Download Chapter 4 - Central Nervous System

CHAPTER 4
CENTRAL NERVOUS SYSTEM
Approved by East Sussex Health Economy Medicines Committee
First line drugs –drugs which
are recommended in both
primary and secondary care
Second line drugs –
alternatives (often in specific
conditions) in both primary
and secondary care
Specialist drugs – Drugs
where a specialist input is
needed (see introduction for
definition)
Controlled drugs are highlighted with the symbol
Specialist only drugs –
prescribing within specialist
service only
. Full details of the regulations appear in the BNF.
Page:
4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
4.9
4.10
4.11
Date
1/13
1/13
5/13
6/13
8/13
10/13
01/14
04/14
06/14
07/14
11/14
01/15
03/15
04/15
07/15
12/15
03/16
08/16
09/16
10/16
01/17
04/17
Hypnotics and anxiolytics
Drugs used in psychoses and related disorders
Antidepressant drugs
Central nervous system stimulants and drugs used for ADHD
Drugs used in the treatment of obesity
Drugs used in nausea and vertigo
Analgesics
Antiepileptics
Drugs used in parkinsonism and related disorders
Drugs used in substance dependence
Drugs for dementia
Revision
4.7.4 (NICE guidance)
4.3 (NICE guidance), 4.3.4(MHRA safety update), 4.4 (MHRA drug
safety update), 4.8.1 (NICE guidance)
4.11 (Minor amendment)
4.7.1 (Minor amendment)
4.1 (drug addition), 4.4 (drug addition)
4.1 (minor amendment) 4.2 (NICE guidance)
4.6 (EMA safety update) 4.7(NICE guidance) 4.8 (MHRA update)
4.2.2 (Drug addition)
4.6 (MHRA safety update)
4.7 (Minor amendment) 4.8( drug addition)
4.2 (Drug addition) 4.10 (NICE guidance) 4.11 (Minor amendment)
4.0 (NICE guidance), 4.7.3 (section update)
4.2.3, 4.8 (MHRA safety update), 4.10 (NICE guidance)
4.3 (NICE guidance)
4.2.1 (minor amendment), 4.2.2 (Drug deletion)
4.4 (minor amendment)
4.3 (NICE guidance) 4.4(formulation replacement)
4.6 (drug addition) 4.4, 4.6 (NICE Guidance)
4.11 (NICE guidance)
4.4 (Drug addition); 4.2.2 (drug addition)
4.7 (Drug addition), NICE guidance
4.2, 4.8 (MHRA safety update)
First line drugs
Second line drugs
Contributors
G Ells
A Luck
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
Specialist drugs
1
2
4
10
16
18
19
22
30
34
35
37
Specialist only drugs
Considerations for women of childbearing potential: see NICE CG 192 - Antenatal and postnatal
mental health: clinical management and service guidance (Dec 2014)
4.1 Hypnotics and anxiolytics
4.1.1 Hypnotics
Zolpidem

Tablets 5mg, 10mg
Zopiclone

Tablets 3.75 mg, 7.5 mg
Clomethiazole


Capsules 192mg
Elixir 250mg in 5ml (equivalent to 192mg clomethiazole base)
Loprazolam

Tablets 1mg
Temazepam


Tablets 10 mg, 20 mg
Oral solutionSF 10 mg in 5 ml
Sodium Oxybate

Oral solution 500mg in 1 ml
Notes:
1. Hypnotics should not be used regularly and should be reserved for the acutely distressed.
2. Hynpotics are only licensed and recommended for short-term use. They should not be given for more than 3
weeks (preferably 1 week only). Intermittent use is desirable with the omission of some doses. “Z–hypnotics”
such as zolpidem, are recommended for short-term use only up to four weeks.
3. Hypnotics should be avoided in the elderly who are at risk of becoming ataxic and confused and so liable to fall
and injure themselves.
4. Zolpidem is the first line choice of hypnotic in all patients including the elderly.
5. Loprazolam and temazepam both have short duration of action and have no active metabolites but are
reserved for specialist initiation because of their high cost.
6. Oxazepam can be given as a single dose given at night for insomnia associated with anxiety
7. Temazepam is a Schedule 3 controlled drug but is exempt from prescription and handwriting requirements.
Prescribers are advised to limit quantities to no more than is sufficient to meet the patient’s clinical needs for up to
30 days
8. Nitrazepam has not been included as it is not recommended due to its prolonged action.
9. Although zolpidem and zopiclone are not benzodiazepines they act on the same receptors as benzodiazepine.
They are not licensed for long-term use and there is evidence of dependence in a small number of patients.
10. Chloral hydrate and its derivatives, such as chloral betaine, are considered less suitable for prescribing and
therefore have not been included. They were formerly popular hypnotics for children, although the use of
hypnotics in children is not usually justified. There is no convincing evidence that they are particularly useful in
the elderly.
11. Promethazine is sometimes used as an alternative to benzodiazepines and other hypnotics for nighttime
sedation. However, residual sedation may occur the following day and its sedative effects may diminish after a
few days of continued treatment associated with headache, psychomotor impairment and antimuscarinic effects.
12. Promethazine injection may be used within the Sussex Partnership Trust (SPT) in the management of the acutely
disturbed patient (unlicensed use) in accordance with Trust guidelines.
13. Sodium oxybate is licensed for use in narcolepsy with cataplexy under the supervision of a specialist in sleep
disorders. The specialist will initiate and titrate the dose according to response, which may take up to 3 months.
Patients who respond to treatment are suitable for shared care once their dose has been stabilised. Details of the
shared care guidelines can be found here
First line drugs
Second line drugs
Specialist drugs
2
Specialist only drugs
NICE guidance: Insomnia - newer hypnotic drugs - zaleplon, zolpidem and zopiclone for the management of insomnia
Technology Appraisal No. 77 (April 2004)
NICE has made the following recommendations about the use of zaleplon, zolpidem and zopiclone to treat insomnia.

NICE recommends that doctors should consider using non-medicine treatments, and then, if they think that a hypnotic
medicine is the appropriate way to treat severe insomnia that is interfering with normal daily life, they should prescribe
one for only short periods of time and strictly according to the licence for the drug.

Because there is no firm evidence of differences in the effects of zaleplon, zolpidem, zopiclone and the shorter-acting
benzodiazepines, NICE recommends that doctors should prescribe the cheapest drug, taking into account the daily dose
required and the cost for each dose.

Treatment should only be changed from one of these hypnotics to another if side effects occur that are directly related to
the medicine.
If treatment with one of these hypnotic medicines does not work, the doctor should not prescribe one of the others.
4.1.2 Anxiolytics
Please refer to NICE clinical guideline 113: Generalised Anxiety disorder and panic disorder (with or without
agoraphobia in adults
 Tablets 2 mg, 5 mg, 10 mg
Diazepam
 Oral Solution 2 mg in 5 ml
 Oral Solution 5 mg in 5 ml (“Blacklisted”)
 Inj (emulsion - Diazemuls®) 10 mg in 2 ml
Propranolol

Tablets 10 mg, 40 mg
Lorazepam


Tablets 1mg
Injection 4mg in 1ml
Oxazepam

Tablets 10mg, 15mg
Buspirone

Tablets 5mg, 10mg
Chlordiazepoxide

Capsule 5mg, 10mg
First line for acute agitation in
secondary care
Notes:
1. CSM advice: Benzodiazepines should only be prescribed for short-term use (2-4 weeks) and for anxiety which
is severe, disabling or subjecting the individual to unacceptable distress. The use for short-term, mild anxiety is
inappropriate and unsuitable.
2. Diazepam has a sustained action. Lorazepam and oxazepam are shorter-acting and may be preferred for
patients with hepatic impairment, but they carry a greater risk of withdrawal symptoms.
3. Diazepam is the preferred benzodiazepine for benzodiazepine withdrawal regimes.
4. Lorazepam (oral) is the first line choice for the treatment of acute agitation in secondary care settings.
5. Propranolol is useful in situational anxiety, with prominent somatic symptoms such as tachycardia, sweating and
tremor. Propranolol is unlikely to be of benefit for muscle tension or patients with predominately psychological
symptoms such as worry, tension or fear.
6. Lorazepam injection is used within SPT for the management of acutely disturbed patients, for rapid
tranquillisation, in accordance with Trust guidelines.
7. Response to treatment with buspirone may take up to 2 weeks. It is licensed for short-term use only.
8. Chlordiazepoxide is included as a specialist drug to be prescribed for the management of alcohol withdrawal.
9. Some SSRIs are licensed for the treatment of generalised anxiety disorder (GAD).
4.1.3 Barbiturates
Note:
1. Intermediate-acting barbiturates no longer have a place in therapy, except for those already taking barbiturates for
the management of severe intractable insomnia.
2. Phenobarbital is occasionally used in epilepsy; use as a sedative is unjustified.
3. Thiopental is used in anaesthesia.
First line drugs
Second line drugs
Specialist drugs
3
Specialist only drugs
4.2 Drugs used in psychoses and related disorders
4.2.1 Antipsychotic drugs
Notes:
1. Please refer to the NICE guidance on the following pages for prescribing for patients presenting with acute
psychosis.
2. Prescribing should only be commenced after seeking specialist advice, except in circumstances where prescribers
feel confident to prescribe e.g. an existing patient suffering a recurrent acute episode previously managed on
antipsychotic treatment.
3. Where a specialist opinion has been sought, GP’s will be asked to continue prescribing, where appropriate.
Further guidance is available on the following link: Prescribing Guidelines & Shared Care Prescribing Framework
(September 2005) Atypical (Non-Traditional) Antipsychotics
NICE guideline on the management of Schizophrenia
Acute episode
Approach with optimism and empathy
Provide comprehensive assessment
Principles
of
treatment
Work in partnership with service users and
carers
Ensure confidentiality at all times
Provide comprehensive information
Include written material
Use clear language
Ensure culturally appropriate
Ask for informed consent before treatment
starts
Consult advance directives
Check with care co-ordinator,
notes or GP
Provide comprehensive care plan for
multi-disciplinary approach
Clinical, emotional and social
needs
Provide social, group and physical
activities
Discuss
antipsychotics
with service
user and
decide
jointly on
which to
use
If service user cannot make preference
known, consult advance directive
If no advance directive available,
consider an atypical
antipsychotic as first line
If first episode, offer atypical antipsychotic
Use lower end of standard dose
range in BNF
If a conventional antipsychotic is chosen:

Use 300-1000mg chlorpromazine
equivalents per day for ≥ 6 weeks
(rather than chlorpromazine)

Use minimum effective dose
Clinical response
 Don’t use loading doses of
antipsychotics
 Don’t prescribe antipsychotics
for concurrent use except to
cover short changeover periods
If inadequate response
Consider changing class of drug
Side effects
Monitor
regularly
If antipsychotic is
tolerable
Don’t change drug
If unacceptable
side effects
emerge with
conventional
antipsychotic
Marked behavioural disturbance
First line drugs





EPS/akathisia
Weight gain/diabetes
Sexual dysfunction
Lethargy
Effects on eyes
Consider an atypical
antipsychotic
See rapid tranquillisation algorithm
Second line drugs
Specialist drugs
4
Specialist only drugs
Towards end of acute episode
 Offer service user the opportunity to give his/her
Service user focus
account of the illness written in the case notes
 Enable service user to discuss his/her
experiences
 Enable carers to discuss their experiences
Plan for
recovery
Full needs assessment
Include occupational potential and opportunity
Assess and plan for
psychological interventions


Family interventions, or
CBT
Continue on antipsychotic for 1-2 years
Medication advice
Only withdraw
gradually
After withdrawal, monitor for
relapse for 2 years after acute
episode
NICE guideline on the management of schizophrenia
Management of poor response to treatment and treatment resistance
Inadequate response to treatment
Ensure adequate dose of antipsychotic has been tried over sufficient time to allow
response
Inadequate response despite adequate
trial of antipsychotic
Consider possible causes:
 Comorbid substance misuse
 Poor treatment adherence
 Physical illness
Treat co-existing problem
Consider further psychological
intervention
CBT or family interventions:
 For more than 6 months
 With more than 10 planned sessions
Consider trial of olanzapine or
risperidone for 6-8 weeks if not tried
previously
Inadequate response
Consider trial of clozapine
Inadequate response to full trial
Full assessment and treatment review
Very cautiously consider trial of additional
antipsychotic combined with clozapine
First line drugs
Second line drugs
Specialist drugs
5
Consider further psychological
intervention
Specialist only drugs
NICE guideline on the management of schizophrenia – Management of physical care
Provide routine physical
health checks
To be provided usually in
primary care
Monitor increased risk of
cardiovascular disease
Consider:
 Primary prevention (use standard scoring systems)
 Secondary prevention in those with established
heart disease
 Specific monitoring in relation to certain
antipsychotic drugs (see BNF)
Promote healthy lifestyle
For example, good diet, exercise and smoking
cessation
Monitor side effects
 EPS/akathisia
 Weight gain/diabetes
 Sexual dysfunction
Focus on:
Neurological
Consider:
 Extrapyramidal side
effects
 Tardive dyskinesia
If no contact
with primary
care
Secondary care should monitor physical health
 Lethargy
 Effects on eyes
Metabolic and endocrine
Weight
Other side effects of medication
Consider:
 Routine urine/blood
screen for diabetes
 Selective screen for
other endocrine
disorders (high prolactin)
Consider
routine
weight
monitoring
Photosensitivity and chlorpromazine
Cover key areas on regular basis; agree frequency with service user and document in notes
Regular monitoring
Primary and secondary care services identify/allocate and document responsibilities for monitoring physical
health
Note: Prescribing should only be commenced after seeking specialist advice, except in circumstances where
prescribers feel confident to prescribe e.g. an existing patient suffering a recurrent acute episode previously managed
on antipsychotic treatment.
“Typical” antipsychotics
Butyrophenones:-
Haloperidol




Capules 500microgram
Tablets 1.5mg, 5mg, 10mg, 20mg
Oral liquidSF 2 mg in 1 ml,
Injection 5 mg in 1 ml





Tablets 25 mg, 50mg, 100 mg
Oral solution 25 mg in 5 ml, 100 mg in 5 ml
Tablets 1 mg, 5 mg
Oral solution 5 mg in 5 ml
Syrup 1 mg in 5 ml


Tablets 200mg, 400 mg
Oral solutionSF 200 mg in 5 ml
Phenothiazines:-
Chlorpromazine
Trifluoperazine
Substituted benzamide:-
Sulpiride
“Atypical” antipsychotics
 Tablets 50 mg, 100 mg 200 mg, 400 mg
Amisulpride

First line drugs
Oral solution 100 mg in 1ml
Second line drugs
Specialist drugs
6
Specialist only drugs
Aripiprazole



Tablets 5mg,10 mg,15 mg,30 mg
Orodispersible tablet 10 mg,15 mg
Oral solution 1mg in 1 ml
Clozapine

Tablets 25 mg 100 mg
Lurasidone▼

Latuda® Tablets 18.5mg, 37mg, 74mg
Olanzapine




Tablets 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15mg, 20mg
Orodispersible tablet (Velotab®) 5 mg, 10 mg, 15mg, 20mg
Tablets 25 mg, 100 mg, 150 mg, 200 mg, 300mg
Prolonged release tablets (XL) 50mg, 200mg, 300mg, 400mg



