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Bracknellandascotccg.nhs.uk

Antipsychotic Guidelines GUIDELINES
TREATMENT OF SCHIZOPHRENIA
AND PSYCHOSIS
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines
Authors:
Ms Diane Booth, Chief Pharmacist, Berkshire Healthcare NHS Foundation Trust.
Mrs Kiran Hewitt, Lead Clinical Pharmacist, Berkshire Healthcare NHS Foundation
Trust.
Mrs Katie Sims, Clinical Pharmacist, Berkshire Healthcare NHS Foundation Trust.

Acknowledgements:
The authors would like to thank the members of the pharmacy department, Prospect
Park Hospital and the Drugs & Therapeutics Committee representatives of Berkshire
Healthcare NHS Foundation Trust who provided help, advice and constructive feed
back during the compilation of these guidelines.

Any enquiries regarding these guidelines or other medication related queries
should be forwarded to the MIS (Medicines Information Service), pharmacy
department, Prospect Park Hospital, on 0118 960 5075/5059, or your
ward/locality pharmacist.
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines CONTENTS
Medicines
Formulary
Use of Atypical Antipsychotic Drugs Prescribing Information - Atypicals
Additional Information/Guidance
Use of High Dose Antipsychotic Prescribing
Treatment of Special Patient Treatment Options in Patients with Co-existing or Drug Induced Problems Swapping Maintenance of Primary Care Patients Clozapine -Initiating
Appendices:
Appendix 1: Guidelines for the Management of Older
Patients with Acutely Disturbed or Violent Behaviour

Appendix 2: Guidelines for
Risperidone Long-Acting Injection (Risperdal Consta®) Appendix 3: Atypicals & Stroke – Guidance from the Trust 35 Appendix 4: Physical Monitoring of atypicals
NB: For the most up-to-date Guidelines for Rapid Control/Tranquillisation of Acutely
Disturbed Behaviour in Adults, see policy number CCR052 on the Trust website

References
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines MEDICINES FORMULARY
FIRST LINE TREATMENT CHOICE
Risperidone (oral tablets or liquid)
SECOND LINE/ALTERNATIVE ATYPICALS
Amisulpride
Aripiprazole
Olanzapine (oral tablets)
Quetiapine (either immediate or modified release tablets)
ALTERNATIVE TYPICALS
FOR SECONDARY CARE
INITIATION ONLY
Haloperidol
Depots: Flupentixol
Sulpiride
Fluphenazine
Haloperidol
Pipotiazine
Risperdal Consta®
RESTRICTED INDICATIONS
Zuclopenthixol
need for these must be discussed
with ward pharmacist prior to
Clozapine
prescribing
Sertindole
Olanzapine Velotabs®
Risperidone Quicklets®
Aripiprazole liquid
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Schizophrenia – Treatment Algorithm
Give chosen atypical antipsychotic at lowest
Continue treatment at effective dose
established effective dose for Adjust dose depending on response. Increase dose at least two years (five years if necessary at two weekly intervals for second or later presentations) Assess over 6-8 weeks Withdraw slowly (after careful consideration) under secondary care Ineffective (check or not tolerated Change to a different antipsychotic and follow
Continue treatment following process above (consider atypical and typical
process above agents depending on reason for non tolerance) Change to a depot
Continue with depot therapy Use lowest therapeutic dose at maximum allowable as sole antipsychotic for at interval (unless practical issues demand otherwise) least two years Adjust dose at 2-3 month intervals (five years for second or later presentations) Assess over at least four weeks Withdraw slowly (after careful consideration) under secondary care supervision OR if Ineffective or not tolerated
Change to clozapine
Continue treatment at established Titrate according to licensed dosage regime effective dose for at least two years (five years for second or Optimise treatment later presentations) Withdraw slowly (after careful Assess over at least six months consideration) under secondary care or partially ineffective MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines 1. Consider augmentation strategies:
clozapine plus sulpiride, amisulpride, risperidone,
If clearly measured lamotrigine, or omega-3 triglycerides
improvement, continue and document well in patient's 2. Consider alternatives to clozapine:
Risperidone, high dose olanzapine, quetiapine,
omega-3 triglycerides, or ECT

(Patient consent must be documented in the notes)
Contact ward pharmacist/MIS for information
Use of Atypical Antipsychotic Drugs

