Combining

antipsychotics

Can it be justified ?

workbook
POMH UK
P R E S C R I B I N G O B S E R VAT O R Y
F O R M E N TA L H E A L T H
 Can it be justified ?

DEBIT

Acknowledgements
This workbook is based on the text of a workbook developed for the DEBIT study
by Dr A Thompson MRCPsych, MSc (Department of Psychiatry, University of Bristol)
and Dr P Rogers R.M.N., PhD, (Institute of Psychiatry, London).

The DEBIT project was undertaken with a UK Department of Health grant;

the lead investigator was Professor Glynn Harrison.

This workbook was printed thanks to funding from Oxleas NHS Foundation Trust.
 Introduction
Thank you for taking the time to work through this workbook.

The use of combinations of antipsychotics (‘antipsychotic polypharmacy’) has become

a major issue in clinical practice.

This workbook is designed for all those involved in prescribing, dispensing or

administering antipsychotic drugs, and is also relevant to all staff who discuss this
medication with patients. It will to help you to review the use of combined
antipsychotics in your own clinical practice, and provides an update of the latest
evidence in this area.

The workbook is yours to keep and we hope you will find it useful and refer to it again
in the future.

If you complete all of the tasks in the workbook you can receive a certificate of
participation in this POMH-UK audit project. Appendix 4 contains full details of how to
do this.

Carol Paton and Thomas Barnes

Joint Heads of POMH-UK
Can it be justified ?
 Contents Page
Section 1: An overview Page
What do clinical guidelines recommend?……………………………........ 5
What happens in practice?...................................................................... 7
How often are combinations of antipsychotics prescribed?………......... 7
Why are combinations of antipsychotics used?………………………..... 8
How good is the evidence that two antipsychotics are better than one? 9
Summary…………………………………………………………………... 11
What are the potential problems with combined antipsychotics?…....... 11
How good is the evidence?……………………………………………....... 12
What do patients think?.......................................................................... 13
Prescribing and administering of medicines………………………........... 14

Section 2: Routes to the use of combined antipsychotics

Understanding combined antipsychotics; the four steps ...................... 17
The SOMETHING that happens ………………………............... 18
The INTERPRETATION ………………………………….............. 19
The PERMISSION GIVING THOUGHTS ………….................... 21
The ACTION…………………………………………...................... 21
Section 3: Breaking the cycle
Begin now……………………………………………………………........... 22
Work as a team……………………………………………………….......... 23
Be aware of your interpretation of events………………………….......... 23
Use the alternatives (Non-pharmacological)…………………………..... 24
Use the alternatives (Pharmacological)……………………………......... 28
As required (PRN) medication………………………………………......... 28
Be aware of giving yourself permission thoughts…………………......... 29
Summary…………………………………………………………............. 30
References……………………………………………………................. 31
Appendix 1:
Recommended dose ranges for individual antipsychotics..................... 33
Appendix 2:
Antipsychotic dose ‘ready reckoner’...................................................... 35
Appendix 3:
Summary of the evidence supporting the use of combined antipsychotics.. 37
Appendix 4:
How to obtain a certificate of your participation in this topic................. 39
Your Notes............................................................................................. 40
 Section 1: An overview
What do guidelines recommend?

Antipsychotic medication is the mainstay of treatment for psychotic disorders such as

schizophrenia. NICE has produced:

1. A clinical guideline for the treatment of schizophrenia. You can find

this at www.nice.org.uk/pdf/cg1niceguideline.pdf. NICE have also
produced a training package to help you understand how the guideline
was developed and to take you through the main recommendations
(www.rcpsych.ac.uk/cru/sts/index.htm).

2. A clinical guideline for the management of violence. You can find this
at www.nice.org.uk/cg025niceguideline.pdf

3. A health technology appraisal for the use of atypical antipsychotics

in schizophrenia (HTA 43). You can find this at
www.nice.org.uk/page.aspx?o=38947

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TASK A

This task could be shared between the clinical team with each member looking at
one guideline and sharing their findings with others. This task will take time; you
can progress through the workbook while your team is still working on this task.

Look at the HTA and the NICE guidelines listed opposite. What are the key
recommendations for the use of antipsychotic drugs?

1. In the management of behavioural disturbance?

2. To treat an acute episode of schizophrenia?

3. In treatment resistant schizophrenia?

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What happens in practice?

In line with published prescribing guidelines such as those developed by NICE, most
people with a psychotic illness only receive one antipsychotic at a time (‘antipsychotic
monotherapy’). However, the use of more than one antipsychotic medication
(‘combined antipsychotics’) for an individual patient is a common clinical strategy.
There is a lack of good evidence for the therapeutic effectiveness of this approach,
and concerns about possible harm.

How often are combinations of antipsychotics prescribed?

National and international

surveys have consistently
found that the use of
more than one
antipsychotic medication
is common.

For example, a recent UK

survey by the Royal
College of Psychiatrists’
Research Unit found that
nearly half (48%) of those
patients on
antipsychotics were
prescribed two or more
(Harrington et al 2002a).
There was a wide variation between Trusts in the number of patients prescribed
combinations (Harrington et al, 2002b). Combined antipsychotics were more
commonly used in patients who were young, male, detained under the Mental Health
Act, had a diagnosis of schizophrenia and occupied a rehabilitation or forensic bed.
These factors accounted for only a small proportion of the variance between services;
much was unexplained.

Prescribing in this way is not only seen in the UK. In a US survey, over 50% of all
patients with persistent psychotic disorders in extended care units received more than
one antipsychotic (Ereshefsky, 1999).

Canadian research found that 27.5% of discharged patients diagnosed with

schizophrenia were prescribed antipsychotic combinations (Procyshyn et al, 2001).

In the US, a recent study of polypharmacy within the California Medicaid program
showed that 11% of patients received two antipsychotic for more than 60 consecutive
days (Stahl et al., 2002).

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Why are combinations of antipsychotics used?

Combinations of antipsychotics are usually used for one of the following reasons:

Reasons given by clinicians

1. To manage acute behavioural disturbance (oral PRN)

2. To manage acute behavioural disturbance (IM ‘Rapid Tranquillisation’)

3. To manage chronic behavioural disturbance

4. To manage relapse in a patient previously stabilised on a single antipsychotic
5. While switching from one drug to another
6. To speed up the onset of effect or enhance the size of the therapeutic effect
7. To target different symptoms/symptom domains
8. To reduce side effects
9. To allow administration by a different route
10. Individual patient’s/carer’s choice
11. Treatment resistant schizophrenia

TASK B:

Look through the medicine cards on your ward today. How many patients are
prescribed combinations of antipsychotics (include PRN prescriptions whether they
have been administered or not)?

