Antipsychotic Prescribing Guideline

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Antipsychotics – Prescribing Guideline

V1.0 Last reviewed: June 2021 Review date: June 2024

Antipsychotics
Traffic light classification - Amber 2
Prescribing Guideline for Primary Care Prescribers

Scope
This prescribing guideline is for the use of antipsychotic medication (excluding clozapine) in
the context of mental illness.

Contents
1) Therapeutic Summary
2) Antipsychotic Initiation
3) Depot Antipsychotic Injections
4) Duration of Treatment
5) Monitoring Requirements and Responsibilities
6) ECG Monitoring
7) Monitoring of Antipsychotic Blood Levels
8) Management of Antipsychotic Induced Weight Gain
9) Switching Antipsychotics
10) Special Populations – Older People
11) Special Populations – Children and Young People
12) Special Populations – Learning Disability
13) Special Populations – Pregnancy and Breastfeeding
14) Discontinuation of Treatment
15) Contraindications
16) Cautions
17) Side effects of Antipsychotics
18) Drug Interactions
19) Patient Information
20) References and Version Control

Appendix 1 - Criteria for Transferring Antipsychotic Prescribing to Primary Care


Appendix 2 - Monitoring Requirements for Adults and Older People
Appendix 3 - Antipsychotic Clinical Information (licensed indications, doses and
available products)

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Therapeutic Summary
NICE guidance for psychosis and schizophrenia in adults does not specifically recommend
an antipsychotic class or individual antipsychotic as first-line treatment for schizophrenia but
instead emphasises the importance of patient choice (taking into account adverse effects
and service user/carer views where possible)1.

NICE guidance for Bipolar Disorder recommends Haloperidol, Olanzapine, Risperidone or


Quetiapine for the treatment of mania or hypomania (taking into account patient preference,
any advance statements and clinical context)2. For moderate to severe bipolar depression,
Olanzapine (either on its own or combined with Fluoxetine) or Quetiapine are the
antipsychotics recommended by NICE. NICE guidance for bipolar disorder does not make
any specific reference to the use of Aripiprazole in adult bipolar disorder but does refer to the
NICE technology appraisal guidance (TAG)3 on Aripiprazole for treating moderate to severe
manic episodes in adolescents with bipolar I disorder.

NICE guidance for depression in adults suggests an antipsychotic such as Aripiprazole,


Olanzapine, Quetiapine or Risperidone as augmentation to antidepressant therapy4.
Modified-release Quetiapine is licensed as an adjunct in the treatment of major depression;
this is an off-label use of other antipsychotics. Note that oral Flupentixol is also licensed for
use in depressive illness but rarely used.

NICE guidance for obsessive-compulsive disorder suggests an antipsychotic (in addition to a


SSRI or Clomipramine) as a treatment option when other strategies have failed5.

Antipsychotics may be prescribed for patients with dementia who are experiencing agitation,
hallucinations or delusions that are causing them severe distress6. Refer to the
Nottinghamshire APC Dementia - managing behavioural and psychological symptoms
guideline.

Long-acting intramuscular (depot) antipsychotic injections are licensed for the maintenance
treatment of schizophrenia and other psychoses. Depot antipsychotic injections are a useful
option when compliance with oral antipsychotic treatment is unreliable1.

Antipsychotic Initiation
Oral antipsychotics should not be started in primary care unless in consultation with a
specialist.

Depot antipsychotics should only be initiated by specialist secondary care mental health
services. A small test dose is given initially and the patient observed for side-effects. If there
have not been any problems 4-7 days following the test dose the dose can be gradually
titrated to the lowest effective maintenance dose. In the case of Aripiprazole, Paliperidone
and Risperidone there are no injectable test doses so patients are given a small dose of the
oral antipsychotic to assess tolerability.

Prescribing of antipsychotics for off-label indications should not be transferred to primary


care unless upheld within a nationally recognised formulary such as the BNF, BNFC or
national guidance such as NICE guidelines. This should be discussed and agreed with the
GP prior to the transfer of prescribing.

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Appendix one outlines the criteria for transferring antipsychotic prescribing to primary care.

Administration of Depot Injections


Practitioners must have the necessary knowledge, skills and competency to safely
administer depot antipsychotic injections by deep intramuscular injection using the “z-track
technique”. Take particular care when selecting the needle gauge and length to ensure the
drug is given deep into the muscle. For obese patients a longer 2-inch 20g/21g needle
should be selected for gluteal administration and a 1.5-inch 22g needle for deltoid
administration.

Reduction of local injection site reactions


 Use the lowest practical volume
 Inject less frequently if possible to prevent hard plaques of tissue forming.
 Use the Z-tracking technique to avoid extravasation
 Use a needle of the right length for the patient to ensure deep intramuscular
administration (longer needles are required for people with a higher body mass index
(BMI))
 Use alternate buttocks or arms (rotate injection sites) to allow time to heal. Note that
not all depot antipsychotic injections are licensed for administration into the deltoid
muscle.

Duration of Treatment
As stated in NICE guidance, following the treatment of an acute episode of psychosis, the
risk of relapse is high if antipsychotic medication is stopped within 1 to 2 years1. For bipolar
disorder treatment should be reviewed within 4 weeks of resolution of symptoms and if
continued, reviewed every 3-6 months2.

Monitoring Requirements and Responsibilities


During antipsychotic treatment, improvement in the patient’s clinical condition may take
several days to some weeks. Throughout this period the patient should be closely
monitored. Please note that the occurrence of suicidal behaviour is inherent in psychotic
illnesses and mood disorders, and in some cases has been reported early after initiation or
switch of antipsychotic therapy. High risk patients should be closely supervised during
treatment.

Secondary care should maintain responsibility for monitoring physical health and the effects
of antipsychotic medication for at least the first 12 months or until the person’s condition has
stabilised. However, GP input may be sought if concerns are identified with the patient’s
physical health during this time. Thereafter, the responsibility for this monitoring may be
transferred to primary care.

