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ANTIPSYCHOTICS IN CLINCAL
PRACTICE: Guidelines for safe and
effective use in adults with
schizophrenia and includes
information on the use in early onset
psychosis in adolescence
Medicines Management
Guideline
Staff group to whom it
applies:
All prescribers, pharmacy and clinical
staff within the Trust
Distribution:
The whole Trust
How to access:
Intranet
Issue date:
Version 4.2
March 2013
Next review:
March 2015
Approved by:
Drug and Therapeutics Sub
Committee
Approvals EMT
Developed by:
Lynn Haygarth, Chief Pharmacist
Kate Dewhirst, Deputy Chief
Pharmacist
Director leads:
Medical Director
Contact for advice:
[email protected]
Document name:
1
CONTENTS
ABBREVIATIONS USED IN THIS DOCUMENT ................................................... 3
FORMULARY CHOICES FOR ANTIPSYCHOTICS ............................................... 4
IMPORTANT POINTS FOR PRESCRIBERS ....................................................... 5
ALGORITHM FOR THE DRUG TREATMENT OF ADULTS WITH SCHIZOPHRENIA ..... 6
INTRODUCTION ......................................................................................... 8
BACKGROUND INFORMATION ON SCHIZOPHRENIA ........................................ 8
GENERAL PRINCIPLES OF TREATMENT ........................................................ 9
ANTIPSYCHOTICS ..................................................................................... 11
Atypical antipsychotics ....................................................................... 12
Commonly used typical antipsychotics ............................................. 13
Prescribing recommendations for Early-Onset Psychosis in
Adolescents ......................................................................................... 14
Antipsychotic Drug Interactions......................................................... 15
Depot antipsychotics and long acting injectables ............................ 16
Risperidone depot/Paliperidone depot .............................................. 18
CLINICAL QUERIES PROFORMA ................................................................. 22
PHYSICAL HEALTH MONITORING ................................................................ 23
REFERENCES ........................................................................................... 26
APPENDIX 1
HIGH DOSE ANTIPSYCHOTIC MEDICATION .................................................... 27
APPENDIX 2
EQUALITY IMPACT ASSESSMENT TOOL....................................................... 30
APPENDIX 3
CHECKLIST FOR THE REVIEW AND APPROVAL OF PROCEDURAL DOCUMENT .. 31
APPENDIX 4
VERSION CONTROL SHEET........................................................................ 32
2
In line with NICE Guidance No. 82 issued in 2009
ABBREVIATIONS USED IN THIS DOCUMENT:
ADRs
BNF
BP
D&T
DVLA
ECG
EPSE
GP
LFT
RLAI
NICE
NSF
SPC
U&E
SWYPFT
Adverse drug reactions
British National Formulary
Blood Pressure
Drug and Therapeutics Sub Committee
Driver and Vehicle Licensing Agency
Electrocardiogram
Extra pyramidal Side Effects
General Practitioner
Liver Function Test
Risperidone Long Acting Injection
National Institute for Health and Clinical Excellence
National Service Framework
Summary of Product Characteristics
Urea and Electrolytes
South West Yorkshire Partnership NHS Foundation Trust
RELATED TRUST GUIDELINES
Reference document for physical health monitoring
Protocol for rapid tranquilisation
Guidelines for the pharmacological treatment of bipolar disorder
Aripiprazole communication
Patient information leaflet – antipsychotics for use in psychosis and mania
Patient advice leaflets from the Choice and medication website on individual antipsychotics
Clozapine policy
Psychotropics in pregnancy and breastfeeding
Dementia guidelines
Olanzapine communication
3
FORMULARY CHOICES OF ANTIPSYCHOTICS
Risperidone oral (lower cost
generic)
Amisulpride (lower cost generic)
Olanzapine (lower cost generic)
Quetiapine Immediate release
(lower cost generic)
Quetiapine XL Higher cost so
reserve for existing users
Aripiprazole –high cost
Classified as GREEN with
specialist initiation within
Calderdale Kirklees and
Wakefield. These should be
initiated in secondary care but
prescribing can be continued in
primary care.
These are
subject to
shared care
guidelines with
Amber status in
Barnsley.
Zotepine is no longer available in the UK
Clozapine is recommended for
treatment resistant schizophrenia
Prescribing restrictions apply. Classified
as RED –prescribing must take place in
secondary care.
The following oral typical antipsychotics are in current use:
Chlorpromazine
Classified as GREEN status –no
prescribing restrictions.
Haloperidol
Sulpiride
Zuclopenthixol
Trifluoperazine is no longer available
The following depot antipsychotics are in current use:
Zuclopenthixol
Classified as GREEN with
Classified as RED in
specialist initiation status
Barnsley
Flupentixol
with
in
the
local
health
Fluphenazine
economy – these should be
Haloperidol
initiated in secondary care
Pipothiazine
and can be prescribed in
primary care
The following are restricted use only
Risperidone depot
Classified as RED –prescribing must take place in
Paliperidone depot
secondary care
Available via trust clinical queries mechanism section 17
medicines code
For full prescribing information please refer to full Summary of Product Characteristics, and the current BNF.
4
IMPORTANT POINTS FOR PRESCRIBERS
Arrangements for physical health monitoring need to be considered when prescribing
antipsychotics. See Trust reference document for physical health monitoring in mental
health.
The side effects, cost and licensed indications of the antipsychotic should be considered
when prescribing. When prescribing an antipsychotic for the first time, wherever possible,
prescribe a generic antipsychotic. All the atypicals with the exception of aripiprazole are now
available as generic products.
Having considered the NICE Guideline for Schizophrenia (CG82), Bipolar Disorder (CG38)
and large naturalistic studies such as the Clinical Antipsychotic Trials of Intervention
Effectiveness (CATIE), we concluded there is no clinical reason why not to endorse the
prescribing of the ‘generic’ atypical antipsychotics amisulpride, olanzapine, quetiapine
immediate release and risperidone as first line, in preference to ‘non generic’ atypical
antipsychotics.
If aripiprazole is prescribed, the rationale for this should be documented in the notes Service users should be involved in the decisions relating to treatment and be informed of
the potential risks and benefits.
Risperidone and amisulpride have a low acquisition cost and are available as generics but
have risks of dose related EPSE and prolactin elevation.
Olanzapine has now become a generic preparation with a lower acquisition cost. The
orodispersible preparation continues to be high cost in the community so ensure patients on
orodispersible are reviewed before discharge and prescribe plain tablets wherever possible.
It has been linked to weight gain and therefore the metabolic syndrome.
Quetiapine has now become generic for both the immediate release and XL preparations.
However the cost of the XL preparation is still high so consider immediate release for new
users. There are no liquid or orodispersible preparations so quetiapine should NOT be
prescribed for persons with swallowing difficulties.
Aripiprazole has a higher acquisition cost and the cost increases dramatically with dose
increases. It should usually only be prescribed at doses up to 15mg only as above this there
is limited evidence of efficacy and a dramatic cost increase.
Clozapine remains the antipsychotic of choice for treatment resistant schizophrenia. It
should be considered whenever there has been no response to an adequate trial of two
antipsychotics, one of which should be an atypical.
Typical depot antipsychotics should be tried where there is a service user preference or
compliance need. Pipothiazine palmitate has shown fewer EPSE’s in clinical practice.
Risperidone depot has not shown any proven therapeutic advantage but is a considerable
cost pressure to the organisation. All current prescriptions should be reviewed every six
months to ensure continued response to treatment.
Paliperidone depot is now available. The use is restricted within the Trust. It should not be
considered for use until after a traditional depot antipsychotic has been tried or this is
contraindicated. In addition there must have been an adequate response to oral risperidone.
As a monthly injection with no cold chain it has advantages for service users over
risperidone depot.
5
ALGORITHM FOR THE DRUG TREATMENT OF ADULTS WITH SCHIZOPHRENIA
Newly diagnosed schizophrenia
 Treat with atypical antipsychotic
at minimum effective dose
Evaluate over 6-8 weeks
 Increase gradually to required
dose to within BNF limits
Previously diagnosed schizophrenia
Effectively treated but experiencing
unacceptable side effects
 Review dosage & concomitant
therapies
 Consider alternative antipsychotic
treatment with different side effect
profile
Refer to chart for use of antipsychotic drugs
Persistent non-compliance
Change to long acting injections
 Use lowest therapeutic dose at
maximum allowable intervals
(unless practical issues demand
otherwise)
 Adjust dose only at 2-3 monthly
intervals
Lack of satisfactory clinical improvement despite
sequential use of recommended doses for 6-8 weeks of at
least two antipsychotics, at least one being an atypical
 Review diagnosis
 Check compliance
Remains treatment resistant
Poor compliance and/or non responder
Consider review of diagnosis /
formulation
Consider alternative antipsychotic
with a different profile
 Alternative atypical
OR
 Typical antipsychotic
Treatment resistant schizophrenia
Effectively treated / Not experiencing
unacceptable side effects
 Continue with sole antipsychotic
therapy (2-5 years recommended by
NICE)
 Withdrawal from antipsychotic
medication should be undertaken
gradually whilst regularly monitoring
signs & symptoms for evidence of
potential relapse