Choose one patient who is currently being prescribed multiple antipsychotics, and
consider the following questions:

1. Why has more than one antipsychotic been prescribed for this patient?

2. How good do you think the evidence is to support prescribing in this

way?

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8
How good is the evidence that two antipsychotics are better than one?

1. In managing acute behavioural disturbance (oral PRN)?

Poor. Several studies show that some oral antipsychotics are effective in managing
acute behavioural disturbance (eg Currier & Simpson, 2001). These studies recruited
patients who presented when acutely unwell. The majority were not taking regular
antipsychotics. The effectiveness of oral PRN in patients who are already taking a
regular antipsychotic drug is very poorly studied.

2. In managing acute behavioural disturbance (IM ‘RT’)?

Poor. NICE recommends IM olanzapine or IM haloperidol in patients whose behaviour
is driven by psychosis. Trial evidence is in patients not receiving regular antipsychotics
(eg Wright et al, 2001; Alexander et al, 2004).

Patients who are acutely disturbed are at increased risk of having electrolyte
disturbances (secondary to dehydration) and a prolonged QTc interval on their ECG
(a risk factor for developing a cardiac arrhythmia; Hatta et al, 1999). Street drugs can
precipitate acutely disturbed behaviour. These drugs are commonly used and some,
such as cocaine and methadone can also increase the risk of cardiac arrhythmias.

In the short term, a benzodiazepine alone may be as effective and safer than an
antipsychotic.

The manufacturers of IM olanzapine warn against the use of IM olanzapine in higher

than recommended doses (20mg/day including oral) and in combination with
benzodiazepines (see www.medicines.org.uk).

3. In managing chronic behavioural disturbance?

None. There is no evidence from systematic studies to support the use of combinations
of antipsychotics. There is some evidence that clozapine alone is useful in the
management of chronic aggression (eg Glazer & Dickson, 1998).

4. In managing relapse in a patient previously stabilised on a single antipsychotic?

Poor. There are no studies of antipsychotic combinations. One unpublished study

found that increasing the dose of an established antipsychotic in a relapsed patient
is no more effective than continuing with the same dose.

5. While switching from one drug to another?

Limited. The dose of some antipsychotics (eg clozapine) needs to be increased slowly
and cross titration is sensible. This should be complete in 4-6 weeks. For drugs that
do not require initial dosage titration (eg olanzapine and aripiprazole), a washout period
or tapering of the dose is probably unnecessary when switching.

6. To speed up the onset of effect or enhance the size of the therapeutic effect?
Poor. High initial doses do not produce an earlier or better response (eg Rifkin et al,
1991). There is no convincing evidence that combinations improve outcome (eg
Centorrino et al, 2004). The sedation and physical slowing (parkinsonism) caused by
high doses of antipsychotics are side effects that should not be confused with
antipsychotic effect.

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7. To target different symptoms/symptom domains?
Poor. Antipsychotics have differential sedative effects but there is limited evidence to
support clinically meaningful differences on positive, negative or affective symptoms.

8. To reduce side effects?

Poor. In most patients it is likely that side effects will be increased (Centorrino et al,
2004).

9. To allow administration by a different route?

Uncertain. Very few antipsychotics are available in short acting IM, depot or
oro-dispersible formulations. Reasonable attempts should be made to choose and use
one route of administration. Combinations may be useful in some clinical
circumstances.

10. Individual patient’s/carer’s choice?

Limited. Choice is not real choice unless it is informed. If the patient can understand
the potential risks/side effects and benefits of combining antipsychotics and can come
to a reasoned decision, this should be supported.

11. Treatment resistant schizophrenia?

Equivocal. Combinations involving clozapine are better studied than combinations
involving any other drug. Some studies show a modest clinical benefit from adding a
second antipsychotic such as sulpiride (Shiloh et al, 1997) or risperidone (Jossiassen et
al, 2005) to clozapine. Other studies have found no benefits (eg Yagcioglu et al, 1995).

If other antipsychotic treatments, including clozapine and clozapine augmentation,

have failed to produce any improvement, a time-limited, individual trial of combined
antipsychotics may be one of very few treatment options left (Stahl 2002)

TASK C:

Take a few minutes to think about the strength of the evidence for combinations of
antipsychotics.

1. Do you think that combinations of antipsychotics should be used as

often as they are?

2. Why do you think this?

10
 Summary
What is being advised?

In the UK, the BNF, the NICE guideline for the treatment of schizophrenia and the
Maudsley Prescribing Guidelines (Taylor et al, 2005) all advise against the routine
prescribing of more than one antipsychotic. Similar guidelines/consensus statements
from three other English speaking countries (the American Psychiatric Association
1997; RANZCP 2003, working group for the Canadian Psychiatric Association and the
Canadian Alliance for Research on schizophrenia 1998) provide similar advice.

A summary of the evidence from which this guidance is derived can be found in
Appendix 3.

Are combinations ever justified?

From existing guidelines and the available evidence there are three situations where
antipsychotic polypharmacy may be justified:-

1. Where patients are being changed over from one antipsychotic to

another. In such cases a short crossover period (of four to six weeks for
example) is acceptable.

2. When giving a more sedating and/or injectable antipsychotic drug to

someone who is very agitated and who is already receiving another
antipsychotic drug on a regular basis (“rapid tranquillisation”).

3. In cases where the patient is receiving clozapine but has not achieved
adequate symptom control.

What are the potential problems with combined antipsychotics?

The following problems can all occur:

Potential problems
1. Difficulty in attributing any benefit
2. Higher than necessary total dosage
3. Complex regimen increasing the risk of non-adherence
4. Increased cost
5. Increased side effects (acute or longer term)
6. Drug interactions (pharmacokinetic and pharmacodynamic)
7. Increased duration of hospitalisation
8. ?? Increased mortality

11
How good is the evidence?

1. Difficulty in attributing any benefit

Not knowing which antipsychotic has helped in the short term may lead to the patient
continuing to receive a combination/high dose unnecessarily in the long term.

2. Higher than necessary total dosage

There is no evidence that high doses of antipsychotics are more effective than standard
doses (Lehman et al, 1998). The major cause of high dose prescribing is combinations
of antipsychotics (Harrington et al, 2002a). Appendix 1 shows the maximum dose of
commonly used antipsychotic drugs and how using more than one antipsychotic can
lead to the use of a high dose.

TASK D:

Use the ‘ready reckoner’ in Appendix 2 to calculate the total dose of antipsychotic
prescribed for a patient on combined antipsychotics. A sample calculation can be
found in Appendix 1.

