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SH CP 111

Antipsychotic Guidelines
Version: 7

Summary: Guidelines for the prescribing of Antipsychotics

Keywords (minimum of 5): Antipsychotics, schizophrenia, psychosis, depot, amisulpride,


(To assist policy search aripiprazole, clozapine, flupentixol, haloperidol, paliperidone,
engine) risperidone, olanzapine, quetiapine, zuclopenthixol

Target Audience: All clinical staff

Next Review Date: June 2020

Approved & Ratified by: Medicines Management Date of meeting:


Committee 17 January 2018
Chair approval 12 June 2018
Date issued: June 2018

Author: Prof David Kingdon, Rebecca Henry, Principal Pharmacist,


Juliet Wells, Principal Pharmacist

Sponsor: Dr Karl Marlowe, Medical Director

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Version Control
Change Record

Date Author Version Page Reason for Change


Feb 2017 Rebecca 5 4, 6 Table updated as per literature review (original literature search
Henry held by Medicines Management Team). Flow chart updated to
improve clarity from previous version and as per literature review.
Feb 2017 Tom Schlich 5 4, 6 Table updated as per literature review (original literature search
held by Medicines Management Team). Flow chart updated to
improve clarity from previous version and as per literature review.
March Alex Weston 5 All Added appendices 1to 3 to reduce number of standalone LAI
2017 guidelines: Appendix 1a originally SH CP 29 (author: Steve
Bleakley). Reformatted by Rebecca Henry to be consistent with
Appendix 1b. Appendix 1b written by Juliet Wells to clarify
information surrounding new 3 monthly Paliperidone LAI
formulation. Appendix 4 originally SH CP 175 (author: Vanessa
Lawrence). Appendix 5 originally SH CP 186 (authors: Marion
Wetherill and Rebecca Henry).Hyperlinks added to other relevant
guidelines. Information added for OPMH and LD patients to assist
prescribing.
October Cheryl Field 6 All All references to aripiprazole approval forms removed throughout
2017 guideline.
Jan 2018 Juliet Wells 6 All Added key table to abbreviations. Hot contents added to aid
navigation. LAI guide added plus flow chart. Merged bottom
2 cells of table p2 and added risperidone licensing. Physical
monitoring table added to p3. Corrected spelling, grammar,
formatting. Aripiprazole administration expanded to enable
correct selection of different LAI strengths.
March/ Juliet Wells 7 2, 3, 6, Guidelines table (p2); advice for prescribing for LD patients, in
April 2018 Kuljit Bhogal 7, 14 Weight Gain added RFT and B12. Pharmacology flow chart (p3);
added relapse to back arrow, also added smoking cessation and
co-morbidities to baseline investigation box, and Trust logo,
formatted. LAI flow chart (p6) formatted. Added footnotes; Where
the ticks are not a measure of severity but in relation to one another
and Where  is lower, and  is higher probability to LAI side-
effect comparison table (p7). Appendix 2: Aripiprazole LAI, added
footnote, *If slow metaboliser, to metabolism table.

Reviewers/contributors

Name Position Version Reviewed & Date


Medicines Management Committee V3, February 2011
Medicines Management Department V3, February 2011
Portsmouth Area Prescribing Committee V3, February 2011
Medicines Management Committee V4 October 2014
Portsmouth Area Prescribing Committee V4 February 2015
District Prescribing Committee V4 February 2015
Juliet Wells Principal Pharmacist AMH & LD divisions V5 March 2017
Prof David Kingdon Clinical Director (AMH) V7 December 2017
Dr Cory de Wet Consultant Psychiatrist AMH and West CSD V7 December 2017
Dr Kuljit Bhogal Consultant Psychiatrist LD V7 December 2017

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
CONTENTS

Page

Guideline 4
Pharmacological Management (flow chart) 5
References 6
Guidelines (flowchart) on the Prescribing of Antipsychotic Long Acting 7
Injections
Guidelines on the Prescribing of Antipsychotic Long Acting Injections 8

Appendices
A1a Paliperidone palmitate LAI (Xeplion®) 9
A1b Paliperidone palmitate 3 monthly LAI (Trevicta®) 10
A2 Aripiprazole LAI (Abilify Maintena®) 11
A3a Olanzapine LAI (Zypadhera®) 12
A3b Olanzapine long acting injection Monitoring Form 13
A4 Non formulary request form 14
A5 Zuclopenthixol acetate (Acuphase®) 18
A6 High Dose Antipsychotic Treatment (HDAT) summary sheet 19

Key

EPSE Extrapyramidal side effects


BPSD Behavioural and psychological symptoms of dementia
FGA First generation antipsychotic (typical)
SGA Second generation antipsychotic (atypical)
TDM Therapeutic dose monitoring
LAI Long acting injection
ECT Electro Convulsive Therapy
OPMH Older People’s Mental Health
LD Learning Disability
SPC Summary of Product Characteristics
PMR Patient’s Medication Record

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Guidelines for Prescribing of Antipsychotics (jointly produced by primary and secondary Care)