This policy takes account of the following facts concerning atypical antipsychotics:
• NICE recommends that atypical antipsychotics should be considered in the
choice of first-line treatment of patients with schizophrenia – newly diagnosed, relapsed or in those with unacceptable side effects from typical antipsychotics.1 • the tolerability of the atypical antipsychotics in terms of EPSE, makes them superior to conventional drugs. • risperidone has been chosen as first-line treatment in our guidelines, based on
consideration of atypicality, equal efficacy and cost.2,3 • one of the other atypicals should be considered when risperidone is an unsuitable choice due to intolerance, or previous non response. • where there is a past history of intolerance or non-response to typical agents, an atypical antipsychotic should be used. • where two atypical agents are not effective, clozapine treatment should be • atypical agents should be prescribed as monotherapy and never in combination with another atypical antipsychotic unless it is during a swap over period (or in combination with clozapine for a refractory illness). • atypical antipsychotics should not be prescribed on a "prn" basis or solely for their sedative properties. Benzodiazepines are more appropriate for this indication (for short-term use only). For example, lorazepam may be useful in controlling extreme agitated behaviour and symptoms during the initial weeks (up to four generally) of atypical antipsychotic therapy.2 General Treatment Principles
• if a patient is stable on a conventional antipsychotic with no significant side effects, a switch to an atypical antipsychotic should not be made 3 • typical antipsychotics are associated with severe movement disorders such as tardive dyskinesia, akathisia and acute dystonic reactions • patients should only be treated with ONE antipsychotic at a time (unless they are swapping treatments or being treated for a refractory illness) MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • oral and parenteral doses of the same drug should be prescribed separately because they can vary in bioavailability • intramuscular chlorpromazine should not routinely be prescribed
• anticholinergic drugs should ideally be prescribed on a "prn" basis if and when EPSE occur. Not all patients experience these side effects. Most patients do not require them long term and withdrawal should be attempted if the patient is no longer experiencing troublesome side effects – refer to anticholinergic guidelines. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Prescribing Information – Atypicals
Drug Available
Available
Strengths
Amisulpride
5mg, 10mg, 15mg, Clozapine
Olanzapine
2.5mg, 5mg, 7.5mg, Quetiapine
The XL preparation Oral XL® (modified offers no
release) tablets improvement in side Risperidone
0.5mg, 1mg, 2mg, MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • Consider the quantity of antipsychotic medication prescribed. Patients must
be able to obtain their medication easily and maintain regular contact with health care professionals such as their GP or community pharmacist. • Concordance. Compliance is a key issue in the management of schizophrenic
patients. Keep drug regimens as simple as possible and avoid poly-pharmacy. • Co-prescribing. Many drug combinations worsen side effects or can result in
altered blood levels and potential toxicity. Prescribe small quantities initially and review regularly, once a week if need be. • OTC medication. Examples of problematic over the counter (OTC) or herbal
remedies include cold remedies containing pseudoephedrine, sedating preparations and some antihistamines. These can either cause drug interactions, be sedating and/or have an effect on the QTc interval. St John's Wort is also a major problem in terms of drug interactions with other medication. • Side effects. Warn patients and their carers of the main side effects they may
experience when taking antipsychotic medication. This may prevent them from discontinuing medication unnecessarily. Reassure patients about milder and transient side effects such as increased appetite, sedation or dizziness and give advice on the management of more severe side effects such as sexual dysfunction, excess weight gain or extreme movement disorders. • Effects of lifestyle on medication. Alcohol acts centrally, affects dopamine and
will interact with antipsychotics. The metabolism of some antipsychotics can be affected by smoking and dose adjustment may be required (usually by secondary care). Recreational abuse of drugs such as cannabis can have extreme effects on mental state and this is particularly pronounced in patients suffering from schizophrenia. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Guidance on the use of High Dose Antipsychotics
(unlicensed use of antipsychotics)
NB: Doses or regimes outside the manufacturers' recommendations must be
considered unlicensed.
In 1994 the Royal College of Psychiatrists published a consensus statement on the
use of high dose anti-psychotics in emergencies as well as long-term oral treatment.
High doses have been associated with sudden death, cardiac toxicity, CNS toxicity,
respiratory depression and seizures. This statement was reviewed and updated in
2006 and addresses the use of high dose antipsychotic medication in adult mental
health services only (the full statement can be found on the Pharmacy pages of
BHFTs intranet site).
Identification of High Dose Antipsychotic Use
High dose antipsychotic prescribing can be achieved in two ways:
1) single antipsychotic prescribed at a daily dose that is above the BNF maximum dose (high dose single drug) 2) more than one antipsychotic prescribed concurrently where the combined total percentages is above 100%. The maximum daily dose of each drug is equal to 100% (high dose combined drugs). Maximum licensed doses are shown on pages 14. BNF/SPC maximum doses of antipsychotic medication should be adhered to and not exceeded, as there is little or no evidence to support this practice in most cases. In fact, the use of high dose antipsychotics tends to increase side effects without increasing treatment response 5. High doses antipsychotics are sometimes stated as equivalent to over 1000mg of chlorpromazine in 24 hours. However, if they are to be used, the recommendations are as follows: • the decision to use high doses should be discussed with the multidisciplinary team. The reasons must be discussed and explained thoroughly by the secondary care team to the patient and/or patient's relative or carer, and consent obtained where possible. This should include the reasons for initiating the unlicensed drug/dosage and details of dose, period of review, possible problems and side effects and any monitoring required • the responsibility for prescribing high/unlicensed doses lies with the patient's consultant psychiatrist and so the decision should only be made by that person • Supplementary prescribers should not make the decision to proceed to the use of MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • full documentation of the treatment plan in the patients notes; reasons for its use, previous response, outcome expectations, reasons for continuation and the patient's physical and mental state • the drug charts of patient's receiving high doses of either individual drugs or as a result of combinations, will be highlighted by the use of a pharmacy high dose antipsychotic sticker • not to routinely prescribe high doses by prescribing more than one drug
concomitantly (even if each individual drug is within the BNF maximum dose), or by allowing extra "prn" medication. There may be a need to prescribe in this way in an emergency or acute situation – if this case, it must be discussed with the RMO before being prescribed • consideration of any complicating factors such as co-morbidity, cardiac status and history, (particularly MI, arrythmias, abnormal ECG), obesity, substance abuse, elderly • consideration of potential drug interactions e.g. tricyclics, anti-histamines, diuretics, anti-hypertensives, anti-arrythmics, drugs that can prolong QTc interval, drugs that can increase antipsychotic plasma levels, OTC and herbal products (e.g. St John's Wort), alcohol • obtain a baseline ECG. If QTc is prolonged (above 440ms) then review treatment and consider a cardiac assessment. If it is decided to continue treatment, the reasons must be documented in the patient's case notes • continue to monitor ECG periodically (depending on baseline and clinical indication) – after 1 week then every 1-3 months while the high dose treatment continues. If an ECG is not performed, the reason should be documented in the case notes • gradual changes of dose, not more than once weekly • baseline and regular pulse, blood pressure, temperature and electrolyte checks, and ensure adequate fluid intake • regular review of progress with dose reduction to the normal range if there is no improvement after 3 months. Use validated rating scales to measure improvements in psychotic symptoms and side effects. File in patient's case notes • a confirmation letter should be sent to the patient's GP to ensure continuity of care on discharge. The consultant remains responsible for the use of the unlicensed medication within the recommended regime. Problems with symptoms and side effects must be referred back to the consultant. The use of high dose antipsychotics within BHFT will be regularly audited as part of the POMH-UK initiative, details of which can be found on the Pharmacy pages of the Trusts intranet site. Although the responsibility for treating a patient with high dose antipsychotics lies with the consultant, members of the multidisciplinary team – nursing, pharmacy and medical staff, are all responsible for ensuring adherence to these recommendations, highlighting patients who are prescribed high doses, whether it be planned or inadvertent, and for monitoring the patient. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Antipsychotics – Maximum and Equivalent Doses
Consensus
Possible Range of
Equivalent Dose
Equivalent Values
Maximum Dose
in Literature
(mg per day)
(mg per day)
(mg per day)
Chlorpromazine 100 Thioridazine 100 (hospital pt's only) Trifluoperazine 5 Zuclopenthixol 25 Atypicals *
1-12.5mg per week 50mg per week Haloperidol 15mg (4/52ly recommended) Flupentixol 10mg Pipotiazine 10mg 50mg two weekly (follow manufacturer's guidelines) *Equivalent doses for atypical antipsychotics are not particularly useful and so
manufacturers guidelines should be followed.
Equivalent doses should only be used as a guide, as assessment methods used for
determining equivalent doses can produce huge variations in their
recommendations.10 It is also important not to confuse antipsychotic equivalence
with sedation.

MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Antipsychotics – Relative Side Effects

Drug Anti-
Sedation
cholinergic
pyramidal
Typicals
+++ ++ ++ +++
Atypicals
NB: These are approximate side effect comparisons

Key:

+++ high incidence/severity
++ moderate
+ low
- very low
**
high potency antipsychotics low potency antipsychotics MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Important Investigations
The healthcare professional carrying out the initial assessment of a patient
(whether in primary or secondary care), is responsible for ensuring the
following investigations are performed.

• Full blood count, including haemoglobin and red blood cell parameters -
which may reveal neutropenia, anaemia, B12 and folate deficiencies. • B12 and folate - deficiencies may compromise cognitive function and produce
confusional states (folate deficiencies are not only implicated in the symptoms of psychosis, but can also reverse the beneficial effects of many antidepressants). • Metabolic function can be investigated by checking urea and electrolyte plasma
levels. Disturbances may arise due to dehydration or physical causes.
(antipsychotics can cause water dysregulation including hyponatraemia).
• Thyroid abnormalities often lead to changes in mental state and thyroid function
tests should be performed routinely, particularly during the early stages of
treatment.
• Liver function tests, although altered by some antipsychotics, may be useful in
revealing possible cases of alcohol abuse. • Blood glucose level to be measured initially to provide a baseline value and
because diabetes mellitus has been known to manifest itself as psychosis or delirium. It is important to continue monitoring blood glucose levels due to the increase in use of atypical agents, some of which can cause hyperglycaemia/type 2 diabetes. • Body weight to be measured initially to provide a baseline value; this is
increasingly important due to the increase in use of atypical agents, some of which can cause substantial weight gain. Hence, ongoing monitoring of body weight is also recommended (and can be minimised with careful diet and exercise). • Blood pressure
• Lipids – All patients should receive an initial lipid profile test.
• Prolactin should be checked at baseline in children and adolescents for all
antipsychotics. Adult patients about to receive typical antipsychotics or risperidone should receive a baseline test. • ECG – an initial ECG should be performed if indicated by history or clinical
picture (see trust ECG policy).
Ongoing monitoring will really depend on the individual patients circumstances;
baseline values of the above, co-morbidity, which antipsychotic has been prescribed
and so forth. It may also be indicated when there is a change in the mental or
physical health of the patient or when the treatment is modified.
• Blood glucose – At start and at 3 months (and at 1 month if taking olanzapine);
more often if there is evidence of elevated levels. • Body weight – see above
• Prolactin levels should be monitored in patients with suspected
hyperprolactinaemia and in patients reporting sexual side effects. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • Illicit drug use can be confirmed by urinary and/or blood drug screen.
• Blood pressure should be monitored during the first two weeks of treatment with
antipsychotics, especially clozapine (where the monitoring should be continued if the titration period is longer). Postural hypotension is usually more common in the elderly and can be unpredictable. ECG is essential when treating patients with high dose antipsychotics due to
the cardiac side effects of these drugs (notably prolongation of the QTc interval). • Lipids should be repeated after three months (or sooner if baseline level was
elevated). If the levels are normal, then the level should be tested annually only in patients over 40 years old. An agreement between consultant psychiatrist and GP should be reached regarding the need for an ECG to be performed and any subsequent monitoring requirements.
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Treatment of Special Patient Populations

Condition/
1st Choice
Alternative
Comments
Population
2nd Choice
Pregnancy chlorpromazine haloperidol (1) Lack of data
although limited atypicals –
Contact MIS,
Prospect Park
Hospital,
01189605075/50
59 for most up
to date info.
Lactation sulpiride (1) Lack of data
on safety of
atypicals.
(2) Choice may
depend on drug
used during
pregnancy.
Contact MIS for
most up to date
info.
Cardio-vascular amisulpride quetiapine (3)
(3) Choice
clozapine (3)
specific cardiac contact MIS for
specific info
Epilepsy haloperidol Start low and go interactions with (4) Start low and
haloperidol (4)
contact MIS for
specific info
haloperidol (5)
(5) Start low and
GFR). ADR's
more frequent –
contact MIS for
specific info
Typicals (6) (6) May reduce
risk in this group amisulpride (7)
(7) Choice is
morbidity. Start MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines low, go slow.
More susceptible
to all side effects
so monitor
Treatment Options in Patients with Co-existing
or Drug Induced Problems
Condition/
1st Choice
Alternative Avoid
Comments
Population
2nd Choice
Diabetes amisulpride clozapine (7)
(7) monitor
olanzapine (7)
levels regularly clozapine (8)
(8) Prevention
cure. Warn/counsel and monitor all patients olanzapine(9) most typicals
(9) may cause
associated with quetiapine aripiprazole amisulpride a transient rise Aripiprazole (Abilify™) seems to have a low incidence for inducing hyperprolactinaemia, hyperglycaemia/type 2 diabetes, or weight gain. Hence, this may be an appropriate choice of antipsychotic in those patients who have developed these problems with previous medication. In addition, risperidone and olanzapine should not be used to manage behavioural symptoms in patients with dementia, due to an increased risk of cerebrovascular events.11 Non medicinal interventions should be used to manage these patients. If this is unsuccessful, refer to the Trusts guidelines on this matter (Appendix 3). MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Antipsychotics - Swapping and Stopping
When switching from one antipsychotic to another, abrupt withdrawal of the first drug should be avoided, in order to prevent problems such as: -relapse or destabilisation of illness/symptoms -cholinergic rebound (nausea, vomiting, restlessness, anxiety, insomnia, fatigue, -myalgia, headaches) -withdrawal EPSE -combined side effects and drug interactions (from 1st and 2nd drug) However, where a severe, acute adverse effect has occurred (e.g. clozapine "red" blood result), immediate discontinuation may be necessary. No specific regimes for swapping antipsychotics are available. When selecting an appropriate regimen, a number of factors must be taken into consideration: • speed– how quickly the swap over needs to be carried out (taking into consideration how ‘unwell' the patient is) • individual susceptibility and patient tolerability • current dose of the first drug and its half life • individual drugs and their effects
"Cross tapering" is usually the preferred option, where the dose of the first drug is
slowly reduced (over anything up to 8 weeks), whilst the new agent is being
introduced.12

Contact the Medicines Information Service (MIS), pharmacy department,
Prospect Park Hospital (or your ward pharmacist), on 0118 960 5075/5059, for
advice on specific swapping regimes.
Discontinuation
Discontinuation symptoms have a number of characteristics:
• they usually start within 48 hours of stopping the drug
• they are resolved within 24 hours of restarting the drug • symptoms usually persist for 7-14 days, and could be longer • they include tardive dyskinesias, psychosis, cholinergic rebound headache • diarrhoea, vomiting and restlessness
Reducing the rate of drug withdrawal can reduce the incidence of discontinuation
syndrome and relapse of symptoms dramatically.


MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome (NMS) is a sudden loss in control of body
temperature during drug therapy. It occurs in up to 1% of patients receiving
antipsychotic medication and has also been seen in patients treated with
antidepressants, lithium, carbamazepine, metoclopramide and on sudden
discontinuation of levodopa therapy. It may be due to sudden changes in
dopaminergic function upsetting thermoregulatory centres in the brain.
NMS can be fatal due to renal and respiratory failure. The incidence of fatalities is
around 20% although higher figures have been quoted in patients receiving depot
antipsychotics.5, 8
Onset of NMS is variable; it may be as early as 45 minutes or as late as 65 days
after initiation of the antipsychotic.13

Main Symptoms
• hyperthermia or fever within 24–72 hours (not always seen e.g. if concomitant
carbamazepine is being given ) usually to over 38.50c • severe muscle rigidity and tremor • mental state changes - confusion, agitation, altered (reduced) level of consciousness, irritability, mutism • hypertension, fluctuating blood pressure and tachycardia • incontinence, retention, obstruction • raised creatinine phosphokinase (CPK) levels - over 1000iu in 1L • raised white cell count
Risk Factors
• being
• having an affective disorder • being on a MAOI • Being on fluphenazine depot
Treatment
• immediate withdrawal of all antipsychotic, antidepressant and lithium treatment
• transfer to medical or ICU ward, for general supportive medical intervention • supportive treatment to correct dehydration and hyper-pyrexia • use diazepam for sedation and as a muscle relaxant • bromocriptine 2.5 to 20mg TDS or IV dantrolene • monitor blood pressure, rigidity and muscle tone, and temperature every four MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • monitor white cell count, U&E, and liver function tests daily.
Rechallenge with antipsychotics
• review diagnosis of NMS to ensure key features were present and review
diagnosis to confirm the need for antipsychotic medication • consider alternative strategies where possible, e.g. ECT, benzodiazepines etc • a minimum of 5–14 days should elapse post recovery before restarting the • depot medication must never be used • for rechallenge, choose a drug from a different class from the one which caused NMS, or select a low potency drug (e.g. chlorpromazine) or an agent with low D2 receptor blockade (e.g. quetiapine, clozapine) • use low starting dose and increase slowly • perform alternate day CPK levels and monitor pulse, temperature and muscle tone daily until stable • inform patients and carers of the risks and how to recognise the syndrome in the Extra Pyramidal Side Effects (EPSE)

Akathisia, pseudoparkinsonism, dyskinesias and dystonias have all been associated
either acutely or chronically with antipsychotic drugs and are thought to be due to
non-selective dopamine (D2) receptor blockade.14
They are generally dose related, more likely to occur with typical antipsychotics (high
potency ones) but uncommon with most atypicals.7

Pseudoparkinsonism

Pseudoparkinsonism has been estimated to occur in 15-50% of patients. It is more
common in elderly females.15 Symptoms usually appear within one month of onset of
treatment or dose increase.
Characteristics
• muscle
• decreased/slow physical and/or mental activity • lack of facial expression • slow monotonous speech

Treatment
• reduce dose of antipsychotic
• prescribe antimuscarinic drug - e.g. procyclidine 5mg when required, up to three times a day (see antimuscarinic prescribing guidelines)
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • switch to an antipsychotic less likely to produce parkinsonian symptoms e.g. atypicals or sulpiride
The condition should resolve itself upon termination of treatment with the
antipsychotic, but may take several weeks to disappear depending on the individual
patient.
Acute Dystonia and Dyskinesia
Dystonic reactions have been estimated to affect 2-10% of patients.14 It is more
common in young males (especially antipsychotic naive males) given high potency
drugs. Acute dystonia can occur within hours of commencing treatment with oral
antipsychotics.
Characteristics
• uncontrolled muscle spasms
• involuntary tongue protrusion
Treatment
• reduce dose of antipsychotic
• prescribe antimuscarinic/cholinergic drug - e.g. procyclidine 5mg when required up to three times a day – see antimuscarinic prescribing guidelines
• switch to an antipsychotic less likely to produce parkinsonian symptoms e.g. atypicals or sulpiride
Akathisia
Akathisia is estimated to be a problem in 20-30% of patients taking antipsychotics.
It can occur within a few weeks of commencing treatment with antipsychotics or
increasing the dose.
Characteristics
• motor restlessness/compulsion to move/inability to stay still - rocking, foot
stamping and tapping, pacing • mental unease • irritability, agitation and aggression (often mistaken for worsening of the patient's symptoms or behavioural problems)
Treatment
• reduce dose of antipsychotic
• switch to lower potency or atypical antipsychotic • prescribe propranolol (30 - 160mg/day in divided doses) – unlicensed indication
• prescribe clonazepam (up to 1.5mg daily in divided doses) – unlicensed
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • anticholinergic drugs e.g. procyclidine may be effective if parkinsonism is also present, but are not very useful for the relief of akathisia
Upon discontinuation of the antipsychotic, akathisia symptoms generally resolve
within 7 days, but may take several weeks to disappear.
Tardive Dyskinesia
The prevalence of tardive dyskinesia (TD) has been estimated at around 10-20%
(may be up to 40% in long term patients). It is more common in elderly females,
those with an affective illness, negative symptomology and those who have had
acute EPSE.16 It usually occurs after months to years of treatment.
Characteristics
• abnormal, involuntary orofacial movements – lip smacking, chewing, tongue

TD is potentially irreversible in 50% of cases. After antipsychotic withdrawal,
symptoms may improve or worsen within several weeks, but this is usually followed
by a long slow recovery over the next months or years.

Treatment
• withdraw all antimuscarinics (which can exacerbate symptoms)
• reduce dose of, or discontinue antipsychotic • consider change to clozapine, olanzapine or quetiapine17 • withdraw other drugs which may exacerbate TD e.g. metoclopramide, antidepressants, antimuscarinics, and antiparkinson drugs • consider use of tetrabenazine 12.5-200mg/day *
• consider other treatments-
clonazepam (1-4mg/day in divided doses) **
buspirone **
vitamin E (400iu increasing to 1600 iu/day) **
calcium-channel blockers **

* only licensed treatment of TD in the UK
** unlicensed treatment options – contact MIS for specific information