3. Complex regimen increasing the risk of non-adherence

In the general population, simple medication regimens involving a small number of
tablets are more likely to be taken than complex regimens (Chen, 1991). This is
particularly likely to be true in patients with schizophrenia, who may be disorganised,
lack motivation and have cognitive deficits. Poor adherence to medication is a major
cause of relapse and hospitalisation.

4. Increased cost
An average NHS Trust spends about 3% of its total income on medicines and this
spend is currently rising by 10-12% a year. Atypical antipsychotics are expensive;
most cost £100-£200 for a month’s treatment.

5. Increased side effects (acute or longer term)

All antipsychotics have side effects. Profiles differ. One study shows that patients who
receive combinations have 50% more side effects than those who receive only one
drug (Centorrino et al, 2004).

6. Drug interactions (pharmacokinetic and pharmacodynamic)

The safety of combinations of antipsychotics has not been studied systematically but
there are many published case reports of serious side effects such as cardiac
arrhythmias (Chong et al, 1997) and neuroleptic malignant syndrome (Kontaxakis et al,
2002). Interactions may be pharmacokinetic (where one drug interferes with the
absorption, metabolism or excretion of another drug) or pharmacodynamic (where two
drugs have opposing or additive effects on physiological functioning). For example,
there are case reports of risperidone causing a significant rise in clozapine serum levels
(a pharmacokinetic interaction; eg Koreen et al, 1995) and a combination of haloperidol
and olanzapine causing severe parkinsonian symptoms (a pharmacodynamic
interaction; Gomberg, 1999).

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7. Increased duration of hospitalisation
One study found that the average length of hospital stay was more than 50% longer in
patients who were prescribed combinations of antipsychotics (Centorrino et al, 1994).

8. ?? Increased mortality
One study found that patients who were prescribed combinations were twice as likely
to die over a 10 year period as those who took one antipsychotic (Waddington et al,
1998).

A summary of the potential problems associated with combined antipsychotics can be

found in Appendix 3.

What do patients think?

Service user groups and national service user bodies have expressed concerns
regarding the side effects of medication and antipsychotic polypharmacy. The National
Schizophrenia Fellowship document “A Question of Choice” (2000) surveyed patients’
views on medication and other interventions for mental illness. They found that over
16% of respondents with schizophrenia were prescribed two or more antipsychotics.

They found, as expected, that side effects were widely experienced and that almost
half the respondents said that;

• The side effects of their medication affected their ability to live their
everyday life
• They had stopped their medication due to side-effects.

TASK E:

Identify a patient currently on the ward who is prescribed a complex medication

regimen.

1. How many tablets does the patient have to take each day?

2. How many times a day is medication prescribed?

3. If you were prescribed these medications, how would you make sure
that you remembered to take them all, at the right time each day?

13
Prescribing and administration of medicines

All professionals are responsible for their own actions irrespective of what others say
or do, or the pressure on services.

It should be standard practice for prescribers to document the rationale for using
combined antipsychotics in clinical notes along with a clear account of any benefits
and side effects.

For nurses, The Nursing and Midwifery Council ‘Guidelines for the Administration of
Medicines’ states that:

“As a registered nurse you must maintain your professional knowledge and
competence” and that “You are personally accountable for your practice. This means
that you are answerable for your actions and omissions, regardless of advice or
directions from another professional”

“The administration of medicines is an important aspect of the professional practice of

persons whose names are on the Council’s register. It is not solely a mechanistic task
to be performed in strict compliance with the written prescription of a medical
practitioner. It requires thought and professional judgement…..”

“In exercising your professional accountability in the best interests of your patient you
must:

• Know the therapeutic uses of the medicine to be administered, its normal

dosage, side effects, precautions and contra-indications
• Have considered the dosage, method of administration, route and timing
of the administration in the context of the condition of the patient and
co-existing therapies.”

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TASK F:

Patients should receive only one antipsychotic drug unless they meet one of the
three exceptions.

Can you remember what the three exceptions are?

1.

2.

3.

Can you think of any other reasonable exceptions?

TASK G:

Look at the medicine cards of all patients currently on the ward.

Do all patients who are prescribed combined antipsychotics meet one of the
three exceptions?

15
 Section 2: Routes to the use of combined antipsychotics
A study conducted by the University of Bristol identified four factors that clinicians
(nurses and doctors) felt were important in moulding their practice;

1. The individual clinician’s acquired knowledge and learning

2. The individual clinician’s interpretation of that knowledge and learning

3. The individual clinician’s own past experiences

4. The influence of the social and clinical context in which the individual
clinician practices.

1. Acquired “knowledge” and learning (“What I have been told”)

This theme relates to personal prescribing and administration habits that have been
shaped over the years from accumulated “knowledge” gathered from various sources
(eg medical and nursing training, opinions of respected colleagues, journals, internet,
conferences etc).

2. Interpreted knowledge (“What I make of what I have been told”)

This theme relates to how individual clinicians interpret their acquired knowledge.
Two clinicians can interpret similar information in two entirely different ways. When
discussing a case where two separate antipsychotic medications were being
administered, one consultant psychiatrist reported the following interpretation:

“Conventional clinical wisdom is that you try another compound as

different as possible to the first compound, and if the first compound
is a compound that targets D2 receptors, then it seems to me to
make sense that the second compound should be a compound
that has fairly low potency for D2 receptors”

However, another consultant psychiatrist reported the following interpretation:

“It [combining antipsychotics] really does not make a lot of

pharmacological sense to me”

3. Individual past experiences (“What I have learnt from my personal

experiences”)
This theme relates to how clinical decisions are often guided by an individual clinician’s
own personal experiences. This leads to drug preferences. These drug preferences can
outweigh the evidence base. One consultant psychiatrist reported:

“I have only used clozapine on a total of three occasions. I had a very bad experience;
the first ever patient I put on it ended up in ICU… so I was obviously unlucky with that
but it stayed in my mind so that has made me reluctant to go down the clozapine line”

16
One nurse also gave an example of the influence of experience when discussing a
hypothetical admission:

“…I do not prescribe or diagnose, my job is to nurse and I am very aware of that but
I have got experience enough to know what does and does not work”

4. The social and clinical context (“What are the other pressures I face in the real
world”)
This theme relates to what clinicians described as the difference between the ideal and
the real world of patient care. Many factors are at play such as “inherited cases” with
established treatment patterns, patients requiring rapid tranquillisation, and practical
issues relating to time and other resources affecting prescribing decisions. One
consultant psychiatrist gave an example of this: -

“It is not the way I would want to ideally treat them

[prescribing more than one antipsychotic] but it is very
difficult when patients you have inherited have been on that long term”

Understanding combined antipsychotics: The four steps

Given that most clinicians understand that there is no good evidence to support the
increased efficacy of combined antipsychotics and that prescribing in this way
increases the risk of an adverse event, it should be a general rule in psychiatric clinical
practice that antipsychotic polypharmacy (apart from the three exceptions noted)
should not occur.