GPs and other primary healthcare professionals should monitor the physical health of people
prescribed antipsychotic medication when responsibility for monitoring is transferred from
secondary care, and then at least annually1,2. See Appendix two for the recommended
general monitoring requirements and physical health monitoring schedule.

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ECG Monitoring
A baseline ECG should be considered for all patients but is recommended by NICE1,2 in the
following scenarios:

 Specified in the SPC of the prescribed medication


 Physical examination has identified cardiovascular risk
 There is a personal history of cardiovascular disease
 The service user is admitted as an inpatient

Antipsychotics may prolong the QTc interval. Particular caution is required in the following
instances7:

 Antipsychotic co-prescribed with other medicines that can prolong the QTc interval
 Antipsychotic prescribed above the BNF dose limit (high dose antipsychotic therapy)
 Underlying cardiac disease (e.g. ischaemic heart disease, congestive heart failure,
bradycardia, personal history of long QTc, left ventricular hypertrophy)
 Family history of long QTc
 Severe renal or severe hepatic impairment
 Physiological risk factors for long QTc and arrhythmia (hypokalaemia,
hypomagnesaemia, hypocalcaemia, anorexia nervosa, extreme of age, stress,
shock, female gender and extreme physical exertion).
 Co-existing alcohol or substance misuse

Annual ECG monitoring should take place if any of these risk factors are present or if there
has been a previous abnormality. More regular ECG monitoring may be indicated.

Management of QTc prolongation in patients prescribed antipsychotics7,8


QTc Action
<440ms (men) or  No action required unless other ECG abnormalities
<460ms (women)*
>440ms (men) or  Repeat ECG (consider checking the QTc calculation manually
>460ms (women) in case of machine error)
but <500ms**  Check for other prescribed medication which can lengthen the
QTc interval – www.crediblemeds.org
 Check electrolytes – potassium, magnesium and calcium
 Discuss with the specialist mental health team – may consider
dose reduction or switching to an antipsychotic with less effect
on QTc
 Discuss with cardiology if in doubt
>500ms  Red flag - immediate action required
 Repeat ECG (consider checking the QTc calculation manually
in case of machine error)
 Check for other prescribed medication which can lengthen the
QTc interval – www.crediblemeds.org
 Stop the suspected causative drug(s)
 Check electrolytes – potassium, magnesium and calcium
 Discuss with the specialist mental health team
 Discuss with cardiology
*Widely recognised QTc limits can’t be applied in patients with atrial fibrillation, bundle branch block, paced rhythm, excessive
tachycardia or bradycardia.

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**There is no validity in an ECG acquired in the context of resting right or left bundle branch block as the QT interval will be
inherently prolonged.

Effects of antipsychotics on QTc7


No effect Low effect Moderate effect High effect Unknown effect
Lurasidone Aripiprazole Amisulpride Pimozide Trifluoperazine
Clozapine Chlorpromazine Zuclopenthixol
Flupentixol Haloperidol All
Olanzapine Levomepromazine antipsychotic
Paliperidone Quetiapine doses
Risperidone exceeding the
Sulpiride recommended
maximum

Monitoring of Antipsychotic Blood Levels


A MHRA drug safety update (August 2020) states that blood level monitoring of
antipsychotics for toxicity may be helpful in certain circumstances, where testing and
reference values are available9.

Locally, routine blood level monitoring is not recommended for antipsychotics (excluding
Clozapine in certain clinical circumstances). The availability of assays and reference values
for other antipsychotics varies; results can take several days to report and reference values
are of limited use where they exist.

If toxicity related to antipsychotic medication is suspected, immediate action should be taken


in response to the symptoms displayed.

Management of Antipsychotic Induced Weight Gain


A significant proportion of people with diagnosis of severe mental illness develop risk factors
for cardiovascular disease and diabetes (smoking, overweight/obesity, alcohol misuse).
Factors driving weight gain and the risk of diabetes include: poor lifestyle, effects of
antipsychotic treatment (which varies between drugs and which can result in profound
weight increase in the first few weeks of treatment), pharmacogenetic differences between
individuals and direct effects of some antipsychotic medications to interfere with insulin
secretion10.

Lifestyle interventions should almost always be part of the first line of approach and in most
circumstances should be continued alongside any additional intervention. Switching to one
of the antipsychotic medications with lower propensity for weight gain is a strategy that
should also be considered. This must balance the possible benefit on weight against the
risks of inducing relapse of the mental illness.

Metformin can be considered as an adjunct to attenuate or reduce weight gain following


antipsychotic medication8; prescribing for this indication is Amber 2 classification on the
Nottinghamshire Joint Formulary. Lifestyle interventions should have been fully explored and
the other interventions considered first. In clinical trials metformin leads to a modest
reduction in weight (approximately 2 kg) over the short and long term but is less effective
than intensive lifestyle intervention10. There are some risks attached to Metformin that
require appropriate monitoring (renal function and vitamin B12).

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Switching Antipsychotics
Switching from one antipsychotic medication to another requires careful cross titration and
should usually be done under specialist supervision. If a patient who is no longer open to
mental health services requests a change in antipsychotic, or there are concerns about
tolerability or side effects, consider discussing this with the relevant mental health team.

Special Populations

Older People (>65 years)


Due to changes in pharmacokinetics and pharmacodynamics, older people are more
susceptible to adverse effects from antipsychotic medication. Consider the need for more
frequent reviews of antipsychotic dose, side effects and monitoring requirements (e.g. ECG
monitoring). For antipsychotic prescribing in the context of treating behavioural and
psychological symptoms of dementia, refer to the appropriate Nottinghamshire APC
guidance.

Children and Young People


Oral antipsychotic medication may be prescribed in the context of first episode psychosis,
recurrence of psychosis or schizophrenia, psychotic depression, bipolar disorder and as
augmentation therapy for obsessive compulsive disorder and body dysmorphic disorder2,
3,5,11
.
The choice of antipsychotic medication should be made by the parents or carers of younger
children, or jointly with the young person and their parents or carers and healthcare
professionals11. At the start of treatment, give doses below the lower end of the licensed
range for adults if the medication is not licensed for children and young people or at the
lower end of the licensed range if the medication is licensed. The dose should be slowly
titrated upwards within the dose range given in the BNF, the BNFC or the product SPC11.

