Prescribing Guideline
Pharmacological Treatment of
Schizophrenia and Related Psychoses
PG10
Contents:
Summary - Treatment Pathway
Choice of Treatment
Minimum Effective Doses
Relative Side-Effects
Switching Antipsychotics
Combination Antipsychotics
High Dose Monitoring
Depots
Clozapine
Stopping Treatment
Negative Symptoms
Physical Health Monitoring
Rapid Tranquilisation
Pregnancy & Breastfeeding
Resources
A
1.
First episode
Offer oral antipsychotic medication
Provide information and discuss the benefits of treatment and the relative side-effect profile of each
medication with the individual. The individual should be as involved as possible in the choice of
medication, considering:
 the likely effects of taking and not taking medication (including unpleasant subjective
experiences)
 the views of the carer if the individual agrees.
At the start of treatment give a dose at the lower end of the licensed range (see minimum effective
doses) and slowly titrate upwards within the dose range given in the British National Formulary (BNF)
or SPC. The lowest possible dose should be used. Doses that are effective acutely should be
continued prophylactically.
Carry out a trial of the medication at the optimum dosage for 4–6 weeks.
In individuals with a first psychotic episode with full and sustained remission, antipsychotic treatment
should be continued for at least 12 months after the beginning of remission.
Choice of antipsychotic
A generically available antipsychotic is considered the treatment of choice if there is no clear
preference between available antipsychotic treatments.
A decision aid is available at http://www.choiceandmedication.org/devon/pdf/handychartpsychosis.pdf
which allows comparison of different treatments for schizophrenia. Please note that some treatments
in this aid may be subject to local formulary restrictions.
The locally approved (or formulary) oral medicines for schizophrenia are:
First Generation:
Haloperidol
Sulpiride
Zuclopenthixol
Second Generation:
Amisulpride
Aripiprazole
Olanzapine
Quetiapine*
Risperidone
*Quetiapine modified-release is only approved for use when individuals cannot tolerate immediate-release
quetiapine or if concordance with a twice daily regime of quetiapine has proven difficult. It is also recommended
where rapid titration is required.
Minimum effective doses (per day):
Medicine
Haloperidol
Sulpiride
Zuclopenthixol
Amisulpride
Aripiprazole
Olanzapine
Quetiapine
Risperidone
First episode
2mg
400mg
Not known
400mg
10mg
5mg
150mg
2mg
Multi-episode
4mg
800mg
Not known
Unclear, possible 400mg
10mg
7.5mg
300mg
3mg
PG10 – Pharmacological Treatment of Schizophrenia and Related Psychoses
Approved by Drugs and Therapeutics Committee: Sept 2016
Review date: Sept 2020
Page 3 of 8
Relative side-effects:
Medicine
Sedation
Weight
gain
Akathisia
Parkinsonism
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+++ high incidence/severity, ++ moderate, + low, - very low
Amisulpride
Aripiprazole
Clozapine
Haloperidol
Olanzapine
Quetiapine
Risperidone
Sulpiride
Zuclopenthixol
Anticholinergic
Hypotension
Prolactin
elevation
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Epilepsy, hepatic, cardiac and renal impairment
These are complex areas with many potential problems and possible treatment options.
specialist advice from the Medicines Optimisation Team should these arise.
Seek
2. Relapse prevention and subsequent episodes
Refer to the individual’s history looking for previous evidence of successful pharmacological
treatment. The same principles of individual-led choice apply in order to promote improved
concordance with the prescribed regime. Take into account the clinical benefit and side effects
experienced by the individual with any previous medication as well as an Advanced Directives.
Switching antipsychotics
There are 3 accepted ways of switching antipsychotics. The most appropriate way will depend on the
clinical circumstances, the setting and the person. These methods are
1. Drug-free interval (discontinue first antipsychotic, leave a break, then start second)
2. No interval (stop one, immediately start second)
3. Overlap (can be partial or full, depends on circumstances)
Seek specialist advice from the Medicines Optimisation Team when switching antipsychotics,
especially when long-acting injections are involved.
Combination antipsychotics
Do not routinely use combinations of two or more antipsychotics except where:
 Cross-tapering between two different antipsychotics and only then for a short time
 Augmenting clozapine with an evidence-based antipsychotic agent which does not compound
the side effects of the clozapine; e.g. risperidone, sulpiride or aripiprazole.
 PRN medication
If combination antipsychotics are prescribed ensure there is a clear rationale and treatment
plan documented and communicated to all clinicians involved in the person’s care.