However, although this is the general rule, in certain cases, this general rule is broken
or “over-ridden” and combined antipsychotics are used OUTSIDE of the three
exceptions. A chain of events is necessary to influence the prescribing and
administration of antipsychotic combinations. This pathway is illustrated below in its
simplest form.

Something happens

Interpretation

Permission-giving thoughts

Action

17
The “SOMETHING” that happens

The “something” can be viewed as the “trigger”. This trigger invariably acts as a
catalyst and begins a sequence of events. It does not always result in the use of more
than one antipsychotic but often does.

There are many examples of the ‘something’ from clinical practice, obvious ones
include: -

• A patient displaying agitated behaviour

• A self-harming incident
• A request from carers or staff to improve symptoms
• A violent incident
• An incident of damage to property
• An absconding incident
• A refusal to take medication
• A verbal “outburst”
• A known violent patient being newly admitted

TASK H:

List up to three ‘somethings’ that have happened while you have been on duty over
the last four weeks:

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The “INTERPRETATION”

The interpretation of the “something” is crucial. The interpretation will often determine
whether the next stage of the pathway is reached. Clinicians can interpret the same
occurrences differently. Often these interpretations are “personal” in their content.

However, for individuals these interpretations can be consistent and, with some
personal effort be predictable.

Possible interpretations that occur following violence, agitated behaviour and a carer’s
request to improve acute symptoms are shown below.

Common interpretations by ward staff of a violent incident.

The “Trigger” Common interpretations

It was preventable. I should have...

A violent incident
His medication is not working
I have failed my team

It was my fault
If I do nothing and this happens again then it will
be my fault
He will really hurt someone next time
The other patient’s will not be able to cope with this
We have not got the staff to manage this

These interpretations can lead to a range of feelings including a sense of not being in
control, fear, anxiety, anger, apprehension, guilt, etc.

Common interpretations of a patient displaying agitated behaviour.

The “Trigger” Common interpretations

If I do not do anything he/she will become
A patient displaying agitated violent
behaviour
If I do not do anything someone will get hurt

Lorazepam will only disinhibit him/her further

19
Common interpretations of a carer asking you to improve the patient’s symptoms
quicker.

The “Trigger” Common interpretations

If I do not do anything then I will lose the trust of

Carers requests something to the carer
improve ‘voices’ more rapidly
If I do nothing and he/she fail’s to improve I will
look bad in front of peers/carer

I am not making a difference, we are failing

Again, these interpretations can lead to a range of feelings including a sense of not
being in control, fear, anxiety, anger, apprehension, guilt, etc.

The way that these interpretations and feelings are managed will also to a large extent
determine what is done next.

In the recent Bristol study, one nurse gave an example of this:

“I was really concerned that his voices would go from being good voices to bad voices
and he could hit out because he did have a history of it. Now if I thought he was
escalating I would start giving PRN medication, anything………”

A consultant psychiatrist was quoted as saying:

“The patient is coming to you and saying I am no better; what do you do? If you try and
educate a patient who is distressed and is not responding to treatment about the
dangers of polypharmacy the patient might consider that you are uncaring and you are
denying treatment”

These interpretations lead us to move onto the next stage of the pathway – giving
ourselves permission.

TASK I:

Think about a recent situation where a patient refused to take oral medication, and
write a brief summary of how you interpreted this.

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The “PERMISSION-GIVING THOUGHTS”

‘Giving ourselves permission’ is crucial in the chain of events leading to prescribing

combined antipsychotics. It allows a clinician to break the general rule that two
antipsychotics should not be prescribed at the same time. Giving ourselves permission
allows us to justify to others and ourselves this course of action.

The “ACTION”

The action is the prescribing and administration of more than one antipsychotic
medication (outside the three exceptions), even if for just one day.

21
 Section 3: Breaking the cycle
This section will provide six simple steps to breaking the cycle of using combinations
of antipsychotics.

1. Begin now

The longer you over-ride the general rule of not using more than one antipsychotic,
the harder it will be to change your practice.

• Make an effort to re-examine those patients who are currently prescribed

combinations of antipsychotics. Think about the evidence base. Do all
patients meet one of the three exceptions? If not, could anything different
be done to avoid using combinations of antipsychotics?
• Determine a plan (both medical and non-medical) with your clinical
colleagues for future cases. This means developing a new “general rule”.
Using the guidance available in this booklet, it may be possible to develop
an agreed team plan for managing and caring for new cases.

TASK J:

1. Write down three things you could do to reduce the use of combined
antipsychotics on your ward.

2. Write down three obstacles you might face.

3. Identify how you would manage these obstacles if and when they
occurred.

4. Identify a specific start date for trying to change your practice in this
way.

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2. Work as a team
Although it is usually the doctor who prescribes, the medication regimen of an inpatient
should be regularly reviewed by the clinical team, and this usually occurs at the ward
round. Psychiatry is one of the few specialties in medicine where multidisciplinary
decisions are the norm. Prescribing decisions should be, and are, influenced by all
team members. Each professional should also have a defined role in the process. For
example, if a doctor prescribes a combination of antipsychotics and the patient suffers
from intolerable side-effects, the ward staff have a key role in influencing the decision to
alter the prescription. Conversely, the doctor must not feel pressured into prescribing
when he/she is reluctant, and when the patient could be managed without resorting to
combinations of antipsychotics, or other medication.

On acute adult psychiatry wards there will undoubtedly be pressure on bed resources
and therefore pressure to improve symptoms quickly. This can lead to combinations of
antipsychotics being prescribed. Evidence also shows that high doses of medication do
not speed up the remission of symptoms. Staffing difficulties can lead to problems or
worries about disturbed behaviour from patients. Doctors and nursing staff feel these
pressures but in different ways. Doctors may feel pressured into prescribing, or to try to
‘do something’; nurses may feel they need to have medication at hand ‘just in case’ or
to ‘protect other patients’. However, the patient may suffer most in terms of side effects.
There are times when prescribing more than one antipsychotic is unavoidable (such as
acute disturbance leading to rapid tranquillisation) but the number of these occasions
can be reduced with the techniques discussed below.

The decision to start someone on more than one antipsychotic should NEVER be taken
lightly and it is best if the whole treating team are involved in that decision.

3. Be aware of your interpretations of events

Be aware of how events are interpreted. A common example is the interpretation of
behavioural disturbances. It is rare for a single cause to lead to a single event.
However, often you will come across situations where medication is seen as the only
answer to behavioural disturbances. This “all or nothing” thinking often can introduce
cognitive bias as it ignores the “grey areas”. Such thinking also has a tendency to
ignore alternative ways of looking at a problem and therefore new solutions.