The Child and Adolescent Mental Health Service (CAMHS) should maintain responsibility for
monitoring physical health and the effects of antipsychotic medication for at least the first 12
months or until the condition has stabilised. Thereafter, the responsibility for this monitoring
may be transferred to primary care. The physical health monitoring requirements for this
population are different from the schedule outlined in Appendix two of this guidance. Please
see NICE Clinical Guideline 155 or contact the specialist team for more information.

Learning Disability
If antipsychotic medication is prescribed for a mental illness, there is the expectation that the
treatment will follow the recommendations of the relevant NICE guidance.

People with a learning disability, autism or both are more likely to be prescribed psychotropic
medication (including antipsychotics) than other people. The use of antipsychotic medication
in this patient group should be challenged if there is no clear or appropriate indication for the
prescription. NICE12 suggests that specialists consider prescribing antipsychotic medication
to manage behaviour that challenges only when:

 Psychological or other interventions alone do not produce change within an agreed


time

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 Treatment for any coexisting mental or physical health problem has not led to a
reduction in the behaviour
 The risk to the person or others is very severe (for example, because of violence,
aggression or self-injury)

In all instances of antipsychotic prescribing for behaviour that challenges, regular review is
essential and should include a review of effectiveness, side effects and plans for stopping. It
is expected that all antipsychotic prescribing for this indication will be short term unless there
is a specialist decision to continue based on the following:

 There is evidence that the person with a learning disability, autism or both has gained
significant benefit from the use of the antipsychotic and recent attempts to withdraw
has resulted in a deterioration
 The nature of the behaviours experienced prior to prescribing the antipsychotic was
so severe that withdrawal is considered clinically inappropriate by the carers and
others

For more information on reducing the inappropriate prescribing of psychotropic drugs in


learning disability, autism or both see:
STOMP - NHS England Information
STOMP – GP prescribing information

Pregnancy and Breastfeeding


Refer to perinatal mental health services for any patient who is taking antipsychotic
medication and has a planned or confirmed pregnancy or is breastfeeding.

Discontinuation of Treatment
Acute withdrawal symptoms have been occasionally described after abrupt discontinuation
of oral antipsychotics e.g. sweating, insomnia, tremor, anxiety, nausea or vomiting. It is
recommended that oral antipsychotics are discontinued gradually, usually over many weeks
or months. The risk of relapse on cessation of antipsychotics may be minimised by more
gradual tapering.

If a patient has been discharged from mental health services and stops oral antipsychotic
medication, primary care is advised to follow up the patient and monitor for signs and
symptoms of relapse for at least two years after discontinuation1. A re-referral to mental
health services should be considered if there are concerns about deterioration in mental
state.

Withdrawal symptoms are unlikely following the discontinuation of a depot antipsychotic as


blood levels will fall slowly over some weeks after the last injection. If a patient has been
discharged from mental health services on depot antipsychotic and expresses a desire to
stop their depot (or if they have been stable on the depot for over five years) they should be
referred by the GP back to mental health services for advice and assessment.

Contraindications
Refer to the manufacturer’s Summary of Product Characteristics (SPC) for the individual
product.

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Cautions (for all antipsychotics)13


Blood dyscrasias, cardiovascular disease, conditions predisposing to
seizures, depression, diabetes (may raise blood glucose), epilepsy (may lower seizure
threshold), history of jaundice, myasthenia gravis, Parkinson’s disease (may be
exacerbated), photosensitisation (may occur with higher dosages), prostatic hypertrophy (in
adults), severe respiratory disease, susceptibility to angle-closure glaucoma and
pregnancy/breastfeeding (refer to the perinatal mental health team).

Refer to the manufacturer’s Summary of Product Characteristics (SPC) and BNF for further
cautions relevant to the individual product.

Side Effects (for all antipsychotics)13


Side effects Action
Common (≥1% and <10%) or very common (≥10%)
Extrapyramidal symptoms Parkinsonism: may remit if the dose is reduced or
 Parkinsonism (including joint the drug withdrawn. An antimuscarinic (e.g.
stiffness and tremor) procyclidine) may be helpful.
 Dystonia (abnormal face and
body muscle contractions) Dystonia: Dose reduction or an antimuscarinic
 Akathisia (restlessness) (e.g. procyclidine) may be helpful.
 Tardive dyskinesia (rhythmic,
involuntary movements of Akathisia: refer to the mental health team. A
tongue, face and jaw) reduction in dose, discontinuation or change to an
alternative atypical antipsychotic maybe required.

Tardive Dyskinesia: refer to the mental health


team. A reduction in dose, discontinuation or
change to an alternative atypical antipsychotic
maybe required. Review use of antimuscarinics
as these can often worsen Tardive Dyskinesia.
Please note that these symptoms can temporarily
deteriorate or can even arise after discontinuation
of treatment.

Insomnia Consider dose reduction


Drowsiness Give as a single night-time dose. Consider
temporary dose reduction. Advise patients not to
drive/operate machinery if affected
Constipation High fibre diet, good fluid intake, exercise,
laxative.
Dizziness Give as a single night-time dose. Consider
temporary dose reduction. Advise patients to take
time to stand up and not to drive/operate
machinery if affected.
Raised prolactin Can be asymptomatic or symptomatic
(hyperprolactinaemia) (galactorrhoea, gynaecomastia, disturbances of
menstrual cycle/amenorrhoea and sexual
dysfunction).
Dose-related. Consider dose-reduction or
switching to an alternative antipsychotic. Refer to
the mental health team.

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Hypotension (dose related) Initiate slowly.


