mg Flupenthixol 12 mg √
24 Olanzapine 5 mg Haloperidol 45 mg √
25 Pipothiazine palm. 150 2/52 Chlorpromazine 300 mg √
26 Fluphenazine 75 1/52 Trifluoperazine 15 mg √
Karen P Hayhurst Date of Report: September 2007
29
Table 12 sets out the %MaxBNF doses for patients receiving combination treatment
or monotherapy, showing that %MaxBNF doses of co-prescribed patients were
higher than those treated with a single antipsychotic drug in both sites (p=0.001). In
the Oldham (intervention) site 86% of patients receiving a high dose, using this
definition, were on combination treatment; in the Stockport (control) site this figure
was 62%.
Table 12: Pre-Intervention Prescribing Audit: %MaxBNF doses
Oldham
(Intervention) site
Stockport
(Control) site
Monotherapy
Group
N=191
Co-prescribed
Group
N=53
Monotherapy
Group
N=209
Co-prescribed
Group
N=39
%MaxBNF
Dose
Mean (SD) 39% (30.33) 84% (50.32) 53% (30.51) 82% (46.44)
Median 33% 87.5% 50% 75%
Range 1% - 175% 12.5% - 212.5% 3% – 150% 5% – 180%
Karen P Hayhurst Date of Report: September 2007
30
Summary: Pre-Intervention Prescribing Audit
Oldham (Intervention) Site
Out of a sample of 244 patients, 53 patients (22%) were treated with combination
antipsychotic treatment in the Oldham site. Four of these were taking three drugs
concurrently. The most used combination was olanzapine together with flupenthixol
depot. The use of the CPZEq dose conversion gave a 5% rate of high dose
prescribing, whereas the use of the %MaxBNF dose conversion gave a higher rate of
9%. Treatment with combination therapy was associated with significantly higher
dose prescribing regardless of the definition used, with between 86% and 91% of
high dose prescribing made up of combination treatment.
Stockport (Control) Site
Of a sample of 248 patients, 39 patients (16%) in the Stockport site were treated with
combination prescribing. The combination used most often was also olanzapine with
flupenthixol depot. The CPZEq dose conversion gave a 5% rate of high dose
prescribing, whereas the %MaxBNF dose conversion gave a higher rate of 10%.
Treatment with combination therapy was again associated with significantly higher
dose prescribing regardless of the definition used, with between 62% and 69% of
high dose prescribing made up of combination treatment.
Karen P Hayhurst Date of Report: September 2007
31
Prescribing Intervention
A prescribing intervention was delivered to all mental health clinicians working in
Adult Psychiatry at the Royal Oldham Hospital, with the aim of reducing rates of
combination antipsychotic prescribing. The period covered by the intervention began
in June 2006 and ended in March 2007. Details of the intervention are available on
request.
Karen P Hayhurst Date of Report: September 2007
32
Post-Intervention Antipsychotic Prescribing Audit
Post intervention antipsychotic prescribing rates were measured in the original
samples of 244 patients in the Oldham (intervention) site and 248 patients in the
Stockport (control) site.
Karen P Hayhurst Date of Report: September 2007
33
Monotherapy prescribing
Oldham (Intervention) Site
Following the end of the intervention period ten patients were not receiving any
antipsychotic drug treatment in the Oldham site. Olanzapine was again the SGA drug
prescribed alone to most patients and flupenthixol the depot drug prescribed singly to
most patients. Table 13 sets out drugs prescribed to the group as monotherapy.
Table 13: Oldham (Intervention) Site: antipsychotic drugs prescribed as monotherapy
Antipsychotic
Drug
N Mean Dose Median
Dose
Dose Range
Amisulpride 4 400 mg 350 mg 200 – 700 mg
Aripiprazole 5 21 mg 20 mg 15 – 30 mg
Clozapine 30 423 mg 400 mg 200 – 650 mg
Olanzapine 38 12 mg 10 mg 3.75 – 27.5 mg
Quetiapine 6 258 mg 250 mg 150 – 400 mg
Risperidone oral 26 4 mg 4 mg 1 – 12 mg
Risperidone consta 15 37.5 2/52 37.5 2/52 25 2/52 – 50 2/52
Chlorpromazine 6 185 mg 100 mg 25 – 350 mg
Flupenthixol dec. 37 140 5/52 50 2/52 20 6/52 – 150 2/52
Fluphenazine dec. 11 37.5 2/52 25 2/52 12.5 8/52 – 100 2/52
Haloperidol oral 1 10 mg -------- --------
Haloperidol dec. 2 150 4/52 150 4/52 100 4/52 – 200 4/52
Pipothiazine palm. 2 50 2/52 50 2/52 50 4/52 – 150 4/52
Sulpiride 1 1200 mg -------- --------
Trifluoperazine 1 4 mg -------- --------
Zuclopenthixol oral 1 100 mg -------- --------
Zuclopenthixol dec. 6 590 5/52 200 2/52 100 3/52 – 600 2/52
Karen P Hayhurst Date of Report: September 2007
34
Stockport (Control) Site
Eleven patients were taking no antipsychotic drug treatment following the intervention
in this site. Clozapine was the oral drug prescribed to most patients on monotherapy
and flupenthixol the depot most often prescribed (see Table 14 for further details).