Tablets 500 micrograms, 1 mg, 2 mg, 3 mg, 4 mg, 6 mg
Orodispersible tablet (Quicklets®) 0.5mg, 1mg, 2mg, 3mg, 4mg
Liquid 1 mg in 1 ml
Quetiapine
Risperidone
Daily formulation
Notes:
1. Clozapine is usually prescribed in secondary care only. All patients must be registered with the appropriate
clozapine monitoring service.
2. Olanzapine has been associated with an increased risk of hyperglycaemia, diabetes mellitus and exacerbations
of diabetes. Therefore the CSM (Ref: Current Problems in Pharmacovigilance, Volume 28, April 2002)
recommends that in diabetes and in patients with risk factors for diabetes mellitus, appropriate clinical and blood
glucose monitoring is conducted. All other antipsychotics have also been implicated with development of
metabolic syndromes.
3. Quetiapine is available in a both immediate release (IR) and prolonged release formulations (MR, SR, XL). Care
should be taken in ensuring that the correct formulation is prescribed for the dosing frequency.
4. Lurasidone is a new antipsychotic which appears to have a favourable metabolic profile. It has been approved for
use in the following situations:
· Third line use after two previous antipsychotics (of which one must be aripiprazole) have been tried and at
least one was effective but not tolerated
AND
· Second line use in patients identified as having significant metabolic risk factors, eg. diabetes, obesity
provided aripiprazole has been tried first and has been found to be ineffective or not tolerated.
Prescribers should be cautious when considering the use of higher doses as there is little evidence to support
this approach.
Atypical antipsychotic drugs and stroke. Prescribing Advice:
 Committee on Safety of Medicines has advised that risperidone or olanzapine should not be used for the treatment
of behavioural symptoms of dementia.
 Use of risperidone for the management of acute psychotic conditions in elderly patients who also have dementia
should be limited to short-term and should be under specialist advice (olanzapine is not licensed for management
of acute psychosis).
 Prescribers should consider carefully the risk of cerebrovascular events before treating any patient with a previous
history of stroke or transient ischaemic attack. Consideration should also be given to other risk factors for
cerebrovascular disease including hypertension, diabetes, current smoking and atrial fibrillation.
 Patients with dementia who are currently treated with an atypical antipsychotic drug should have their treatment
reviewed.
Although there is presently insufficient evidence to include other antipsychotics in these recommendations, there is
a weight of opinion that the risk of stroke may be applicable to all antipsychotics and therefore prescribers should
bear in mind that a risk of stroke cannot be excluded.
First line drugs
Second line drugs
Specialist drugs
7
Specialist only drugs
Atypical Antipsychotics – Suggested Choices:
1st Choice
Consideration
Alternatives
First episode psychosis or acute
relapse, where drug choice is free of
contraindications & other considerations
Predominantly negative symptoms
Symptomatic, acute extrapyramidal
side-effects or dystonic reaction1
Symptomatic hyperprolactinaemia1
Significant weight gain1
Cheapest atypical, excluding
clozapine
Traditional antipsychotic
Amisulpride or olanzapine
Quetiapine or olanzapine
Risperidone
Aripiprazole or risperidone (<6mg/day)
Aripiprazole or quetiapine
Amisulpride or aripiprazole
Impaired glucose tolerance1
Significant sedation1
Significant (postural) hypotension1
QT prolongation1
Treatment refractory condition
(unresponsive to two adequate trials of
antipsychotic therapy)
Amisulpride or risperidone
Aripiprazole or amisulpride
Amisulpride or aripiprazole
Amisulpride
Clozapine
Olanzapine
Lurasidone. There is considerable
patient variability to this risk. Weight
management and lifestyle advice should
be made available. In some cases
metformin may be recommended to
manage weight gain which has not
responded
to
conventional
management.
Aripiprazole, lurasidone
Risperidone
Olanzapine
Olanzapine or aripiprazole
The relative risks of blood dyscrasias,
other side effects, and the need for
blood tests must be fully discussed with
the patient (and carer).
1
History of this event and/or specific need to avoid it.
Note: This table provides only a rough guide to treatment choice. Relative incidence and/or severity of side effects must always be
balanced against predicted efficacy of the medication, suitability and predicted concordance etc. Informed patient choice must
also be taken into consideration.
NICE – Guidance on the use of newer (atypical) antipsychotic drugs for the treatment of schizophrenia.
Number 43, June 2002
1.1
The individual and the clinician should make the choice of antipsychotic drug jointly responsible for
treatment based on an informed discussion of the relative benefits of the drugs and their side-effect profiles.
The individual's advocate or carer should be consulted where appropriate.
1.2
It is recommended that the oral atypical antipsychotic drugs amisulpride, olanzapine, quetiapine, risperidone and
zotepine be considered in the choice of first-line treatments for individuals with newly diagnosed
schizophrenia.
1.3
The oral atypical antipsychotic drugs listed in Section 3.3 (NICE No. 43) should be considered as treatment
options for individuals currently receiving typical antipsychotic drugs who, despite adequate symptom
control, are experiencing unacceptable side effects, and for those in relapse who have previously
experienced unsatisfactory management or unacceptable side effects with typical antipsychotic drugs.
The decision as to what are unacceptable side effects should be taken following discussion between the patient
and the clinician responsible for treatment.
1.4
It is not recommended that, in routine clinical practice, individuals’ change to one of the oral atypical
antipsychotic drugs if they are currently achieving good control of their condition without unacceptable side
effects with typical antipsychotic drugs.
1.5
In individuals with evidence of treatment-resistant schizophrenia (TRS), clozapine should be introduced at the
earliest opportunity. TRS is suggested by a lack of satisfactory clinical improvement despite the sequential use
of the recommended doses for 6 to 8 weeks of at least two antipsychotics, at least one of which should be an
atypical.
1.6
The clinician responsible for treatment and the multidisciplinary team regarding concordance with medication
should perform a risk assessment, and depot preparations should be prescribed when appropriate.
1.7
Where more than one atypical antipsychotic drug is considered appropriate, the drug with the lowest
purchase cost (taking into account daily required dose and product price per dose) should be
prescribed.
1.8
When full discussion between the clinician responsible for treatment and the individual concerned is not
possible, in particular in the management of an acute schizophrenic episode, the oral atypical drugs should be
considered as the treatment options of choice because of the lower potential risk of extrapyramidal symptoms
(EPS). In these circumstances, the individual's carer or advocate should be consulted where possible and
First line drugs
Second line drugs
Specialist drugs
8
Specialist only drugs
appropriate. Although there are limitations with advanced directives regarding the choice of treatment for
individuals with schizophrenia, it is recommended that they are developed and documented in individuals' care
programmes whenever possible.
1.9
Antipsychotic therapy should be initiated as part of a comprehensive package of care that addresses the
individual's clinical, emotional and social needs. The clinician responsible for treatment and key worker should
monitor both therapeutic progress and tolerability of the drug on an ongoing basis. Monitoring is particularly
important when individuals have just changed from one antipsychotic to another.
1.10 Atypical and typical antipsychotic drugs should not be prescribed concurrently except for short periods to
cover change over of medication.
1.11
NICE guidelines (TA 213: Aripiprazole for the treatment of schizophrenia in people aged 15 to 17 years
(January 2011) recommends that aripiprazole is a treatment option for schizophrenia in people aged 15 to 17
years who have contraindications to or are intolerant of risperidone, or who are not adequately controlled on
risperidone.
1.12
NICE TA 292 (July 2013) recommends the use of aripirazole within its marketing authorisation to treat severe
manic episodes in bipolar 1 disorder in adolescents (13 years and over).
4.2.2
Antipsychotic depot injections
Notes:
1. Nodules, muscle granulomas, abscesses or fibrosis occur in 20% of patients. These reactions can be minimised
by: Using the smallest volume possible
 Using concentrates where available (ideally no more than 2 ml / site)
 Administering at the lowest frequency. Avoid weekly injections if possible.
 Use a good technique: z-track advisable
 Rotate injection sites
2. Risperidone injection should be initiated in accordance with Sussex Partnership Foundation Trust protocol
3. It is important to establish whether the patient has an allergy to sesame oil or coconut oil before selecting
appropriate treatment, although the incidence of such allergy is extremely low.
4. Paliperidone palmitate is available as a monthly and a 3 monthly depot injection. The 3 monthly preparation is
only available to patients who have been stable on the monthly preparation for at least 6 months.
 Injection 400mg powder for reconstitution
Aripiprazole
(Abilify maintena®)



Flupentixol decanoate
(Depixol®)
Injection 20 mg / ml - 20mg in 1ml, 40mg in 2ml,
Injection 100 mg /ml (“Concentrate”) - 50mg in 0.5ml, 100mg in 1ml,
Injection 200 mg / ml (“Low-volume”) - 200mg in 1ml
Diluent = Coconut oil
Fluphenazine decanoate
(Modecate®)


Injection 25 mg / ml – 12.5 mg in 0.5 ml, 25 mg in 1 ml, 50 mg in 2 ml
Injection 100 mg / ml (“Concentrate”) – 50 mg in 0.5 ml, 100 mg in 1 ml
Diluent = Sesame oil


Haloperidol
(Haldol®)
Injection 50 mg in 1 ml
Injection 100 mg in 1 ml
Diluent = Sesame oil
Risperidone

Prolonged release injection 25mg, 37.5mg, 50mg

Prolonged release suspension for injection 25mg, 50mg, 75mg, 100mg,
150mg

Prolonged release suspension for injection 175mg, 263mg, 350mg,
525mg


Injection 200 mg in 1 ml
Injection 500 mg in 1 ml (“Concentrate”)
(Risperdal® Consta)
Paliperidone palmitate
Xepilon® (monthly injection)
Paliperidone palmitate
Trevicta® (3 monthly
injection)
Zuclopenthixol
decanoate
(Clopixol®)
First line drugs
Diluent = Coconut oil
Second line drugs
Specialist drugs
9
Specialist only drugs
4.2.3
Carbamazepine
Antimanic drugs

Refer to Section 4.8.1
Lithium carbonate
(Priadel®)


M/R tablet 200mg,
M/R tablet 400mg
Lithium citrate

(Priadel®)
Valproic acid as semisodium valproate
SF syrup 520mg (equiv to 5.4 mmol Li+) in 5ml
(5ml ≡ 200mg lithium carbonate MR tablets)