Consider dose reduction or dividing the dose.
Weight gain/increased appetite Encourage a healthy balanced diet and regular
exercise. Monitor and refer to a dietician and/or
consultant if appropriate. See information above.
QTc interval prolongation See information in ECG monitoring section above.
Monitor and refer to the mental health team as
appropriate.
Vomiting Generally self-limiting. Consider taking after food
and/or dividing doses.
Dry mouth Recommend chewing sugar-free gum. Consider
taking after food and/or dividing doses. If severe
and persistent consider prescribing artificial
saliva.
Arrhythmias and tachycardia Check pulse, blood pressure and ECG.
Refer to the mental health team.
Uncommon (≥ 0.1% and <1%)
Hyperglycaemia (mostly associated Manage according to local diabetes guidelines.
with olanzapine, risperidone, Refer to the mental health team if appropriate.
quetiapine and clozapine)
Blood dyscrasias Perform blood counts if unexplained infection or
fever develops
Refer to the mental health team.
Embolism and thrombosis All possible risk factors for Venous
Thromboembolism should be identified before
and during antipsychotic treatment and
preventative measures undertaken14
Neuroleptic Malignant Syndrome Very rare.
(NMS) - hyperthermia, muscle Discontinue ALL antipsychotic(s). If suspected
rigidity, autonomic instability, altered immediate referral to an acute hospital is
consciousness, elevated Creatine required.
Kinase levels
Refer to the manufacturer’s Summary of Product Characteristics (SPC) and BNF for further
side effects relevant to individual products.

Drug Interactions
Refer to the manufacturer’s Summary of Product Characteristics (SPC) and BNF for
information on drug interactions.

Patient Information
Patient information leaflets for antipsychotics and mental health conditions can be can be
found at:

https://www.choiceandmedication.org/nottinghamshirehealthcare

https://www.rcpsych.ac.uk/mental-health

https://www.mind.org.uk/information-support/a-z-mental-health/

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References
1. National Institute for Health and Care Excellence. Psychosis and schizophrenia in
adults: prevention and management [Internet]. [London]. NICE;2014 [updated 2014
March]. (Clinical guideline [CG178]). Available from:
https://www.nice.org.uk/guidance/cg178
2. National Institute of Health and Care Excellence. Bipolar disorder: assessment and
management [Internet]. [London]. NICE; 2014 [updated 2020 February]. (Clinical
guideline [CG185]). Available from: https://www.nice.org.uk/guidance/cg185
3. National Institute of Health and Care Excellence. Aripiprazole for treating moderate to
severe manic episodes in adolescents with bipolar I disorder [Internet]. [London].
NICE; 2013. (Technology appraisal guidance [TA292]). Available from:
https://www.nice.org.uk/guidance/ta292
4. National Institute for Health and Care Excellence. Depression in adults: recognition
and management [Internet]. [London]: NICE; 2009 [updated 2016 Apr; cited 2016
Dec 16]. (Clinical guideline [CG90]). Available from:
https://www.nice.org.uk/guidance/cg90
5. National Institute for Health and Care Excellence. Obsessive-compulsive disorder
and body dysmorphic disorder: treatment [Internet]. [London]. NICE; 2005. (Clinical
guideline [CG31]). Available from: https://www.nice.org.uk/guidance/cg31
6. National Institute for Health and Care Excellence. Dementia: assessment,
management and support for people living with dementia and their carers [Internet].
[London]: NICE; 2018. (NICE guideline [NG97]). Available from:
https://www.nice.org.uk/guidance/ng97
7. Taylor, DM., Barnes, T. & Young, AH. (2018). The Maudsley Prescribing Guidelines
in Psychiatry (13th Ed.). Available from:
https://ebookcentral.proquest.com/lib/shu/detail.action?docID=5349044
8. Personal Communication with Dr Sukhbinder Bassi, Cardiologist, Sherwood Forest
Hospitals. April 2021.
9. MHRA. (2020). Clozapine and other antipsychotics: monitoring blood concentrations
for toxicity. Available from: https://www.gov.uk/drug-safety-update/clozapine-and-
other-antipsychotics-monitoring-blood-concentrations-for-toxicity
10. British Association for Psychopharmacology. (2016). BAP guidelines on the
management of weight gain, metabolic disturbances and cardiovascular risk
associated with psychosis and antipsychotic drug treatment. Available from:
https://www.bap.org.uk/pdfs/BAP_Guidelines-Metabolic.pdf
11. National Institute for Health and Care Excellence. Psychosis and schizophrenia in
children and young people: recognition and management [Internet]. [London]. NICE;
2013. (Clinical guideline [CG155]). Available from
https://www.nice.org.uk/guidance/cg155
12. National Institute for Health and Care Excellence. Challenging behaviour and
learning disabilities: prevention and interventions for people with learning disabilities
whose behaviour challenges [Internet]. [London]. NICE; 2015. (NICE guideline
[NG11]). Available from https://www.nice.org.uk/guidance/ng11
13. Joint Formulary Committee. British National Formulary (online) London: BMJ Group
and Pharmaceutical Press. [Accessed 17th February 2021]. Available from:
https://bnf.nice.org.uk/

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14. MHRA. (2009). Antipsychotics: risk of venous thromboembolic events. Available


from: https://www.gov.uk/drug-safety-update/antipsychotics-risk-of-venous-
thromboembolic-events

Mental Health Pharmacy Contacts


Nottinghamshire Healthcare NHS Foundation Trust

Wells Road Centre Pharmacy - 01159 555 356


Highbury Hospital Pharmacy - 0115 854 2247
Millbrook Mental Health Unit Pharmacy - 01159 560 883
Medicines Information Email: [email protected]

Version Control: Antipsychotics - Prescribing Guideline


Version Author(s) Date Changes
1.0 Hannah Godden, Specialist June Previous information sheets for
Mental Health Interface and 2021 second generation (atypical)
Efficiencies Pharmacist, antipsychotics consolidated
Nottingham and into a single document
Nottinghamshire covering all antipsychotics
CCGs/Nottinghamshire (excluding clozapine)
Healthcare NHS Foundation
Trust

John Lawton, Clinical


Pharmacy Manager,
Nottinghamshire Healthcare
NHS Foundation Trust

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Appendix One - Criteria for transferring oral and depot antipsychotic prescribing to
primary care