 Continue to monitor for side effects
especially EPSE
 Monitor compliance
 Consider treating Parkinsonism side
effects with anticholinergic drugs as
necessary but withdrawal should be
attempted after 2-3 months without
symptoms
 Continue to encourage comprehensive
package of care which addresses
individual’s clinical, emotional & social
needs
Consider clozapine
 Extreme caution in elderly / special risk groups
 Titrate slowly to 300-400mg/day & then by 25-50mg
increments to give a plasma level above 250g/l
 Assess over 6 months
 Maintain patient in secondary care
 Immediate differential white cell count is necessary if
signs or symptoms of infection develop
Ineffective / Experiencing unacceptable side effects
 Agranulocytosis
- Stop treatment
- Follow appropriate monitoring service advice
 With other side effects consider risk/benefit ratio
options
- Dose reduction
- Adjunctive therapies
 If ineffective consider unproven therapies
- The choice of drugs will be partly based on clinical
experience & the most recent scientific evidence.
(This might include adding an additional
antipsychotic or sodium valproate)
6
General Practitioners have an important
role in the prompt identification,
treatment, referral & continuing shared
care of patients with psychotic
symptoms.
In particular the monitoring of physical
healthcare.
Choice of treatment should be based on
patient factors, e.g.
 Informed patient consent
 Previous response
 Side effects
 Co-morbid psychiatric or medical
condition
 Concurrent drug therapy
 Metabolic changes associated with age,
gender, ethnicity
 Lower doses in older people
 Consider age limits of licence
 Assess efficacy & side effects
 Consider use of recognised rating scales
Risk assessment
 To self
 To others
 Neglect/exploitation
Choosing an antipsychotic:
The choice of an antipsychotic will
depend on a number of factors
 Risperidone is well tolerated at less
than 6mg/day in adults, 4mg/day
maximum in older adults. It has a low
cost and a low incidence of
cardiotoxicity. It may cause mild
hypotension, mild weight gain &
prolactin elevation. It may cause dose
related EPSE’s.
 Sulpiride and Amisulpride has a low
cost and a low incidence of
cardiotoxicity, sedation, EPSE’s &
weight gain but a high incidence of
prolactin elevation.
 Olanzapine has a low incidence of
cardiotoxicity, EPSE’s & prolactin
elevation but may cause
hyperglycaemia, moderate sedation &
weight gain.
 Typical antipsychotics are
characterised by relatively high risk of
EPSE’s and prolactin elevation. Some
are available as depot preparations.
Costs are low. Incidence of weight gain
and metabolic syndrome vary but may
be less than some atypicals.
 Aripiprazole has a low incidence of,
weight gain, EPSE’s, cardiotoxicity &
hyperprolactinaemia.
 Quetiapine has a low incidence of
EPSE’s, cardiotoxicity &
hyperprolactinaemia.
Good Practice Guidelines
 Consider advance directives
 Patient should ideally be prescribed only one
antipsychotic, preferably in single dose form
 Lowest possible effective dose should be used.
Patients should be given an adequate trial on low
doses before any further increases. This applies to
both atypical & typical drugs
 Anticholinergic drugs should be given for
Parkinsonism or dystonia but withdrawal should be
attempted after 2 months without symptoms
 Anticholinergics are liable to misuse & impair
memory
 Treatment in consultation with user, carer &/or
advocate at all stages
 Doses to be within BNF limits. If above BNF limits
refer to consensus statement from the Royal College
of Psychiatrists
 BNF advice on prescribing in older adults
 Where more than one antipsychotic is considered
appropriate the most cost effective should be used
7
1.
INTRODUCTION
This document is produced in line with NICE1, 2 Guidance issued in 2002 and updated
March 2009. The National Institute for Health and Clinical Excellence (NICE) is part of the
NHS. It produces guidance for both the NHS and patients on medicines, medical
equipment, diagnostic tests and clinical and surgical procedures and where they should
be used.
The D&T (2003) produced an algorithm which reflects key points of the NICE guidance
and accompanies this document. The guidelines have been further reviewed by the D&T
to incorporate newly licensed products and current evidence on safety and efficacy of
antipsychotics.
The changes in the NICE guidance for 2009 reflect that both typical and atypical
antipsychotics should be available as they are equally effective but incur different side
effects.
The atypical antipsychotics cause less EPSE’s and less sedation than the typical
antipsychotics. They are better tolerated and have an improved safety profile although
they are not without their individual side effect profiles, in particular in relation to metabolic
processes.
Clozapine is proven to be effective in treatment-resistant schizophrenia. Atypical
antipsychotics were more expensive and this has led to a growing debate about cost
effectiveness. However less expensive generic preparations of amisulpride, olanzapine,
quetiapine immediate release and risperidone are now available and these should be
considered as first line choices.
Aripiprazole costs more and if chosen the dose and preparation should be carefully
considered. Risperidone depots and paliperidone depot are the most expensive option
and the use of these is restricted with the Trust.
2.
BACKGROUND INFORMATION ON SCHIZOPHRENIA
1 in 100 of the population will suffer from schizophrenia at some point in their lives. The
incidence of schizophrenia is higher in the homeless and in people living in deprived
urban areas. The consequences of schizophrenia include deterioration in school and
work performance, social isolation and poverty.
15% of people with schizophrenia commit suicide and the standardised mortality rate is 24 times higher than that of the general population. 45% of people with schizophrenia also
have concurrent physical morbidity.
Compliance with treatment is poor (50% do not adhere to treatment in the short term) and
this should be considered in cases of relapse and poor response to treatment.
Almost half of the people with schizophrenia lose contact with the mental health services
and are cared for solely in primary care.
8
3. GENERAL PRINCIPLES OF TREATMENT
3.1
The choice of antipsychotic medication should be made jointly by the individual
and the clinician responsible for treatment based on an informed discussion of the
relative benefits of the individual medications and their side-effect profiles. The
views of the individual’s advocate or carer should be considered where
appropriate.1
3.2
Service users, carers and advocates should be given adequate information about
their treatment options including medication. Service users should be reminded of
their duty to inform the DVLA and insurers of any change in their health, and
implications for health and safety at work.
3.3
When full discussion between the clinician responsible for treatment and the
individual concerned is not possible, in particular in the management of an acute
psychotic episode or an acute exacerbation of schizophrenia, the oral atypical
antipsychotics should be considered as the treatment options of choice because of
the lower potential risk of extra pyramidal side effects (EPSE). In these
circumstances, the views of the individual’s carer or advocate should be
considered where possible and appropriate. Although there are limitations with
advanced directives regarding the choice of treatment for individuals with
schizophrenia, it is recommended that they are developed and documented in the
individual’s care programme wherever possible.1
3.4
Non-pharmacological treatments should be considered as well as antipsychotic
medication.
3.5
Service users and their carers should be involved in the choice of treatment.
 Give patients information on side effects and efficacy so that they can choose a
medication that suits their lifestyle.
3.6
Make service users aware of the effects of alcohol, tobacco, prescribed or over the
counter medicines and illicit substances on their prescribed mental health
medicines.
3.7
Before patients are commenced on antipsychotics they should have an
appropriate assessment including psychiatric history, mental state examination,
physical examination and appropriate investigations. The nature of this
assessment will depend on the individual clinical circumstances. The clinician must
be satisfied that the antipsychotic will be well tolerated, safe and appropriate to the
clinical condition.
 An ECG must be taken prior to prescribing an antipsychotic for all inpatients
and other at risk patients.
 Use only one antipsychotic and prescribe within BNF limits. Short term cross
tapering for change over of medication is acceptable. Avoid co-prescribing of
typical and atypical antipsychotics.
 Results of the Prescribing Observatory for Mental Health (POMH) national audit
showed a high incidence of co-prescribing on inpatients units in the Trust.
3.8
The choice of antipsychotic will depend on a number of factors including
pharmacological considerations, previous response to treatment, previous side
9
effects, concomitant medication and medical conditions, adherence to treatment
plan and the ability to swallow tablets.
 If an antipsychotic is used, start with a minimally effective dose and increase
gradually as necessary depending on clinical response. Short-term adjunctive
therapies may initially be necessary e.g. for sedation.
 Caution should be exercised when treating service users with potential
metabolic change related to age, gender and ethnicity.
 After commencing treatment, the clinical response and side effects should be
carefully monitored and recorded (e.g. with appropriate rating scales).
 Trial of any antipsychotic should be for at least 4-6 weeks unless there are
serious adverse effects.
 Antipsychotics should be withdrawn gradually.
3.9
Physical health should be regularly monitored (at least once a year) especially for
antipsychotic induced adverse physical health effects:





Focus on cardiovascular disease and lipid monitoring
Measure weight routinely due to risk of weight gain particularly with atypical
antipsychotics
Monitor for metabolic syndrome and in particular risk of diabetes. 2 (e.g. blood
glucose, blood pressure etc).
Agreement should be reached with the service user, multi-disciplinary team and
the GP as to who will co-ordinate this monitoring and where it will be carried
out.
Abnormal results should be acted upon and referral made for treatment as
necessary.
See table 1 and the reference document for physical health monitoring.
3.10
Service users commenced on antipsychotics should be reviewed on a regular
basis and this should include good documentation and an assessment of
adherence. Clear and effective communication with service users, carers and all
appropriate multidisciplinary professionals is essential. Service users who fail to
attend clinics or other settings should be followed up to clarify reasons for this.
3.11
If compliance with oral treatment is identified as an issue in the individual’s risk
assessment, check the individual’s patient record to see if depot preparations have
been considered by the clinician responsible for treatment.2
3.12
Clozapine should be available for the management of treatment resistant
schizophrenia/psychosis at the earliest opportunity. Registration with the
appropriate monitoring service is mandatory. See the full Trust guidance on the
use of clozapine.
10
4. ANTIPSYCHOTICS
For full prescribing information please refer to full Summary of Product Characteristics,
and the current BNF.