Tablets E/C 250mg, 500mg
(Depakote®)
Notes:
For guidance on the treatment of Bipolar disorder see NICE CG 185: Bipolar disorder: the assessment and
management of bipolar disorder in adults, children and young people in primary and secondary care
1. Different brands of lithium and carbamazepine are not equivalent. Please specify the brand when prescribing
lithium and carbamazepine to ensure that the patient receives the same preparation.
2. It is not intended that patients stabilised on Camcolit® should be changed to Priadel®. Priadel® should be
preferred for all new patients.
3. Valproic acid (as semisodium valproate Depakote®) should be prescribed by brand to avoid potential
confusion with sodium valproate.
4. MHRA drug safety update (April 2017): Children exposed in utero to valproate are at a high risk of serious
developmental disorders (in up to 30-40% of cases) and/or congenital malformations (in approximately 10% of
cases)
o
do not prescribe valproate medicines for epilepsy or bipolar disorder in women and girls unless other
treatments are ineffective or not tolerated; migraine is not a licensed indication
o
ensure women and girls taking valproate medicines understand the 30–40% risk of neurodevelopmental
disorders and 10% risk of birth defects and are using effective contraception
o
valproate use in women and girls of childbearing potential must be initiated and supervised by specialists
in the treatment of epilepsy or bipolar disorder
5. Carbamazepine may be used for the prophylaxis of bipolar disorder in patients unresponsive to lithium; it seems
to be particularly more effective in patients with rapid cycling manic-depressive illness (4 or more episodes per
year).
6. Olanzapine, quetiapine and risperidone are all licensed for the treatment of episodes of mania. Olanzapine is
licensed for maintenance therapy.
7. In an acute attack of mania, treatment with a benzodiazepine or an antipsychotic drug (see above), is usually
required because it may take a few days for lithium to exert it’s antimanic effect.
8. Sodium valproate is used for the treatment of manic episodes associated with bipolar disorder or psychoses and
continuation therapy, but is unlicensed for this indication.
Lamotrigine is used for the long-term management of bipolar affective disorder but is unlicensed for this indication.
Antidepressant drugs
4.3
Refer to NICE Clinical Guideline 90 – Depression in adults (update) (December 2004)
NICE Clinical Guideline 28 – Depression in children and young adults: Identification and
management in primary, community and secondary care (update March 2015)
Antidepressants – prescribing advice
Summary
1. When an antidepressant is to be prescribed in routine care, it should be a selective serotonin reuptake
inhibitor (SSRI), because SSRIs are as effective as tricyclic antidepressant (TCAs) but are less likely to be
discontinued because of side effects.
2. All patients prescribed antidepressants should be informed that although the drugs are not associated with
tolerance and craving, discontinuation and withdrawal symptoms may occur on stopping, missing doses or,
occasionally on reducing the dose of the drug. These symptoms are usually mild and self-limiting but can
occasionally be severe, particularly if the drug is stopped abruptly.
All patients should be informed about the delay in onset of effect of antidepressants, the anticipated time
course of treatment, and the need to take medication as prescribed. Written information should be made
First line drugs
Second line drugs
Specialist drugs
10
Specialist only drugs
available appropriate to the patient’s needs.
Key Treatment Considerations in Depression
Patients presenting in Primary Care with mild depression who do not want an intervention or who in the opinion of
the GP, may recover with no intervention, should be encouraged to re-attend for a further assessment within the next
two weeks. This is “watchful waiting”. Healthcare professionals should consider recommending a guided selfhelp programme based on cognitive behavioural therapy (CBT), if this is available.
1. Antidepressants are not recommended for the initial treatment of mild depression, (normally assessed and treated
in Primary Care), because the risk-benefit ratio is poor. However, in moderate depression antidepressants should
be offered to all patients routinely, before psychological intervention.
2. When patients present initially with severe depression, a combination of antidepressant and individual CBT
should be considered as the combination is more cost effective than either treatment on its own.
3. For patients with a moderate or severe depressive episode, antidepressants should be continued for at least 6
months after remission. The need for continued therapy should then be reassessed, taking into consideration the
number of previous episodes, the presence of residual symptoms, and any concurrent psychosocial difficulties.
4. Patients who have had two or more depressive episodes in the recent past and who have experienced
significant functional impairment during the episodes, should be advised to continue antidepressants for two years
after remission.
5. For patients whose depression is treatment resistant the combination of antidepressants with CBT should be
considered.
6. CBT should be considered for patients with recurrent depression who have relapsed despite antidepressant
treatment or if a preference for psychological therapies is expressed.
7. If a patient fails to respond to the first antidepressant prescribed, consideration must be given to whether the
drug has been taken correctly at the prescribed dose.
8. If response to a standard dose is inadequate and there are no significant side effects, the dose should be
gradually increased within the schedule suggested by the Summary of Product Characteristics (SPC / data sheet).
9. If there is no response after one month, consideration should be given to switching to another antidepressant. If
there has been a partial response, the decision to switch should be delayed for a further two-week assessment
period. (The switch may be to another antidepressant of the same class or to one of a different class).
10. For older patients with depression, give antidepressant treatment at an age appropriate dose for a period of at
least six weeks before considering that it may be ineffective. If there is partial response within this period,
continue treatment for a further six week assessment period.
11. When prescribing for older patients consider the significantly increased risk of drug interactions, adverse effects
and intolerance.
12. In the treatment of patients in secondary care, consideration may be given to the re-introduction of any previous
treatments that were inadequately delivered or adhered to in primary care.
13. The management of treatment resistant depression should normally only be undertaken by mental health
specialists. When considering specialist therapies such as antidepressants in high dose or in combination,
augmentation with lithium, anticonvulsants or antipsychotics, or thyroid supplementation etc, full regard must be
given to the risks associated with such options and the level of evidence to support their use.
14. The dose of antidepressant used for prevention of relapse should be the same as that at which acute treatment
was effective.
15. Patients who have had multiple episodes of depression and who have had good response to treatment with an
antidepressant plus lithium should remain on this combination for at least six months. If one drug is then to be
discontinued it should be the lithium rather than the antidepressant.
16. Patients with psychotic depression will normally need to be treated with a combination of antidepressant and
antipsychotic medication.
Choice of Antidepressant in Depression
In moderate to severe depression, for routine care use an SSRI. These are as effective as TCAs but are less likely
to be discontinued due to side effects.
1. Consider using a generic form of SSRI (eg fluoxetine or citalopram) as first line, but note the higher propensity for
drug interactions with fluoxetine.
2. First choices for a second antidepressant should normally be a different SSRI or mirtazapine, or possibly a TCA,
(but usually not dosulepin).
3. When switching from one antidepressant to another, consideration must be given to the potential need for a
washout period or for cross-tapering, and to the need for gradual and modest incremental dose increases. Also,
to the risk of drug interactions and the risk of serotonin syndrome.
4. Whenever possible, treatment with antidepressant medication should be with a single agent.
5. St John’s Wort may be of benefit in mild to moderate depression but normally should not be prescribed or
advised because of uncertainties about appropriate doses, the quality of the preparation and the potential for
serious interactions with other drugs.
First line drugs
Second line drugs
Specialist drugs
11
Specialist only drugs
6. In chronic depression, antidepressant medication should be considered with CBT whenever possible.
7. In chronic depression, patients who have not responded to a SSRI should be considered for treatment with a
TCA. Particularly men, as they are usually more tolerant of the side effects attributable to these drugs (imipramine
should normally be avoided in female patients).
8. In treatment resistant depression, consideration may be given to the use of venlafaxine at doses in line with the
recommendations of the BNF and the SPC. (Although consideration must also be given to the risk of
cardiotoxicity).
9. The monoamine oxidase inhibitor phenelzine can be considered for patients who have failed to respond to
alternative antidepressants and who are prepared to tolerate the side effects and dietary restrictions associated
with its use.
10. Tranylcypromine should be avoided, due to its significant stimulant action and the general opinion that it is more
hazardous in use. (MAOIs are not normally used in primary care).
11. All patients receiving phenelzine (or other MAOIs) require careful monitoring (including blood pressure) and
prescribers must ensure that patients receive clear and full advice regarding interaction with other medication and
with foodstuffs.
Specific considerations
1. Paroxetine and venlafaxine are most likely to cause withdrawal symptoms due to their short half-lives.
2. Fluvoxamine may be less well tolerated than other SSRIs.
3. Escitalopram, an isomer of citalopram is not included in the formulary but is sometimes used by secondary care.
However, it is licensed and has a role in the management of generalised anxiety disorder.
4. Mirtazapine can cause significant sedation and weight gain, and may also cause agranulocytosis.
5. Reboxetine may cause hypokalaemia and is not licensed for use in the elderly.
6. Mianserin can cause agranulocytosis, particularly in older patients and is rarely used.
7. If switching to or from an MAOI antidepressant, a washout period of up to two weeks will be required.
8. Treatments such as dosulepin, MAOIs, combinations of antidepressants and augmentation therapies should
only be initiated and managed by specialists, or by GPs with a special interest in mental health.
9. TCAs are cardiotoxic and consideration should be given to their potential risk, particularly in patients assessed as
being at risk of self-harm. Of the TCAs and related drugs, dosulepin is the most toxic and lofepramine is the least.
10. Duloxetine (Cymbalta®) belongs to the same class as venlafaxine (SNRI) but appears to produce less
cardiotoxicity and was not found to prolong QTc intervals in clinical trials. However, due to the limited clinical data
available, it should not be considered for first line use, (nor second-line in routine practice).
17. Trazodone is a particularly sedating antidepressant and may be a useful choice in those patients with associated
sleep disturbance.
Information the patient should know:






The risk of recurrence of depression is high and increases with each episode.
The risk of relapse is greatly reduced by taking antidepressants.
Antidepressants are effective, not addictive, do not lose their efficacy over time, are not known to cause long-term
side effects.
Medication needs to be continued at the treatment dose for at least 6 months after you are completely better.
If you stop medication suddenly it can lead to unpleasant discontinuation symptoms.
If patient drives: advise about possible drowsiness & impaired driving ability. Reaction times may be reduced
even if patient doesn’t feel drowsy.
Antidepressants – prescribing in special situations
Special Situation
Breast feeding
Low risk
Moderate risk
High Risk
Amitriptyline
Tricyclics (most)
Venlafaxine
Cardiovascular disease
Fluoxetine
Mirtazepine
Trazodone
Fluoxetine
Citalopram
Trazodone
Venlafaxine
Fluoxetine
Fluoxetine
Citalopram
Mirtazepine
Trazodone
Venlafaxine
Citalopram
Diabetes
Epilepsy
First line drugs
Tricyclics
Fluoxetine
Tricyclics
Mirtazepine
Tricyclics (most)
Second line drugs
Specialist drugs
12
Specialist only drugs
Citalopram
Narrow angle glaucoma
Mirtazepine
Trazodone
Venlafaxine
Liver disease
Old age
Lofepramine
Mirtazepine
Citalopram
Venlafaxine
Pregnancy
Renal disease
Tricyclics
Trazodone
Mirtazepine
Trazodone
Venlafaxine
Fluoxetine
Citalopram
Tricyclics
Fluoxetine
Tricyclics
Citalopram
Mirtazepine
Trazodone
Venlafaxine
Lofepramine
Trazodone
Tricyclics (most)
Fluoxetine
Tricyclics
Citalopram
Mirtazepine
Trazodone
Venlafaxine
Fluoxetine
Citalopram
Mirtazepine
Fluoxetine
Venlafaxine
It is not intended to change patients stabilised on non-formulary antidepressants to formulary choice. The following choices are
recommended for new patients and when considering an alternative treatment.
4.3.1 Tricyclic and related antidepressant drugs
Tricyclic and related antidepressants
Amitriptyline
Imipramine
Lofepramine
Clomipramine
Trazodone
First line drugs