Condition / Side Effect (SE) First Choice Second Choice


2 3, 4, 5
Acute Psychotic episode Risperidone Low dose typicals oral or
1
If first episode use low doses , more sensitive to neurological SE. Amisulpride depot
2 2
Agree choice of antipsychotic FGA/SGA with patient and carer. Treatment should Olanzapine Haloperidol < 5mg
be individualised on efficacy, SE, relevant medical history and cost. 2
Quetiapine Aripiprazole
Extrapyramidal SE (EPSE) Olanzapine Clozapine
Consider reducing dose. More common in young men. Quetiapine Aripiprazole
2
Tardive Dyskinesia (caused by other antipsychotics) Quetiapine Clozapine
1 2
Reduce dose if possible. More common in elderly . Olanzapine
2
Aripiprazole
Caution with anticholinergic use. 2
Amisulpride
2
Hyperprolactinaemia Add Low dose Aripiprazole Olanzapine
1
More common in pre-menopausal women . Monitor for osteomalacia or 5 to10mg
6
Clozapine
2

osteoporosis (see vitamin D guidelines) Or switch to Quetiapine,


2
2
or Aripiprazole
Sexual Dysfunction Aripiprazole Clozapine
Caused by antipsychotics Olanzapine
Quetiapine
2, 7, 8
Weight gain Aripiprazole Risperidone
If significant, check for diabetes. Give advice and support on lifestyle interventions. Amisulpride
2, 7, 8
Flupentixol
st
More common with 1 episode, and pronounced in patients with a low BMI and Sulpiride Quetiapine
10
psychosis, than in BPAD .Consider switching antipsychotic (be aware of risk of 2, 7
10 Haloperidol
relapse) or add aripiprazole 5 to15mg , consider Metformin, up to 2g/day (monitor
7,10
RFT and vitamin B12) , both unlicensed indication.
Diabetes / Glucose intolerance Amisulpride Risperidone
Sulpiride Haloperidol,
Aripiprazole
2 2
Dyslipidaemia Aripiprazole Haloperidol
Offer dietary advice and consider treatment with a statin. Amisulpride
2

2
Postural hypotension Amisulpride Haloperidol
1
More common in elderly Sulpiride Trifluoperazine
Aripiprazole Olanzapine
2
QTc Prolongation Aripiprazole Flupentixol
Risks higher with high doses. Paliperidone
5
Olanzapine
2

Avoid drugs that prolong QT interval – see ECG guidelines SH CP 204 Risperidone
2
2
Clozapine
2 2
Sedation Amisulpride Risperidone
Review timings of administration with respect to time to peak drug levels Aripiprazole
2
Haloperidol
2
5
Sulpiride
Treatment Resistant Psychosis Clozapine High dose Olanzapine (refer to
1
Psychosis after unsuccessful trials of two antipsychotics (at least one atypical) at (Refer to Clozapine HDAT appendix A6)
maximum tolerated dosages for 6 – 8 weeks Guidelines SH CP 114)
Inadequate response to Clozapine Add Sulpiride Add Haloperidol
Check for co-morbidities (e.g. substance misuse, depression). Check plasma level Add Amisulpride ECT
1
for compliance and interactions. Trial any changes for at least 10 weeks Add Risperidone
Add Aripiprazole
Add Lamotrigine
Pregnancy and Breastfeeding Folic Acid 5mg, 3 months Any previous effective
(see Perinatal Current Evidence and Consensus) Seek advice from/ refer to before and after conception antipsychotic – continue/ restart if
9 1
Perinatal Service. Try to avoid starting depots . Use minimum effective dose, clearly indicated at minimum
12
monotherapy and TDM. Haloperidol effective
Consider risks, gestational diabetes and excessive weight gain. Quetiapine
11
9
Encourage breast feeding unless on clozapine, and monitor baby for side effects. 11
Olanzapine monitor for
gestational diabetes
11
Risperidone
Adolescents Aripiprazole Olanzapine: discuss increased
Use lower doses, titrate slowly. SE may be more pronounced, notably EPSE, Quetiapine risk of greater weight gain
14
hyperprolactinaemia, metabolic and cardiovascular Risperidone
Older persons, learning disability and those with organic brain changes OPMH: use cautiously, monitor closely. For BPSD: follow
Consider lower doses Managing Behaviour Problems in patients with dementia
guideline SH CP 02. Risperidone is the only licensed
antipsychotic in BPSD.
LD: as above. Start at half regular adult dose, be vigilant for side
effects and risk of lowering seizure threshold
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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Pharmacological Management (flowchart) of Schizophrenia-like Psychosis

Risk Benefits of Prescribing


 Consider and discuss with the
patient and family/carer to aid
choice.
 Include co-morbidities, substance
use and physical health

Perform Baseline Investigations (current Maudsley Guidelines)


 Prescribe one antipsychotic starting at a low dose
 Consider drug interactions and side effects

1,5
Consider social and psychological interventions
 Consider smoking cessation and treat co-morbidities

Review
At least every 2 weeks for response, side effects and
adherence to treatment.
Relapse. If issues with adherence: consider depot/ LAI.
After 2 trials,
consider
clozapine

Poor Response Good Response


Change or adjust Continue medication
drug/dose. and monitor.
Be aware of HDAT
when cross-tapering.