PG10 – Pharmacological Treatment of Schizophrenia and Related Psychoses
Approved by Drugs and Therapeutics Committee: Sept 2016
Review date: Sept 2020
Page 4 of 8
High dose antipsychotic prescribing
High dose antipsychotics are defined as doses of a single antipsychotic above BNF limits, or a
combination of antipsychotics whose total % of BNF maximum add up to over 100%. Justify and
record reasons for dosages outside the range given in the BNF or SPC.
Devon Partnership NHS Trust’s clinical protocol on High Dose Antipsychotics (CP10) is available. The
specialist should work with the GP to ensure all the monitoring recommended in this document (in line
with Royal College of Psychiatrists recommendations) is performed.
Depot antipsychotics (long-acting antipsychotic injections)
Please see separate prescribing guidance relating to the prescribing of long-acting
antipsychotic injections/depot antipsychotics. Click here to access PG23.
Consider offering depot/long-acting injectable antipsychotic medication to people with schizophrenia:
 who would prefer such treatment after an acute episode
 where avoiding covert non-adherence (either intentional or unintentional) to antipsychotic
medication is a clinical priority within the treatment plan.
When initiating depot/long-acting injectable antipsychotic medication:
 Take into account the individual’s preferences and attitudes towards the mode of administration
(regular intramuscular injections) and organisational procedures (for example, home visits and
location of clinics)
 Provide information and discuss the benefits of treatment and the relative side-effect profile of
each drug with the individual
 Initially use a small test dose where required as set out in the BNF or SPC.
 For non-approved medicines (see Medicines Directory), follow the non-approved process
(MM26)
3. Inadequate or no response to pharmacological treatment
For people with schizophrenia whose illness has not responded adequately to pharmacological and/or
psychological treatment:
 review the diagnosis
 establish that there has been adherence to antipsychotic medication, prescribed at an adequate
dose and for the correct duration
 review engagement with and use of psychological treatments
 consider other causes of non-response, such as comorbid substance misuse (including
alcohol), the concurrent use of other prescribed medication or physical illness.
Offer clozapine to people with schizophrenia whose illness has not responded adequately to
treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs.
At least one of the drugs should be a non-clozapine SGA. See CP19.
For people with schizophrenia whose illness has not responded adequately to clozapine at an
optimised dose, healthcare professionals should consider the points above (including measuring
therapeutic drug levels) before adding a second antipsychotic to augment treatment with clozapine.
An adequate trial of such an augmentation may need to be up to 8–10 weeks.
PG10 – Pharmacological Treatment of Schizophrenia and Related Psychoses
Approved by Drugs and Therapeutics Committee: Sept 2016
Review date: Sept 2020
Page 5 of 8
For people who have declined clozapine or not been able to receive treatment with clozapine (due to
intolerance or contraindications) consider reviewing the treatment options in the Maudsley Guidelines
or contact the Medicines Optimisation Team for advice.
4. Stopping treatment
Inform the individual that there is a high risk of relapse (80% of individuals with schizophrenia relapse
within 5 years of stopping treatment). If withdrawing antipsychotic medication, reduce the dose
gradually and monitor regularly for signs and symptoms of relapse. After withdrawal from
antipsychotic medication, continue monitoring for signs and symptoms of relapse for at least 2 years.
In cases of acute and severe adverse effects (i.e. blood dyscrasia with clozapine) where abrupt
discontinuation of medication is required, specialist advice should be sought to ensure adequate
support is available and to ensure an urgent review of treatment is completed.
5. Negative symptoms of schizophrenia
Up to 20% of people with schizophrenia have enduring primary negative symptoms. Psychotic illness
should be identified and treated as early as possible as this may protect against the development of
negative symptoms.
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Consider augmentation of antipsychotics with an antidepressant such as an SSRI or
mirtazapine.
If clozapine is prescribed, consider augmenting with lamotrigine or a suitable second
antipsychotic (eg amisulpride).
There are insufficient data to make recommendations about other pharmacological
strategies at this point.
6. Physical health monitoring
Life expectancy of people with schizophrenia is reduced by up to 20 years, with 60% of the excess
mortality due to physical illness. Physical health monitoring is essential in order to identify abnormal
results promptly, reducing morbidity and mortality by managing risk factors.
In addition to the annual physical health check all individuals with a diagnosis of schizophrenia should
receive, additional physical health monitoring is indicated for individuals prescribed an antipsychotic
medication.
Refer to Practice Standard 11: Physical Health Monitoring for recommended monitoring that should
be completed for individuals prescribed an antipsychotic medication (prior to and during treatment).