Tablets 10 mg, 25 mg, 50 mg
Oral solution 25 mg in 5 ml, 50 mg in 5 ml
Tablets 10 mg, 25 mg



Tablets 70 mg
Oral suspension 70 mg in 5 ml
Capsule 10mg, 25mg, 50mg



Capsules 50 mg, 100 mg
Tablets 150 mg
LiquidSF 50 mg in 5 ml
Second line drugs
Specialist drugs
13
For Obsessive Compulsive
Disorder only
Specialist only drugs
Notes:
1. Due to the risk of toxicity in overdose, consider limiting the quantity prescribed on each prescription.
2. Lofepramine is associated with fewer anticholinergic side effects, is less sedating and is considered to be safer
in overdose.
3. Amitriptyline, imipramine and clomipramine should be avoided where there is a suicide risk.
4. Dosulepin has been excluded from this formulary. It is more toxic than other tricyclic antidepressants particularly
due to its pro-convulsive and cardiac arrhythmic effects and it is very dangerous in overdose. It is associated with
an increased risk of ischaemic heart disease even when adjusted for other risk factors. The NICE guidance on
the management of depression recommends that dosulepin should only be routinely initiated by specialist mental
health professionals (including GPs with a Special Interest in Mental Health).
5. When initiating therapy, start low and increase to a therapeutic dose over 1 – 3 weeks.
6. Weight gain can be significant with tricyclic antidepressants.
7. If the patient drives, always counsel the patient about sedation and slower reaction times. (The latter may occur
even if patient doesn’t feel drowsy.)
8. Arrhythmias and heart block occasionally follow the use of tricyclic antidepressants, particularly amitriptyline,
and may be a factor in the sudden death of patients with cardiac disease.
9. Renal impairment – Tricyclic antidepressants are excreted by kidneys, therefore, start with low doses and
increase slowly. Accumulation may occur causing adverse drug reactions. Dividing total daily dose into 2-3 doses
may be helpful.
10. Myocardial infarction – Avoid tricyclic antidepressants if previous MI. Trazodone (see below) may be used but
try to avoid any antidepressant therapy for first two months post MI if possible.
11. Elderly and dementia – AVOID tricyclic antidepressants in dementia or where significant cognitive impairment is
present.
12. Clomipramine is included for the management of Obsessive Compulsive Disorder only
4.3.2 Monoamine-oxidase inhibitors
Notes:
1. No MAOIs have been included as these should only be used on the recommendation of a specialist
2. The BNF classifies phenelzine, isocarboxazid and tranylcypromine as preparations less suitable for prescribing.
3. Hypertensive crisis can occur following ingestion of tyramine or other pressor amines in foods or medication.
Patients should avoid consuming large amounts of tyramine-rich food (such as mature cheddar, yeast extracts,
red wine and fermented soya bean products) and sympathomimetics (such as ephedrine, pseudoephedrine and
phenylpropanolamine).
4. Patients should be advised to take last dose before 3 pm in order to minimise sleep disturbance / insomnia.
4.3.3 Selective serotonin re-uptake inhibitors (SSRIs)
Fluoxetine


Capsules 20 mg
Liquid 20mg in 5ml
Citalopram


Tablets 10 mg, 20 mg, 40 mg
Oral dropsSF (as hydrochloride) 40 mg in 1 ml
8 mg (4 drops) may be considered equivalent to 10 mg tablet
Although 60mg capsules are
available, it is more cost
effective to supply 3 X 20mg
First choice for the elderly but
see MHRA dose restrictions
below
Notes:
1. SSRIs are usually the first choice for the management of depression rather than tricyclic antidepressants.
2. Fluoxetine is the SSRI of choice except in the elderly, when citalopram is the product of first choice.
3. Sertraline may be used for Obsessive Compulsive Disorder.
4. Escitalopram may be used for Generalised Anxiety Disorder (GAD).
5. If no / poor response achieved with an SSRI, for optimal effect, switch between classes rather than within a class.
This should provide a better therapeutic effect.
6. SSRIs may exacerbate sleep disturbance and cause symptoms such as anxiety, restlessness and agitation
initially. If sedation is required or in agitated depression, or panic disorder consider prescribing a benzodiazepine
concurrently for the first 1 – 2 weeks (max 4 weeks). Alternatively, a sedating antidepressant can be considered.
7. Advise patients to take their SSRI in the morning as nocte administration may increase sleep disturbance.
8. If there is no response to fluoxetine at lower doses, increasing the dose is unlikely to produce any additional
benefit but side effects would be expected to increase.
9. SSRIs have fewer anticholinergic and cardiotoxic effects than tricyclic antidepressants.
10. Sexual dysfunction is more likely to be a complication of treatment with SSRIs, than with TCAs
11. CVA - SSRIs are the treatment of choice in depression post CVA or depression following acquired brain injury
(NB Check interactions with warfarin, if appropriate).
12. Parkinson’s disease - SSRIs should be used with caution as there are no controlled trials available and there
have been case reports of fluoxetine and paroxetine exacerbating motor symptoms.
13. Arrhythmias or previous MI - SSRIs are preferred over tricyclic antidepressants if post MI. SSRIs are
antidepressants of choice if history of arrhythmias
14. Hepatic impairment – restrict doses to lower end of dose range. Avoid in severe liver disease
First line drugs
Second line drugs
Specialist drugs
14
Specialist only drugs
15. MHRA Update December 2011: Citalopram and escitalopram are associated with dose-dependent QT interval
prolongation and should not be used in those:
 With congenital long QT syndrome;
 With known pre-existing QT interval prolongation; or
 taking other medicines that prolong the QT interval.
ECG measurements should be considered for patients with cardiac disease, and electrolyte disturbances should be
corrected before starting treatment.
For citalopram, new restrictions on the maximum daily doses now apply:
 40 mg for adults;
 20 mg for patients older than 65 years;
 20 mg for those with hepatic impairment.
For escitalopram, the maximum daily dose for patients older than 65 years is now reduced to 10 mg/day; other
doses remain unchanged.
4.3.4 Other antidepressant drugs
Mirtazapine

Tablets 15mg, 30mg, 45mg
Venlafaxine
Vortioxetine▼
Duloxetine




Tablets 37.5mg, 75mg
M/R capsules 75mg, 150mg
Brintellix®Tablets 5mg, 10mg, 20mg
Cymbalta ® Capsules 30 mg, 60 mg
Agomelatine▼