Physical Health Monitoring (for normal dosing.  additional for HDAT – see appendix 6)
Weight / HbA1C / Lipids Prolactin FBC eGFR/ LFT GASS ECG RC
BMI blood U & Es (ensure use (see review
correct one for Appendix
sugar clozapine) 6)
Baseline          
<1    
month
<3     
months
<6         
months
Annual         clinical
decision

Other prescribing points


 Do not initiate regular combined antipsychotic medication except for short periods e.g. when switching or in combination with clozapine.5
 Be aware anticholinergics may be misused, worsen tardive dyskinesia and impair memory; minimise use and review regularly.
 Control of behavioural disturbance alone should not be accepted as adequate treatment response; aim for relief from positive symptoms;
reduction of negative symptoms; improved functioning; minimal side effects; acceptability to the patient (‘recovery’) and adherence.
 For short term sedation consider a benzodiazepine with or without antipsychotics as required for psychotic symptoms with regular review.
 When changing drug regimen ensure adequate contraception as appropriate.
 Be aware of the risk of VTE when using antipsychotics, particularly stroke in patients with dementia.
 Plasma levels of Clozapine and Olanzapine may be reduced by up to 50% with smoking. Offer help to stop smoking.
 Citalopram and Escitalopram are contra-indicated with other drugs which prolong QT intervals such as antipsychotics.
 After trials of 2 antipsychotics, clozapine should be considered and the outcome documented. Be aware of previous clozapine use and
outcome.
 Concurrent use of a depot/ LAI with clozapine is contra-indicated and the consultant has to take full responsibility in writing for the
continued prescribing of clozapine to the clozapine monitoring service.
 Adherence issues; consider depot to ensure treatment; consider supervision of oral therapies; try to improve by exploring issues to
adherence with the patient; trying psychoeducation or concordance therapies; consider practical solutions (phone reminders, repeat
prescriptions, delivery of medication); and medicine usage review.

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
References

1. Barnes TRE and the schizophrenia consensus group of the British Association for Psychopharmacology.
Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the
British Association of Psychopharmacology. Journal of Psychopharmacology, 2011; 1-54
2- Hasan A, Falkai P, Worbrock T, Liberman J, Glenthoj B, Gattaz WF et al. World Federation of Societies of
Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 1: Update 2012 on
the acute treatment of schizophrenia and the management of treatment resistance. The World Journal of
Biological Psychiatry, 2012; 13: 318-378
3. Sussex Partnership NHS Foundation Trust. Guidance on the Use of Antipsychotics. Version 3, October 2015.
4. National Prescribing Service. Comparative information for common oral antipsychotic medicines. Accessed
via www.nps.org.au (23/9/16)
5. Clinical Guideline CG178: Psychosis and schizophrenia in adults: prevent and management. National
Institute for Health and Care Excellence 2014. Accessed via www.nice.org.uk (13/9/16)
6. Qiao Y, Yang F, Li C, Guo Q, Wen H, ZZhu S et al. Add-on effects of a low dose aripiprazole in resolving
hyperprolactinemia induced by risperidone or paliperidone. Psychiatry Res, 2016; 30;237: 83-89
7.Cooper SJ, Reynolds GP, Barnes TRE, England E, Haddad PM, Heald A et al. BAP guidelines on the
management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and
antipsychotic drug treatment. Journal of Psychopharmacology, 2016; 1-32
8. Bak M, Fransen A, Janssen J, van Os J, Drukker M. Almost all antipsychotics result in weight gain, a meta-
analysis. PLOS One, 2014; 9,4: 1-19
9. Clinical Guideline CG192: Antenatal and postnatal mental health: clinical management and service guidance.
National Institute for Health and Care Excellence 2014. Accessed via www.nice.org.uk (13/9/16)
10. Mizuno Y, Suzuki T, Nakagawa A, Yoshida K, Mimura M, Fleischhacker WW et al. Pharmacological
strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a
systematic review and meta-analysis. Schizophrenia bulletin, 2014; 40,6: 1385-1403
11. BCPT, pregnancy exposure to olanzapine, risperidone, aripiprazole and risk of congenital malformations
12. Hasan A, Falkai P, Worbrock T, Liberman J, Glenthoj B, Gattaz WF et al. World Federation of Societies of
Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 3: Update 2015
Management of special circumstances: depression, suicidality, substance use disorders and pregnancy and
lactation. The World Journal of Biological Psychiatry, 2015; 16: 142-170
13. Hasan A, Falkai P, Worbrock T, Liberman J, Glenthoj B, Gattaz WF et al. World Federation of Societies of
Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 2: Update 2012 on
the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. The World
Journal of Biological Psychiatry, 2013; 14: 2-44
14. Clinical Guideline CG155: Psychosis and schizophrenia in children and young people: recognition and
management. National Institute for Health and Care Excellence 2014. Accessed via www.nice.org.uk (13/10/16)
th
Current Maudsley Prescribing Guidelines 12 edition have been used throughout.
rd
BNF 73 edition was used, but always check against the current BNF.
SPCs were accessed from https://www.medicines.org.uk/emc/ from September – January 2017/ 18, but always
check the latest on-line SPC.