A person may be agitated, aggressive or violent towards others. However, even with the
more classically considered violence-inducing psychotic symptoms (eg command
hallucinations) a direct cause and response should not be assumed. For example, it is
possible that the person was agitated and feeling stressed, which in turn increased the
urgency of the command hallucinations and that these two things combined led to the
violence? Even if the patient had heard command hallucinations instructing violence,
why did they comply? It is important to gain a full as possible understanding of the
psychotic symptoms and how emotional states (eg anger) and the environment
(eg high noise levels) influence these psychotic symptoms.

The Royal College of Psychiatrists (Wing et al 1998) guidelines on the management of

imminent violence highlight environmental factors, overcrowding (or an inability to find
somewhere that is private), lack of privacy, lack of activities and long waiting times to
see staff as important precipitants of violence.

23
Social factors, such as poor communication between patients and staff, and weak
clinical leadership, may contribute to feelings of frustration and tension among all
parties. Dealing with these issues in advance may reduce the risk of violence and
aggression (Wing et al 1998).

NICE have developed a treatment guideline for the management of violence. The
importance of de-escalation skills are emphasised.

As mentioned before, there are other important ‘somethings’ that happen. The
cross-over period when switching from one antipsychotic drug to another deserves
special mention. Patients often get caught in the “cross-over trap” and left on two
antipsychotic medications if they improve during the cross-over period. A common
interpretation is that it is the combination that has benefited them and polypharmacy
continues. Alternative interpretations could be that the improvement is due to
monotherapy alone (a time effect) or a relative dose increase has occurred due to
drug-drug interactions which improves the efficacy of the initial drug.

4. Using the alternatives (non-pharmacological)

Coping strategies

Assist the patient to identify simple but effective coping strategies when their
symptoms become distressing. This involves two stages:

1. Checking all the strategies that the patient has previously tried and then
rating these strategies on a 0-8 scale of how effective they have been
(0 = no effect up to 8 = complete cessation of symptoms)

2. Having identified the effective coping strategies, work out together how
the patient can use these in future situations.

This can be a challenge when patients are in an acute inpatient setting as the
environment may in fact provide its own constraints (eg long walks may not be
possible). However, if you examine the core characteristics of the successful coping
strategy then you may be able to try a similar approach.

Example

Although not always possible, long walks may allow the patient to have time alone,
without interruption or demands on their attention. In addition, they may allow time
away from a negative environment, or the exercise may divert their attention. By
examining the core characteristics of successful coping strategies it should be possible
to come up with coping strategies that have a similar effect and a jointly agreed plan for
the future. For example, the intervention could involve going to a guaranteed quiet area,
where the patient is free from any interruption and where they can do some gentle
exercise.

24
Alternative strategies

Other approached which can be clinically useful, are:

The use of noise reducing earplugs.

The use of loud music with headphones so as not to disturb others. Many
patients report that loud music helps drown out distressing voices and that it can
divert their attention. However, loud music can often be a source of conflict
between staff and patients as it disturbs other residents, especially at night. It
may help to have some relatively cheap personal music players with headphones
available for ward issue. It is helpful to ask patients to “experiment” with different
“types” of music. Many patients report that although loud music can divert their
attention, the type of music can also influence their mood and agitation. For
example, heavy bass music with aggressive and provocative lyrics can cause
further agitation. It is often helpful to give patients a selection of music tapes and
ask them to try out different types of music the next time they are hallucinating.
The patient is then helped to determine what noise level and type of music has
the best effect for them.

Access to and support in listening to a relaxing tape, somewhere quiet and

away from disruption.

Access to and support in engaging in non-aggressive physical exercise.

The key to successful coping strategies is that the patient has several to choose from.
Therefore, it is helpful to equip patients with at least three options, so if one fails, they
have something else that they can try. The more strategies available, the more in
control and the less distressed they will feel.

Early warning signs for future behavioural disturbances

This involves using the previous or last episode of behavioural disturbance as a means
of identifying the early signs that something is wrong. In effect, you can use previous
behavioural disturbances to try and reduce the chances of further episodes.

Identifying first signs

This involves the doctor or nurse sitting down with the patient to try and understand
from the PATIENT’S PERSPECTIVE how and why the last behavioural disturbance
occurred.

• What was the first sign to the patient that something was wrong?
• Is this a consistent first sign?
• Is this a usual first sign?
• In future, what could they use as their FIRST SIGN?

Remember, first signs can be many things. For example, feelings of frustration,
clenched fists, something a voice says, a certain thought that starts their paranoia, the
way someone talks to them, having a request turned down that was important to them,
the way other patients treat them, etc.

25
Having identified this first sign, then establish what the patient tends to do when they
notice it.

• Do they tend to react impulsively?

• Do they try to suppress it and, if so, how long can they manage to do that
before acting?

This information provides both the patient and you with an idea of the “window of
opportunity” that you have between first sign recognition and action. For patients who
report impulsive action, you may be limited in the interventions that you can try.

Agreeing future responses to the appearance of first signs

After identifying the first signs, and time available to intervene, the next stage is asking
the patient to consider what they could do themselves immediately they notice their
first signs to try and avoid the situation deteriorating.

• What can they try to do the next time this happens?

• If that fails, what else might be worth trying?
• What would the patient prefer the clinician’s role to be when they are
doing this?
• Should they actively engage with the patient, or merely observe from a
distance?

It is useful to have medication as a part of this plan, and to agree at what stage the
patient should ask for it or the nurse should suggest it. It is also useful to consider the
previous section on coping strategies when designing interventions to break the cycle
between first signs and behavioural disturbance.

When medication is used, NICE recommends that patients should be encouraged to

record their account of the incident in their clinical notes. This account may give staff
valuable insight into precipitants and useful management strategies.

Reviewing progress

Remember that it is very important to regularly review with the patient how well an
intervention has worked. Formally evaluate it at least weekly in the early stages. Try
and build into the intervention the expectation that the patient will inform staff
whenever they have used the agreed plans so that they can be supported and helped
further. If the intervention that a patient chooses to break their cycle is self-initiated
then it may be that they are successfully doing this three times a day but no one else
knows about it. When evaluating whether an intervention is successful or not, try to
see what could be done next time to improve it further.

Interventions that are known to be helpful should be recorded in the patient’s clinical
notes. Consideration should be given to including this information in advance
directives.

26
TASK K:

1. Identify a patient who has recently been troubled and distressed by

psychotic symptoms.

2. Write down any strategies you can think of, other than medication, that
may have helped.

3. Write down any barriers or obstacles you can think of that could stop
you trying these alternative strategies.

4. Write down what steps you could take to manage these barriers if and
when they occur.

5. Make a plan to implement these strategies with that patient (including a

specific time frame to carry it out).