Valdoxan® Tablets 25mg
In certain circumstances should be specialist
initiated only – see notes below
Notes:
1. Mirtazapine appears to be safe in overdose and is thought to cause less insomnia, anxiety and agitation. Sexual
dysfunction is rare and the likelihood of drug interactions is low. Weight gain may be significant.
2. Duloxetine should be prescribed under the brand name Cymbalta® to avoid confusion with another formulation
used to treat stress incontinence.
3. Venlafaxine: for major depressive disorder only
4. CSM warning - in severely depressed or hospitalised patients who require daily doses of 300mg or above,
venlafaxine should only be initiated under specialist supervision.
5. Co-prescribing of venlafaxine with SSRIs should only be carried out under specialist supervision since the risk
of serotonin syndrome and pharmacokinetic interations will be significantly increased, especially in overdose.
6. Venlafaxine is contra-indicated in patients who have been identified as being at very high risk of a serious
cardiac ventricular arrhythmia. In addition, venlafaxine should be used with caution in patients with established
cardiac disease that may increase the risk of ventricular arrhythmias e.g. recent myocardial infarction.
7. Venlafaxine is contra-indicated in patients with uncontrolled hypertension. In patients in whom BP is
controlled, blood pressure measurement is recommended and dose reduction or discontinuation should be
considered in those experiencing a sustained increase (more common with doses above 200mg).
8. In moderate renal and hepatic disorders or impairment the dose needs to be reduced by 50%.
9. Co-administration of venlafaxine with potent CYP3A4 inhibitors e.g. most SSRIs, TCAs, erythromycin,
ketoconazole, should only occur if strictly indicated, due to the risk of clinically significant interactions. Similarly,
co-administration with drugs that inhibit both CYP3A4 and CYP2D6 e.g. most SSRIs, TCAs, duloxetine, should
be avoided.
10. Patients with increased risk factors for suicide should be carefully evaluated for the presence or worsening of
suicide-related behaviour. A maximum of two weeks' supply of medication should be considered in these patients
at initiation of treatment, during any dosage adjustment and until improvement occurs. In UK analyses of the rate
of antidepressant overdose deaths per million prescriptions, (not adjusted for other risk factors), the rate for
venlafaxine is higher that that for SSRIs, but lower than that for TCAs.
11. Doses below 150 mg of venlafaxine produce a predominantly SSRI action. If the patient had no response to an
SSRI, doses of at least 150 mg venlafaxine per day may be required. The dose should be titrated gradually.
12. Agomelatine is a new type of antidepressant that is a melatonin receptor agonist and a selective serotonin
receptor antagonist. It is licensed for the treatment of major depressive episodes in adults only (18+) and 3rd
line after the failure/ intolerance of two SSRIs or an SSRI and mirtazapine.
13. Agomelatine can affect liver function resulting in elevated serum transaminase levels, hence LFTs must be
monitored at baseline, 6,12,24 weeks thereafter when clinically indicated.
14. Agomelatine has been designated red status – hospital prescribing only.
15. MHRA Drug Safety Update October 2012 There have been several serious cases of hepatotoxicity reported
with agomelatine (Valdoxan/Thymanax). These include six reports worldwide of hepatic failure. The existing
recommendations to perform liver function tests in all patients receiving agomelatine at treatment initiation and
during treatment have been extended to include testing when the dose is increased.
Agomelatine should be immediately discontinued if patients present with symptoms or signs of potential liver
injury, or if an increase in serum transaminases in liver function tests exceeds 3 times the upper limit of normal.
Patients should be informed of the symptoms of potential liver injury and advised to stop taking agomelatine
First line drugs
Second line drugs
Specialist drugs
15
Specialist only drugs
immediately and seek urgent medical advice if these symptoms appear.
16. Vortioxetine is recommended by NICE as an option for treating major depressive episodes in adults whose
condition has responded inadequately to 2 antidepressants in the current episode (NICE TA 367). This treatment
is suitable for initiation in primary care and acute settings outside of mental health but clinicians are advised that
there is no evidence that clearly demonstrates that vortioxetine is superior to other antidepressants in terms of
clinical effectiveness.
Switching antidepressants
When no response or an inadequate response is obtained or a patient cannot tolerate an antidepressant, the following table may
assist when switching to an alternative therapy
From
MAOIs
Tricyclic
antidepressants
(TCA)
SSRIs (except
fluoxetine)
From
Fluoxetine
Venlafaxine
Mirtazapine
To
Advice
Any other drug
Withdraw and wait two weeks
Other TCA
SSRIs
Venlafaxine
Mirtazapine
MAOIs
TCA
Venlafaxine
Mirtazapine
Cross taper cautiously
Halve dose, add SSRI and withdraw slowly
Cross taper cautiously, start with venlafaxine 37.5 mg at night
Withdraw then start mirtazapine cautiously
Withdraw and wait 2 weeks
Cross taper cautiously with low dose TCA
Withdraw and start venlafaxine 37.5 mg at night
Withdraw and start mirtazapine cautiously
To
MAOIs
TCA
Venlafaxine, mirtazapine
MAOIs
TCAs, SSRIs
Mirtazapine
MAOIs
TCAs, SSRIs, venlafaxine
Advice
Withdraw and wait 5-6 weeks
Withdraw, wait 4-7 days, start TCA at very low dose, increase slowly
Withdraw, wait 4-7 days, start alternative drug cautiously
Withdraw and wait at least one week
Cross taper cautiously with very low doses
Withdraw before starting mirtazapine cautiously
Withdraw and wait at least two weeks
Withdraw and start alternative drug
Discontinuation symptoms
What are discontinuation symptoms?
1. At least one third of patients experience these symptoms after stopping antidepressants.
2. Onset varies from 12 hours to 5 days after the last dose (or missed dose) determined by the half-life of the drug.
3. Occasionally experienced after a dose reduction.
4. Usually mild and self-limiting, but can be severe and prolonged.
Common: all antidepressants

Anxiety, irritability, aggression, agitation, low mood, tearfulness.

Excitation, hyperactivity, impulsive behaviour, impairment of concentration

Insomnia, excessive/vivid dreaming, nightmares

Lethargy, malaise, fatigue, weakness, myalgia

Nausea, anorexia, abdominal discomfort, diarrhoea, vomiting
Common: particularly SSRIs
 Dizziness, giddiness, lightheadedness, vertigo
 Uncoordination, unsteadiness
 Paraesthesia, numbness, ‘shock-like’ sensations
 Rhinorrhoea, salivation, tremor, sweating, tension, restlessness
Uncommon / rare:
 Cardiovascular changes e.g. arrythmia
 Withdrawal related delirium or mania
 Movement disorders; akathesia, bradykinesia, dyskinesia, dystonia, tremor.
Risk factors?
 Antidepressants with a short half life (e.g. paroxetine and venlafaxine)
 Taking an antidepressant for 8 weeks or longer.
 Those who developed anxiety symptoms at the beginning of antidepressant therapy (especially with SSRIs)
 Children and adolescents
First line drugs
Second line drugs
Specialist drugs
16
Specialist only drugs
How to treat:
1. If symptoms are mild: reassurance
2. If symptoms are severe: reintroduce the original antidepressant and gradually taper the dose e.g. half the dose
every two weeks. Consider liquid forms to assist this. Consider switching to fluoxetine (long half-life).
How to avoid:
Wherever possible antidepressants should be discontinued over at least 4 weeks. The shorter the half-life the more
important this is.
Serotonin Syndrome
1. Serotonin Syndrome results from serotonin hyperstimulation.
2. Symptoms are usually mild and can be managed by drug withdrawal.
3. Severe cases can lead to multiple organ failure and death.
4. Symptoms include:

restlessness

diaphoresis

tremor, shivering

myoclonus

confusion

convulsions
5. Onset is usually soon after starting / changing dose.
4.4 Central nervous system stimulants and drugs used for ADHD
Atomoxetine
Dexamfetamine Sulphate
Guanfacine ▼
Lisdexamfetamine▼
Methylphenidate

Capsules 10mg, 18mg, 25mg, 40mg, 60mg

Tablets 5mg

Intuniv® Tablets, prolonged release 1mg, 2mg, 3mg,
4mg

Elvanse® Capsules 20mg,30mg, 40mg 50mg,60mg
70mg



Tablet 5mg, 10mg, 20mg
Tablet M/R (Matoride® XL) 18mg, 36mg, 54mg
Capsule M/R (Equasym XL®) 10mg, 20mg, 30mg

Capsule M/R (Medikinet XL) 10mg, 20mg, 30mg,
Prescribe
MR
preparations
by brand
name
40mg
The different brands of methylphenidate MR preparations are not bioequivalent and contain different ratios of
immediate release to modified release drug. They should therefore be prescribed by brand name.
Matoride® XL – 20% immediate release, 80% modified release (bioequivalent to Concerta®)
Equasym® XL – 30% immediate release, 70% modified release
Medikinet® XL – 50% immediate release, 50% modified release
Standard release formulations should be prescribed generically
NICE Clinical Guideline CG 72: Attention Deficit Hyperactivity Disorder - Diagnosis and management of ADHD
in children, young people and adults (September 2008)
Summary:
Care should be managed by specialist ADHD teams for children (Age 3-11), young people (age 12-18) and adults.
In moderate ADHD in children or young people drug treatment is not recommended first line. A parenttraining/education programme and/or cognitive behavioural therapy should be tried first.
In school-age children and young people with severe ADHD, drug treatment should be offered as first line along with
a parent-training/education programme
If a child or young person needs treatment with medication for ADHD doctors should consider the following:

Methylphenidate for ADHD without significant co-morbidity
First line drugs
Second line drugs
Specialist drugs
17
Specialist only drugs

Methylphenidate for ADHD with comorbid conduct disorder

Methylphenidate or atomoxetine when tics, Tourette’s syndrome, anxiety disorder, stimulant misuse or risk of
stimulant diversion are present

Atomoxetine if methylphenidate has been tried and has been ineffective at the maximum tolerated dose, or
the child or young person is intolerant to low or moderate doses of methylphenidate

the side effects of each medicine

factors that might make it difficult for the person to take the medicine at the right time (for example, if it is
difficult to take a dose during school hours)

the individual preference of the child or adolescent and/or their family or carer.
Drug treatment in all patients with ADHD should always form part of a comprehensive treatment programme that includes
psychological, behavioural and educational/occupational needs.
If drug treatment is indicated in adults, methylphenidate should normally be tried first.
Methylphenidate and dexamfetamine and do not currently have UK marketing authorisation for use in adults with ADHD.
Lisdexamfetamine is licensed for the treatment of ADHD in children aged 6 years and over when response to previous
methylphenidate treatment is considered clinically inadequate. At least 2 forms of modified release methylphenidate
should be tried as different release parameters of the MR products may provide more effective symptom control or
minimise side effects.
Treatment with methylphenidate, lisdexamfetamine, atomoxetine or dexamfetamine in children and young people
(Under 18) should only be started after a specialist who is an expert in ADHD has thoroughly assessed the individual
and confirmed the diagnosis. Once treatment has been started it can be continued and monitored by a GP in
accordance with shared care guidelines .
Guanfacine is a non-stimulant treatment for ADHD licensed for use in 6-17 year olds. It is for third line treatment after
stimulant treatments and atomoxetine have failed. Inititation, prescribing and monitoring should remain with the
specialist.
Additional NICE Guidance
NICE CG 142 June 2012 (rev Aug 2016): Autism spectrum disorder in adults: diagnosis and
management
Modafinil