Table 14: Stockport (Control) Site: antipsychotic drugs prescribed as monotherapy
Antipsychotic Drug N Mean Dose Median
Dose
Dose Range
Amisulpride 11 655 mg 700 mg 200 – 1200 mg
Aripiprazole 10 17 mg 15 mg 10 – 30 mg
Clozapine 53 445 mg 438 mg 150 – 900 mg
Olanzapine 39 16 mg 15 mg 2.5 – 30 mg
Quetiapine 9 606 mg 700 mg 50 – 950 mg
Risperidone oral 23 6 mg 6 mg 1 – 12 mg
Risperidone consta 18 37.2 2/52 37.5 2/52 25 2/52 – 50 2/52
Chlorpromazine 1 50 mg -------- --------
Flupenthixol oral 2 4.5 mg 4.5 mg 3 – 6 mg
Flupenthixol dec. 14 75 2/52 40 2/52 25 4/52 – 200 2/52
Fluphenazine dec. 4 140 5/52 90 5/52 37.5 3/52 – 125 2/52
Haloperidol oral 3 5 mg 5 mg 1 – 10 mg
Haloperidol dec. 3 85 5/52 25 2/52 25 2/52 – 100 4/52
Pipothiazine palm. 4 110 5/52 50 2/52 50 4/52 – 100 4/52
Promazine 3 67 mg 75 mg 25 – 100 mg
Sulpiride 1 400 mg -------- --------
Trifluoperazine 2 3.5 mg 3.5 mg 2 – 5 mg
Zuclopenthixol oral 2 37.5 mg 37.5 mg 25 – 50 mg
Zuclopenthixol depot 10 286 2/52 300 2/52 200 3/52 – 400 2/52
Karen P Hayhurst Date of Report: September 2007
35
Combination Antipsychotic Prescribing
Oldham (Intervention) Site
Patients receiving treatment with combination therapy following the intervention,
comprised 20% of the sample in the Oldham site (50 patients). Two patients had
received such treatment for less than one month and a further five patients were
treated with oral risperidone and injectable risperidone together; not defined as co-
prescribing in this study.
Combinations prescribed in the intervention site are listed in Table 15. Four patients
were again treated with three antipsychotic drugs. The most common combination
remained olanzapine together with flupenthixol depot. The majority of co-prescribed
patients were treated with an SGA oral drug together with a FGA depot (44% of
combination-treated patients).
A further 20% of co-prescribed patients received two oral SGAs (five olanzapine with
another SGA and five clozapine plus a second SGA); 16% were treated with an FGA
depot (mainly flupenthixol) together with an oral FGA; 10% were taking an oral SGA
together with an oral FGA and three of the four taking three antipsychotic drugs
comprised olanzapine together with an FGA depot and an oral FGA (see figure 3).
Karen P Hayhurst Date of Report: September 2007
36
Figure 3: Post-Intervention pattern of co-prescribing: Oldham
0
5
10
15
20
25
SGA o
ral &
FGA d
epot
FGA d
epot &
FGA o
ral
SGA o
ral &
SG
A ora
l
SGA o
ral &
FGA o
ral
SGA o
ral &
SG
A dep
ot
3 AP d
rugs
pa
tie
nts
(N
)
Karen P Hayhurst Date of Report: September 2007
37
Table 15: Oldham (Intervention) Site: antipsychotic drugs co-prescribed
SGA oral + FGA Depot SGA oral + SGA oral
Olanzapine 30 + flupenthixol 30 2/52 Clozapine 700 + amisulpride 400
Olanzapine 20 + flupenthixol 150 2/52 Clozapine 600 + amisulpride 800
Olanzapine 20 + flupenthixol 60 2/52 Clozapine 300 + amisulpride dose NK
Olanzapine 20 + flupenthixol 40 2/52 Clozapine 700 + risperidone 8
Olanzapine 20 + flupenthixol 20 2/52 Clozapine 600 + risperidone 4
Olanzapine 15 + flupenthixol 150 2/52 Olanzapine 25 + amisulpride 100
Olanzapine 10 + flupenthixol 100 1/52 Olanzapine 20 + amisulpride 400
Olanzapine 5 + flupenthixol 200 1/52 Olanzapine 20 + amisulpride 50
Olanzapine 5 + flupenthixol 80 1/52 Olanzapine 15 + amisulpride 400
Olanzapine 5 + flupenthixol 160 2/52 Olanzapine 15 + aripiprazole 10
Olanzapine 2.5 + flupenthixol 50 4/52 SGA oral + FGA oral
Olanzapine 20 + fluphenazine 40 4/52 Clozapine 600 + sulpiride 600
Olanzapine 15 + fluphenazine 100 4/52 Clozapine 400 + promazine 200
Olanzapine 10 + fluphenazine 37.5 2/52 Olanzapine 20 + chlorpromazine 150
Olanzapine 40 + zuclopenthixol 100 2/52 Risperidone 2 + chlorpromazine 100
Olanzapine 20 + zuclopenthixol 300 2/52 Amisulpride 400 + Promazine 75
Olanzapine 10 + zuclopenthixol 200 2/52 SGA oral + SGA depot
Olanzapine 15 + pipothiazine palm. 60 2/52 Olanzapine 15 + risperidone 50 2/52