There is now no distinction made by NICE between typical and atypical antipsychotics
(as equally cost effective and no major differences in side effects).
When prescribing an atypical antipsychotic for the first time, wherever possible,
prescribe a generic antipsychotic e.g. amisulpride, olanzapine, quetiapine or
risperidone oral.
Consider the side effect load and the cost of the drug when choosing an antipsychotic.
When there is need of an antipsychotic start at the low end of the licensed range and
then slowly increase the dose, ref NICE2.
Full details of the Area Prescribing Committee Drug Classifications can be found at
www.formulary.cht.nhs.uk for Calderdale, Kirklees and Wakefield. These are different
in Barnsley and can be found at
http://nww.barnsleypct.nhs.uk/prescribing/guidelines/sharedcareguidelines.html


All service users with severe mental illness require the following tests prior to
prescribing (at baseline) and annually:
1.
FBC
2. Renal function
3. Liver function
4. Thyroid function
5. EPSE (eg AIMS/Lunsers)
6. Prolactin
7. BP and pulse
8. Blood glucose
9. Lipid profile
10. Weight/Height including BMI and waist measurements
11. ECG (only required annually if clinically required)
See Trust physical health monitoring document.
11
Oral atypical antipsychotics
Cost per 28 days
Medication
Risperidone
(Risperdal ®)
Amisulpride
(Solian ®)
Olanzapine
(Zyprexa ®)
Aripiprazole
(Abilify ®)
Doses of
30mg are not
recommended
(grey list)
Quetiapine
(Seroquel®)
Clozapine
(Clozaril ®)
(Denzapine ®)
(Zaponex®)
(See
Clozapine
Policy)
Potential Advantages
Potential Disadvantages
Generic - consider first line.
Below 6mg/day there is a low
incidence of EPSE’s, sedation
and anticholinergic side effects.
Low risk of QTc prolongation
Lowest acquisition cost
Dose related
hyperprolactinaemia & EPSE’s,
hypotension, weight gain
Moderate risk of other
cardiovascular complications
NB cost of orodispersible can
be more than ten times the
price
Generic - consider first line.
Where one wishes to avoid
sedation, weight gain,
hypotension, and EPSE’s
Low risk of all cardiac effects
Low acquisition cost if use
50mg and 200mg tablets
Generic - consider first line.
Low risk of cardiac adverse
effects, including QTc
prolongation
Very low incidence of weight
gain and a low incidence of
EPSE’s and
hyperprolactinaemia
Immediate release is generic so
consider first line
There is a low incidence of
hyperprolactinaemia & EPSE’s
Restrict XL preparations to
existing users and reveiw
Indicated for treatment-resistant
psychosis. No EPSE’s or
tardive dyskinesia at any dose.
Very low prolactin elevation.
Low risk of QTc prolongation
Risperidone
depot
(Risperdal
Consta®)
No longer a choice for new
users in the organisation as it
has no benefits over PPLAI
Paliperidone
depot
(Xeplion®)
Recently introduced. Can only
be initiated via the clinical
queries mechanism
Low ≤ £25, Medium £26 - £75
High £75- £150
Very High ≥ £150
6mg - total daily dose
Plain tablets
Low
Orodispersible tablets
Medium
Liquid
High
800mg - total daily
dose
Prolactin elevation
400mg tablets and liquid cost
more than 200mg tablets
High levels of weight gain,
sedation, hyperglycaemia
Dyslipidaemia
NB cost of orodispersible can
be more than ten times
higher
Akathesia, nausea and vomiting
common during initiation
Partial agonist action may
antagonise the effects of other
antipsychotics e.g. in Rapid
tranquilisation
High cost. Do not routinely
use doses above 15 mg
Sedation, hypotension, weight
gain. Dyslipidaemia
No liquid preparation is
available.
Do not prescribe quetiapine
liquid.
Risk of neutropenia –
compulsory blood monitoring
required, sedation, hyper
salivation, high levels of weight
gain, moderate to high risk of
cardiovascular complications,
dyslipidaemia.
Dose related seizure risk.
Glucose intolerance,
constipation and paralytic
ileus.
Requires injections every 2
weeks. It has a complex giving
device.
Requires cold chain transport. It
has a high acquisition cost
Very high acquisition cost
Low
50mg, 100mg 200mg
tablets
400mg tablets
High
Liquid
15mg - total daily dose
High
Plain tablets
Low
Orodispersible tablets
Medium/
High
5, 10, 15 mg tablets
once daily
High
30mg tablets once
daily
Very
high
600mg - total daily
dose
Low
Plain tablets
Extended release
tablets (XL)
Medium
500mg - total daily
dose
High
Plain tablets
27.5mg, 37.5mg, 50
mg every two weeks
Very
high
50mg, 75mg, 100mg
monthly
Very
high
12
4.1
Commonly used typical antipsychotics
Cost per 28 days
Medication
Potential
Advantages
EPSE’s, anticholinergic effects,
sedation, hypotension, prolactin
elevation.
Prolonged QTc, Dyslipidaemia
Chlorpromazine
(Largactil ®)
Haloperidol
(Haldol ®)
(Serenace ®)
Trifluoperazine
(Stelazine ®)
Sulpiride
(Dolmatil ®)
Zuclopenthixol
(Clopixol®)
Flupentixol
(Depixol ®)
Fluphenazine
(Modecate®)
Pipotiazine
(Piportil ®)
Potential Disadvantages
Lower incidence of
sedation & anticholinergic
activity than
chlorpromazine.
Depot available
As chlorpromazine.
Higher incidence of EPSE’s than
chlorpromazine
Lower incidence of
sedation & anticholinergic
activity than
chlorpromazine.
Not currently available –
May 2012
Contact pharmacist for advice
Very low incidence of
sedation & low
anticholinergic activity.
Prolactin elevation.
Lower incidence of
sedation & anticholinergic
activity than
chlorpromazine.
Depot available
As chlorpromazine.
Higher incidence of EPSE’s than
chlorpromazine
Lower incidence of
sedation, EPSE’s &
anticholinergic activity
than chlorpromazine
Depot available
Lower incidence of
sedation & anticholinergic
activity than
chlorpromazine.
Depot available
Lower incidence of
sedation, EPSE’s &
anticholinergic activity
than chlorpromazine
Non oily carrier may be
more suitable for those
with nut allergy
Only Depot available
Low ≤ £25, Medium £26 - £75
High £75- £150
Very High ≥ £150
300mg – total
daily dose
Tablets
Low
liquid
Low
10mg - total daily
dose
as tablets
Low
as liquid
Low
Depot 150mg
Low
every four
weeks
10mg - total
daily dose
Very high at
as tablets
present
1200mg - total
daily dose
as tablets
as liquid
50mg - total daily
dose
Low
High
as tablets
Depot 500mg
every two
weeks
Low
Low
As chlorpromazine
Mood elevating
Depot 100mg
every two
weeks
Low
Depot 100mg
every four
weeks
Low
As chlorpromazine
As chlorpromazine.
No oral preparation available
Depot 50mg
every four
weeks
Low
Compiled from information in the Summary of Product Characteristics8, Maudsley
Prescribing guidelines9 and Psychotropic Drug Directory10. Lower doses are required in
older people. Prescribing by brand or proprietary name will increase costs, use generic
names on all prescriptions including FP10s.
There are enormous variations in price relating to liquid and orodispersible preparations.
Please see table 1 for advice but do not hesitate to contact the medicines information
service for advice on the most suitable preparation to choose on 01924327619 or email
queries to [email protected]
13
4.3
Prescribing recommendations for Early-Onset Psychosis in Adolescents
Early onset psychotic disorders are often chronic and may require antipsychotic medication (Schizophrenia Bulletin 2008).
Three major Randomised Controlled trials (RCTs) of typical antipsychotics have shown high incidences of extrapyramidal side effects (EPS) and
significant sedation in children and adolescents. Typical antipsychotics should generally be avoided in those under 18 years
In RCTs atypical antipsychotics have been shown to be effective in the treatment of acute exacerbations of psychosis in adolescents, but intensive
monitoring for metabolic effects is required.
Antipsychotic
Recommendation
Adverse drug reactions (ADRs) reported more frequently in the 14 to
18 years age group than in the adult population.
Risperidone
1st line treatment
Aripiprazole
2nd line treatment
After a trial of
risperidone
Somnolence /sedation, fatigue, headache, increased appetite,
vomiting, upper respiratory tract infection, nasal congestion,
abdominal pain, dizziness, cough, pyrexia, tremor, diarrhoea, and
enuresis.
The effect of long-term risperidone treatment on sexual maturation
and height has not been adequately studied.
Somnolence /sedation and extrapyramidal disorder were reported
very commonly, and dry mouth, increased appetite and orthostatic
hypotension were reported commonly.
Olanzapine
3rd Line treatment
A few RCTs have
shown it to be
effective in psychosis.
Quetiapine
3rd line treatment
(Open label pilot study
showed it to be less
effective than
risperidone)
Clozapine
3rd line treatment
Side-Effect Scale
0 little or minimal effect
Weight gain, elevated triglyceride levels, increased appetite,
sedation (including: hypersomnia, lethargy, somnolence). Dry
mouth and elevated cholesterol levels are commonly seen.
Decreased total bilirubin increased GGT, ALT and AST and
elevated plasma prolactin levels have also been recorded
frequently.
.
ADRs reported more frequently: Increased appetite, extrapyramidal
symptoms, elevations in prolactin, increases in blood pressure.
Irritability is commonly reported. Weight gain occurs more
frequently than in adults
Effective in treatment resistant psychosis in adolescents, but they are more
prone to neutropenia and seizures.
+ mild/transient effect
++ moderate effect
Licensed for
Schizophrenia
Not licensed for
under 18 years but
may be used
under specialist
supervision.
EPS
Metabolic side
effects
+
Sedation
+
Hyperprolactinaemia
++
Licensed for
under 18 years.
Age 15 years and
over Start at 2 mg
for 2 days, 5 mg
for 2 days and
increase to 10mg
daily as
appropriate.
Age 18 years and
over
0
0
+
0
0
Transient
+++
++
Age 18 years and
over
++
++
++
+
Age 16 years
0
0
+++
+++
+++ marked effect
14
+
4.4
ANTIPSYCHOTIC DRUG INTERACTIONS
Potential additive side-effects
Most problematic antipsychotic(s)
Drug or class combined with
antipsychotic
QT prolongation
haloperidol
pimozide
high-dose antipsychotic prescribing
escitalopram
citalopram
high-dose methadone
erythromycin
clarithromycin
co-trimoxazole
mefloquine
sotalol
amiodarone
ciclosporin
hydroxyzine
tamoxifen
Increased risk of neutropenia /
agranulocytosis
clozapine
carbamazepine
carbimazole
chloramphenicol
cyctotoxics
long-acting depot
antipsychotics
penicillamine
phenylbutazone
sulphonamides, eg cotrimoxazole
Increased sedation
chlorpromazine
clozapine
olanzapine
quetiapine
pericyazine
zuclopenthixol
alcohol
antihistamines
benzodiazepines
mirtazapine
opioid analgesics
trazodone
tricyclic antidepressants
Increased risk of anticholinergic
Side-effects, eg constipation,
urinary retention, blurred vision,
confusion
chlorpromazine
clozapine
pimozide
trifluoperazine
zuclopenthixol
Anticholinergic drugs, eg