Tablet 100 mg, 200mg
For narcolepsy
Notes:
1. Narcolepsy should be diagnosed and treatment initiated by a specialist.
2. There is little evidence to support routinely changing current patients, well-controlled on amphetamines, to
modafinil.
3. For newly diagnosed patients and those intolerant of amphetamines, there may be a role for using modafinil, but
treatment should be agreed between patient and specialist.
4. MHRA Drug Safety Update - August 2010 The European Medicines Agency has recommended that the use of
modafinil should be restricted to treat only sleepiness associated with narcolepsy and that it should no longer be
used for the treatment of excessive sleepiness associated with obstructive sleep apnoea or chronic shift work
sleep disorder.
5. MHRA Drug Safety Update – March 2011 Further information and advice is available to support safer use of
modadafinil.
4.5 Drugs used in the treatment of obesity
Notes:
Obesity is associated with many health problems including cardiovascular disease, diabetes mellitus, gallstones and
osteoarthritis. Factors that aggravate obesity may include depression, other psychological problems and some
drugs.
NICE CG 189 Obesity (November 2014) offers guidance on the management of obesity.
When to consider drug treatment:
Discuss with the patient the potential benefits and limitations, including the mode of action, adverse effects and their
potential impact on the patient’s motivation.
When prescribing, make arrangements for appropriate healthcare professionals to offer information, support and
counselling on additional diet, physical activity and behavioural strategies.
Give information on patient support programmes.
First line drugs
Second line drugs
Specialist drugs
18
Specialist only drugs
Follow the drug’s summary of product characteristics.
Continued prescribing and withdrawal
Review regularly, to monitor the effect of drug treatment, and to reinforce lifestyle advice and need for adherence.
Drug treatment may be used to help people to maintain weight loss, as well as to continue to lose weight.
Consider withdrawing drug treatment if the person does not lose enough weight
Consider less strict goals for people with type 2 diabetes, because they may lose weight more slowly.
Agree goals with the person and review regularly.
If concerned about micronutrient intake, consider recommending a supplement providing the reference nutrient intake
for all vitamins and trace elements, particularly for vulnerable groups such as older people, who may be at risk of
malnutrition.
If withdrawing a person’s drug treatment, offer support to help maintain weight loss because their self-confidence and
belief in their ability to make changes may be low.
4.5.1 Anti-obesity drugs acting on the gastro-intestinal tract
 Capsules 120mg
Orlistat
Notes:

Prescribe only as part of an overall plan for managing obesity in adults who have:
– a BMI of 28.0 kg/m2 or more with associated risk factors, or
– a BMI of 30.0 kg/m2 or more.

Continue treatment for longer than 3 months only if the person has lost at least 5% of their initial body weight
since starting drug treatment (less strict goals may be appropriate for people with type 2 diabetes).

Continue for longer than 12 months (usually for weight maintenance) only after discussing potential benefits and
limitations with the patient.
4.5.2 Centrally acting appetite suppressants
NB: The European Medicines Agency suspended the marketing authorisation for rimonobant (Acomplia) on
23rd October 2008 because of the high level of psychiatric side effects observed with this drug. Further
information can be found here
NB: The European Medicines Agency suspended the marketing authorisation for sibutramine (Reductil) on
21 January 2010 because of emerging evidence suggesting an increased risk of non-fatal heart attacks and
strokes with this medicine. Further information van be found here
4.6
Drugs used in nausea and vertigo
Anti-emetics should be prescribed only when the cause of vomiting is known because otherwise they may delay
diagnosis, particularly in children. The following table and diagram summarise the actions and uses of the most
commonly used anti-emetics and can be used as a guide to choosing an appropriate agent.
Class of anti-emetic
Anti-emetic
Anticholinergic (also known
as sphincter modulators)
Antihistamine
Hyoscine
Cannabinoid
Nabilone
Dopamine antagonist
Gastroprokinetic
agents
Metoclopramide
Domperidone
Phenothiazine and
related drugs
Prochlorperazine
Cyclizine
Promethazine
Histamine analogue
Betahistine
5-HT3 antagonist
Granisetron
Odansetron
First line drugs
Useful for vomiting caused
by…
Motion sickness
Motion sickness
Post-operative vomiting
Pregnancy
Cytotoxic therapy,
unresponsive to conventional
antiemetics
Migraine
Cytotoxic therapy
Labyrinthitis
Migraine
Post-operative vomiting
Pregnancy
Labyrinthitis
Cytotoxic therapy
Second line drugs
Specialist drugs
19
Mode of action
Act on the vomiting centre as well as on
the gastrointestinal tract directly
Act on H1 receptors in the vomiting
centre, as well as having weak
anticholinergic and sedating effects
Thought to act on opiate receptors
Act on the chemo receptor trigger zone
and has direct effects on the
gastrointestinal tract
Act on the chemo receptor trigger zone
Thought to reduce endolymphatic
pressure by improving the
microcirculation in the inner ear
Exact mode of action unclear, but is
probably both central and peripheral
Specialist only drugs
Palonosetron (with
netutipant)
Nausea and vomiting – main sites of action
Notes:
1. The underlying cause of the nausea should be treated before starting treatment with an anti-emetic wherever
possible.
2. Anti-nausea drugs (including haloperidol) should be prescribed prophylactically when giving opioid analgesics.
Palliative Care Guidelines in Chapter 16 contain details for special situations.
3. Nausea in the first trimester of pregnancy does not require drug therapy. On rare occasions, if vomiting is severe,
short-term treatment with an antihistamine (e.g. promethazine) may be required. Prochlorperazine or
metoclopramide may be considered as second line treatments. If symptoms do not settle in 24 to 48 hours then
specialist advice should be sought.
4. Please refer to BNF Chapter 8: Malignant disease for guidance on nausea and vomiting in patients receiving
chemotherapy.
5. Haloperidol and levomepromazine (section 4.2.1) are also used for the relief of nausea. See also Chapter 16 –
Palliative Care.
Antihistamines
Cyclizine


Tablet 50mg
Injection 50mg in 1ml
Promethazine
hydrochloride



Tablets 10mg, 25mg
Elixir 5mg/5ml
Injection 25mg/ml
Note: Cyclizine should be used with caution in the community because of its potential for abuse.
Phenothiazines and related drugs
Prochlorperazine
First line drugs





Tablet 5mg
Syrup 5mg in 5ml
Suppository 5mg, 25mg
Intramuscular injection 12.5mg in 1ml
Buccal tablet 3mg
Second line drugs
Specialist drugs
20
Specialist only drugs
Notes:
1. Severe reactions to prochlorperazine should be treated with procyclidine injection, 5mg to 10mg given intramuscularly, repeated if necessary after 20 minutes, maximum of 20mg daily. In children, the dose range is as
follows: Age 1-2yrs, 500micrograms to 2mg, age 2-12yrs 2mg to 5mg, age 12-18yrs 5mg to 10mg. Subsequent
oral doses may be needed for the next 2 or 3 days.
2. Prochlorperazine should not be prescribed for patients with Parkinson’s disease and should be used with caution
in the elderly.
3. Prochlorperazine buccal tablets have been included only for use as an alternative to injection in certain
circumstances (e.g. GP call out). They should be prescribed in small quantities not exceeding 10 tablets.
Domperidone and metoclopramide
Metoclopramide
Domperidone






Tablet 10mg
Syrup 5mg in 5ml
Injection 10mg in 2ml
Tablet 10mg
Suspension 5mg in 5ml
Suppository 30mg
Notes:
1. Metoclopramide is not as effective as prochlorperazine or cyclizine for the treatment of postoperative nausea and
vomiting.
2. Metoclopramide (and to a lesser degree prochlorperazine) is associated with a high risk of dystonias and
oculogyric crises particularly in children, young adults and the elderly. It is not licensed for use in people
under 20 years of age. Other anti-emetics are preferred for these groups of patients.
3. Severe reactions to metoclopramide should be treated with procyclidine injection, 5mg to 10mg given intramuscularly, repeated if necessary after 20 minutes, maximum of 20mg daily. In children, the dose range is as
follows: Age 1-2yrs, 500micrograms to 2mg, age 2-12yrs 2mg to 5mg, age 12-18yrs 5mg to 10mg. Subsequent
oral doses may be needed for the next 2 or 3 days.
4. Metoclopramide should not be prescribed for patients with Parkinson’s disease. Domperidone does not readily
cross the blood-brain barrier and is therefore the preferred option. It may also be useful in reducing the side
effects of levodopa and bromocriptine.
5. In August 2013 the EMA advised that the benefits of metoclopramide were outweighed by the risks for high dose
and long- term use and recommended a restriction on dosing and duration of treatment.

For adults, the maximum dose in 24 hours is 30 mg (or 0.5 mg per kg bodyweight). The usual dose is 10 mg up
to three times a day.