 The patient’s mental health is stable (this can mean stable but with some residual
symptoms)
 The patient is tolerating and accepting a regular dose of antipsychotic medication (or
consistently attends for their depot injection)
 If prescribed depot antipsychotic, the patient has been receiving the depot
medication for at least 12 months.
 Suitable support arrangements for community care are in place
 An agreed care plan is in place with respect to monitoring the patients' mental and
physical health, assessing the effects and side-effects of medication, and actions
required if the patient does not collect prescriptions/attend for their depot, shows
signs of relapse or intolerable side-effects
 It should be clearly documented in correspondence who will be responsible for
prescribing and carrying out the routine monitoring

Mental Health Team Responsibilities

 To assess the patient, establish the diagnosis, determine a management strategy


and devise a care plan in conjunction with the GP, other healthcare professionals
and appropriate support agencies
 To initiate the antipsychotic medication, titrate to the minimum effective maintenance
dose, monitor response and assess/manage initial side-effects
 When prescribing depot antipsychotics to specify the form, strength, dose and dosing
interval between injections, and brand where appropriate
 To provide the patient with written information about the illness and the antipsychotic
treatment
 To provide primary care with a copy of the agreed care plan
 The care plan should state who is responsible for monitoring the patients mental and
physical health at the appropriate time intervals
 To be available for advice and agree an action plan if the GP reports signs of
relapse, side-effects, compliance problems or level of risk to self or others is
increased
 To have procedures in place for rapid referral by the GP where appropriate
 To prescribe the antipsychotic medication until the GP takes over care
 To notify the GP as soon as practical of any changes to drug treatment or care plan
 For both the GP and the mental health team to receive a copy of any blood test
results, the name and address of BOTH parties should be specified on the pathology
blood sample form
 To advise on dose adjustments, when it is appropriate to stop and how to stop the
antipsychotic medication
 To discharge the patient to primary care when appropriate following agreement with
the GP

Primary Care Responsibilities


 To check that the patient engages with the practice and is compliant with oral
antipsychotic medication or attends for their antipsychotic depot injection at the
agreed times and to follow up the patient in cases of non-attendance

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 When prescribing depot antipsychotics to specify the form, strength, dose and dosing
interval between injections, and brand where appropriate
 To monitor at regular intervals the mental health, general health and wellbeing of the
patient, assess compliance, monitor and manage side-effects, in liaison with the
mental health team if necessary
 To ensure the patient has the necessary blood tests and to interpret the results,
seeking advice where necessary
 For both the GP and the mental health team to receive a copy of any blood test
results, the name and address of BOTH parties should be specified on the pathology
blood sample form
 To notify the mental health team as soon as practical of any test results or changes
to antipsychotic treatment, if appropriate
 To place the patient on the practice severe mental illness (SMI) register and
undertake annual reviews as described above

Patient Responsibilities

 Your mental health team will give you written information about your antipsychotic
medication. A good on-line resource is the Royal College of Psychiatrists at
http://www.rcpsych.ac.uk/mentalhealthinfoforall.aspx

 If you are unable to attend for your depot injection at the agreed appointment time
please could you contact the clinic as soon as possible and make another
appointment.

 If you have questions about the possibility of changing your treatment or switching
from a depot injection to an oral or tablet preparation, or you are thinking about
stopping your treatment, please discuss this first with your GP who can then refer
you back to specialist mental health services if necessary.

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Appendix Two – Monitoring Requirements for Adults and Older People

General Monitoring Requirements


Ask about compliance and side effects at every consultation.
All patients should be offered an annual physical health check by their GP (more often if clinically indicated). A
copy should be sent to the care coordinator and psychiatrist and put in the secondary care notes.

Lifestyle factors Smoking, alcohol, substance misuse, diet, level of physical activity
sexual health, contraceptive advice

Response to treatment Including changes in symptoms and behaviour

Cardiovascular risk Blood pressure and lipids


factors

Endocrine disorders Hyperglycaemia/diabetes and hyperprolactinaemia

Other side-effects Such as weight gain (monitor BMI and waist circumference), sexual
dysfunction (check prolactin), lethargy, emergence of extrapyramidal
movement disorder side-effects (including tardive dyskinesia)

Schedule for Physical Monitoring1,2

Initial Baseline Health Check Annual Health Check


(Secondary Care) & During First By GP
Year
(frequency may increase if
clinically indicated)
Thyroid Function √ √

Liver Function √ √

Renal Function √ √
(dependent upon age)
Full Blood Count √ (only if indicated)

E.C.G. √ (only if indicated – see


(if indicated) information above on ECG
monitoring)

Fasting Blood Plasma √ √


Glucose and HbA1c (repeat at 3 months and 12 months)
Weight / Height (B.M.I.) √ √
(plotted on chart) (weekly for 6 weeks and at 3 months
and 12 months)
Waist circumference √ √
(plotted on chart)
Lipid Profile √ √
(repeat at 3 months and 12 months)
Pulse and Blood √ √
Pressure (repeat at 3 months and after every
dose change)
Prolactin √ (only if indicated)

1. National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management [Internet]. [London]. NICE;2014[updated 2014 March]. (Clinical
guideline [CG178]). Available from: https://www.nice.org.uk/guidance/cg178
2. National Institute of Health and Care Excellence. Bipolar disorder: assessment and management [Internet]. [London]. NICE; 2014 [updated 2020 February]. (Clinical guideline [CG185]).
Available from: https://www.nice.org.uk/guidance/cg185

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Appendix Three - Summary of licensed indications, recommended doses and available products

Drug Licensed indications and recommended doses Oral products Additional


available - Information
Nottinghamshire
Joint Formulary
Amisulpride1,2 Acute and chronic schizophrenic disorders in which positive Generic tablets - Doses of up to
symptoms and/or negative symptoms are prominent. 50mg, 100mg, 300mg can be
200mg and 400mg administered once
Acute psychotic episodes daily. Higher doses
Doses between 400-800mg daily in 2 divided doses. Maximum should be given twice
1200mg daily. 100mg/ml oral daily.
solution sugar-free.
Schizophrenia with predominantly negative symptoms
50-300mg daily

No specific titration is required. For patients with mixed negative


and positive symptoms doses should be adjusted to obtain optimal
control of positive symptoms.