procyclidine, hyoscine, tricyclic
antidepressants
Decreased blood pressure or falls
chlorpromazine
clozapine
pericyazine
pimozide
risperidone
ACE inhibitors
alcohol
antihypertensives
tricyclic antidepressants
Increased risk of seizures
chlorpromazine
clozapine
most phenothiazines
sudden benzodiazepine
withdrawal tricyclic
antidepressants
Increased weight gain / metabolic
changes
chlorpromazine
clozapine
olanzapine
perphenazine
lithium
mirtazapine
other antipsychotics
tricyclic antidepressants
valproate
Common pharmacodynamic interactions to consider with antipsychotic drugs (the drugs in bold italics indicate
particularly hazardous interactions and should be avoided)
Taken from Progress in Neurology and Psychiatry April 2012 Volume 16 Issue 2 Stephen Bleakley
15
4.5
Depot antipsychotics and long acting injectables
Depot preparations are solutions of antipsychotics, usually in an oily base, designed to be
released over two to four weeks. They are administered by deep intramuscular injection.
Depot preparations are a treatment option where a service user expresses a preference
for such treatment because of its convenience, or as part of a treatment plan in which the
avoidance of covert non-adherence with antipsychotic medication is a clinical priority. 2
Any decision to use depot antipsychotic/long acting injections should take into account
the preferences and attitudes of the service user towards the mode of administration and
organisational procedures (home visits, location of clinics) related to the delivery of
regular intramuscular injections.2
General principles
4.5.1
Test doses should normally be given to assess tolerability prior to the titration
to maintenance dose, with the exception of risperidone and paliperidone.
4.5.2
Side effects may not be apparent for several days and may be long lived.
Allow 4 to 10 days after the test dose before beginning regular treatment.
4.5.3
The same principles in terms of using minimally effective doses, monotherapy
and monitoring of efficacy and adverse effects should be applied to depot
antipsychotics and oral antipsychotics.
4.5.4
Prescribe at the maximum allowable interval initially and then review. There
is no evidence to suggest shorter intervals improve efficacy.
4.5.5
Dose increments should not normally be sooner than 2 or 3 months taking
into account the time taken for the antipsychotic to reach steady state.
When considering dosage and dose increments remember the dose cannot
easily or immediately be altered if side effects develop.
4.5.6
4.5.7
The maximum volume of a depot given in one site should normally be 2ml
and should never exceed 3ml.
4.5.8
The SPCs of the antipsychotic depot injections (with the exception of
risperidone) allow the mixing of different strengths of the same brand of the
same medication to be mixed in one syringe. It is recommended that the
more concentrated solution be drawn up first.
4.5.9
Depot injections should be administered by trained and experienced nursing
staff using the Z track technique to ensure delivery to the muscle and to
prevent leakage of the solution and resultant reduction in delivered dose.
o The injection should be administered into the upper outer quadrant of the
buttock (gluteal region).
o Please see January 2012 communication Risperidone/Paliperidone use in
the Trust.
4.5.10 Always remember these are painful injections.
4.5.11 Extreme caution should be taken when transferring to or from RLAI in view of
the delayed release properties and the long half-life.
16
4.5.12 Further information is available in the policy for the use of RLAI.
4.5.13 Depot antipsychotics (including RLAI) should NEVER be given with clozapine
due to the additive risks of neutropenia and the prolonged release of the
depot antipsychotic.
4.514
Caution is required when switching from a depot to clozapine
Dosing information (older people require lower doses – check BNF)
Antipsychotic
Test dose
Recommended
interval (weeks)
BNF MAX (mg
per week)
Time to
steady state
Flupentixol
decanoate
(Depixol ®)
20mg
2
400
10-12 weeks
Fluphenazine
decanoate
(Modecate ®)
12.5mg
2-4
50
6-12 weeks
Haloperidol
decanoate
(Haldol ®)
25mg*
4
75
10-12 weeks
Pipotiazine palmitate
(Piportil ®)
25mg
4
50
8-12 weeks
Zuclopenthixol
decanoate
(Clopixol ®)
100mg
2-4
600
10-12 weeks
Risperidone depot
(Risperdal
Consta ®)
Use oral
2
25
6-8 weeks
Paliperidone depot
(Xeplion®)
Use oral
risperidone
Monthly
Not applicable
*The SPC for Haldol® does not include a recommended test dose but the Maudsley
Prescribing guidelines suggest 25mg
17
4.6
Risperidone depot / Paliperidone depot use in the Trust
Communication January 2012
4.6.1 Background
Risperidone depot (Risperdal Consta) is more complex to manage in practice than typical
antipsychotic depot injections. As well as the cost of the drug both pharmacy and nursing
resources are required to ensure the medication is used effectively. It is required to be
given every two weeks; it requires storage in a fridge therefore requiring cold chain
management.
With the advent of paliperidone depot (Xeplion) the Trust has decided not to consider
risperidone depot for new users and all existing users are required to undergo a
medication review.
Paliperidone, which is a metabolite of risperidone, may be considered for new users
under the clinical queries mechanism (section 17, medicines code) following strict criteria.
Before prescribing paliperidone it is important to have approval under the clinical queries
mechanism.
Both paliperidone and risperidone depots are classed “red” drugs in the local health
economy which means prescribing will always remain in secondary care.
Each service user prescribed paliperidone and risperidone depot should have response
and tolerability to treatment reviewed and documented at least at six monthly intervals.
4.6.2 Administration in the deltoid
Training and competence assessments within SWYPFT are based on administration of
depot injections in the gluteal site. However both paliperidone and risperidone depots are
licensed for administration in the deltoid.
Where nursing staff are currently trained and have the requisite competencies for deltoid
administration then it is acceptable to administer the depot in the deltoid. At all times it is
important to work within your scope of practice. Training will be developed for those
identified as being required to administer via the deltoid route to ensure competency.
4.6.3 Risperidone depot
This has a complex reconstitution device and the needle provided with the package must
be used. There are two needles with the package one for gluteal administration and one
for deltoid administration. Please ensure the appropriate needle is chosen. The longer
needle should be used for gluteal administration. There have been reports of service
users experiencing pain at the site of injection and risks associated with using the wrong
needle in the wrong site.
Risperidone depot should be stored in the fridge, and any removed from the fridge then
has an expiry date of 7 days—even if it is returned to the fridge.
It has complex release properties requiring oral treatment (or existing depot treatment) to
continue for 3 to 4 weeks after the injection has been initiated. A minimum of 3 to 4
18
injections (i.e. six to eight weeks) at one dose should be given before a dose increase is
attempted. The maximum dose is 50mg fortnightly.
It is important that the views of the service users and all the complexities around
administering treatment are considered when prescribing. Dose titration requires strict
monitoring and in practice prescribing errors have been seen.
Following discontinuation of risperidone depot the pharmacokinetics are such that plasma
levels do not begin to drop until five to six weeks after the last injection. Risperidone is
not completely eliminated until eight weeks after the last injection.
4.6.4 Paliperidone depot
This has just recently become available and the SPC suggests that it will be more
acceptable to use than risperidone long acting injection for these reasons.
 Once a month injection
 Injection made up ready to administer
 No requirement for cold chain storage
Paliperidone depot should only be considered for: service users who satisfy the NICE
guidelines for depot antipsychotic prescribing and who meet the product licence
requirements:
These are:
a) Service users who have experienced severe EPSE from their typical depot
antipsychotic injection.
AND
b) Service users who have a history of response to, but poor compliance with, oral
risperidone. These service users must have a preference for a long acting
injection as above.
Paliperidone depot is one of the options for patients who satisfy NICE criteria for
depot antipsychotic prescribing, but would not be an automatic choice for patients
currently prescribed risperidone.
The choice of injection site should not influence the choice of depot.
If all relevant criteria above are met for the favoured option—paliperidone depot— the use
of the deltoid route of administration could be considered.
However the availability of deltoid administration should not influence of the choice of
depot.
4.6.6 Administration Guidance on Paliperidone depot (Xeplion®) for use following
agreement through the clinical queries mechanism
Paliperidone depot (paliperidone palmitate long acting injection) is indicated for
maintenance treatment of schizophrenia in adult patients stabilised on paliperidone or
risperidone, with previous responsiveness to oral risperidone.
19
*Only use the deltoid site if injection training has been given
Day
Dose
Day One
150mg
Which
site
Deltoid
muscle*
Comments
In order to attain therapeutic concentrations
rapidly
Day Eight *
Patients may be given
the second dose 2
100mg
days before.
Deltoid
muscle*
In order to attain therapeutic concentrations
rapidly
Recommended
Monthly Maintenance
Dose*
Gluteal
muscle
or
deltoid
*muscle
Patients may benefit from lower or higher
doses within the recommended range of
50mg to 150 mg based on individual patient
tolerability. Patients who are overweight or
obese may require doses in the upper range.
75mg
*Only use the deltoid site if injection training has been given
Deltoid muscle administration
Needle size for administration depends on
weight
Alternate between the two deltoid muscles
Recommended needle size
Weight ≥ 90 kg
1½ inch, 22 gauge needle (38.1 mm x 0.72
mm)
Weight < 90 kg
1-inch, 23 gauge needle (25.4 mm x 0.64
mm)
Gluteal muscle administration
Alternate between the two gluteal muscles
Administration should be made into the
upper-outer quadrant of the gluteal area.
1½-inch, 22 gauge needle (38.1 mm x 0.72
mm)
Switching from oral risperidone