27
Using the alternatives (pharmacological)

1. Avoid ‘as required’ (PRN) prescription of antipsychotic medication for

sedation in psychotic patients who are on established medication doses
(including depot medication) and who are no longer in the acute phase of
illness. (Using this strategy alone would half the number of patients
receiving combined antipsychotics). If PRN sedation is required, a
benzodiazepine or promethazine are effective alternatives.

2. Make sure you do not forget to stop the first antipsychotic drug after
cross-tapering to a new one. Do not assume that improvement during
cross-tapering is due to combination treatment.

3. Consider other reasons for poor response with monotherapy

(eg non-adherence, side effects, drug interactions, continued drug/alcohol
or other substance use). Antipsychotics have limited therapeutic effects in
many patients. Do not assume that high doses or combinations will lead to
greater improvement. If combinations are used, always document the
symptoms targeted, and document the side effects before and after
starting the combination to ensure that unsuccessful treatments are not
continued.

4. Consider longer trials of monotherapy or the use of clozapine in

treatment resistant cases.

As required medication (PRN)

1. Consider all non-pharmacological interventions.

2. If PRN (as required medication) is required in a patient with active

psychosis who is receiving a regular antipsychotic, use a
benzodiazepine (eg lorazepam) or the same antipsychotic for both
regular and PRN. Make sure the PRN prescription is time limited and
the indication is clearly written on the drug chart.

3. If PRN is required for a patient where there is no diagnosis of

psychosis, first consider a benzodiazepine (eg lorazepam). Make sure
the PRN prescription is time limited.

4. In cases when PRN medication is required for rapid tranquillisation, first

consider lorazepam. In the rare cases where lorazepam is not indicated,
consider haloperidol or olanzapine (see NICE clinical guideline, 2002).
Make sure the PRN prescription is time limited.

28
5. Being aware of giving yourself “permission thoughts”

Giving ourselves permission to break the rule of antipsychotic monotherapy can, if we

are not challenged by anyone about it, become easier each time we do it and become
a habit. The problem with such habits is that fewer and fewer “permission giving thoughts”
are required each time. Hence, the exception may slowly but surely become a rule.

Perhaps the general rule of no more than one antipsychotic at a time (apart from the
exceptions) has lost some of its authority. Given how commonly combinations are
used, this will continue until one of two things happens:

1. The lack of evidence for the effectiveness of combined antipsychotics

persuades clinicians to make a concerted effort to re-introduce the rule
(prescribe antipsychotic monotherapy).

2. Serious adverse consequences of antipsychotic polypharmacy occur

which reinforce the need for the general rule.

TASK L:

1. Identify the last patient to whom you administered an antipsychotic

combination (outside of the three exceptions).

2. How or why did you over-ride the rule not to prescribe or administer
antipsychotic polypharmacy (outside of the three exceptions)?

3. Work out two ways in which you can manage these permission-giving
thoughts when they occur in future.

29
 Summary
This workbook has been provided for you to reconsider your own clinical practice as
it relates to combining antipsychotics. It provides you with an update about the latest
evidence on the prescribing and administering of antipsychotic medication.

Although it may feel like it is not the most important area of your practice that needs
reviewing, putting it off further will only lead to a short term avoidance of the problem,
and in the long term may increase the likelihood that combining antipsychotics will
occur.

This workbook offers some simple steps that can be taken. It will not be possible to
implement this guidance overnight. However, by beginning to discuss the issues in
clinical team meetings, by thinking about current cases that could be reviewed,
and by examining the alternatives you may well find that, slowly but surely, practice
is changing for the better.

30
References:
Alexander J, Tharyan P, Adams C et al, 2004. Rapid tranquillisation of violent or agitated patients in a
psychiatric emergency setting. British Journal of Psychiatry 185,63-69.

Centorrino F, Goren JL, Hennen J et al., 2004. Multiple versus single antipsychotic for hospitalised
psychiatric patients ; case-control study of risks versus benefits. American Journal of Psychiatry 161,
700-706.

Chen, A., 1991. Noncompliance in community psychiatry: a review of clinical interventions. Hospital and
Community Psychiatry 42, 282-287.

Chong SA, Tan CH, Lee HS., 1997. Atrial ectopics with clozapine-risperidone combination. Journal of
Clinical Psychopharmacology 17, 130-131.

Currier GW & Simpson GM., 2001. Risperidone liquid concentrate and oral lorazepam versus
intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. Journal of
Clinical Psychiatry 62, 153-157.

Ereshefsky, L., 1999. Pharmacologic and pharmacokinetic considerations in choosing an antipsychotic.

Journal of Clinical Psychiatry 60, 20-30.

Freudenreich, O. & Goff, D. C., 2002. Antipsychotic combination therapy in schizophrenia. A review of
efficacy and risks of current combinations. Acta Psychiatrica Scandinavica 106, 323-330.

Glazer WM & Dickson RA, 1998. Clozapine reduces violence and persistent aggression in
schizophrenia. Journal of Clinical Psychiatry 59 (Suppl.3), 8-14.

Gomberg, R.F., 1999. Interaction between olanzapine and haloperidol (letter). Journal of Clinical
Psychopharmacology 19, 272-273.

Harrington, M., Lelliott, P., Paton, C., et al, 2002a. The results of a multi-centre audit of the prescribing
of antipsychotic drugs for inpatients in the UK. Psychiatric Bulletin 26, 414-418.

Harrington, M. & Lelliott, P., 2002b. Variation between services in polypharmacy and combined high
dose of antipsychotic drugs prescribed for inpatients. Psychiatric Bulletin 26, 418-420.

Hatta K, Takahashi T, Nakamura H et al., 1999. Laboratory findings in acute schizophrenia. Relevance
to medical management on emergency admission. General Hospital Psychiatry 21, 220-227.

Josiassen RC, Ashok J, Kohegyi E et al., 2005. Clozapine augmented with risperidone in the treatment
of schizophrenia : a randomized, double-blind, placebo-controlled trial. American Journal of Psychiatry
162, 130-136.

Koreen, A. R., Lieberman, J. A., Kronig, M. & Cooper, T. B., 1995. Cross-tapering clozapine and
risperidone. American Journal of Psychiatry 152, 1690.

Kontaxakis VP, Havaki-Kontaxi BJ, Stamouli SS et al., 2002. Toxic interaction between risperidone
and clozapine: a case report. Progress in Neuropsychopharmacology and Biological Psychiatry 26,
407-409.

Lehman AF, Steinwachs DM, and co-investigators of the PORT project, 1998. Translating research
into practice: The schizophrenia patient research outcome team (PORT) treatment recommendations.
Schizophrenia Bulletin 24,1-10.