Quetiapine 600 + flupenthixol 100 2/52 3 antipsychotic drugs
Quetiapine 250 + flupenthixol 20 2/52 Clozapine 700 + haloperidol 2 + sulpiride 400
Risperidone 6 + fluphenazine 100 1/52 Olanzapine 20 + flupenthixol 80 1/52 + chlorpromazine 50
Risperidone 2 + fluphenazine 50 3/52 Olanzapine 35 + chlorpromazine 250 + flupenthixol 100 2/52
FGA Depot + FGA Oral Olanzapine 20 + flupenthixol 150 2/52 + haloperidol 30
Flupenthixol 80 1/52 + chlorpromazine 300
Flupenthixol 150 2/52 + chlorpromazine 100
Flupenthixol 100 2/52 + chlorpromazine 100
Flupenthixol 40 3/52 + chlorpromazine 50
Flupenthixol 30 2/52 + sulpiride 400
Flupenthixol 50 2/52 + promazine 100
Flupenthixol 50 2/52 + promazine 50
Fluphenazine 25 3/52 + chlorpromazine
Karen P Hayhurst Date of Report: September 2007
38
Stockport (Control) Site
Those receiving treatment with antipsychotics in combination following the
intervention comprised 14% of the Stockport site sample (35 patients). Four patients
received a second antipsychotic listed as ‘prn’, one patient had received combination
treatment for less than one month, three patients were treated with oral risperidone
and injectable risperidone together and one patient was taking oral flupenthixol
together with a flupenthixol depot: these patients were not defined as receiving
combination treatment.
Combinations prescribed in the control site are listed in Table 16. The most common
combination was olanzapine and flupenthixol depot together. The majority of co-
prescribed patients (40%) were still treated with a SGA oral together with a FGA
depot.
A further 37% were treated with an oral FGA together with a FGA depot; 11%
received two oral SGAs; 9% were taking an oral SGA together with an oral FGA and
one patient was taking a combination of an SGA depot and an oral FGA (see figure
4).
Figure 4: Post-Intervention pattern of co-prescribing: Stockport
02468
10121416
SGA o
ral &
FGA d
epot
FGA d
epot &
FGA o
ral
SGA o
ral &
SG
A ora
l
SGA o
ral &
FGA o
ral
SGA d
epot &
FGA o
ral
pa
tie
nt (N
)
Karen P Hayhurst Date of Report: September 2007
39
Table 16: Stockport (Control) Site: antipsychotic drugs co-prescribed
FGA Depot + FGA Oral SGA oral + FGA Depot
Flupenthixol 100 2/52 + chlorpromazine 50 Olanzapine 20 + flupenthixol 70 2/52
Flupenthixol 100 3/52 + chlorpromazine 110 Olanzapine 20 + flupenthixol 50 4/52
Flupenthixol 40 3/52 + chlorpromazine 350 Olanzapine 20 + flupenthixol 20 2/52
Flupenthixol 100 1/52 + trifluoperazine 5 Olanzapine 10 + flupenthixol 40 3/52
Flupenthixol 50 2/52 + trifluoperazine 15 Olanzapine 5 + flupenthixol 20 2/52
Flupenthixol 40 2/52 + trifluoperazine 15 Olanzapine 20 + fluphenazine 50 4/52
Flupenthixol 40 1/52 + promazine 100 Olanzapine 5 + fluphenazine 25 1/52
Fluphenazine 37.5 2/52 + haloperidol 7 Olanzapine 5 + fluphenazine 37.5 6/52
Fluphenazine 75 1/52 + trifluoperazine 15 Olanzapine 5 + zuclopenthixol 200 2/52
Fluphenazine 75 2/52 + promazine 50 Risperidone 8 + fluphenazine 12.5 3/52
Pipothiazine palm. 50 2/52 + promazine 50 Risperidone 4 + fluphenazine 50 1/52
Pipothiazine palm. 75 4/52 + promazine 150 Risperidone 6 + flupenthixol 40 4/52
Zuclopenthixol 500 2/52 + chlorpromazine 300 Quetiapine 600 + flupenthixol 250 3/52
SGA oral + SGA oral Quetiapine 200 + pipo palm. 150 2/52
Clozapine 575 + amisulpride 800 SGA oral + FGA oral
Clozapine 700 + quetiapine 400 Quetiapine 800 + haloperidol 20
Olanzapine 15 + amisulpride 800 Quetiapine 750 + haloperidol 6
Olanzapine 10 + amisulpride 1200 Risperidone 6 + Promazine 75
SGA Depot + FGA oral
Risperidone 37.5 2/52 + Promazine 100
Karen P Hayhurst Date of Report: September 2007
40
High Dose antipsychotic prescribing
Oldham (Intervention) Site
Fourteen patients in the Oldham site (6%) were treated with a defined high dose
(>1000 mg CPZEq) at follow-up. All but one of these were receiving combination
treatment and three of the sample were taking three antipsychotics concurrently (see
Table 17).