Previous oral risperidone can be discontinued at the time of initiation of treatment
with paliperidone, only if deltoid muscle has been used for initiation.

Where the deltoid route is unavailable the use of the gluteal route is advised but is
off-licence and this should be recorded using the trust procedure. The following
information should be considered:
Percentage of patients reaching “therapeutic concentration” at day 8
Dose on day 1
Deltoid injection
Gluteal injection
100 mg
73 %
52 %
150 mg
84 %
66 %
20
Switching from risperidone depot to paliperidone

The initiation dosing regimen including the intramuscular injections on day 1 and 8
are not required, it is appropriate to use the gluteal muscle when switching.

Start paliperidone depot therapy in place of the next scheduled injection.

Paliperidone depot should then be continued at monthly intervals.
Equivalent doses of risperidone and paliperidone depots
Risperidone depot - dose
Paliperidone depot –dose
25 mg every 2 weeks
50 mg monthly
37.5 mg every 2 weeks
75 mg monthly
50 mg every 2 weeks
100 mg monthly
This communication should be read in conjunction with detailed prescribing information
available in the Summary of product characteristics for paliperidone depot (Xeplion)
risperidone depot (Risperdal Consta) from http://emc.medicines.org.uk
It will be updated in light of new evidence and on receipt of comments.
Information is also available from Trustwide medicines information
Tel 01924 327619 email [email protected]
As a new product Xeplion is intensively monitored by the MHRA and CHM and
carries a black triangle. ALL adverse reactions should be reported using the
Yellow Card Scheme
References
Summary of product characteristics for Xeplion (Janssen)–paliperidone palmitate
prolonged release suspension for injection.26th October 2011
British National Formulary 62 September 2011
Lynn Haygarth Chief Pharmacist on behalf of the Drug and Therapeutics Sub Committee
updated from D&T members comments January 2012.
21
CLINICAL QUERIES PROFORMA
Subject:
Name of enquirer:
Date:
BDU:
Service Line:
WAA
OPS
Patient initials:
RiO Number:
Consultant:
LD
EIS
Forensic
Current meds:
Recommendations:
Clinical Outcome:
Pharmacist:
dBase Ref:
Initial Follow-up:
22
Patient Choice leaflet
Antipsychotics for schizophrenia, psychosis and mania
What are antipsychotics?
Medicines used to treat psychotic symptoms such as positive and negative symptoms
(see below) are termed “antipsychotics”. The old names for this type of medication are
neuroleptic and major tranquilliser. The older antipsychotics are called “typical
antipsychotics” and the newer antipsychotics are called “atypical antipsychotics”.
Antipsychotics come in different forms including tablets, dispersible tablets, liquids, short
acting and long-acting injections. There are two names both the “generic name” and the
name given by the manufacturer (an ® used indicated the manufacturers name in this
leaflet)i
Typical antipsychotics
Chlorpromazine Largactil®
Flupentixol oral
Fluanxol®
Flupenthixol depot Depixol®
Fluphenazine
Modecate®
Haloperidol
Haldo®Serenace®
Levomepromazine Nozinan®
Pericyazine
Perphenazine
Fentazin®
Pimozide
Orap®
Pipotiazine
Piportil®
Prmazine
Sparine®
Sulpiride
Dolmatil®
Trifluoperazine (no longer available)
Zuclopenthixol oral
Clopixol®
Zuclopenthixol depot Clopixol ®
Atypical antipsychotics
Amisulpride
Solian®
Aripiprazole
Abilify®
Asenapine
Sycrest®
Clozapine Clozaril,Zaponex Denzapine®
Olanzapine
Zyprexa®
Paliperidone depot Xeplion®
Quetiapine
Seroquel®
Risperidone
Risperdal®
Why have I been prescribed an antipsychotic?
Antipsychotics are medicines used to help treat schizophrenia and other similar
conditions including psychosis and mania. When people have schizophrenia or psychosis
they may hear voices, see things that are not present, may become suspicious or
paranoid and feel that people can control or read their thoughts. These symptoms are
termed “positive symptoms”. Antipsychotics can help relieve these symptoms. Many
patients with schizophrenia also experience “negative symptoms” such as feeling tired,
lacking energy and becoming withdrawn. Antipsychotics may help relieve these
symptoms as well. Mania is when you are excessively happy, irritable, have increased
energy, talk very quickly and are full of ideas and plans and are unable to sleep.
Antipsychotics can help your mood return to normal. Antipsychotics are sometimes used
for other conditions such as anxiety, feeling sick, and problems with sleep.
Are antipsychotics safe to take?
They normally are but you should let your prescriber know if any of the following apply to
you:
 Epilepsy, diabetes, heart, liver of kidney trouble
 If you take any other medication including medication bought over the counter and
alternative therapies
 If you are pregnant or breast-feeding or wish to become pregnant.
This will help the prescriber choose the safest medicines for you.
23
Benefits of Antipsychotics
Antipsychotics can help relieve or reduce the symptoms of the illness and also the impact
it may have on daily life. They can reduce the risk of suicide, reduce the need for
admission to hospital or shorten the length of stay and help you be able to work and live
independently.
Antipsychotics do not work straight away. For example, it may take several days or even
weeks for some of the symptoms to improve. To begin with, most people find that these
medications will help them feel more relaxed and calm. It usually takes 2-4 weeks, and
sometimes longer, for an antipsychotic to produce its full benefits. Generally all
antipsychotics as are effective as each other, however, individuals do not respond the
same to each medication so if one does not help another one could. Clozapine is the
only proven effective medication for treatment-resistant schizophrenia. This is prescribed
when other antipsychotics have not helped enough with the symptoms
About 80% of people who do not take their medication will become ill again.
Antipsychotics are generally required over a long period and you should discuss with your
doctor if you intend to stop them as they should be stopped slowly to prevent you
becoming ill.
Risks of Antipsychotics
Antipsychotics can cause side-effects although there are differences between the
medications available so if you have a side-effect with one medication it could be
changed to a different one which may not cause that side-effect. The dose can be
important with respect to side-effects. The side-effect may reduce or disappear if the dose
of medication is lowered. There may also be other ways to manage the side effect.
The typical antipsychotics are more likely to cause restlessness, abnormal movements,
stiffness and tremors. The atypical antipsychotics are less likely to cause these sideeffects.
Antipsychotics can cause weight gain, which may have long-term health effects. Some
like clozapine and olanzapine are more likely to cause this while aripiprazole, amisulpride
and haloperidol are the least likely antipsychotics to cause this side-effect.
Antipsychotics can cause other side-effects such as drowsiness, lowering of blood
pressure, changes to the hearts rhythm, raised cholesterol and raised blood glucose. The
long-term side-effects of antipsychotics can include movement disorders. There can also
be effects on the heart, some hormones and sexual function.
24
Side effect
Movement disorders
Weight gain
Drowsiness
Anticholinergic
effects(constipation, dry
mouth, blurred vision)
Raised prolactin
(hormone which can
affect sexual function)
Altered glucose
metabolism (how the
body handles sugar,
diabetes)
More Common with
Typical antipsychotics
and higher doses of
risperidone
Olanzapine
Clozapine
Most typical
antipsychotics
Olanzapine
Clozapine
Quetiapine
Levomepromazine
Chlorpromazine
Most typical
antipsychotics
Clozapine
Typical antipsychotics
Amisulpride/sulpride
Higher doses of
risperidone
Olanzapine
Clozapine
Some typical
antipsychotics
Less Frequent with
Atypical antipsychotics
Amisulpride/sulpiride
Aripiprazole
Risperidone
Amisulpride/sulpiride
Aripiprazole
Other atypical
antipsychotics
Clozapine
Quetiapine
Aripiprazole
Olanzapine
Amisulpride
Aripiprazole
Risperidone
Some typical
antipsychotics
Alternatives
There are many antipsychotics available in the UK so please speak to a healthcare
professional about the most suitable medication for you. Leaflets are available on each
individual antipsychotic so please ask for one
Medication helps but may not be the whole solution. Relieving some symptoms with
medication can make it easier for other kinds of help to work.
Cognitive behavioural therapy can help you feel better about yourself and learn new ways
of solving problems or coping with symptoms
Counselling, supportive psychotherapy and family work can all help the individual and
their family with the problems of daily life and solve some practical problems caused by
the symptoms of the illness.
For further more detailed information please discuss with a doctor, non-medical prescriber
or pharmacist from the mental health trust, or ask for a more detailed information leaflet
about antipsychotics or alternative medicines.
Information leaflets on individual antipsychotics can be found on the can be found on the
South West Yorkshire Partnership NHS Foundation Trust intranet which a member of
staff can access for you.
More information can be found at www.choiceandmedication.org.uk,swyp
25
Please talk to a healthcare professional if you can before stopping or making any
changes to your medicines..
Information on medicines used in mental health for service users, carers and healthcare
professionals can accessed by telephoning medicines information on 01924 327619 or
emailing med.information @swyt.nhs.uk
26
4.7
Physical Health Monitoring
All service users prescribed antipsychotics should have routing physical health monitoring. There is an increased risk of weight gain with atypical
antipsychotics. These recommendations include requirements for individual medicines and those checks required to monitor the physical well being of
patients with severe or long-term mental illness. The schedule relates to adults. Children and adolescents may require increased monitoring such as height.
Table 1.1 Atypical antipsychotics
Monitoring for all
patients with SMI
Test or
Measurement
Baseline
Annual
check up
Full blood count
Renal function
(eGFR)
Y
Y
Y
Y
Liver Function
Thyroid function
ECG
Y
Y
Y
Y
Y
If
additional
risk
factors are
identified
EPSE
Prolactin
Y
Y
Y
Hyponatramia
Blood pressure
and Pulse
Y
Y
Y
Y
Amisulpride
/
sulpiride
Aripiprazole
Clozapine
Olanazpine
Quetiapine
Risperidone (including
long acting injection)
After dose
changes and
when
maintenance
dose reached
After dose changes if
additional cardiac risk
factors present or if
clinically indicated eg
tachycardia
As SPC
Consider
reduced
dose in renal
impairment
After dose
changes if
additional
cardiac risk
factors
present or if
clinically
indicated eg
tachycardia
3-6 monthly
At 3 and 6 months
When maintainance
dose reached. After
dose changes if
additional cardiac
risk factors present
or if clinically
indicated eg
tachycardia
After dose
changes if
additional cardiac
risk factors present
or if clinically
indicated eg
tachycardia
At 6 months
then yearly
If symptoms occur
(rare)
Frequently
during
titration
Frequently during
titration
Frequently during
titration
At 6 months then yearly
Frequently
during
titration
Frequently during
titration
27
Monitoring for all
patients with SMI
Test or
Measurement
Baseline
Annual
check up
Amisulpride
/
sulpiride
Aripiprazole
Clozapine
Olanazpine
Quetiapine
Blood glucose
Y
Y
At 4-6
months
At 4-6
months
Monthly for the first
3 months then 3
monthly for one year
then 4-6 monthly
At 4-6 months
Lipid profile
Y
Y
At 3 months
At 3 months
Weight including
BMI and waist
measurement if
possible
Height
Smoking/
alcohol/other
substance misuse
Serum levels of
medicine
Y
Y
Frequently
for first
three months
Monthly for the
first 3 months
then3 monthly for
one year then 4-6
monthly
3 monthly for first
year
Frequently for
three months then
at 6 , 9 and 12
months then yearly
3 monthly for first
year
Frequently for three
months then at 6 , 9
and 12 months then
yearly
3 monthly for first
year
Frequently for first
three months
Y
Y
Y
May be used to
optimise treatment
and minimise side
effects. Further
advice is available
from locality
specialist mental
health pharmacist
May be used to
assess non-adherence
or non response at
maximum dose.
Rarely used
Risperidone
(including
long acting
injection)
At 4-6 months
At 3 months
Frequently for
first three
months
28
Table 1.2 Antipsychotics – Typicals and High dose
Monitoring for all Monitoring for specific drugs
patients with SMI
Test or
Measurement
Full blood count
Renal function
(eGFR)
Liver Function
Baseline
Y
Y
Annual
check up
Y
Y
Y
Y
Thyroid function
ECG
Y
Y
Y
If
additional
risk
factors are
identified
EPSE
Prolactin
Hyponatramia
(electrolytes)
Blood pressure
and Pulse
Blood glucose
Lipid profile
Weight including
BMI and waist
measurement if
possible
Height
Smoking/
alcohol/other
substance misuse
Serum levels of
medicine
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Depots (excluding
risperidone)
Oral typicals (excluding
phenothiazines)
Phenothiazines
High dose
More Frequently if clinical need
More frequently if clinical need
Additional test are recommended
for chlorpromazine
Mandatory
requirements for
Haloperidol and
pimozide see
SPC/BNF
Mandatory requirements for
haloperidol. After dose
changes if additional cardiac
risk factors present or if
clinically indicated eg
tachycardia
After dose changes if additional
cardiac risk factors present or if
clinically indicated eg tachycardia
In the first few days of high dose
treatment, 1-3 monthly during early
treatment then as clinically
indicated
As individual medicine
Y
At 4-6 months
At 3 months
Frequently for the first
three months
Frequently during initiation
Frequently during initiation
Frequently during dose increases
At 4-6 months
At 3 months
Frequently for the first three
months
At 4-6 months
Every 3 months for first year
Frequently for the first three
months
See individual medicine(s)
See individual medicine(s)
See individual medicine(s)
29
5. REFERENCES