MI = Medicines Information service at Prospect Park Hospital
Tel: 0118-960-5075, Monday – Friday 9am – 5pm
Email: [email protected]
Berkshire Healthcare NHS Foundation Trust
Edition 6.0 March 2010
Antipsychotic Guidelines Maintenance of Primary Care Patients
Where possible, patients maintained in the community on continuation therapy should be stable and free from side effects of their medication. These patients should be maintained on treatment for at least two years (five years for second or recurrent episode presentations). Unfortunately, few patients fall into this category and secondary care advice may be required for a number of reasons. Reasons for acute deterioration in mental state should be investigated, such as:- • substance misuse (including alcohol) • non-concordance • drug induced side effects Secondary care specialists should be consulted when the cause or source of
the problem is not obvious and will be happy to give advice concerning their
patients
Advice should be sought as soon as possible in the following circumstances: • Patients suffering from rapid weight gain in the first 3 months (steady weight gain over a long period may be managed with diet and exercise) • Patients suffering from movement disorders such as EPSE, akathisia and tardive • Patients suffering from sexual dysfunction or hyperprolactinaemia related • Patients suffering from significant deterioration in renal or hepatic function or • Patients suffering from excessive and prolonged sedation (lasting more than 4 – • Patients receiving an unlicensed drug or dose should have all their problems • Patients who remain partially resistant to treatment • Patients receiving depot medication. If the patient remains without symptoms for 5 years, consult with secondary care • Patient receiving poly-pharmacy. Refer those who are unstable and receiving multiple psychotropics and/or have coexisting medical conditions
NB: Clozapine doses must not be altered without secondary care advice.
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Clozapine

Initiating Treatment

• Clozapine can only be initiated under a consultant psychiatrist's
supervision/advice. • Each patient, doctor prescribing and pharmacist dispensing, has to be registered with the manufacturing company and blood testing is a mandatory part of treatment. This takes place weekly for the first 18 weeks, then fortnightly for the next 32 weeks and monthly thereafter. • Slow initiation of clozapine is essential to minimise common side-effects such as hypotension and sedation, which are dose-dependent and more frequent at the beginning of treatment. • Blood pressure (lying and standing) and pulse checks should be carried out twice a day during the titration period. • The initial dose should be 12.5mg, given at night (to avoid the need for blood pressure checks over the first few hours). • Doses are increased slowly (see table below), given twice daily, until a daily dose of 450mg daily is achieved (if tolerated). Response should be observed over several weeks at this dose before increasing further, in increments of 50-100mg/week. • If a dose is not tolerated, decrease to a dose which was tolerated and increase more slowly if need be. • If the patient has not taken clozapine for more than 48 hours, it should be re- commenced at the starting dose but the increasing regime can be done more quickly. Morning Dose (mg)
Evening Dose (mg)
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Clozapine Plasma Level Monitoring
Studies suggest that efficacy in treatment-resistant schizophrenia may be associated with "trough" clozapine concentrations of 0.35mg/L or above.18 Although clozapine dosage adjustment is normally made according to clinical response and tolerance, a clozapine plasma level may be useful in the following situations: • Poor responders after 3-6 months at over 400mg/day - if the level is less than 0.35mg/L, dosage adjustment can be made until the level exceeds this and then reviewed again • Suspected non-concordance with medication – total or erratic non-concordance is predictable from clozapine plasma levels • Managing drug-interactions (e.g. concurrent SSRIs or enzyme-inducing drugs, which could result in an unexpectedly high or low level of clozapine). A level will assist decisions on dose changes. Dose related adverse-effects can also be easily diagnosed particularly where clozapine clearance may be reduced, e.g. hepatic impairment. • Investigating clozapine overdose Metabolic differences between individuals can lead to large variations in values. A level is only useful after the titration period has elapsed and if the clozapine dose has been stable within the last week. The blood sample should ideally be taken 6-8 hours after a dose, but a trough sample (immediately before the next dose) can be taken if more convenient. Please make requests for plasma levels prior to the patient's next routine blood test and send to the pharmacy clozapine service, so that blood for a plasma level can be taken at the same time (to avoid patients having to have additional blood tests). The pharmacy clozapine service will arrange samples to be sent to the appropriate place (Medical Toxicology Unit, Kings College Hospital, London); do not send blood samples yourself. Clozapine Monitoring in the Community
Once a patient has been receiving clozapine for 52 weeks with no haematological problems, blood sampling is carried out every four weeks and prescriptions can be dispensed monthly. If appropriate, prescribing and management of the sampling can be transferred to the patient's GP. Transfer of prescribing responsibility needs to be agreed between the consultant, the GP, the pharmacy supplying the clozapine (which needs to be registered with the company) and the pharmaceutical company. The patient must be advised that the timings for blood sampling and supply of medication differ in the community. The patient must visit the GP for a blood test two weeks prior to the next supply of clozapine being due. If the result is green, a supply MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines of clozapine can be prescribed and collected from the nominated pharmacy in two
weeks time.

For further advice please contact the pharmacy clozapine service, Prospect
Park Hospital on 0118 960 5296.
Management of Clozapine-Induced Side-Effects

Side-Effect
Likely Time Frame
Management
Suggestions
First 4 weeks. May be Give larger proportion at persistent, but tolerance night. May need single night-time dose. Decrease dose if necessary First 4 weeks, but may Use a towel to cover pillow. persist. Common at night If distressing, try anti-muscarinic agent, e.g. hyoscine 300mcg sucked and swallowed at night. Discuss alternative agents with pharmacy First 4 weeks. May persist. Slow down dose escalation. Often dose-related Reduce dose. Consider small dose of beta-blocker Any time. Usually persists High fibre diet. Bulk forming/stimulant laxatives. Check for/encourage adequate fluid intake Take care when standing up. Reduce dose or slow down rate of increase. Give largest dose at bedtime. Consult pharmacy if severe. First 4 weeks, sometimes Monitor closely and slow down dose increases if necessary. Hypotensive therapy is rarely necessary. First year – or at anytime. Dietary counselling before and during treatment. Monitor weight. Exercise. Give antipyretic but check FBC. Not usually related to blood dyscrasias. Any time. More frequent at Avoid rapid dose increases. doses over 600mg/day After a fit, withhold dose for (and/or plasma levels above 1 day & resume at half 0.6 micrograms per litre) dose. Consider EEG/neurology referral and valproate prophylaxis. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Try an anti-emetic e.g. domperidone. Avoid metoclopramide and prochlorperazine (which can cause EPSE) Nocturnal Enuresis Avoid night-time doses (last dose before 6pm) and fluids before bedtime. Consider desmopressin. First 18 weeks usually Stop clozapine. Admit Depot Injections

General Guidance
The main advantage and general indication for giving antipsychotic medication in
depot form is that compliance with therapy can be assured. Disadvantages include a
suspected higher incidence of extra-pyramidal side effects (EPSE), local
complications due to the administration of an intramuscular injection and other side
effects associated with antipsychotic medication (see previous). These are more
common in elderly patients and when using high doses.