Table 17: Oldham (Intervention) Site: high dose prescribing (CPZEq)
Drug 1 Drug 2 Drug 3 poly
1 Risperidone 12 mg Risperidone 50 2/52 X
2 Olanzapine 20 mg Flupenthixol 150 2/52 √
3 Olanzapine 15 mg Flupenthixol 150 2/52 √
4 Olanzapine 10 mg Flupenthixol 100 1/52 √
5 Olanzapine 5 mg Flupenthixol 200 1/52 √
6 Clozapine 700 mg Amisulpride 400 mg √
7 Clozapine 600 mg Amisulpride 800 mg √
8 Clozapine 700 mg Risperidone 6 mg √
9 Quetiapine 600 mg Flupenthixol 100 2/52 √
10 Risperidone 6 mg Fluphenazine 100 1/52 √
11 Flupenthixol 80 1/52 Chlorpromazine 300 mg √
12 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg √
13 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg √
14 Olanzapine 20 mg Flupenthixol 150 2/52 Haloperidol 30 mg √
Karen P Hayhurst Date of Report: September 2007
41
Stockport (Control) Site
Fourteen of the Stockport sample (6%) were treated with a defined high dose (>1000
mg CPZEq) at follow-up. Over two-thirds of these were receiving combination
treatment (see Table 18).
Table 18: Stockport (Control) Site: high dose prescribing (CPZEq)
Drug 1 Drug 2 poly
1 Quetiapine 950 mg X
2 Quetiapine 800 mg X
3 Quetiapine 800 mg X
4 Amisulpride 1200 mg X
5 Olanzapine 15 mg Amisulpride 800 mg √
6 Olanzapine 10 mg Amisulpride 1200 mg √
7 Clozapine 575 mg Amisulpride 800 mg √
8 Clozapine 700 mg Quetiapine 400 mg √
9 Quetiapine 800 mg Haloperidol 20 mg √
10 Quetiapine 750 mg Haloperidol 6 mg √
11 Quetiapine 600 mg Flupenthixol 250 3/52 √
12 Quetiapine 200 mg Pipothiazine palm. 150 2/52 √
13 Flupenthixol 100 1/52 Trifluoperazine 5 mg √
14 Fluphenazine 75 1/52 Trifluoperazine 15 mg √
Karen P Hayhurst Date of Report: September 2007
42
Table 19 shows CPZEq doses of monotherapy-treated patients and combination-
treated patients. The median CPZEq dose was again higher in the co-prescribed
group compared with the monotherapy group in both sites (p<0.001). Receiving high
dose treatment was associated with co-prescribing: in the Oldham (intervention) site
93% of high dose patients were receiving combination treatment; in the Stockport
(control) site this figure was 71%.
Table 19: Post-Intervention Prescribing: CPZEq doses
Oldham
(Intervention) site
Stockport
(Control) site
Monotherapy
Group
N=194
Co-prescribed
Group
N=50
Monotherapy
Group
N=213
Co-prescribed
Group
N=35
CPZEq
Dose
Mean (SD) 317.54 (189.29) 782.33 (458.12) 399.09 (244.55) 716.52 (421.98)
Median 300.00 666.67 400.00 550.00
Range 20.83 – 1400.00 175.0 – 2150.0 33.33 – 1266.67 183.33 – 1733.34
Karen P Hayhurst Date of Report: September 2007
43
High Dose Antipsychotic Prescribing
Oldham (Intervention) Site
Twelve per cent of the Oldham site sample (29 patients) were defined as receiving a
high dose at follow-up when these were converted into percentage of maximum BNF
recommended dose. At least one drug taken by 72% in this group was olanzapine.
The majority of this high dose group were, again, receiving combination treatment
and four of this group were prescribed three antipsychotic drugs concurrently (see
Table 20).