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Guidelines (flowchart) on the Prescribing of Antipsychotic Long Acting Injections
(LAI)/ Depot

Patient

Consider an Antipsychotic Depot/LAI (NICE CG178 2014);


 To improve adherence (intentional or unintentional)
 For patients who would prefer such treatment
 For a reduction in relapses, rehospitalisation and severity of relapse
 Discuss treatment options with patient - see Choice and Medication site
http://intranet.southernhealth.nhs.uk/our-services/clinical-support-services/medicines-
management/

Check;
 capacity and risk assessment, record on RiO and review T2/T3 where applicable
 there is a successful trial of 2 weeks of the oral as per SPC

Choosing a LAI / Depot

First Line
Minimal side effects  First Generation Antipsychotic (FGA); Flupentixol Decanoate, Develops side effects
Haloperidol Decanoate or Zuclopenthixol Decanoate.
 Record discussion around this.
Manage side effects
with anticholinergics
and dose reduction.
Second Line
Consider Paliperidone Monthly Injection (baseline Prolactin), If dose reduction
or increases symptoms
Aripiprazole LAI or side effects are
intolerable.

Consider decreasing Consider changing to


frequency of LAI 3-monthly Paliperidone Injection
with monitoring for (Trevicta®), after 4 months on
relapse Paliperidone Monthly (Xeplion®)
CPN can continue monthly follow – ups
if deemed necessary.

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Guidelines on the Prescribing of Antipsychotic Long Acting Injections (LAI)

LAI Drug Licensed Oral trial Test Oral License Duration Time Comment Adult Dosing
Indication dose cross- d Route of action to Frequency
(mg) over (IM) steady
state ~
Flupentixol Maintenance Not specified 20 n/a Gluteal or 3 to 4 9 weeks Caution in agitation 50mg every 4
decanoate in lateral weeks or mood elevation. weeks, to
Schizophrenia thigh C/I if circulatory 400mg/ week
& other collapse or loss of
psychosis consciousness
Haloperidol Maintenance Implied in See n/a Gluteal 6 weeks 14 In adults aim to use 50mg every 4
decanoate in SPC, dosing weeks 10 to 15 times the weeks, increasing
Schizophrenia as it states initial previous daily oral by 50mg
& other dose is dose of haloperidol increments to max
determined by
psychosis for maintenance of 300mg/ 4 weeks
oral dose
required to Elderly, 12.5 to
maintain the 25mg every 4
patient before weeks
starting
Zuclopenthixol Maintenance Not specified 100 n/a Gluteal or 2 to 4 12 High doses used for 200mg to 500mg
decanoate in lateral weeks weeks aggression (off every 1 to 4 weeks,
Schizophrenia thigh licence) max
& other 600mg/ week
psychosis
Paliperidone Maintenance Oral n/a n/a, as Deltoid Depends 20 50 to 150mg
palmitate in risperidone for loading initially for on route/ weeks monthly. Adjust
Schizophrenia 14 days to regimen for loading, dose, 25 to monthly
(Xeplion®) check the LAI then 49 days
response and deltoid or
tolerability gluteal
Paliperidone Maintenance Start with n/a n/a Deltoid or Up to 18 n/a Every
palmitate in adults with monthly gluteal months 3 months
Schizophrenia Paliperidone
(Trevicta®) who are then switch
clinically after 4 months
stable on
monthly
paliperidone
(Xeplion®)
Aripiprazole Maintenance 14 days n/a 14 days, Deltoid or Not 20 300mg or 400mg
maintena® in to check additional to gluteal available weeks monthly.
Schizophrenia response and oral trial (or less dependent
for adults tolerability after 1st on drug/
stabilised on injection pharmacodynamic
the oral interactions – see
Appendix )
Olanzapine Maintenance Check n/a Supplement Gluteal 6 weeks 12 Post injection 2 to 4 weekly.
in response and with oral if weeks syndrome requiring Dose depends on
pamoate Schizophrenia tolerability to clinically 3 hours of oral dose. See
(Zypadhera®) for adults oral first indicated monitoring. appendix 3a.
Non- stabilised on Complete form. Elderly see SPC.
formulary the oral

LAI drug Weight/BMI Lipids Diabetes EPSE TDK Akathisia Prolactin


Flupentixol No data No     
data
Haloperidol       
Zuclopenthixol No data No     
data
Paliperidone       
Aripiprazole       neutral
Olanzapine       
Where the ticks are not a measure of severity but in relation to one another.
Where  is lower, and  is higher probability.

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Appendix 1a: Paliperidone palmitate LAI (Xeplion®)
Prescribing information
 The patient must have been stabilised on and tolerate oral risperidone.

