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Medicines Information e-bulletin
Dec 2014 Issue No. 89
Welcome to the Medicines
Information Centre’s
electronic bulletin for
Mersey Care NHS Trust
staff.
Medicine and Safety News
BNF Update November 2014
http://www.pharmpress.com/
mailouts/bnf/nov14/BNF_ene
wsletter.html◘
The aim of this e-bulletin is
to bring you current
awareness information on
various topics of interest.
MHRA Drug Safety Update,
Nov 2014, Vol. 8 Issue 4.
http://www.mhra.gov.uk/hom
e/groups/dsu/documents/publ
ication/con475313.pdf◘
UK five year antimicrobial
resistance strategy, 2013 to
2018.
https://www.gov.uk/governm
ent/publications/uk-5-yearantimicrobial-resistancestrategy-2013-to-2018◘
Antibiotics: secondary
prescriber's checklist
care
https://www.gov.uk/government
/uploads/system/uploads/attach
ment_data/file/366944/Secondar
y_care_prescribers_checklist.pdf
Risk of distress and death from
inappropriate doses of
naloxone in patients on longterm opioid/opiate treatment
https://www.cas.dh.gov.uk/View
andAcknowledgment/ViewAlert.a
spx?AlertID=102247◘
New reporting site
Yellow Card Scheme
for
the
https://yellowcard.mhra.gov.uk/
Strengthened warnings on use of
valproate in women and girls due
to risk of malformations and
developmental problems in babies
exposed to valproate in-utero.
http://www.ema.europa.eu/docs/e
n_GB/document_library/Press_rel
ease/2014/11/WC500177638.pdf◘
NHS Safety Thermometer Report October 2013 to October 2014
http://www.hscic.gov.uk/catalogu
e/PUB15877◘
NICE is consultation on controlled
drugs.
http://www.nice.org.uk/guidance/ind
evelopment/gid-cdgpg/documents
Recent Publications
In this issue:
Page
Medicine and Safety News
1
Recent Publications
1
Other News
1
Updated Consensus Statement
on High Dose Antipsychotics 2
Royal College of Psychiatrists,
Occasional
Paper
OP94.
Principles for responding to
people’s
psychosocial
and
mental health needs after
disasters
http://www.rcpsych.ac.uk/use
fulresources/publications/colle
gereports/op/op94.aspx◘
Antimicrobial
prescribing
toolkits and resources
Centre for Mental
Costs of perinatal
health problems
NICE guideline consultation:
Violence
and
aggression
(update):
http://www.nice.org.uk/guida
nce/indevelopment/gidcgwave0619/consultation◘
Health.
mental
http://www.centreformentalheal
th.org.uk/publications/costs_peri
natal_mh_problems.aspx?ID=711
https://www.gov.uk/governmen
t/publications/antimicrobialprescribing-resources-forprofessional-development-andpractice/antimicrobialprescribing-resources-forprofessional-development-andpractice◘
Don’t
use
antipsychotics
routinely to treat agitation and
aggression
in
people
with
dementia
http://www.bmj.com/content/34
9/bmj.g6420◘
NICE TA325. Nalmefene for
reducing alcohol consumption in
people with alcohol dependence.
http://www.nice.org.uk/guidance/t
a325◘
Good Pharmaceutical Medical
Practice; Nov2014
https://www.fpm.org.uk/policypu
blications/gpmp2014◘
Other News
NHS England, Monitor and the
NHS
Trust
Development
Authority
to
co-produce
guidance for commissioners.
http://www.england.nhs.uk/our
work/sop/◘
MyNHS – This new website
will allow patients to compare
NHS care and services
http://www.nhs.uk/ServiceSearch/performance/search◘
Duty of Candour and Fit and
Proper Persons Test–guidance
for the NHS.
http://www.cqc.org.uk/sites/def
ault/files/20141120_doc_fppf_fi
nal_nhs_provider_guidance_v10.pdf◘
Winterbourne View – Time for
Change.
Transforming
the
commissioning of services for
people
with
learning
disabilities and/or autism
http://www.england.nhs.uk/wpcontent/uploads/2014/11/transf
orming-commissioningservices.pdf◘
New
Drug
Application
submitted in US for a threemonthly
formulation
of
paliperidone palmitate.
http://www.biospace.com/News/
janssen-research-developmentsubmits-newdrug/355416/source=MoreNews
Paliperidone palmitate is now
licensed
in
US
to
treat
schizoaffective disorder.
http://www.biospace.com/News/jan
ssen-pharmaceutical-inc-release-us-fda/354540◘
Time limiting opioid substitution
therapy
https://www.gov.uk/government/up
loads/system/uploads/attachment_d
ata/file/371521/ACMD_RC_Time_lim
iting_OST_061114.pdf◘
Government to establish a new
Mental
Health
Taskforce
to
improves services
https://www.gov.uk/government/ne
ws/mental-health-taskforceannounced◘
Topic of this issue of e-bulletin
Updated Consensus Statement on High Dose Antipsychotics
Introduction
In November 2014, the Royal College of Psychiatrists published
an updated consensus statement on high-dose antipsychotic
medication, college report CR190. This statement replaces an
earlier report, CR138 (of the same title), from 2006. The report
reflects the consensus views of a group of clinicians on the
risks and benefits of high-dose antipsychotic medication for a
range of clinical indications for which antipsychotic medication
is commonly used in psychiatric practice. Members of the
Consensus Working Group took account of the evidence from
the published literature and their clinical experience, and
considered the clinical implications.