Guidance on the use of newer (atypical) antipsychotic drugs for the treatment of
schizophrenia. Technology Appraisal Guidance No.43. NICE, June 2002.
www.nice.org.uk/pdf/ANTIPSYCHOTICfinalguidance.pdf

Schizophrenia: Core interventions in the treatment and management of
schizophrenia in primary and secondary care (update). Clinical Guideline 82.
NICE, march 2009. www.nice.org.uk

Curran S, Harris L, MacDonald A, Pollock C, Roney G, Silkstone D. Antipsychotics
in clinical practice: guidelines for safe and effective use. Human
Psychopharmacology: Clinical and Experimental. 2002 17:75-82

British National Formulary, 62. Published by the British Medical Association,
London and the Royal Pharmaceutical Society of Great Britain. London.
September 2011. www.bnf.org

Department of Health. National Service Framework for Mental Health. 1999.
www.doh.gov.uk

Consensus Statement on the Use of High Dose Antipsychotics. The Royal College
of Psychiatrists. May 2006

Baxter HS, Walters C. Trust-wide audit of the prescribing of typical and atypical
antipsychotic drugs for schizophrenia. December 2003. QED 550

Summary of product characteristics www.medicines.org.uk

Maudsley Prescribing Guidelines. 10th Edition 2009

Efficacy and tolerability of second generation antipsychotics in children and
adolescents with schizophrenia. Schizophrenia Bulletin 2008