Karen P Hayhurst Date of Report: September 2007
44
Table 20: Oldham (Intervention) Site: high doses (>100% Max BNF Dose)
Drug 1 Drug 2 Drug 3 poly
1 Olanzapine 27.5 mg X
2 Risperidone 12 mg Risperidone consta 50 2/52 X
3 Risperidone 6 mg Risperidone consta 37.5 2/52 X
4 Risperidone 3 mg Risperidone consta 50 2/52 X
5 Olanzapine 30 mg Flupenthixol 30 2/52 √
6 Olanzapine 20 mg Flupenthixol 150 2/52 √
7 Olanzapine 20 mg Flupenthixol 60 2/52 √
8 Olanzapine 20 mg Flupenthixol 40 2/52 √
9 Olanzapine 20 mg Flupenthixol 20 2/52 √
10 Olanzapine 20 mg Fluphenazine 40 4/52 √
11 Olanzapine 15 mg Fluphenazine 100 4/52 √
12 Olanzapine 40 mg Zuclopenthixol 100 2/52 √
13 Olanzapine 20 mg Zuclopenthixol 300 2/52 √
14 Olanzapine 15 mg Pipothiazine palm. 60 2/52 √
15 Olanzapine 25 mg Amisulpride 100 mg √
16 Olanzapine 20 mg Amisulpride 400 mg √
17 Olanzapine 20 mg Amisulpride 50 mg √
18 Olanzapine 15 mg Amisulpride 400 mg √
19 Olanzapine 15 mg Aripiprazole 10 mg √
20 Olanzapine 15 mg Risperidone consta 50 2/52 √
21 Olanzapine 20 mg Chlorpromazine 150 mg √
22 Clozapine 700 mg Amisulpride 400 mg √
23 Clozapine 600 mg Amisulpride 800 mg √
24 Clozapine 700 mg Risperidone 8 mg √
25 Risperidone 6 mg Fluphenazine 100 1/52 √
26 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg √
27 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg √
28 Olanzapine 20 mg Flupenthixol 150 2/52 Haloperidol 30 mg √
29 Clozapine 700 mg Sulpiride 400 mg Haloperidol 2 mg √
Karen P Hayhurst Date of Report: September 2007
45
Stockport (Control) Site
Using the %MaxBNF dose as the definition of high dose prescribing, 24 patients
(10%) in the Stockport site were categorised as receiving a high dose following the
intervention period (see Table 21).
Table 21: Stockport (Control) Site: high doses (>100% Max BNF Dose)
Drug 1 Drug 2 poly
1 Olanzapine 30 mg X
2 Olanzapine 30 mg X
3 Olanzapine 25 mg X
4 Olanzapine 25 mg X
5 Olanzapine 25 mg X
6 Quetiapine 950 mg X
7 Quetiapine 800 mg X
8 Quetiapine 800 mg X
9 Risperidone 1 mg Risperidone 50 2/52 X
10 Risperidone 50 2/52 Zuclopenthixol 50 mg prn X
11 Olanzapine 20 mg Flupenthixol 70 2/52 √
12 Olanzapine 20 mg Flupenthixol 50 4/52 √
13 Olanzapine 20 mg Flupenthixol 20 2/52 √
14 Olanzapine 20 mg Fluphenazine 50 4/52 √
15 Olanzapine 15 mg Amisulpride 800 mg √
16 Olanzapine 10 mg Amisulpride 1200 mg √
17 Quetiapine 200 mg Pipothiazine palm. 150 2/52 √
18 Quetiapine 600 mg Flupenthixol 250 3/52 √
19 Quetiapine 800 mg Haloperidol 20 mg √
20 Quetiapine 750 mg Haloperidol 6 mg √
21 Clozapine 575 mg Amisulpride 800 mg √
22 Clozapine 700 mg Quetiapine 400 mg √
23 Risperidone 4 mg Fluphenazine 50 1/52 √
24 Fluphenazine 75 1/52 Trifluoperazine 15 mg √
Karen P Hayhurst Date of Report: September 2007
46
Table 22 shows %MaxBNF doses for patients on monotherapy treatment and
patients on combination treatment. The median %MaxBNF dose was again higher in
the co-prescribed group compared with the monotherapy group in both sites
(p=0.005). In the Oldham (intervention) site 86% of patients receiving a high dose
were treated with combination therapy; in the Stockport (control) site this figure was
58%.
Table 22: Post-Intervention Prescribing Audit: %MaxBNF doses
Oldham
(Intervention) site
Stockport
(Control) site
Monotherapy
Group
N=194
Co-prescribed
Group
N=50
Monotherapy
Group
N=213
Co-prescribed
Group
N=35
%MaxBNF
Dose
Mean (SD) 41% (31.45) 93% (56.63) 53% (31.65) 79% (49.42)
Median 36% 97% 50% 72%
Range 1% - 175% 8% – 237.5% 2% – 150% 5% – 177%
Karen P Hayhurst Date of Report: September 2007
47
Summary: Post-Intervention Antipsychotic Prescribing
Oldham (Intervention) Site
Out of a sample of 244 patients, 50 patients (20%) were treated with combination
therapy in the Oldham site following the intervention. Four of these patients were
taking three drugs concurrently. The most used combination was olanzapine with
flupenthixol depot. The use of the CPZEq dose conversion gave a 6% rate of high
dose prescribing; the %MaxBNF dose conversion gave a higher rate of high dose
prescribing of 12%. Treatment with antipsychotics in combination was associated
with significantly higher dose prescribing regardless of the definition used, with
between 86% and 93% of high dose treatment comprised of combination therapy.