National Institute for Clinical Excellence (NICE), 2002. Guidance on the use of newer (atypical)
antipsychotic drugs for the treatment of schizophrenia. London: NICE.

31
National Institute for Clinical Excellence (NICE), 2002. Schizophrenia: core interventions in the
treatment and management of schizophrenia in primary and secondary care. Clinical Guideline 1, NICE.

National Schizophrenia Fellowship, 2000. A Question of Choice. London: NSF.

Procyshyn, R.M., Kennedy, N.B., Tse, T. & Thompson, B., 2001. Antipsychotic polypharmacy: A survey
of discharge prescriptions from a tertiary care psychiatric institution. Canadian Journal of Psychiatry 46,
334-339.

Rifkin A, Doddi S, Karajgi B et al, 1991. Dosage of haloperidol for schizophrenia. Archives of General
Psychiatry 48, 166-170.

Royal College of Psychiatrists, 1993. Consensus Statement on the Use of High Dose Antipsychotic
Medication. Council Report CR26. London: Royal College of Psychiatrists.

Shiloh, R., Zemishlany, Z., Aizenberg, D., et al., 1997. Sulpiride augmentation in people with
schizophrenia partially responsive to clozapine. British Journal of Psychiatry, 171, 569-573.

Taylor D, Paton C, Kerwin R, 2005. The Maudsley Prescribing Guidelines. 8th Edition. Martin Dunitz,
London.

Stahl, S.M., 2002. Antipsychotic polypharmacy: evidence based or eminence based? Acta Psychiatrica
Scandinavica, 106, 321-322.

Tyson, S. C., Devane, C. L. & Risch, S. C., 1995. Pharmacokinetic interaction between risperidone and
clozapine. American Journal of Psychiatry, 152, 1401-1402.

Waddington, J.L., Youssef, H.A. & Kinsella, A., 1998. Mortality in schizophrenia: antipsychotic
polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective
study. British Journal of Psychiatry, 173, 325-329.

Wing, J.K., Marriott, S., Palmer, C. & Thomas, V., 1998. The Management of Imminent Violence:
Clinical Practice Guidelines to Support Mental Health Services. Occasional Paper OP41. London: Royal
College of Psychiatrists.

Wright P, Birkett M, avid SR et al, 2001. Double-blind, placebo controlled comparison of intramuscular
olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia. American
Journal of Psychiatry 158, 1149-1151.

Yagcioglu AEA, Akdede BBK, Turgut TI et al, 2005. A double-blind controlled study of adjunctive
treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety.
Journal of Clinical Psychiatry 66, 63-72

32
 Appendix 1
Understanding Maximum Doses of Antipsychotics

Every drug has a recommended dosage range. This recommended range is determined
after careful consideration of the efficacy and toxicity data for each drug. Doses below
the recommended range are unlikely to be effective. Doses above the recommended
range have not been demonstrated to have greater efficacy and are generally
associated with an unacceptably high burden of side effects.

The recommended dosage range for each drug is reflected in the summary of product
characteristics (SPC) for that drug. All SPCs are available at www.medicines.org.uk.
Recommended dosage ranges can also be found in the BNF.

The table below shows the maximum recommended dose for commonly used
antipsychotic drugs.

Maximum
Short acting Maximum BNF
Oral BNF
intramuscular daily dose
Antipsychotics daily dose
injections (mg)
(mg)

Amisulpride 1,200 Chlorpromazine 200

Aripiprazole 30 Haloperidol 18

Chlorpromazine 1,000 Olanzapine 20

Clozapine 900

Flupentixol 18 Intermediate
acting
intramuscular
injections

Fluphenazine 20 Zuclopenthixol 150mg

(‘acuphase’)

Haloperidol 15

Olanzapine 20 Long acting Maximum BNF

intramuscular weekly dose
injections (mg)
Quetiapine 750 Flupentixol 400

Quetiapine (mania) 800 Fluphenazine 50

Risperidone 16 Haloperidol 75

Sulpiride 2,400 Pipotiazine 50

Trifluoperazine 50 Risperidone 25

Zuclopenthixol 150 Zuclopenthixol 600

33
It is possible for a patient to receive a high (above maximum) dose in two ways:

1. A single drug prescribed in a dose above the BNF maximum eg olanzapine

30mg.

2. A combination of antipsychotic drugs when:

a. The dose of each drug is converted to a percentage of the maximum dose

for that drug
b. And the percentages are added together
c. Giving a value above 100%.

For example amisulpride 800mg plus risperidone 8mg each day. The maximum dose of
amisulpride is 1200mg, so 800mg is 67% of the maximum. The maximum dose of
risperidone is 16mg, so 8mg is 50%. When 67% and 50% are added together, the
total dose of 117% is considered to be a high dose.

34
 Commonly used Percentage of BNF maximum adult daily dosage
antipsychotics
Oral/IM: dose in mg/day
Depot: dose in mg/week 5 10 15 20 25 30 33 40 45 50 55 60 67 70 75 80 85 90 95 100%
Amisulpride Oral 400 600 800 1000 (83%) 1200
Aripiprazole Oral 10 15 20 30
Chlorpromazine Oral 100 300 500 600 750 1000
Clozapine Oral 150 (17%) 300 400 (44%) 450 600 900
Haloperidol Oral 1.5 3 5 (17%) 10 15 20 25 (84%) 30

Olanzapine Oral 5 7.5 (37.5%) 10 15 20

Quetiapine Oral 75 100 150 300 375 450 600 750*

Risperidone Oral 2 (12.5%) 4 6 (37.5%) 8 12 16

Sulpiride Oral 400 (17%) 800 1200 1600 2000 2400

35
Trifluoperazine Oral 5 10 15 20 25 30 35 40 45 50**

Zuclopenthixol Oral 20 (13%) 30 50 100 150

Appendix 2

Chlorpromazine IM 25 (12.5%) 50 100 150 200

Haloperidol IM 5 (28%) 10 (56%) 15 (84%) 18

ANTIPSYCHOTIC DOSAGE READY RECKONER

Olanzapine IM 5 10 15 20

Flupentixol Depot 20 40 100 200 300 400

Fluphenazine Depot 12.5 25 37.5 50

Haloperidol Depot 25 37.5 50 75

Pipotiazine Depot 12.5 25 37.5 50

Risperidone Long 12.5 18.75 25

acting
Zuclopenthixol Depot 100 (17%) 200 300 400 500 (83%) 600

*750mg/day maximum for schizophrenia, 800mg/day maximum for mania: % given are for schizophrenia treatment.
**There is no maximum dose for trifluoperazine stated in the BNF or SPC; 50mg is used by convention.
 Less commonly used Percentage of BNF maximum adult daily dosage
antipsychotics