• always give a test dose when initiating treatment
- to minimise potential side effects of the drug and adverse reactions to the oil. It should be noted that some EPSE occur only after several doses of the depot (see BNF or contact MIC for manufacturers recommended test doses) • continue with the lowest therapeutic dose - low doses are better tolerated, less expensive and may also be at least as effective as higher doses.7 • administer at the longest possible licensed interval - all depots can be safely administered at their maximum licensed dosing interval - there is no evidence to suggest shortening the dose interval improves efficacy and less frequent administration is less stressful (injections are painful). y administer the smallest volume of depot possible (injections are painful). • adjust doses only after an adequate period of assessment - peak plasma levels and achievement of steady state are delayed with depot injections so should be increased only after careful assessment over at least one month. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Points to Remember
• at the start of therapy, plasma levels of antipsychotic released from a depot
increase over several weeks, without increasing the given dose • depot preparations take at least two months to achieve steady plasma levels • true relapse seems only to occur three to six months after withdrawing depot
• injections should be given into the buttock as a large muscle is needed for steady
absorption of the drug MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Appendix 1
GUIDELINES FOR THE MANAGEMENT OF OLDER PATIENTS
WITH ACUTELY DISTURBED OR VIOLENT BEHAVIOUR
(GUIDELINES FOR RAPID TRANQUILLISATION)

Acute behavioural disturbance can occur in the setting of delirium, psychiatric illness, dementia or/and alcohol misuse. Causes of delirium, for example infection, hypoxia, stroke, metabolic disturbance, dehydration and physical illness, need to be assessed. Agree and document management plans and risk assessment prior to the implementation of these guidelines. The practice of rapid tranquillisation in older people is ONLY to be used when
appropriate psychological and behavioural approaches have failed and where all
attempt has been made to correct the underlying physical causes.

The aims of rapid tranquillisation are:

To reduce suffering for the patient. 2. To reduce the risk of harm to others by maintaining a safe To do no harm (by prescribing in a safe way and to monitor physical health.) This protocol must be reviewed at 24 hours and if the patient is not settling within 24-
48 hours, a senior colleague should be consulted.

Prior to rapid tranquillisation:

• Ensure adequate numbers of staff who are trained in Control and Restraint, and life support training. Try to calm patient in a reassuring and confident manner. Try non-pharmacological approaches such as talking, distraction, time-out, and environment. Make a careful assessment of any medication previously received
and their response to it.
Check for any physical factors, which may be a contra-indication to rapid tranquillisation, for example, avoid use of lorazepam in respiratory depression. Check that all clinically relevant information is available and reviewed by a senior clinician where appropriate. Check that the management plan is clearly documented. If not, then
document it.
Try to obtain consent to accept medication/treatment and document response. If patient unable to give verbal consent, the emergency situation then applies. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Ensure that all emergency resuscitation equipment is available
before treatment is commenced.
In an emergency situation:
N.B. Treatment in an emergency is given under common law but must take account of a
person's rights under the Human Rights Act 98. This is particularly important in any use of
restraint, which must always be a final resort. The emergency situation applies when it is in
the best interests of the patients i.e. to save life, relieve serious suffering, prevent deterioration
in an emergency situation or represents minimum interference necessary to prevent the
patient from behaving violently and being a danger to others or themselves.
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines STEP INTERVENTION
1. Distraction, time out, environment etc.
If unsuccessful, go to step 2:
2. Offer oral treatment as below (take into account patient's size and physical status)
MAX DOSE IN 24 HOURS
Lorazepam
0.5 – 1mg
Or Trazodone
50 – 75mg
150 – 200mg
3. If unsuccessful or patient showing signs of, or known to be disinhibited, consider
the following antipsychotics orally:
MAX DOSE IN 24 HOURS
Quetiapine
25 – 50mg
100 – 150mg
Haloperidol
0.25 – 0.5mg
Risperidone Quicklets
Caution in dementia, CVA and
cerebrovascular risk factors
Olanzapine Velotabs
Caution in dementia, CVA and cerebrovascular risk factors 4. If oral medication refused, consider the following I/M:
INSTRUCTION
MAX
DOSE
IN
24HRS
I/M Lorazepam
Repeat in 1 hour if not settled. 2-4mg
If Lorazepam is contra-indicated (i.e.
Repeat 3-4 hourly
respiratory depression) or
unsuccessful, consider:
Or I/M Olanzapine
Repeat after 2 hours. Max 3 20mg
Especially if Parkinsons Disease or – 5mg
injections in 24 hours. Monitor for
disinhibition. Caution in dementia, CVA sedation and cardio-respiratory
and cerebrovascular risk factors depression if patient has had I/M
benzodiazepine. Avoid giving
olanzapine I/M and lorazepam I/M
within an hour of each other.
Or I/M Haloperidol
Repeat 1-2 hourly
OBSERVATIONS and further management:
• Monitor pulse and respiratory rate every 10 minutes for 1 hour after IM injection • Monitor BP 30 and 60 minutes after • Ensure availability of anticholinergics such as Procyclidine 2.5mg – 5mg IM in case of acute dystonic reactions • Ensure availability of Flumazenil to reverse the effects of Lorazepam. Flumazenil must be given by a doctor if the respiratory rate drops below 10/min after lorazepam has been used. If this happens during standard working hours, contact a doctor on the ward or within the hospital ASAP and consider calling 999. Outside standard working hours, contact the on-call doctor AND call 999. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Consider use of Mental Health Act in patients where repeated enforced medication is N.B. THE MENTAL HEALTH ACT HAS NO REMIT TO TREAT PATIENTS FOR PHYSICAL ILLNESS.

References
Working group for Faculty of Old Age Psychiatry RCPsych, RCGP, BGS and Alzheimers Soc
summary.htm#notes
Committee on Safety of Medicines
www.mca.gov.uk.aboutagency/refframework/csm/csmframe.htm
Howard R, Ballard C. O'Brien J, Burns A. Guidelines for the management of agitation in
dementia. International Journal of Geriatric Psychiatry 2001; 16:714-717
BNF September 2004
NICE guidelines
HRA 98 articles 3,5,8.
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Appendix 2

Guidelines for the Use of Risperidone Long-Acting
Injection (Risperdal Consta®): SUMMARY
Risperdal Consta® is indicated for the treatment of schizophrenia and other psychotic
conditions in which positive symptoms and/or negative symptoms are prominent. It
should be considered for:

1. Patients who have responded to treatment with an oral atypical antipsychotic, but who
are non-compliant, or 2. Patients who have responded well to a depot preparation of a typical antipsychotic, but
are suffering from side effects.
Risperdal Consta® should not be used as first line treatment or for patients who have
a history of treatment resistance to atypical antipsychotic agents.
Treatment Guidelines