Stockport (Control) Site
Of a sample of 248 patients, 35 patients (14%) in the control site were treated with
combination therapy following the intervention period. The most used combination
was olanzapine with flupenthixol depot. The use of the CPZEq dose conversion gave
a 6% rate of high dose prescribing; the %MaxBNF dose conversion gave a higher
rate of high dose prescribing of 10%. Treatment with antipsychotics in combination
was again associated with significantly higher dose prescribing regardless of the
definition used, with between 58% and 71% of high dose treatment comprised of
combination therapy.
Karen P Hayhurst Date of Report: September 2007
48
Effectiveness of Intervention
Rates & Pattern of Combination Prescribing
Oldham (Intervention) Site Pre-Intervention vs. Stockport (Control) Site Pre-
Intervention
Although the rate of combination prescribing in the Stockport (control) site prior to the
commencement of the intervention (16%) was lower than that in the Oldham
(intervention) site of 22%, it did not differ statistically (χ2 =3.211, p=0.073). Different
rates aside, there were similar patterns of co-prescribing in the two sites prior to the
deployment of the intervention package. The majority on combination treatment in
both sites were treated with an SGA oral drug together with an FGA depot, which in
both sites was usually olanzapine together with flupenthixol depot. Four co-
prescribed patients in the Oldham site (7%) received three antipsychotics together,
whereas only one co-prescribed patient (3%) in the Stockport site received three
antipsychotics concurrently.
Pre-Intervention to Post-Intervention change
Rates of combination prescribing in both sites fell by two per cent during the two
time-periods but rates in the Oldham (intervention) site post-intervention (20%) did
not differ statistically from that of the Stockport (control) site (14%, χ2 =3.423,
p=0.064).
Karen P Hayhurst Date of Report: September 2007
49
High Dose Prescribing (Chlorpromazine equivalents)
Oldham (Intervention) Site Pre-Intervention vs. Stockport (Control) Site Pre-
Intervention
Using doses over 1000 mg chlorpromazine equivalents (CPZEq) as the definition for
a high dose, 5% of patients in both sites were treated with a high dose prior to the
use of the intervention. There was a non-significant trend for CPZEq doses in the
Oldham (intervention) site to be lower (Median=333 mg CPZEq) than in the
Stockport/ control site (Median = 400 mg CPZEq) prior to the use of the intervention
(p=0.075). Whereas all patients prescribed a high dose in the Oldham (intervention)
site were taking more than one antipsychotic, four patients in the Stockport (control)
site were prescribed high dose monotherapy (three of these on quetiapine). Three
patients in the high dose group in the Oldham (intervention) site were taking more
than two antipsychotics together (all taking olanzapine plus flupenthixol depot and an
additional oral FGA).
Pre-Intervention to Post-Intervention change
Rates of high dose prescribing rose by one per cent to six percent in both sites
following the intervention period. CPZEq doses were again lower in the Oldham
(intervention) site (Median=333 mg) compared with the Stockport/ control site
(Median=400 mg CPZEq) following the use of the intervention (p=0.081). Similar
differences were seen between the two sites post-intervention as pre-intervention in
patterns of high dose prescribing. All high dose-treated patients in the Oldham
(intervention) site were prescribed more than one antipsychotic drug concurrently,
whereas four patients in the Stockport (control) site were taking high dose SGA
monotherapy. The high dose combination prescribed most often in the Oldham
(intervention) site was olanzapine together with flupenthixol depot; in the Stockport
(control) site the most common combination was quetiapine together with an FGA
depot.
Karen P Hayhurst Date of Report: September 2007
50
High Dose Prescribing (Percentage Maximum BNF Recommended Dose)
Oldham (Intervention) Site Pre-Intervention vs. Stockport (Control) Site Pre-
Intervention
Using the percentage of maximum recommended dose in the BNF (%MaxBNF Dose)
and defining over 100% as a high dose led to 9% of patients in the Oldham
(intervention) site and 10% of patients in the Stockport (control) site being
categorised as in receipt of a high dose prior to the start of the intervention period;
not a statistically significant difference. The median dose rate in the Stockport/
control site (50% of MaxBNF Dose) was higher than that of the Oldham/ intervention
site (40% of MaxBNF Dose, p<0.001).
The two sites had different patterns of high dose prescribing. In Stockport 38% were
receiving high dose monotherapy; in Oldham the rate of such prescribing was 14%.