Oral/IM dose in mg/day 5 10 15 20 25 30 33 40 45 50 55 60 67 70 75 80 85 90 95 100%

Benperidol Oral 0.5 0.75 1 1.5
Flupentixol Oral 3 (17%) 6 9 12 15 18
2.5 7.5 12.5
Fluphenazine Oral (12.5%) 5 (37.5%) 10 (62.5%) 15 17.5 20
Levomepromazine Oral 100 250 500 750 1000
Pericyazine Oral 75 100 150 200 300

Perphenazine Oral 4 (17%) 12 16 24

Pimozide Oral 2 4 6 8 10 12 20

36
Promazine Oral 150 300 400 800
(18.5%) (37.5%)
Sertindole Oral 4 (17%) 12 16 24

Zotepine Oral 50 (17%) 75 100 150 200 300

25 50 100 150 200
Levomepromazine IM (12.5%)
25 50 100 150 200
Promazine IM (12.5%)

To calculate the total antipsychotic percentage dose prescribed for an individual, use the table to determine the
percentage of BNF maximum dosage for each antipsychotic that is prescribed, and then sum the percentages. For
example, for a person prescribed clozapine 400mg a day and oral haloperidol 5mg PRN up to 3 times a day, the
respective percentages would be 44% and 50%, giving a total antipsychotic prescribed dosage of 94% .

Combining Antipsychotics?
Why?
To manage acute
behavioural disturbance
(oral PRN)
To manage acute
behavioural disturbance
(IM ‘RT’)
To manage chronic
behavioural disturbance
To manage relapse in a
patient previously
stabilised on a single
antipsychotic
While switching from one
drug to another
To speed up the onset of
effect or enhance the size
of the therapeutic effect
To target different
symptoms/symptom
domain
To reduce side effects
To allow administration
by a different route
Individual patient’s/carer’s
choice
Treatment resistance
Overall there is a lack of evidence supporting benefit
Appendix 3
How good is the evidence that two antipsychotics
are better than one?
Poor Some studies show that some oral antipsychotics are
effective in managing behavioural disturbance.
See caveats under IM below.
Poor NICE recommends IM olanzapine or haloperidol in
patients whose behaviour is driven by psychosis.
Trial evidence is in patients not receiving regular
antipsychotics. A benzodiazepine alone may be as
effective and safer.
None Some evidence supports the use of clozapine
(monotherapy) in managing chronic aggression.
Poor One study has shown that increasing the dose of an
established antipsychotic in a relapsed patient is no
more effective than continuing the same dose.
Combinations have not been systematically studied.
Limited The dose of some antipsychotics (eg clozapine) needs
to be increased slowly and cross titration is sensible.
This should be complete in four to six weeks.
Poor Response takes time. High initial doses do not speed
up the onset of response. Combinations have not
been studied. There is no evidence that combinations
improve outcome.
Poor Antipsychotics have differential effects on sleep but
there is limited evidence to support clinically
meaningful differences on core psychotic symptoms.
Poor In most patients it is likely that side effects will be
increased.
Uncertain Very few antipsychotics are available in short acting
IM, depot or orodispersible formulations. Reasonable
attempts should be made to choose and use one
route of administration. Combinations may be useful
in some clinical circumstances.
Limited Choice is not real choice unless it is informed. If a
patient can understand the potential benefits and risks
of antipsychotic combinations and come to a
reasoned decision, this should be supported.
Equivocal Combinations of clozapine should be considered
before those involving other antipsychotic drugs.
37
What are the potential
problems?
Difficulty determining cause and effect
Higher than necessary total dosage
Complex regimen increasing the risk of
non-adherence
Increased cost
Increased side effects (acute or long term)
Drug interactions (pharmacokinetic and
pharmacodynamic)
Increased duration of hospitalisation
?? Increased mortality
How good is the evidence for this?
Not knowing which antipsychotic has helped
in the short term may lead to the patient
receiving a higher than necessary dose (and
more side effects) in the longer term.
There is no good evidence that high doses of
antipsychotics are more effective than
standard doses. The major cause of high dose
prescribing is combinations of antipsychotics.
In the general population, simple medication
regimens involving a small number of tablets
are more likely to be taken than complex
regimens. This is particularly likely to be true
in patients with schizophrenia who may be
disorganised, lack motivation and have
cognitive deficits.
Some antipsychotics are expensive (£100-
£200/month). Two cost more than one.
All antipsychotics have side effects. Profiles
differ. One study showed that patients who
received combinations had 50% more side
effects than those who received one
antipsychotic drug.
The safety of combinations of antipsychotics
has not been studied systematically but there
are many published case reports of serious
side effects such as cardiac arrhythmias and
neuroleptic malignant syndrome.
One study found that the average duration of
hospital stay was more than 50% longer in
patients who were prescribed combinations of
antipsychotics.
One study found that patients who were
prescribed combinations were twice as likely
to die over a 10 year period than those who
took one antipsychotic.
38
 Appendix 4
If you would like to receive a certificate of participation in this POMH-UK topic:

1. Complete tasks A-L.

2. Complete your name and address below

Name:…………………………………………..

Address:………………………………………..

…………………………………………………..

…………………………………………………..

…………………………………………………..

…………………………………………………..

3. Send your completed booklet, along with a stamped (A4) self addressed
envelope to:

Prescribing Observatory for Mental Health,

Royal College of Psychiatrists Research Unit,
Standen House,
21 Mansell Street,
London E1 8AA

Your completed booklet and certificate

of participation will be returned to you.

39
0
Can it be justified ?
Your notes

40
Your notes

41
Can it be justified ?

42
 POMH-UK
The Prescribing Observatory for Mental Health (POMH-UK)
is a national quality improvement programme open to all
specialist mental health services in the UK. POMH-UK
works with mental health services to help improve
prescribing practice in discrete areas ('Topics') of
prescribing practice. Each Topic involves an audit cycle.
Participating teams collect data for a baseline audit of
their practice. This is followed by teams engaging in a
number of quality improvement interventions and the audit
cycle is completed with a follow-up audit of practice.

This workbook is one of the quality improvement

interventions that have been made available for
Topic 1; Prescribing of high dose and combination
antipsychotics for patients on adult acute and
psychiatric intensive care wards.

POMH-UK is based at the

Royal College of Psychiatrists Centre
for Quality Improvement, 4th Floor,
Standon House, 21 Mansell Street,
London, E1 8AA.

Te l : 0 2 0 7 9 7 7 6 6 4 0 Fax: 020 7481 4831

POMH UK
P R E S C R I B I N G O B S E R VAT O R Y
F O R M E N TA L H E A L T H