®
Should be prescribed as Paliperidone (Xeplion ).
 Target maintenance dose is 75mg per month (range 25mg-150mg) MONTHLY.
 Consider lower doses in the elderly and patients with diminished renal function. If creatinine clearance is
50 to 80 mls/min the dose must be reduced. Caution if severe hepatic impairment. No data available for
<18years old. Refer to SPC for more details.
 Switching; there is no need for oral supplementation.

From oral Risperidone Paliperidone Xeplion® dose


Day 1 150mg(deltoid muscle)
Day 8 (+/- 2days) 100mg(deltoid muscle)
Day 36 (+/-7days) Maintenance dose(deltoid or gluteal muscle)
From Risperidone LAI Risperidone oral Paliperidone Xeplion® dose, give on the day the
(Consta®) equivalence depot is next due
25mg monthly
25mg every 2 weeks 1-2mg 50mg monthly
37.5mg every 2 weeks 3mg 75mg monthly
50mg every 2 weeks 4mg 100mg monthly
6mg 150mg monthly
®
From traditional depot Paliperidone Xeplion dose, give on the day the depot is next due
No specific dose Dose based on clinical experience and individual patient assessment. No
equivalents titration needed

Administration information for Paliperidone (Xeplion®)


 Supplied as pre-filled syringes stored at room temperature
 Give IM slowly, deep into either deltoid (22 gauge needle if >90kg and 23 gauge needle if <90kg) or
gluteal (22 gauge needle) muscle
 Must be shaken vigorously, tip pointing upwards, with a loose wrist, for at least 15 seconds. Re-
shake if not given after 5 minutes.

Missed doses
Paliperidone Xeplion® can be given +/- 4 days with the second initiation dose, and +/-1week of the maintenance
dose date. Otherwise follow guidance below;
Missed second
Action
initiation dose
<4 weeks 100mg (deltoid) as soon as possible, then 75mg five weeks after first
injection, then continue the normal monthly cycle
4-7 weeks 100mg (deltoid) as soon as possible, then 100mg (deltoid) one week later,
then continue the normal monthly cycle
>7 weeks Re-initiate with Paliperidone Xeplion®
Missed maintenance
Action
dose
1 month-6 weeks Regular maintenance dose as soon as possible, then resume monthly
6 weeks to 6 months Regular maintenance dose as soon as possible (deltoid), repeated after one
25-100mg/month week (deltoid) then continue the usual dose monthly
6 weeks to 6 months As soon as possible give 100mg (deltoid), then 100mg after one week (deltoid)
150mg/month then resume usual monthly dose
>6months Re-initiate with Paliperidone Xeplion®

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Appendix 1b: Paliperidone palmitate 3 monthly LAI (Trevicta®)

Prescribing information

®
The patient must be maintained on Paliperidone monthly for at least 4 months prior to starting Trevicta
and at least 2 of the depots should be of the same dose.

®
Should be prescribed as Paliperidone (Trevicta ).
 Should be started when the next Paliperidone monthly is due +/- 7 days.
 The dose is 3.5 fold higher than the monthly injection, hence dose as follows;

Paliperidone monthly Paliperidone Trevicta®


dose dose
50mg 175mg
75mg 263mg
100mg 350mg
150mg 525mg

Administration information for Paliperidone (Trevicta®)


 Supplied as pre-filled syringe at room temperature
 Give IM slowly into either deltoid or gluteal muscle 22 gauge needle
 Must be shaken vigorously, tip pointing upwards, with a loose wrist, for at least 15 seconds, re-
shake if not given after 5 minutes.

Missed doses
®
Paliperidone Trevicta can be given +/- 2weeks of the due date. Otherwise follow guidance below;

Time since last dose Action


<4 months As soon as possible, then resume at 3 monthly
4 to 9 months Re-initiate as below (next table)
>9 months Re-initiate with monthly Paliperidone then change back
to Paliperidone Trevicta® after 4 months

Re-initiation after missing 4 to 9 months of Paliperidone Trevicta®


Last dose of Dose with Paliperidone Xeplion® Dose Paliperidone
Paliperidone Trevicta®
Trevicta® Day 1 Day 8 1 month after day 8
175mg 50mg 50mg 175mg
263mg 75mg 75mg 263mg
250mg 100mg 100mg 350mg
525mg 100mg 100mg 525mg

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SH CP 111 Antipsychotic Guidelines
Version: 7
June 2018
Appendix 2: Aripiprazole LAI (Abilify Maintena®)
Prescribing Information

 Patients should have a history of response and tolerability to oral aripiprazole for at least two to four
weeks before initiation.
 Aripiprazole LAI is licensed for ONCE MONTHLY (one dose per calendar month NOT 4 weekly).
There should be a gap of at least 26 days between injections.
 The usual recommended starting and maintenance dose is 400mg monthly. Dose adjustment to 300mg
should be considered if there are adverse reactions or the patient is on concomitant interacting drugs
e.g. fluoxetine or erythromycin.
 After the first injection, treatment with 10 mg to 20 mg oral aripiprazole should be continued for 14
consecutive days to maintain therapeutic aripiprazole concentrations during initiation of therapy.