Three of those on high dose treatment were taking three antipsychotics concurrently
in the Oldham site: none of the high dose treated patients in the Stockport site were
taking more than two drugs together.
Pre-Intervention to Post-Intervention change
Using this definition, the rate of high dose prescribing rose by 3% in the Oldham
(intervention) site (to 12%) and remained at 10% post-intervention in the Stockport
(control) site; not a significant difference.
Karen P Hayhurst Date of Report: September 2007
51
Change in pattern of prescribing
Table 23: Pattern of prescribing: Pre-Intervention to Post-Intervention
Pattern of Prescribing Oldham/ Intervention Site
(N)
Stockport/ Control Site
(N)
Mono � Mono 171 194
Poly � Poly 45 30
Mono � Poly 5 5
Poly � Mono 9 8
Mono � No AP drugs 5 3
No AP drugs � Mono 3 0
Poly � No AP drugs 0 1
No AP drugs � No AP drugs 6 7
Total 244 248
Table 23 illustrates the small proportion of switches from monotherapy to
combination treatment (five patients in each site) during the two time-points. This
figure represents new or inception cases of combination therapy in the two samples.
Karen P Hayhurst Date of Report: September 2007
52
Table 24: High Dose Rates: Pre-Intervention to Post-Intervention
High Dose (CPZEq)
Pattern of High Dose Prescribing Oldham/ Intervention
Site (N) Stockport/ Control
Site (N)
Standard Dose � Standard Dose 229 230
High Dose � High Dose 10 9
Standard Dose � High Dose 4 5
High Dose � Standard Dose 1 4
Total 244 248
A similar low number of patients in each site went from a standard dose to a high
dose (using the CPZEq dose conversion, see Table 24).
Table 25: High Dose Rates: Pre-Intervention to Post-Intervention
High Dose (%Max BNF)
Pattern of High Dose Prescribing Oldham/ Intervention Site (N)
Stockport/ Control
Site (N)
Standard Dose � Standard Dose 213 218
High Dose � High Dose 20 20
Standard Dose � High Dose 9 4
High Dose � Standard Dose 2 6
Total 244 248
Table 25 shows that nine patients in the Oldham site and four patients in the
Stockport site switched from standard dose to high dose treatment (using the %Max
BNF definition) during the course of the study.
Karen P Hayhurst Date of Report: September 2007
53
Pattern of antipsychotic monopharmacy
There was a different pattern of antipsychotic monotherapy in the two sites (see
Tables 3, 4, 13 and 14). A greater proportion of patients were treated with
amisulpride, aripiprazole and clozapine in the Stockport site compared with the
Oldham site (patterns of clozapine prescribing are set out in greater detail in the
following section). Chlorpromazine, flupenthixol depot and fluphenazine depot were
prescribed to a greater proportion of monotherapy-treated patients in the Oldham site
compared with the Stockport site.
Karen P Hayhurst Date of Report: September 2007
54
Clozapine Prescribing Rates
Pre-Intervention
Prior to the start of the intervention, 16% in the Oldham (intervention) site (40
patients) and 22% of the Stockport (control) site (55 patients) were prescribed
clozapine. In the Oldham site, six patients were co-prescribed clozapine; three
together with an oral SGA and three with an oral FGA. Two of these were co-
prescribed clozapine at a high dose. Four patients in the Stockport site were co-
prescribed clozapine; all with an oral SGA. Although the rate of clozapine prescribing
was higher in the Stockport (control) site (22%) than in the Oldham (intervention) site
(16%) it was not statistically so (χ2 = 2.712, p=0.100).
Post-Intervention
Similar rates of clozapine prescribing were seen post-intervention: 16% in the
Oldham site and 22% in the Stockport site. Eight patients were co-prescribed the
drug at follow-up in the Oldham site; five together with an oral SGA and three with
oral FGAs. Four of the eight patients co-prescribed clozapine received it at a high
dose. In the Stockport sample only two patients were co-prescribed the drug at
follow-up; both at high doses. The pre-intervention difference in clozapine rates
between the two sites had grown slightly by the post-intervention stage to a non-
significant trend difference (16% intervention site/ 22% control site: χ2 = 3.579,
p=0.059).
The proportion of prescribing made up of the addition of a second antipsychotic to
clozapine ranged from 6% to 16% of combination-treated patients and ranged from
1% to 3% of the overall sample.
Karen P Hayhurst Date of Report: September 2007
55
Change in pattern of antipsychotic prescribing between the two time-points
Oldham (Intervention) Site
Forty-two patients in the Oldham sample (17%) switched their antipsychotic drug
treatment between the two time-points. The pattern of switches was further explored.
The majority of switches were from one antipsychotic drug supplied as monotherapy
to another; of this category most switches were from one SGA drug to another. In this
site a slightly higher proportion of co-prescribed patients pre-intervention switched
antipsychotic drug treatment (20%) compared with patients treated with
monotherapy; 16% of whom switched drug treatment; not a statistically significant
difference.