Risperdal Consta® releases risperidone via sustained release biospheres. Only small
amounts of risperidone are released during the first three weeks. The main drug release
starts in week three and peaks in weeks 5-6. As a result, alternative antipsychotic cover
(ideally oral risperidone) will be needed for the first three weeks of treatment.
• Risperdal Consta should only be initiated by or following consultation with a consultant
psychiatrist
• Risperidone naive patients should undergo a trial of oral risperidone to identify
intolerance to the drug. Oral risperidone should be given for at least three weeks
• patients taking 4mg of risperidone orally (or equivalent dose of another antipsychotic) should
be started on the 25mg dose administered every two weeks • Patients taking higher doses of oral antipsychotic can be stared on 37.5mg every two weeks • any existing antipsychotic medication should ideally be reduced and discontinued three weeks after the first Risperdal Consta® injection • at three 25mg doses of Risperdal Consta should be given at two weekly intervals
prior to increasing the dose, to allow blood levels to peak. • where necessary, (e.g. patients receiving the equivalent or more than 4mg per day of risperidone), the dose of Risperdal Consta® may then be increased to 50mg • if oral supplementation is deemed necessary, consider low dose benzodiazepines (short term) Switching regimes may vary depending on the individual patient and current drug
regime. Contact the Medicines Information Service, pharmacy department, Prospect
Park Hospital, on 0118 960 5075/5059 for specific information.

Storage and General Information

MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Each pack of Risperdal Consta contains one dose of the injection, the diluent and needles,
etc necessary for preparing the dose. The entire box must be refrigerated between 2–80c
for safe storage. Packs should not be exposed to temperatures over 250c. The product must be
used within seven days of the dispensing date; this will be indicated on the pharmacy dispensing
label. Once reconstituted, the suspension must be used within six hours.
NB: Inappropriate storage of Risperdal Consta has lead to much wastage and hence
cost pressures within the Trust. Please help to avoid wastage by ensuring the cold chain
is maintained and that only those injections that are due to be administered within the
next seven are ordered from pharmacy.

Some clinical waste is produced when administering the injection. Staff must carry sharps
boxes and be prepared for the safe disposal of waste products - refer to the most current
Berkshire Healthcare NHS Trust Care and Control of Medicines Policy for full guidelines.
Training for Staff

Nurses should familiarise themselves with the method of reconstitution and injection before
administering. Each member of staff is personally responsible for their own competency to do
this, and should ensure that they maintain this level of training. Janssen-Cilag are happy to
organise training sessions for staff and may be contacted through pharmacy, by the ward or
the CMHT lead.

Precautions and Contra-indications

- patients with a known hypersensitivity to the product or diluent
- patients
- patients with a history of NMS Patient care may be managed by primary care teams/workers when:

- the patient was initiated on Risperdal Consta® in primary care
- OR the patient has been stabilised on a maintenance dose of Risperdal
Consta®
- OR there has been discussion between primary and secondary care to
agree the transfer of responsibility before the patient is stabilised.
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Appendix 3

Atypical Antipsychotics and Stroke
Guidance for Patient Management from Berkshire Healthcare NHS
(March 2004)
Introduction
The CSM recently issued warnings against using risperidone and olanzapine
to treat the behavioural symptoms of dementia. The guidance comes after a
review of safety data revealed a 3-fold increase in stroke risk for older people
with dementia who were treated with risperidone or olanzapine. This takes the
risk of stroke in dementia patients from 1.2% with placebo to 3.3% with
risperidone with similar rates of increased risk for olanzapine.
Prescribers should consider the risk of cerebrovascular events (including risk
factors such as diabetes, hypertension, smoking and AF), before treating
patients with a history of stroke or transient ischaemic attack.
Action
Review all dementia patients currently receiving either olanzapine or
risperidone for behaviour problems within the next 4 weeks.

Antipsychotic withdrawal should be managed slowly, over 2-4 weeks, except
in the following patients, for whom advice from secondary care specialists will
be necessary:
people with a diagnosis of schizophrenia and a history of CVA / TIA people with continuing moderate to severe symptoms despite medication people with a history of serious risk to self or others may prove problematic for other It may be necessary to maintain these patients on a prescription of risperidone or olanzapine. This should only be done with either the patient, relative or carer's consent and under the supervision of a specialist. Many patients who suffer from dementia may be managed without medicines, using psychosocial, behavioural and environmental interventions. A trial period without medication over 2–4 weeks should be attempted. If medication is needed, another alternative (see table below) may be introduced slowly. Doses should always be at the lowest level to maintain improvement, and should be monitored regularly. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Where these options have been tried and found to be unsuccessful in
maintaining the patient's behaviour, a secondary care specialist should be
consulted.

If you would like further advice, please call the Medicines Information Service,
Pharmacy, Berkshire Healthcare NHS Trust, Prospect Park Hospital, 0118 960 5075.
The full Royal College of Psychiatrists treatment guidelines are available at:
Drug treatment options
Indications
Cautions and considerations
daily
dose
Used in acute situation Risk of stroke cannot be excluded. Better tolerated side effects than older Used in acute situation Risk of stroke cannot be excluded. Better tolerated side effects than older Used in acute situation Risk of stroke cannot be excluded. Better tolerated side effects than older A diagnosis of dementia should always be May be of use if confirmed before prescribing. May take cholinesterase patient is suffering some time to take effect and initially need augmentation with other medication. Can increase agitation, the risk of falls and situation. Short acting, aggression. Risk of tolerance and dependence with prolonged use. Prescriptions should be reviewed regularly. May be particularly of use where there is a 50mg- antidepressant. Used diagnosis of depression or depressive in anxiety/ agitation. Used for agitation / May be particularly of use where there is a 200- diagnosis of mood disorder symptoms. High risk of EPSE / TD. Safer than other Used in acute situation older antipsychotics in cardiac risk. Anticholinergic side effects can be a problem in patients suffering from impaired MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines cognitive function. Avoid in Lewy Body dementias. Older antipsychotic with risk of EPSE and TD. Anticholinergic side effects can be a Psychosis, agression, problem in patients suffering from impaired 2mg-50mg cognitive function. Avoid in Lewy Body dementias. Older antipsychotic with risk of EPSE and Sedative, used for TD. Anticholinergic side effects can be a agitation/restlessness, problem in patients suffering from impaired though not a very cognitive function. Avoid in Lewy Body potent antipsychotic. Newer drugs may have fewer side effects. Risk of tolerance and dependence with Severe insomnia. prolonged use. Prescriptions should be reviewed regularly. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Appendix 4