Doses should be reduced in renal impairment - see SPC for further


information. Dosage adjustments are not necessary in patients
with hepatic impairment.
Oral Treatment of schizophrenia in adults Tablets - 5mg, The orodispersible
Initially 10–15mg once daily 10mg, 15mg and tablet should be
Aripiprazole 1,3,4
Usual maintenance dose 15mg once daily 30mg taken immediately
Maximum dose 30mg once daily after removal from
Oro-dispersible the blister and placed
Treatment of moderate to severe manic episodes in Bipolar I tablets - 10mg and on the tongue, where
Disorder and recurrence prevention of mania in adults 15mg it will rapidly disperse
Initially 15mg once daily in saliva. It may be
Maximum dose 30mg once daily Oral solution taken with or without
1mg/1mL – very liquid. It may also be
Elderly: effectiveness not established in patients over 65 years. expensive. dispersed in water.

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Consider lower starting dose (e.g. 5mg once daily) when clinical Reserved for initial
factors warrant. dose titration in The aripiprazole
adolescents and in orodispersible tablets
No dosage adjustment required in renal impairment. No dosage swallowing are bioequivalent to
adjustment required in mild-moderate hepatic impairment. Use difficulties where the the aripiprazole
with caution in severe hepatic impairment – limited experience. orodispersible tablet tablets.
strengths do not
The dose may need to be reviewed if co-prescribed with strong meet the required
CYP3A4/CYP2D6 inhibitors or inducers. dose.

Depot Maintenance of schizophrenia in patients stabilised with oral Abilify Maintena® Administration into
aripiprazole 400mg powder and the deltoid or gluteal
Aripiprazole 1,5
By deep IM injection: 400mg every month, minimum of 26 days solvent for muscle.
between injections. prolonged-release
suspension for Aripiprazole
The dose may need to be reviewed if co-prescribed with strong injection pre-filled Maintena® requires
CYP3A4/CYP2D6 inhibitors or inducers. syringes reconstitution with the
solvent provided.
Abilify Maintena®
400mg powder and Oral aripiprazole
solvent for should be continued
prolonged-release for 14 consecutive
suspension for days after the first
injection vials injection whilst blood
levels reach steady
state.
Chlorpromazine 1,6 Schizophrenia and other psychoses, mania and hypomania Tablets - 25mg, Risk of contact
Initially 25mg three times daily or 75mg once daily at bedtime. 50mg and 100mg sensitisation - tablets
Adjust according to response (usual dose 300mg-600mg per day) should not be
Maximum dose 1g daily Oral solution crushed and
100mg/5mL and solutions should be
Use a third to half of usual adult dose in the elderly patients; with a 25mg/5mL handled with care.
more gradual increase in dosage.

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Antipsychotics – Prescribing Guideline
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Patients should avoid


Start with small doses in severe renal impairment because of direct sunlight – risk
increased cerebral sensitivity. Manufacturer advises caution in of photosensitisation.
severe hepatic failure (increased risk of accumulation).
Clozapine Refer to the separate Nottinghamshire APC Clozapine Information
Sheet

Oral Flupentixol 1,7 Schizophrenia and other psychoses Tablets - 0.5mg,


Initially 3-9mg twice daily, adjusted according to response 1mg and 3mg
Maximum dose 18mg daily

Elderly: Initially 0.5mg-4.5mg twice daily., adjusted according to


response

Depressive illness
Initially 1mg once daily in the morning; increased if necessary to
2mg once daily after 1 week.
Doses above 2mg to be given in divided doses, last dose to be
taken before 4pm.
Maximum 3mg daily

Elderly: Use half adult doses

Not studied in renal impairment. Start with small doses in severe


renal impairment due to increased cerebral sensitivity.

Not studied in hepatic impairment but flupentixol is extensively


metabolised by the liver; use with extreme caution.
Depot Maintenance in schizophrenia and other psychoses Solution for injection Administration into
By deep IM injection 20mg/mL,100mg/mL the upper outer
Flupentixol Usual maintenance dose 50mg every 4 weeks – 300mg every 2 and 200mg/mL buttock or lateral
decanoate weeks thigh
Maximum dose 400mg per week
(Depixol® and

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Antipsychotics – Prescribing Guideline
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Psytixol®) 1,8 Elderly: lower doses used

Oral Schizophrenia and schizoaffective disorder Tablets - 1.5mg, Haloperidol oral


2-10mg daily in 1-2 divided doses. Patients with first episode 5mg and 10mg solution may be
Haloperidol 1,9
schizophrenia generally respond to 2-4 mg daily, whereas patients (0.5mg available but mixed with water to
with multiple-episode schizophrenia may need doses up to 10 mg very expensive, use facilitate dose
daily. Maximum 20mg daily liquid if possible) administration, but it
must not be mixed
Elderly: Initially use half the lowest adult dose and adjust gradually Oral solution with any other liquid.
according to response up to maximum 5mg daily. Doses >5mg 10mg/5mL sugar- The diluted solution
only considered for patients who have tolerated higher doses. free and 5mg/5mL must be taken
sugar-free immediately.
Treatment of mania in bipolar disorder
2-10mg daily in 1-2 divided doses. Maximum 15mg daily. Take care not to
confuse the different
Elderly: Initially use half the lowest adult dose and adjust gradually strengths of liquid
according to response up to maximum 5mg daily. Doses >5mg formulation
only considered for patients who have tolerated higher doses.

Persistent aggression and psychotic symptoms in moderate-


severe Alzheimer’s and vascular dementia
Refer to local guidelines

Caution advised in renal impairment; in severe impairment


consider lower initial dose, adjust the dose in smaller increments
and at longer intervals.

In hepatic impairment it is recommended to halve the initial dose


and then adjust the dose in smaller increments and at longer
intervals.

