Antipsychotic Prescribing Audit

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


2

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


3

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


4

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


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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.


6

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.


7

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.


9

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.


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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


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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




Olanzapine 44 15 mg 15 mg 5 – 30 mg




Chlorpromazine 1 50 mg -------- --------

Flupenthixol oral 1 3 mg -------- --------


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


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 dec 9 130 1/52 100 1/52 200 3/52 – 250 1/52


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Combination antipsychotic prescribing


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

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SGA o

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FGA d

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FGA d

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FGA o

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SGA o

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SG

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SGA o

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FGA o

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FGA o

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pa

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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 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 20 2/52 Olanzapine 20 + aripiprazole 10

Olanzapine 5 + flupenthixol 160 2/52 Clozapine 600 + risperidone 2


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 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


22


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

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FGA d

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FGA o

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SGA o

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SGA o

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FGA o

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pa

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)


23

Table 6: Stockport (Control) Site: antipsychotic drugs co-prescribed

SGA oral + FGA Depot FGA Depot + FGA Oral



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


24

High Dose antipsychotic prescribing


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 √


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 √


10 Olanzapine 20 mg Flupenthixol 60 2/52 Haloperidol 30 mg √

11 Risperidone 12 mg Risperidone 50 2/52 X


25


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



5 Clozapine 700 mg Quetiapine 400 mg √


7 Clozapine 475 mg Amisulpride 800 mg √



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 √


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).


27


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)


1 Olanzapine 30 mg X









10 Olanzapine 20 mg Amisulpride 400 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 √


18 Clozapine 900 mg Sulpiride 800 mg √






28


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








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













23 Olanzapine 20 mg Flupenthixol 12 mg √

24 Olanzapine 5 mg Haloperidol 45 mg √

25 Pipothiazine palm. 150 2/52 Chlorpromazine 300 mg √



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%


30

Summary: Pre-Intervention Prescribing Audit


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.


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.


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.


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.


33

Monotherapy prescribing


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




Olanzapine 38 12 mg 10 mg 3.75 – 27.5 mg




Chlorpromazine 6 185 mg 100 mg 25 – 350 mg


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


Sulpiride 1 1200 mg -------- --------

Trifluoperazine 1 4 mg -------- --------


Zuclopenthixol dec. 6 590 5/52 200 2/52 100 3/52 – 600 2/52


34


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




Olanzapine 39 16 mg 15 mg 2.5 – 30 mg




Chlorpromazine 1 50 mg -------- --------

Flupenthixol oral 2 4.5 mg 4.5 mg 3 – 6 mg


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


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


35

Combination Antipsychotic Prescribing


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).


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

)


37

Table 15: Oldham (Intervention) Site: antipsychotic drugs co-prescribed

SGA oral + FGA Depot SGA oral + SGA oral



Olanzapine 20 + flupenthixol 60 2/52 Clozapine 300 + amisulpride dose NK







Olanzapine 5 + flupenthixol 160 2/52 Olanzapine 15 + aripiprazole 10

Olanzapine 2.5 + flupenthixol 50 4/52 SGA oral + FGA oral


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 30 2/52 + sulpiride 400

Flupenthixol 50 2/52 + promazine 100

Flupenthixol 50 2/52 + promazine 50

Fluphenazine 25 3/52 + chlorpromazine


38


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

)


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 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


40

High Dose antipsychotic prescribing


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)












11 Flupenthixol 80 1/52 Chlorpromazine 300 mg √





41


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




4 Amisulpride 1200 mg X





9 Quetiapine 800 mg Haloperidol 20 mg √



12 Quetiapine 200 mg Pipothiazine palm. 150 2/52 √

13 Flupenthixol 100 1/52 Trifluoperazine 5 mg √



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


43

High Dose Antipsychotic Prescribing


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).


44

Table 20: Oldham (Intervention) Site: high doses (>100% Max BNF Dose)


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










14 Olanzapine 15 mg Pipothiazine palm. 60 2/52 √






20 Olanzapine 15 mg Risperidone consta 50 2/52 √

21 Olanzapine 20 mg Chlorpromazine 150 mg √








29 Clozapine 700 mg Sulpiride 400 mg Haloperidol 2 mg √


45


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










10 Risperidone 50 2/52 Zuclopenthixol 50 mg prn X







17 Quetiapine 200 mg Pipothiazine palm. 150 2/52 √









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%


47

Summary: Post-Intervention Antipsychotic Prescribing


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.


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.


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).


49

High Dose Prescribing (Chlorpromazine equivalents)


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).


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.


50

High Dose Prescribing (Percentage Maximum BNF Recommended Dose)


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.


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.


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.


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.


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.


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.


55

Change in pattern of antipsychotic prescribing between the two time-points


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.


56


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


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.


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.


59

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Documents

Antipsychotic Prescribing Audit