A higher proportion of patients receiving treatment with SGA drugs switched
antipsychotic treatment (18%) compared with those on FGA treatment (11% of whom
switched treatment). Again, this was not a statistically significant difference. A similar
proportion of patients taking clozapine (18%) switched drug treatment compared with
patients on non-clozapine SGA treatment (17% of whom switched).
Forty-five patients (18%) had the dose of their antipsychotic drug treatment increased
during the two time-points. Over a half of these (51%) were dose increases of
antipsychotic monotherapy; 20% were dose increases of combination treatment; 20%
were overall dose increases due to a switch in antipsychotic monotherapy and the
remainder (9%) were due to an overall increase in dose due to patients being
switched from monotherapy to combination treatment.
Forty-nine patients (20%) had the dose of their drug treatment decreased during the
two periods. The majority of these (39%) were monotherapy dose decreases; 22%
were due to a switch in monotherapy treatment; 18% were due to patients being
changed from combination therapy to monopharmacy; 14% were dose reductions of
combination treatment and the remainder (6%) were patients switched from
monotherapy to overall lower dose combination treatment.
In the intervention site there were no statistical differences in terms of total converted
doses prior to switching between switchers and non-switchers.
Karen P Hayhurst Date of Report: September 2007
56
Stockport (Control) Site
Forty-one patients in this sample (17%) switched their antipsychotic drug treatment
between the two time-points. The pattern of switches was further explored. The
majority of switches were from one antipsychotic drug to another as monotherapy
(59%) and of this category most switches were from one SGA drug to another one. A
greater proportion of co-prescribed patients pre-intervention switched antipsychotic
drug treatment (35%) compared with patients treated with monotherapy; 13% of
whom switched drug treatment. This was a statistically significant difference (χ2
=11.788, p=0.001).
A greater proportion of patients receiving treatment with SGA drugs switched
antipsychotic treatment (19%) compared with those on FGA treatment (9% of whom
switched treatment); this was not a statistically significant difference (χ2 =2.651,
p=0.104). Examining the group of patients on SGA treatment further, a smaller
proportion of patients on clozapine (8%) switched drug treatment compared with
patients on other non-clozapine SGA treatment (22% of whom switched). This was a
statistically significant difference (χ2 =4.914, p=0.027).
Fifty patients (20%) had the dose of their antipsychotic drug treatment increased
during the two time-points. Over a half of these (52%) were dose increases of
monotherapy treatment; 24% were overall dose increases due to a switch in
monotherapy (the majority from one SGA to another SGA); 8% were dose increases
of combination treatment; 8% were patients switched from one type of co-prescribing
to another; 6% were due to an overall increase in dose for patients switched from
monotherapy to combination therapy and the remainder’s switch from monotherapy
to co-prescribing resulted in an increased overall dose (2%).
Forty-six patients (19%) had the dose of their drug treatment decreased during the
two periods. The majority of these (48%) were monotherapy dose decreases; 22%
due to a switch in monotherapy treatment (most from one SGA to another SGA);
15% were patients switched from combination prescribing to monopharmacy; 9%
were dose reductions of combination treatment and the remainder (7%) were
patients switched from one type of co-prescribed treatment to another.
In terms of total dose, in this site switchers were on a higher antipsychotic dose prior
to switching, both when converted to CPZEq and to %MaxBNF doses. The mean
Karen P Hayhurst Date of Report: September 2007
57
dose of switchers was 542 mg CPZEq, whereas the mean dose of non-switchers was
417 mg CPZEq (a non-significant trend difference, p=0.052). Using the alternative
high dose definition, the mean dose of switchers was 73% of the maximum
recommended BNF dose; the mean dose of non-switchers 55% prior to switching.
This was a statistically significant difference (p=0.003).
In the Stockport site there were a number of statistically significant findings relating to
antipsychotic drug switchers between the two time-points. In this site (but not in the
intervention site) patients most likely to switch drug treatment between the two time-
points were treated with combination therapy, treated with a non-clozapine SGA and
on a higher %MaxBNF dose at the initial audit.
Karen P Hayhurst Date of Report: September 2007
58
Acknowledgements
Thanks must be expressed to the following: Professor Shôn Lewis and Dr. Richard
Drake of the University of Manchester; Dr. Peter Elton and Paul Campbell of Bury
PCT; Lesley Smith and Dr. Di James of Pennine Care NHS Trust; Trevor Smith of
Pennine Care Audit Department; Kristof Seaton and Claire Beattie, Mental Health
Pharmacists at Stepping Hill Hospital and Oldham Royal Hospital respectively; ward
staff at the two sites; medical records’ staff at the two sites; and staff in the Clinical
Governance Department at Stepping Hill Hospital.
Karen P Hayhurst Date of Report: September 2007
59
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