A baseline ECG is recommended before treatment


Depot Maintenance in schizophrenia and schizoaffective disorders Solution for injection Administration into
By deep IM injection 50mg/mL and the gluteal muscle
Haloperidol Usual maintenance dose 50mg-200mg every 4 weeks 100mg/mL

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Antipsychotics – Prescribing Guideline
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decanoate Maximum dose 300mg every 4 weeks

(Haldol®) 1,10
Elderly: lower doses used

A baseline ECG is recommended before treatment


Lurasidone 1,11 Schizophrenia (adult) Tablets – 18.5mg, Tablets should be
Initially 37 mg once daily, increased if necessary up to 148 mg 37mg and 74mg. taken with food. If
once daily. taken without food
RED traffic light Lurasidone exposure
Schizophrenia (when given with moderate CPY3A4 inhibitors classification on the will likely be
e.g. diltiazem, erythromycin, fluconazole and verapamil) Nottinghamshire significantly lower.
Initially 18.5 mg once daily (max. per dose 74 mg once daily). Joint Formulary

Dosing recommendations for elderly patients with normal renal


function are the same as for adults.

In moderate (CrCl ≥30 and <50mL/min), severe (CrCl ≥15 and


<30mL/min) and End Stage Renal Disease, the recommended
starting dose is 18.5mg once daily, and the recommended
maximum dose is 74 mg once daily.

In moderate hepatic impairment the starting dose should be


18.5mg once daily and the maximum dose should not exceed
74mg once daily. In severe impairment the starting dose should be
18.5mg once daily and the maximum dose should do not exceed
37mg once daily.

Avoid concomitant administration with strong CYP3A4 inhibitors.


e.g.clarithromycin, cobicistat, intraconazole, ketoconazole,
ritonavir, saquinavir, telithromycin, voriconazole and strong
CYP3A4 inducers, e.g. carbamazepine, phenobarbital, phenytoin,
rifampicin, St John’s wort.
Oral Olanzapine 1, Treatment of schizophrenia Tablets - 2.5mg, Oro-dispersible
12, 13 Initially 10mg once daily 5mg, 7.5mg, 10mg, tablets are bio-

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Antipsychotics – Prescribing Guideline
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Usual dose 5-20mg daily 15mg and 20mg equivalent to


Maximum 20mg daily standard tablets and
Orodispersible should be placed in
Treatment of mania in Bipolar Disorder tablets sugar-free - the mouth or
Initially 15mg once daily in monotherapy (10mg once daily in 5mg, 10mg, 15mg dispersed in a full
combination therapy). and 20mg glass of water or
Maximum 20mg daily other suitable
beverage (e.g.
Prevention of recurrence in patients with bipolar disorder orange / apple juice,
Initially 10mg once daily (unless receiving olanzapine therapy for milk or coffee)
treatment of acute mania then continue the same dose for immediately before
prophylaxis). administration.
Maximum 20mg daily
Oro-dispersible
Consider a lower initial dose (2.5mg-5mg/day) for those 65 years tablets are no faster
of age and older when clinical factors warrant, in patients with acting than the
hepatic and/or renal impairment and in patients who have multiple standard tablet
factors (female, elderly, non-smoker) that may result in slower preparation.
metabolism.
Depot Paliperidone palmitate long-acting intramuscular injection is Xeplion® long-acting Given by deep
formulated as a monthly injection (Xeplion®) and a 3-monthly injection - 50mg, intramuscular
Paliperidone injection (Trevicta®). 75mg, 100mg, injection into the
(Xeplion and 150mg gluteal or deltoid
Xeplion® is a monthly injection muscle.
Trevicta®)1 Maintenance treatment of schizophrenia in adult patients stabilised Trevicta® long-
with paliperidone or risperidone. Dose at initiation depends on prior acting injection -
treatment. The optimal monthly maintenance dose is 75mg; some 175mg, 263mg,
patients may benefit from lower or higher doses within the 350mg, 525mg
recommended range of 50 to 150mg based on individual patient
tolerability and/or efficacy.

Trevicta® is a 3-monthly injection


Maintenance treatment of schizophrenia in adult patients who have
been stable on the same monthly dose Xeplion® long-acting

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Antipsychotics – Prescribing Guideline
V1.0 Last reviewed: June 2021 Review date: June 2024

injection for at least four months. The dose is based on the


previous monthly Xeplion® dose.

Quetiapine 1, 14, 15 Treatment of schizophrenia Immediate release Patients who are


Immediate release preparations: tablets - 25mg, being treated with a
Day 1: 25mg twice daily, day 2: 50mg twice daily, day 3: 100mg 100mg, 150mg, once-daily dose of a
twice daily, day 4: 150mg twice daily 200mg and 300mg prolonged-release
Adjust according to response quetiapine tablet may
Maximum dose 750mg daily Modified release be switched to the
Rate of dose titration may need to be slower and daily dose lower tablets - 50mg, equivalent total daily
in elderly patients 150mg, 200mg, dose of immediate-
300mg and 400mg release quetiapine
Modified release preparations (adult): tablets, taken in one
Day 1: 300mg once daily, day 2: 600mg once daily Oral solution or two divided doses.
Adjust according to response 20mg/mL Once above
Maximum dose 800mg daily 300mg/day the
immediate release
Modified release preparations (elderly): quetiapine should be
Initially 50mg once daily. taken in two divided
Adjust according to response in steps of 50mg daily doses.