High dose antipsychotic may be defined as a total daily dose of
a single antipsychotic that exceeds the upper limit stated in the
manufacturer summary of product characteristics (SPC) or BNF
for that drug (with respect to the age of the patient and the
indication being treated). In addition, high dose antipsychotic
may also be defined as a total daily dose of two or more
antipsychotics which exceeds the SPC or BNF maximum in
terms of percentages. This is because the concurrent use of
two or more antipsychotics might result in an individual being
exposed to a cumulatively high dose amount of antipsychotic.
For the majority of people with acute psychotic illness, the
target dose for effective treatment is likely to be below the
licensed maximum. Prescribing a dose higher than is stated in
the SPC is likely to exceed the acceptable risk–benefit ratio for
the drug and constitutes off-label use. This means that the
manufacturer assumes no liability and the prescriber assumes
greater responsibility for any subsequent harm to the patient.
In practice, higher doses of antipsychotics are often prescribed
due to poor response of the illness to standard treatment
doses. Other reasons for high dose antipsychotic prescribing
include attempting to enhance or speed up the therapeutic
effect, managing challenging symptoms such as behavioural
disturbance and aggression or targeting particular symptoms.
Compared with oral antipsychotics, depot or long-acting
injections might increase the risk of excess dosage because
intramuscular injections are often combined with ‘top-up’ doses
of oral antipsychotics leading to cumulatively higher doses of
antipsychotics. Use of antipsychotics on a p.r.n. basis in
addition to regularly prescribed medication (e.g. for the
management of violence, aggression and disturbed behaviour)
can cause a patient to receive total dosages above the licensed
maximum. Factors predicting the use of high dosage include
younger age, longer duration of illness and a history of
violence and aggression.
Patients with more refractory
schizophrenic illness who experience repeated episodes are
also often prescribed accumulating increments in drug dose,
leading to prolonged exposure to high dosage with its
associated risks.
Key recommendations
The main recommendations from the Consensus Working Group
on High Dose Antipsychotics are listed below.
• There is no evidence that high-dose antipsychotic use is
beneficial for patients with first-episode or acute psychosis and
should be avoided. Where antipsychotic response is poor,
switching medication should be the preferred course of action,
rather than increasing doses above BNF limits. Clozapine
should be considered in patients who fail to show complete
remission following adequate trials of two different
antipsychotics.
• There is no convincing evidence that incremental increase of
antipsychotic dose at times of psychotic relapse, with
subsequent continuation of higher dose treatment provides
better relapse prevention in the long term.
• High doses of antipsychotic use is not recommended in rapid
tranquillisation because of the likely increased risk of extrapyramidal side effects (EPS), akathisia, neuroleptic malignant
syndrome (NMS), adverse cardiac events and seizures
associated with rapid dose increase. In rare situations when
BNF 24-hour maximum doses are exceeded, caution, increased
monitoring, and consultant psychiatrist advice is imperative.
• The effectiveness of using high-dose antipsychotic treatment
for controlling persistent aggression is not proven. Regular and
frequent review of treatment plans in relevant clinical settings
might allow for the safe and appropriate use of antipsychotic
medication without any increase in violence
• There is no convincing evidence that antipsychotic dosage
higher than the maximum licensed dose is more effective than
standard dosage for treatment-resistant schizophrenia. Before
prescribing high dosage antipsychotics, use of other evidencebased strategies for should be tried, including optimised use of
clozapine. If high-dose antipsychotic treatment is initiated, this
should be as a limited therapeutic trial, with dosage returned
to normal after a 3-month period unless the clinical benefits
clearly outweigh the risks. The potential side-effects of highdose
antipsychotic
regimens
should
be
monitored
appropriately, by systematic enquiry, physical examination,
ECG and appropriate haematological investigations.
• Clinicians should be aware that prescribing high doses of
antipsychotics might worsen dose-related side effects, EPS,
cardiac side effects, NMS and cognitive function, etc.
In summary, there is little convincing evidence that off-label
prescription of high doses of antipsychotic medication has any
therapeutic advantage. However, there is clear evidence of a
greater side-effect burden and a need for appropriate safety
monitoring. Any prescribing of high-dose antipsychotic
medication should be seen as an explicit, time-limited individual
trial with a distinct treatment target. There should be a clear
plan for regular clinical review including safety monitoring. Highdose antipsychotic treatment should be continued only if benefits
are not outweighed by tolerability or safety problems◘
References
1.
Royal College of Psychiatrists. Consensus statement on high-dose antipsychotic medication (CR190). London: Royal
2.
British National Formulary (BNF), BMJ Group & Pharmaceutical Press, available online at:
https://www.medicinescomplete.com/mc/bnf/current/
Summaries of Product Characteristics are available online from the MHRA or electronic Medicines Compendium
College of Psychiatrists, 2014.http://www.rcpsych.ac.uk/publications/collegereports/cr/cr138.aspx
3.
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