Administration information for Aripiprazole (Abilify Maintena®)


 Reconstitute with the supplied diluent of 1.9mls to give a final concentration of aripiprazole 400mg in 2ml.
 Injection into the gluteal or deltoid muscle.
 After reconstitution it is stable for 4 hours at 25°C. However ideally it should be used immediately.
 There are two different products available and two different strengths, 300mg and 400mg. Smaller doses
e.g. 160 mg, can be achieved via adjustment of the injection volume only by using Abilify Maintena®
powder and solvent for prolonged-release suspension for injection (not the pre-filled syringe).

*If slow metaboliser. Accessed from SPC 12/01/2018 https://www.medicines.org.uk/emc

Missed doses –
nd rd
If 2 or 3 dose is missed and time
Action
since last injection is:
> 4 weeks and < 5 weeks The injection should be administered as soon as possible and then
resume monthly injection schedule.
> 5 weeks Concomitant oral aripiprazole should be restarted for 14 days with next
administered injection and then resume monthly injection schedule.
th
If 4 or subsequent doses are
missed (i.e. after attainment of
Action
steady state) and time since last
injection is:
> 4 weeks and < 6 weeks The injection should be administered as soon as possible and then
resume monthly injection schedule.
> 6 weeks Concomitant oral aripiprazole should be restarted for 14 days with next
administered injection and then resume monthly injection schedule.
SPC Aripiprazole
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SH CP 111 Antipsychotic Guidelines
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June 2018
Appendix 3a: Olanzapine LAI (Zypadhera®)
Prescribing information
 The patient must have been stabilised on and tolerate oral olanzapine. There is no need for oral
supplementation.
 A lower starting dose (150mg/ 4wks) should be considered, in the elderly and those with hepatic or renal
impairment.
 It is essential to ensure that long-term plans for administration and observation are in place before
prescribing / administering this product.

Target oral Recommended starting dose of Maintenance dose after two months
olanzapine dose. olanzapine LAI. of treatment.
10mg / day 210mg / 2 weeks or 405mg / 4 weeks 150mg / 2 weeks or 300mg / 4 weeks
15mg / day 300mg / 2 weeks 210mg / 2 weeks or 405mg / 4 weeks
20mg / day 300mg / 2 weeks 300mg / 2 weeks

Administering information for Olanzapine (Zypadhera®)


 May only be administered by deep intramuscular gluteal injection by nurses or doctors who have been
trained in the appropriate injection technique.
 May only take place in healthcare facility, i.e. inpatient unit or community team, where post-injection 3-
hours observation can be assured by an appropriately qualified staff member e.g. nurse, healthcare support
worker or doctor, as assessed to be competent to identify post-injection syndrome.
 Rapid access to medical (or paramedical) care must be available throughout the observation period, (to
include dialling 999 if a doctor is not on the premises).
 Once reconstituted in the vial, olanzapine LAI should be used immediately. However, if not used right away
it will retain efficacy for up to 24 hours in the vial at room temperature and will re-suspend if shaken
vigorously. Once drawn into the syringe, olanzapine LAI must be used immediately.

Post Injection Syndrome


The exact mechanism remains unknown but the clinical manifestations are consistent with those of oral olanzapine
overdose. These effects can include sedation (from mild in severity up to coma) and delirium, as well as
extrapyramidal symptoms, dysarthria, ataxia, aggression, dizziness, weakness, hypertension and convulsions. In
most cases symptoms appear within one hour of injection but rarely may occur later than one hour and very rarely
later than three hours after injection. Patients usually make a full recovery within 24-72hours. In clinical trials the
syndrome occurred in less than 0.1% of injections and in less than 1.5% of patients.
Appropriate supportive measures include treatment of hypothermia, circulatory collapse and support of respiratory
function.
If overdose is suspected, close medical supervision and monitoring must continue until examination indicates that
signs and symptoms have resolved. Alternatively, if a doctor is not available, an ambulance must be called.
Patients must be advised to be vigilant for signs and symptoms of olanzapine overdose (secondary to post-injection
adverse reactions) for the remainder of the day following administration of olanzapine LAI. Assurance must be
sought that they will remain in a position to obtain assistance if needed and that they will not drive or operate
machinery.
If a patient leaves the healthcare facility before the 3 hours of observation is completed, the care coordinator or
CMHT duty must be contacted to arrange further monitoring of the patient.