There may be occasions where baseline/ on-going monitoring is not feasible. If this is so, the clinician
has to balance the risks and benefits of foregoing these prior to prescribing/ continuing treatment.
7. Rapid tranquillisation (In-patient services only)
Refer to separate Devon Partnership Trust Policy (C36) and Clinical Protocol (CP11) for rapid
tranquillisation. Only for use in ‘psychiatric emergencies’ where the individual is at imminent risk of
PG10 – Pharmacological Treatment of Schizophrenia and Related Psychoses
Approved by Drugs and Therapeutics Committee: Sept 2016
Review date: Sept 2020
Page 6 of 8
harming themselves and/ or others. Only to be prescribed and administered by staff who have had
specific training.
8. Pregnancy and breastfeeding
See PG18 Perinatal Mental Health for specific information on prescribing in this group and up-to-date
contact information for the local perinatal teams.
User-friendly resources
 A patient decision aid (which includes information on relative side effects but also some nonformulary treatments) is available from www.choiceandmedication.org/devon
 DPT Medicines Information Helpline: 01392 675688 (Mon-Fri, 10am-4pm)
 National Prescribing Centre patient decision aid
http://www.npci.org.uk/therapeutics/cns/schizophrenia/pda.php
 Royal College of Psychiatrists (www.rcpsych.ac.uk/ -select ‘Mental Health Info’) - a range of
information leaflets about Schizophrenia and psychosis in several languages
References:
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Taylor, D.; Paton, C; Kapur, S. The Maudsley Prescribing Guidelines in Psychiatry,
12th ed., 2015.
Bazire, S. Psychotropic Drug Directory 2016. 2016.
NICE. CG178 Psychosis and schizophrenia in adults: prevention and management.
2014.
Bleakley, S.; Taylor, D. The Clozapine Handbook. 2013.
BNF 71. 2016
PG10 – Pharmacological Treatment of Schizophrenia and Related Psychoses
Approved by Drugs and Therapeutics Committee: Sept 2016
Review date: Sept 2020
Page 7 of 8
Version
1.0
Document Control
Date Issued
November 2011
2.0
May 2014
3.0
July 2015
4.0
July 2016
Target Audience/staff groups
Ratifying group
Date Ratified
Implementation date
Review date
Document History
Version
Start
date
0.1
0.2
0.3
0.4
1.0
1.0
1.1
14/10/10
15/12/10
08/09/11
04/10/11
End date
14/10/10
15/12/10
08/09/11
04/10/11
04/10/11
24/11/11
Author Name / Job Title / Email
Amanda Gulbranson
Clinical Effectiveness Lead
[email protected]
Amanda Gulbranson
Clinical Effectiveness Lead
[email protected]
James Lee
Senior Clinical Pharmacist
[email protected]
Clinical staff responsible for the prescribing of treatment for schizophrenia
and related psychoses
Drug and Therapeutics Committee
September 2016
September 2016
September 2020
Author
Jan14
CS
CS
CS
CS
KS
AG/CS
1.2
Feb14
AG/CS
1.3
Feb 14
AG/CS
1.4
Apr 14
AG/CS
1.5
Apr 14
AG/CS
2.0
2.0
3.0
Jul 15
3.1
Jul 16
4.0
May14
Jun14
KS
KS
AG
Sep 16
JL
13/09/16
Christopher Sullivan
Network Lead Clinical Pharmacist
[email protected]
JBS
History
First draft of new Prescribing Guideline
Second draft for consultation following MHPF Oct 10
Final changes post-consultation
Comment re:RLAI problems with contractual arrangements
Final version approved by MHPF
Document ratified at MMGG.
Significant changes to guidelines including new protocol for
long acting injections, new advice on choice of treatment, new
physical health monitoring, signposting to medicines
management team for specialist advice
Add reference to CAMHS
Use of “generation antipsychotic” terminology
Addition of adherence section
Minor amendments to the flowchart
Addition of depot decision table
Addition of reference to TA213 aripiprazole in 15-17 yer olds
Newer version of antipsychotic LAI table added
Final minor amendments post DTC ratification
Addition of ECG advice for community teams
Document ratified at DTC and signed off.
Updated link to Lester UK Adaptation tool on page 8
Section 7 amended. Reference & hyperlink to PS11 (Physical
Health monitoring) added.
Update algorithm. Added negative symptoms, min effective
dose & relative side effects. Reordered sections.
Document ratified at DTC September 2016
PG10 – Pharmacological Treatment of Schizophrenia and Related Psychoses
Approved by Drugs and Therapeutics Committee: Sept 2016
Review date: Sept 2020
Page 8 of 8