Psychotropic Drug Directory 2010

Bleakley S. Identifying and reducing the risk of antipsychotic drug interactions.
Progress in Neurology and Psychiatry April 2012.
30
Appendix 1 High Dose Antipsychotic Medication
The Royal College of Psychiatrists produced a consensus statement on the use of high
dose antipsychotic medication in 1994. This was reviewed and updated in May 2006 6.
Although the more wide-spread use of atypical antipsychotics and greater awareness of
the dangers of high dose antipsychotic prescribing may have reduced the incidence of
high dose prescribing, the principles and recommendations should be applied. The
recommendations below are based on the updated statement and current SPCs for the
antipsychotics
What is a high dose of an antipsychotic?
A single antipsychotic prescribed at a total daily dose above the BNF upper
recommended limit (BNF maximum) or a total daily dose of two or more antipsychotics
that exceeds the BNF maximum using the percentage method (see below).
The upper end of the dose range is not clearly established and is usually arrived at from
limits of safety, the SPC and data reviewed by the CSM prior to the granting of a product
license. In routine use exceeding the dose range is likely to lead to higher levels of side
effects, eventually exceeding the acceptable risk benefit ratio.
Unless otherwise stated, doses in the BNF are licensed doses- any higher dose is
therefore unlicensed. Prescribing above the maximum recommended dose constitutes
prescribing off license and liability will lie with the prescriber rather than the manufacturer.
Main Dangers
Sudden cardiac-related death – QT prolongation and torsade de pointes etc
CNS toxicity – CNS and respiratory depression, hypoxia, seizures etc
Increased risk of subsequent development of tardive dyskinesia
Increased general side effect load risk of non-compliance
Calculating the BNF maximum
This should be done by determining the percentage of the maximum BNF recommended
dose e.g. olanzapine 15mg per day is 75% of the BNF maximum of 20mg per day,
chlorpromazine 300 mg per day is 30% of the BNF maximum of 1000mg per day
It is important to take into account all antipsychotics if the service user is on more than
one medication.
For instance olanzapine 15mg per day plus chlorpromazine 100mg three times day is 105
% of the BNF maximum.
Remember to consider when required doses (PRN) and depots which can contribute to
the total daily antipsychotic load.
Evidence of Benefit
31
The evidence and rationale for the effectiveness of high doses of antipsychotics either
singly or combined is limited or lacking (with the exception of the addition of a second
antipsychotic to clozapine in people with treatment resistant schizophrenia for whom
clozapine alone has proved insufficiently effective) for treatment resistant schizophrenia,
rapid tranquillisation, persistent aggression and relapse prevention in psychosis. Current
evidence does not justify the routine use of high dose antipsychotic medication in general
adult mental health services.
Factors to be considered before prescribing high dose antipsychotics
1.
2.
3.
4.
5.
The diagnosis is correct
Plasma levels are therapeutic and compliance assured.
Treatment duration has been adequate.
Clozapine treatment.
Reduced doses have been tried for a trial period (side effects may mimic negative
symptoms).
6. Adverse social and psychological factors are minimized.
7. Alternative pharmacological therapies have been considered (including adjuncts).
When considering exceeding BNF antipsychotic doses:
1. Discuss with the multidisciplinary team, service user and advocate, if available and the
service user wish their presence. The decision should involve an individual risk
benefit assessment by a fully trained psychiatrist.
2. Supplementary prescribers should not make the decision to proceed with the use of
high dose.
3. Record the discussion and decision in the medical notes. Where possible obtain valid
consent. Ensure compliance with the provision of part IV of the Mental Health Act
1983 if appropriate.
4. Obtain baseline ECG, U&E’s, LFTs, BP, pulse and temperature
5. Consider risk factors and possible contraindications to high dose, such as cardiac
history (particularly MI arrhythmias, abnormal ECG) hepatic or renal impairment,
alcoholism, smoking, old age and obesity.
6. Consider potential interactions; avoid concomitant treatment with certain antihistamines (e.g. astemizole, terbinafine); diuretics, anti-arrhythmics, antihypertensives,
tricyclic antidepressants.
32
If proceeding with high dose antipsychotics
1. Document in the medical notes the treatment plan, including the risks and benefits of
the strategy, the aims and how and when the outcome will be assessed.
2. Increase the dose of antipsychotic gradually at intervals of at least one week allowing
adequate time for response.
3. The use of high dose antipsychotics should be treated as a limited therapeutic trial.
Review prescription and progress at least every three months, reducing the dose to
within the licensed range unless the clinical benefits outweigh the risks.
4. Monitor ECG, BP temperature, pulse, hydration status, U&E’s at appropriate intervals
dependent on clinical need. An ECG should be carried out after a few days of high
dose treatment and then repeated every 1-3 months in the early stages of treatment.
The ECG should be repeated as clinically indicated. Any abnormality in any
parameter should be investigated and prescription amendment considered.
5. The use of PRN (when required) medication, and its potential to raise the total daily
dose of antipsychotic above the high dose threshold, should be kept under regular
review.
Adapted from: Consensus Statement on the Use of High Dose Antipsychotics. The Royal
College of Psychiatrists. May 20066
33
Appendix 2 - Equality Impact Assessment Tool
To be completed and attached to any policy document when submitted to the Executive Management Team for
consideration and approval.
Yes/No
1.
Comments
Does the policy/guidance affect one group less or
more favourably than another on the basis of:
 Race
 Ethnic origins
travellers)
NO
(including
gypsies
and
NO
 Nationality
NO
 Gender
NO
 Culture
NO
 Religion or belief
NO
 Sexual orientation including lesbian, gay
and bisexual people
NO
 Age
NO
Recommendations are given for
adolescents as well as adults.
 Disability - learning disabilities, physical
disability, sensory impairment and mental
health problems
NO
Currently have no patient
information leaflets in any other
media other than type face.
2.
Is there any evidence that some groups are
affected differently?
YES
Different age groups may respond
differently to anti-depressants and
there is guidance on this included
in this document.
3.
If you have identified potential discrimination,
are any exceptions valid, legal and/or justifiable?
YES
4.
Is the impact of the policy/guidance likely to be
negative?
NO
5.
If so can the impact be avoided?
N/A
6.
What alternatives are there to achieving the
policy/guidance without the impact?
N/A
7.
Can we reduce the impact by taking different
N/A
action?
If you have identified a potential discriminatory impact of this policy, please refer it to the Director of Corporate
Development or Head of Involvement and Inclusion together with any suggestions as to the action required to
avoid/reduce this impact.
For advice in respect of answering the above questions, please contact the Director of Corporate Development or
Head of Involvement and Inclusion.
34
Appendix 3 - Checklist for the Review and Approval of Procedural Document
To be completed and attached to any policy document when submitted to EMT for consideration and approval.
Title of document being reviewed:
1.
2.
4.
5.
6.
7.
Comments
Title
Is the title clear and unambiguous?
YES
Is it clear whether the document is a guideline,
policy, protocol or standard?
YES
Prescribing guidance
Rationale
Are reasons for development of the document
stated?
3.
Yes/No/
Unsure
YES
Development Process
Is the method described in brief?
YES
Are people involved in the development identified?
YES
Do you feel a reasonable attempt has been made to
ensure relevant expertise has been used?
YES
Is there evidence of consultation with stakeholders
and users?
YES
D&T membership and Area
Prescribing Committee
representation
Content
Is the objective of the document clear?
YES
Is the target population clear and unambiguous?
YES
Are the intended outcomes described?
YES
Are the statements clear and unambiguous?
YES
Evidence Base
Is the type of evidence to support the document
identified explicitly?
YES
Are key references cited?
YES
Are the references cited in full?
YES
Are supporting documents referenced?
YES
Approval
Does the document identify which committee/group
will approve it?
YES
If appropriate have the joint Human Resources/staff
side committee (or equivalent) approved the
document?
N/A
Via trust Intranet
Dissemination and Implementation
Is there an outline/plan to identify how this will be
done?
YES
35
Yes/No/
Unsure
Title of document being reviewed:
Does the plan include the necessary training/support
to ensure compliance?
8.
9.
10.
11.
Comments
N/A
Document Control
Does the document identify where it will be held?
YES
Have archiving arrangements for superseded
documents been addressed?
YES
Process to Monitor Compliance and
Effectiveness
Are there measurable standards or KPIs to support
the monitoring of compliance with and
effectiveness of the document?
NA
Is there a plan to review or audit compliance with
the document?
YES
Review Date
Is the review date identified?
YES
Is the frequency of review identified? If so is it
acceptable?
YES
Overall Responsibility for the Document
Is it clear who will be responsible implementation
and review of the document?
YES
Appendix 4 - Version Control Sheet
This sheet should provide a history of previous versions of the policy and changes made
Version
Date
Author
Status
Comment / changes
1
Written in line with NICE guidance
March
2004
Lynn Haygarth
1.1
April 2005
Lynn Haygarth,
Chief Pharmacist
2
May 2007
Lynn Haygarth
Reviewed to incorporate newly
licensed products and current evidence
of safety and efficacy of
antipsychotics.
3
July 2010
Lynn Haygarth,
Updated in line with NICE guidance
including recommendation for the use
of generic antipsychotics.
4
April 2012
Lynn Haygarth,
Chief Pharmacist
4.1
July 2012
Lynn Haygarth
Chief Pharmacist
Approved by
EMT April 2012
Updated in line with Barnsley Shared
Care requirements and introduction of
paliperidone depot. Changes of generic
preparations.
Changed costs to bandings from actual
costs.
Correction to paliperidone dose.
Addition of antipsychotic drug
interaction table.
36