Other information
Adolescents are more likely than adults to suffer from weight gain, increased appetite, sedation, dry mouth,
elevated levels of; triglyceride, cholesterol, LFTs (ALT/AST/GGT) and prolactin.
®
After administering the injection the nurse / doctor must check that the patient has a Zypadhera patient information
card in their possession. Cards can be obtained from Lilly Medicines Information 01256 31500
SPC Olanazpine

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Appendix 3b: Olanzapine long acting injection Monitoring Form
Observations for post injection syndrome – to be carried out for at least THREE HOURS after olanzapine
depot injection

Patient name ………………… NHS number………………………………

Date of birth ……...................... Ward ………………………………………

Post injection syndrome:


 Usually occurs within three hours of olanzapine depot.
 The risk of post injection syndrome does NOT decrease. It remains the same at EVERY injection.
 Needs urgent medical attention.
 Sign/Symptoms include: sedation and delirium (disorientation, confusion, agitation, anxiety and other
cognitive impairment), extrapyramidal symptoms, dysarthria (slurred speech), ataxia (staggering, uneven
gait), aggression, dizziness, weakness, hypertension and convulsion.
 The three hour observation period should be extended as clinically appropriate for patients who
exhibit any signs or symptoms consistent with olanzapine overdose, until signs/symptoms
resolved.
Date Time Allocated member Observations
of staff alert, orientated and absent of any signs
and symptoms of olanzapine overdose
15mins post injection Name:
___:___
Sig:
30mins post injection Name:
___:____
Sig:
45mins post injection Name:
___:_____
Sig:
1 hour post injection Name:
____:____
Sig:
1 hour 15mins post injection Name:
___:_____
Sig:
1 hour 30mins post injection Name:
____:____
Sig:
1 hour 45mins post injection Name:
____:____
Sig:
2 hours post injection Name:
____:___
Sig:
2 hours 15mins post injection Name:
____:____
Sig:
2 hours 30mins post injection Name:
____:____
Sig:
2 hours 45mins post injection Name:
____:____
Sig:
Prior to leaving healthcare Name:
facility
Sig:

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Appendix 4: Non – formulary request form

Southern Health NHS Foundation Trust (SHFT) is responsible through the Medicines Management
Committee (MMC) for evaluating new drugs and indications for mental health drugs and making
formulary recommendations both within the Trust and in the wider health community. Approved drugs
are added to the Portsmouth and South East Hampshire formulary and Basingstoke, Southampton
and Winchester district formulary.

Non-formulary drugs are often associated with higher costs and limited benefits over formulary
alternatives. On admission therapy should be reviewed especially with regard to non-formulary drugs
which should be changed to a formulary alternative whenever possible. If it is considered essential to
prescribe a non-formulary drug then this form should be completed before the drug can be ordered or
dispensed. This applies to both community and inpatients.

It should not be assumed that a drug will be approved and patients must not be promised the
medication.

The product will only be supplied after this form has been completed and authorisation received by
the supplying pharmacy. Any unused stock purchased may be charged to the consultant’s cost centre
when it expires. For mental health drugs if usage extends to more than TWO patients in a 12 month
period then a formal submission to the SHFT MMC should be made.

For urgent requests the aim is for a decision to be made within 72 working hours (Monday to Friday)

The application should be completed accurately, fully and legibly with all sections completed to avoid
delays in obtaining a decision.

Procedure – follow A or B

A - Patient is admitted to a ward on a non-formulary drug

Ward pharmacist reviews the


medication and assesses need. Chief pharmacist’s office sends
If a supply is required they an authorisation to supply
complete an application form and email/fax to the relevant
fax it to 023 8087 4082 or email it dispensary
to the Chief Pharmacist’s office at
shft.mmt@nhs.net

Chief pharmacist’s office records


the details on the non-formulary
spreadsheet

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B - Request for a new or unauthorised non-formulary drug

Consultant completes a non-formulary If faxed the Chief Pharmacist’s office scans


application form and faxes it to 023 8087 and sends a copy of the application form to
4082 or emails it to the Chief Pharmacist’s shft.mmt@nhs.net. Email subject – patient’s
office at shft.mmt@nhs.net initials and NHS number. Details are
entered on the non-formulary spreadsheet.

NON-
URGENT
URGENT
Added to the agenda of the
next MMC meeting for review.
.
Chief Pharmacist’s office sends a copy
of the application form to the service’s
Not Principal Pharmacist (or deputy), and
Approved Clinical Services Director (CSD)by
approved
NHS email for review and response
and notifies them by SHFT email.

Chief pharmacist’s office


sends a rejection response Approved
to the consultant and Not
principal/ward pharmacist by approved
NHS email.
Principal/ward pharmacist
documents the reasons for
rejection in the patient’s
medical record.
Chair of MMC reviews the
application.
Not .
ratified

Chief Pharmacist’s office sends


the response to the service’s Ratified
Principal Pharmacist (or deputy),
and CSD by NHS email for
further review and comment

Chief pharmacist’s office sends


an authorisation to supply
fax/email to the relevant
dispensary and an email to the
consultant and principal/ward
pharmacist who ensures that the
documentation of the approval is
made in the patient’s medical
record.