Physical Health Monitoring Guidelines for Atypical

All patients should have the following initial physical checks whether prescribed anything or
not:
• Weight and height Children and adolescents should also have prolactin levels checked
Patients who are elderly and have any other cardiac risk factor should also have an initial
ECG. See trust ECG policy for full details.
Drug
Essential
Maintenance
Management
monitoring
monitoring
guidelines
guidelines
s by
BHFT at
baseline
If hyperglycaemia annually if normal or NIDDM suspected, refer/treat in usual way Refer to BHFT for If concerns about electrolyte imbalance weight gain (>7% thought to be drug-induced to be referred to psychiatrist (2) manner if hyperlipidaemia diagnosed Blood dyscrasias possible with all antipsychotics (3) MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Essential
Maintenance
Management
monitoring
monitoring
guidelines
guidelines
s by
BHFT at
baseline
If hyperglycaemia annually if normal or NIDDM suspected refer/treat in usual way If concerns about electrolyte imbalance arise year, then 3 monthly Treat in usually manner if hyperlipidaemia diagnosed phase if abnormalities at baseline 6 monthly for one year, then annually specialist advice if patient complains liver impairment of GI disturbance, suspected abdominal pain, fever, chills, muscle aches, etc (indicative of liver abnormalities) Essential
Maintenance
Management
monitoring
monitoring
guidelines
guidelines
s by
BHFT at
baseline
3/12 if risk factors or diabetic. Otherwise 3.12ly. 3/12ly thereafter Refer to BHFT for MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines hyperprolactinaemia 4.52ly or at every 6/12ly at clinic manner if hyperlipidaemia diagnosed At each clozapine If problems arise, refer to specialist (follow clozapine Weekly for 18/52, 2/52ly for up to a year, then 4/52ly clozapine guidelines 6/12 ly at clinic specialist advice if drug induced liver impairment suspected physical symptoms/fever Essential
Maintenance
Management
monitoring
monitoring
guidelines
guidelines
s by
BHFT at
baseline
If hyperglycaemia factors or diabetic suspected, then 3/12ly. refer/treat in usual Otherwise at 1/12 way and then 3/12 ly for 1 year then annually Refer to BHFT for hyperprolactinaemia If concerns about electrolyte imbalance arise 4/52 ly 4/52ly for 1 year, 3 monthly thereafter MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines After 3/12, then manner if hyperlipidaemia diagnosed Annually (refer to specialist/treat as per hypertension guidelines) specialist advice if drug induced liver Essential
Maintenance
Management
monitoring
monitoring
guidelines
guidelines
s by
BHFT at
baseline
If hyperglycaemia 3/12s, then after refer/treat in usual way. Contact BHFT if occurs within first 12/12 hyperprolactinaemia If concerns about electrolyte imbalance arise 4/52 ly for 1 year After 3/12s then manner if hyperlipidaemia diagnosed specialist advice if patient complains liver impairment of GI disturbance, suspected abdominal pain, fever, chills, muscle aches, etc (indicative of liver abnormalities) MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines Essential
Maintenance
Management
monitoring
monitoring
guidelines
guidelines
s by
BHFT at
baseline
If hyperglycaemia 3/12s, then after refer/treat in usual way. Contact BHFT if occurs within first 12/12 Refer to BHFT for If concerns about electrolyte imbalance arise 4/52 ly for 1 year manner if hyperlipidaemia diagnosed specialist advice if patient complains liver impairment of GI disturbance, suspected abdominal pain, muscle aches, etc (indicative of liver abnormalities) (1) healthy eating and exercise advice to be given routinely to all patients commencing all antipsychotics (2) substantial weight gain (>7% of baseline) thought to be drug-induced to be referred to psychiatrist for advice on management (may involve dietician) (3) blood dycrasias possible with all antipsychotics (4) ECG at baseline, 3/12 ly then annually recommended for all patients who:- MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines • are on high doses and/or combinations of antipsychotics • are elderly patients • are taking concomitant drugs that can prolong QTc interval • have any other cardiac risk factors present The frequency of ECGs will depend on the individual and where clinically indicated; remember these are the minimum monitoring guidelines and clinicians may wish to carry out these tests on a more frequent basis where necessary. See ECG policy for full details. MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010 Antipsychotic Guidelines References
1.
NICE Technology Appraisal Guidance No 43. Guidance on the use of newer antipsychotic drugs for the treatment of schizophrenia Feifel D. Rationale and guidelines for the inpatient treatment of acute
psychosis. J Clin Psych 2000; 61 (suppl 14): 27-32
Adams C et al. Drug treatments for schizophrenia. Effective Healthcare
Bulletin 1999; 5(no.6): ISSN 0965-0288
Monthly Index of Medical Specialities, March 2004 edition. Haymarket Medical Publications Ltd., London, UK Taylor M, Geddes J. Current drug treatments available for psychosis. Prescriber 19/11/02; 31-42 British National Formulary 46 September 2003, British Medical Association, Royal Pharmaceutical Society of Great Britain, London, UK Taylor D, Paton C, Kerwin R. The South London and Maudsley NHS Trust 2003 Prescribing Guidelines. 7th Edition, Martin Dunitz, London, UK Bazire S. Psychotropic Drug Directory 2003/4, Fivepin Publishing Ltd, Salisbury, Wilts, UK Atkins M et al. Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications. Psych Bulletin 1997; 21: 224-226 Rey MJ, Schulz P et al. Guidelines for the dosage of neuroleptics. Chlorpromazine equivalents of orally administered neuroleptics. Int Clin Psychopharmacol 1989; 4: 95-104 Wyatt RJ. Risks of withdrawing antipsychotic medications. Arch Gen Psych
1995; 52(3): 205-208
Perry PJ, Alexander B, Liskow B. Psychotropic Drug Handbook 7th edition 1997, American Psychiatric Press, Inc., Washington, DC UKMIPG, National Prescribing Centre. New developments in antipsychotic drug therapy: an overview 05/2001: 1-12 Love RC. Novel versus conventional antipsychotic treatment.
Pharmacotherapy 1996; 16(1 pt 2): 6S-10S
Barnes TRE, McPhillips MA. Critical analysis and comparison of the side
effect and safety profiles of the new antipsychotics. Br J Psych 1999;
174(suppl 38): 34-43
Glazer W. Expected incidence of tardive dyskinesia associated with atypical
antipsychotics. J Clin Psych 2000; 61(suppl 4): 21-26
Taylor D, Duncan D. The use of clozapine plasma levels in optimising
therapy. Psych Bull 1995; 19: 753-755
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected] Berkshire Healthcare NHS Foundation Trust Edition 6.0 March 2010

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