Treatment of mania in Bipolar Disorder Can be administered


Immediate release preparations: with or without food.
Day 1: 50mg twice daily, day 2: 100mg twice daily, day 3: 150mg
twice daily, day 4: 200mg twice daily.
Adjusted in steps of 200mg daily, according to response
Maximum dose 800mg daily
Rate of dose titration may need to be slower and daily dose lower
in elderly patients

Modified release preparations (adult):


Day 1: 300mg once daily, day 2: 600mg once daily
Adjust according to response
Maximum dose 800mg daily

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Antipsychotics – Prescribing Guideline
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Modified release preparations (elderly):


Initially 50mg once daily.
Adjust according to response in steps of 50mg daily

Treatment of depression in Bipolar Disorder


Immediate release preparations:
Day 1: 50mg once daily at bedtime, day 2: 100mg once daily, day
3: 200mg once daily, day 4: 300mg once daily.
Adjust according to response
Maximum dose 600mg daily
Rate of dose titration may need to be slower and daily dose lower
in elderly patients

Modified release preparations:


Day 1: 50mg once daily at bedtime, day 2: 100mg once daily, day
3: 200mg once daily, day 4: 300mg once daily.
Adjust according to response
Maximum dose 600mg daily

Prevention of mania and depression in bipolar disorder


Continue at the dose effective for treatment of bipolar disorder; use
lowest effective dose for maintenance therapy

Adjunctive treatment of major depression


Modified release preparations (adult):
50mg once daily at bedtime for 2 days, then 150mg once daily for
2 days.
Adjust according to response
Usual dose 150-300mg daily

No dosage adjustment is required in patients with renal


impairment. Quetiapine is extensively metabolised by the liver.
Patients with hepatic impairment should be started on 25mg once

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Antipsychotics – Prescribing Guideline
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daily (immediate release) or 50mg once daily (modified release)


and gradually increased in 25mg or 50mg steps.
Oral Treatment of schizophrenia Tablets – 0.25mg, Risperidone tablets
Day 1: 2mg daily 0.5mg, 1mg, 2mg, may be administered
Risperidone 1, 16
Day 2: 4mg daily 3mg, 4mg and 6mg. once or twice a day.
Usual dose 4-6mg daily
Higher oral doses (8-16mg/day) may not increase therapeutic Oral solution Oro-dispersible and
benefit and result in more extrapyramidal side effects. Maximum 1mg/1mL standard tablets are
dose is 16mg per day bioequivalent.
Oro-dispersible
Treatment of mania in bipolar disorder tablets are non- Oro-dispersible
Initially 2mg once daily then increased in steps of 1mg daily if formulary; not cost tablets are not faster
required. effective. acting.
Usual dose 1-6mg daily
Can be administered
A lower starting dose of 250micrograms - 500micrograms twice with or without food.
daily is generally recommended in those over 65 years of age, and
those with renal or hepatic disease, gradually increasing to 1-2mg The oral liquid may
twice daily. be diluted with any
non-alcoholic drink,
(except tea).
Short term treatment (up to 6 weeks) of persistent aggression
in patients with moderate to severe Alzheimer’s disease.
Refer to local guidelines

Short term symptomatic treatment (up to 6 weeks) of


persistent aggression in conduct disorder in children from the
age of 5 years and adolescents with intellectual disabilities
See BNFC for doses
Depot Schizophrenia and other psychoses in patients tolerant to Risperdal Consta® Administered into the
risperidone by mouth 25mg, 37.5mg and deltoid or gluteal
Risperidone By deep IM injection 50mg powder and muscle.
(Risperdal Usual maintenance dose 25 – 50mg every two weeks. solvent for The powder must be
Maximum 50mg every two weeks. suspension for suspended in the
Consta®) 1, 17

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Antipsychotics – Prescribing Guideline
V1.0 Last reviewed: June 2021 Review date: June 2024

injection vials diluent and


administered using
the correct size
needle provided in
the pack.

During initiation, oral


risperidone should be
continued for 4–6
weeks.

Must be stored in a
refrigerator at
between +2 to +80C.
Please contact your
local mental health
trust pharmacy about
temperature
excursions.
Sulpiride 1, 18 Treatment of schizophrenia with mainly negative symptoms Tablets - 200mg and
200-400mg twice daily 400mg
Maximum 800mg per day
Oral solution
Treatment of schizophrenia with mainly positive symptoms 200mg/5mL
200-400mg twice daily
Maximum 2.4g per day

Elderly and renal impairment: prescribe lower initial doses and


increase gradually. Use with caution in hepatic impairment.
Trifluoperazine 1, 19 Schizophrenia and other psychoses Tablets – 1mg and
Initially 5 mg twice daily, daily dose may be increased to 15 mg 5mg
after 1 week. If necessary, dose may be further increased in steps
of 5 mg at intervals of 3 days. Usually, total daily doses would not Oral solution
exceed 30mg/day. When satisfactory control has been achieved, 5mg/5mL

24
Antipsychotics – Prescribing Guideline
V1.0 Last reviewed: June 2021 Review date: June 2024

reduce gradually until an effective maintenance level has been


established.

Reduce starting dose in elderly or frail patients by at least half.

Renal impairment: Start with small doses in severe renal


impairment because of increased cerebral sensitivity.

Hepatic impairment: The manufacturer advises to avoid

Oral Treatment of schizophrenia and other psychoses Tablets – 2mg,


Initially 20-30mg daily in divided doses 10mg and 25mg
Zuclopenthixol 1, 20
Usual maintenance dose 20-50mg daily
Maximum dose 150mg daily (maximum 40mg per dose)

Elderly: Use lower initial doses (5-15mg daily) and increase


gradually.

Renal impairment: use half the recommended dose in renal failure


and consider using lower initial doses in patients with severe renal
impairment.

Hepatic impairment: use with caution, consider using half the


recommended dose for patients with impaired hepatic function.

Depot Maintenance in schizophrenia and paranoid psychoses Solution for injection Administered into the
By deep IM injection 200mg/mL and upper outer buttock
Zuclopenthixol Maintenance dose: 200–500 mg every 1–4 weeks 500mg/mL or lateral thigh
decanoate Do not exceed 600mg weekly
(Clopixol®) 1, 21
Note: Do not confuse the slow and long-acting zuclopenthixol decanoate
(Clopixol®, Clopixol Conc®) depot with the faster, shorter-acting
zuclopenthixol acetate (Clopixol Acuphase®) formulation which (although
not recommended) is used for rapid tranquillisation. Errors have occurred

25
Antipsychotics – Prescribing Guideline
V1.0 Last reviewed: June 2021 Review date: June 2024

when these products have been interchanged. The drug name and the
packaging are very similar.

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