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NON-FORMULARY DRUG APPLICATION FORM
Patient’s details

Patient’s name: NHS number: Date of birth

Ward or team: Consultant

Patient’s GP:

Drug details
Generic name and dosage form (e.g. tablet):

Approximate cost per month:

Indication
Is this an unlicensed drug or a licensed drug for an unlicensed indication/route? Yes/No
(NB. There is a separate form for IM clozapine. Please contact the Chief Pharmacist’s
office.)
If your answer is YES then you have accepted FULL RESPONSIBILITY for the use of this drug
when initiated by your prescription.

Diagnosis/indication for the drug:

Rationale for request (claimed advantage over formulary drug(s))

Previous relevant medication (doses, duration, effectiveness, tolerability, reasons for stopping)

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AUTHORISATION

1, Patients admitted to a ward on a non-formulary drug

Authorisation
Ward Pharmacist: Signature Date
Printed name

2, New or unauthorised non-formulary medication

Consultant details
Name: Signature Base:

Contact telephone number:

NHS email address:

Authorisation (for office use only)

Printed name Supported Y/N Date


Principal Pharmacist (or deputy):

Clinical Service Director (or deputy):

Ratification (for office use only)

Printed name Ratified Y/N Date


Chair or deputy chair of medicines management
committee

Authorisation fax or email sent to dispensary Initials Date

Notification of authorisation sent to consultant and principal/ward Date


pharmacist by NHS email

Paperwork and authorisation emails uploaded to the R drive Date

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Appendix 5: Zuclopenthixol acetate (Acuphase®)
Prescribing information
Should only be prescribed;
 on the recommendation of a senior psychiatrist, after assessment
 for short term management of acute psychosis and mania
 if the patient is refusing oral medication and requires repeated injections (allowing adequate time to see
the effects of previous medications)
 reduce the dose in renal/ hepatic impairment. In renal/hepatic failure half the dose and consider serum-
level monitoring.

Should never be prescribed;


 for rapid tranquilisation,
 if the patient is neuroleptic naïve,
 if the patient is accepting oral medications,
 if the patient has suffered EPSEs/ movement disorders previously,
 if the patient is unconscious,
 if the patient has medical conditions including; being pregnant, suffering from neurological disease (e.g.
epilepsy, Parkinson’s disease), or cardiovascular disease.

Should never be administered to;


 hasten the antipsychotic effect of other antipsychotics,
 for rapid tranquilisation,
 at the same time as other IM medication (antipsychotics or benzodiazepines).

Administration information for Zuclopenthixol acetate (Acuphase®)


 The sedative effects usually begin after 2 hours, peak around 36 hours, and last for up to 72 hours. A
second dose may be given after 2 to 3 days.
 Maximum of 4 injections and 400mg in any two week period.
 Dose should be reduced to 25-50mg in the elderly and those with unknown tolerability.
 Review and withhold other antipsychotics for the duration of action.
 Zuclopenthixol Decanoate, the depot, may be administered at 200 to 400mg with the last dose of
Acuphase®.

Post injection monitoring

After every dose administered:


 Record temperature, pulse, respiratory rate and blood pressure every 4 hours for 72 hours using the track
and trigger tool.
 If unable to take observation, document reasons and evidence the patient is safe e.g. respiratory rate,
activity, pallor on RiO.
 Assess efficacy and side effects before considering additional doses.
 Consider withholding other antipsychotics for duration of action.
 Use a Food and Fluid chart to ensure adequate hydration.

SPC zuclopenthixol

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Appendix 6: High Dose Antipsychotic Treatment (HDAT) summary
sheet
Before considering HDAT you must consider the following:
 Has the patient been trialled on treatment for sufficient time to show response?
 Have you tried at least 2 antipsychotics (one FGA, if possible)?
 Has clozapine been considered/ trialled and found to be insufficiently effective/ not
suitable?
 Has the patient’s adherence to treatment been reviewed?
 Have adjunctive treatments shown insufficient response?
 Have psychological treatments shown insufficient response or are they deemed
inappropriate?

You must:
 Involve the senior psychiatrist and MDT, including pharmacist,
 Have the patient’s consent (if possible),
 Have the correct T2/3 in place (if applicable), and
 Make appropriate documentation in the PMR.

Before prescribing HDAT you should:


 Rule out complications e.g. ECG abnormalities, hepatic impairment.
 Consider concomitant medications which may increase the QTc interval, cause
electrolyte disturbances and/or drug interactions.
 Document the rationale and target symptoms (using rating scales) in the PMR, and
 Allow adequate time between dose increases for effect.

After starting HDAT you should:


 Monitor the patient, as per physical health monitoring guidelines, including regular
ECGs (baseline, when steady state is reached, after each dose increase and then every
6 months),
 Request additional biochemical tests/ ECG if drugs known to cause problems are
subsequently prescribed,
 Monitor for dose-related SE (e.g. EPSE, sedation, postural hypotension, and
anticholinergic).
 Assess the target symptoms after 6 weeks and again after 3 months.

You should advise the patient:


 To seek medical attention if they suffer from dizziness, palpitations and syncope.

On discharge from services you should:


 Liaise with the GP re ongoing monitoring

If HDAT does not result in sufficient improvement, dose(s) should be


decreased to within the usual range.

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