In children age 1 year or older, the recommended dose is 0.1–0.15 mg per kg bodyweight, repeated up to three
times a day. The maximum dose in 24 hours is 0.5 mg per kg bodyweight.
For further information on indication, use and administration, see here .
6. In May 2014 the MHRA advised that because domperidone is now associated with a small increased risk of
serious cardiac side effects, its use is now contraindicated in patients with underlying cardiac conditions and is
restricted to the relief of nausea and vomiting and for short periods of time only (see MHRA Safety Update May
2014).
5HT3 antagonists
Granisetron



Tablet 1mg
Paediatric liquid 1mg in 5ml
Sterile solution for dilution and use as either infusion or injection, 1mg,
3mg
Ondansetron

Tablet 4mg, 8mg

Syrup SF 4mg in 5ml

Injection 4mg in 2ml, 8mg in 4ml

Akynzeo® 0.5mg/300mg capsule
Palonosetron and
Netupitant▼
Notes:
1. The place of 5HT3 antagonists in non-chemotherapy induced nausea and vomiting is not yet clear. They may be
useful in drug or biochemical induced emesis and stimulation of GI receptor
2. Antiemetic requirements in chemotherapy vary depending on how emetogenic the regimen is and individual
patient response. See also Palliative Care Guidelines, Chapter 16.
3. Antiemetics should be supplied as a full course by secondary care as part of the treatment. It is not anticipated
First line drugs
Second line drugs
Specialist drugs
21
Specialist only drugs
that GPs would be asked to prescribe.
4. Granisetron is the preferred treatment for adults.
5. In paediatrics, ondansetron is preferred for post-operative nausea and vomiting, whereas granisetron is preferred
for paediatric oncology.
6. 5HT3 antagonists should only be used 2nd line in post-operative nausea and vomiting where
prochlorperazine/cyclizine is not effective.
7. Akynzeo® (netupitant and palonosetron) is indicated for the prevention of acute and delayed nausea and
vomiting associated with highly emetogenic chemotherapy in accordance with the chemotherapy induced nausea
and vomiting (CINV) guidelines
Cannabinoid

Nabilone
Capsule 1mg
Note:
Nabilone is used for nausea and vomiting caused by cytotoxic chemotherapy that is unresponsive to
conventional anti-emetics.
 Kwells® ‘melt in the mouth’ tablet 300micrograms
Hyoscine
 Joy-Rides® chewable tablet 150micrograms
hydrobromide
 Scopaderm® TTS Patch 1mg/ 72hrs
 Injection 400micrograms in 1ml, 600micrograms in 1ml
Other drugs for Ménière’s disease
Betahistine

Tablet 8mg, 16mg
Notes:
1. Vertigo and nausea associated with Ménière’s syndrome and middle ear surgery may be difficult to treat.
Hyoscine, antihistamines, and phenothiazines (such as prochlorperazine) are effective in the prophylaxis and
treatment of such conditions. In the acute attack prochlorperazine may be given rectally or by intramuscular
injection or cyclizine may be given by intramuscular injection.
2. Betahistine is of benefit solely in treatment of Ménière’s syndrome and prescribers should ensure that betahistine
is not being prescribed to treat side effects of other medication.
4.7
Analgesics
Refer to: Chapter 10 for Non-steroidal anti-inflammatory drugs
Palliative care formulary for prescribing analgesics in palliative care
Notes:
1. Pain control must be reviewed frequently.
2. It is important that analgesics are given regularly for chronic pain as they are more effective in preventing the
development of pain than relieving established pain.
3. Specific dosage instructions should be written on the prescription, i.e. “X to be taken x hourly when required
for pain”, rather than simply “prn”.
4. Whilst standard release formulations should be considered first line, in some chronic pain management cases,
slow release analgesia may be an advantage.
5. Standard release formulations should be used for exacerbations of pain.
Analgesic Ladder (Adults)
STEP 1:
Mild Pain
Simple analgesia
STEP 2:
Moderate Pain
Weak opioid + simple analgesia
STEP 3:
Severe Pain
Strong opioid + simple analgesia
Adjuvant analgesics: e.g. tricyclic antidepressants or anticonvulsants for pain with neuropathic elements
(see relevant section)
At whatever step on the ladder, if inflammation is present, consider adding an NSAID, e.g. ibuprofen,
naproxen, or topical NSAID (refer to Chapter 10). This may minimise the requirement for other analgesics.
1. It is not necessary to start at the bottom of the ladder. Analgesia should be tried in a logical sequence and given
appropriate to the degree of pain.
First line drugs
Second line drugs
Specialist drugs
22
Specialist only drugs
2. NSAIDs should only be used after careful assessment of risk and consideration of the alternatives. Regular
critical re-assessments of continued use should be made and repeat prescribing avoided. Refer to Chapter 10.
3. Analgesics should be taken regularly in order to achieve and maintain best efficacy.
4. If a NSAID is used for analgesia alone it is recommended the drug should be changed if no response is obtained
after 1 week.
5. If an anti-inflammatory action is required a trial of 3 weeks should be allowed.
6. Prophylactic laxatives should always be prescribed when strong opioids are used, see section 1.6.
7. Prophylactic anti-emetics should always be considered when prescribing opioids if vomiting is likely to be
problematic, see section 4.6.
8. For adjunctive therapy refer to section 4.7.3.
9. Where appropriate refer to the Palliative Care Guidelines.
4.7.1 Non-opioid analgesics
Paracetamol
Co-codamol (Paracetamol
and codeine)

Tablet 500mg

Dispersible tablet 500mg

Oral Suspension (SF) 120mg/5ml, 250mg/5ml,

Suppository 60mg, 120mg, 240mg, 500mg

Oral Suspension 500mg/5ml (Unlicensed)

Intravenous infusion 10mg/ml

Tablets 8/500, 30/500

Effervescent tablets 8/500, 30/500
Paediatric Analgesic Dosage Guidelines
Child’s weight
(kg)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
First line drugs
Paracetamol dose
(oral/PR)
20mg/kg loading dose
followed by 15mg/kg
Max dose 60mg/kg over 24
hours
120mg QDS
Ibuprofen dose
(oral)
Diclofenac dose
(oral/PR)
12.5mg 16hrly
50mg QDS
12.5mg BD
168mg QDS
240mg QDS (oral)
240mg QDS (PR)
100mg QDS
12.5mg TDS
25mg BD
360mg QDS (oral)
365mg QDS (PR)
150mg QDS
400mg QDS
25mg TDS
500mg QDS (oral)
500mg QDS (PR)
200mg QDS
250mg QDS
650mg QDS (oral)
625mg QDS (PR)
Second line drugs
Specialist drugs
23
50mg BD
37.5mg TDS
Specialist only drugs
1g QDS
50 and above
PR loading dose
Max total daily
dose
30mg/kg STAT
90mg/kg
(max 4g)
300-400mg QDS
40mg/kg
(max 2400mg)
50mg TDS
3mg/kg
(max 150mg)
Notes:
1. Paracetamol is usually the simple analgesia of choice.
2. Dispersible / effervescent preparations should be reserved for patients who cannot swallow solid forms. They
are also more expensive.
3. Taking 8 tablets per day of soluble paracetamol or co-codamol may increase intake of sodium chloride by 8g
daily. This may be a significant risk in patients with heart failure or hypertension.
4. Suppositories are very expensive and other forms should be substituted as soon as convenient.
5. Intravenous paracetamol has been included for post-operative analgesia in theatres and protocol driven
treatment elsewhere within ESHT.
6. Co-codamol: There may be advantages to prescribing the opioid and non-opioid separately e.g. paracetamol
500mg tablets and codeine 30mg tablets prescribed separately. This gives flexibility in both the adjustment of
the doses and in the selection of the most appropriate combination. Some patients are unable to metabolise
codeine to morphine and therefore codeine will be ineffective in these patients.
7. Co-codamol containing 8mg codeine phosphate may not provide significant additional relief of pain but is
enough to cause opioid side effects and can complicate the treatment of over dosage. It may be considered
where patients cannot tolerate high doses of codeine.
8. When co-codamol is prescribed and no strength stated, formulations containing codeine 8mg and paracetamol
500mg will be dispensed.
9. Co-proxamol has little more analgesic effect than paracetamol alone in acute pain and is associated with
significant opiate type side-effects including dependence, sedation and increased risk of falls. At recommended
doses, co-proxamol provides sub optimal therapeutic dose of paracetamol.
10. Co-proxamol is dangerous in overdose and reports show that fatal overdoses due to co-proxamol are the
second most frequent means of suicide with prescribed drugs in England and Wales. The risk of death with coproxamol overdose seems to be higher than for either tricyclic antidepressants or paracetamol. This product is
being withdrawn and is no longer recommended.
11. Post Immunisation Analgesia: The recommended dose is 60mg (2.5ml of 120mg/5ml suspension)
paracetamol, repeated if necessary by a second dose 4-6 hours later. Premature babies should not be denied
paracetamol post vaccination, if required. However, as their weight may be significantly less than the 5kg
expected for a 2 month old born at term, paracetamol should be prescribed on a mg/kg basis (see table on
previous page). The recommended dose is 20mg/kg, followed if necessary by a second lower dose of 15mg/kg
4-6 hours later. The maximum dose is 60mg/kg over a 24-hour period as the liver is immature.
12. The dosing for liquid paracetamol products for children available to buy over the counter has been revised to one
that is based on narrower age bands with a single dosing option per band. For details of the new dosing regimes
see the MHRA Drug Safety Update July 2011
13. MHRA has issued new simplified guidance on the use of intravenous acetylcysteine for the treatment of acute
paracetamol overdose. See the MHRA Drug Safety Update September 2012
4.7.2 Opioid analgesics
Notes
1. Opioid analgesics are usually used to relieve moderate to severe pain, particularly of visceral origin.
2. Although repeated administration may cause dependence and tolerance, this should be no deterrent in the control
of pain. Success is demonstrated by monitoring of functional improvements.
3. Regular use of a potent opioid may be appropriate for certain cases of chronic non-malignant pain.
4. Opioid analgesics share many side effects, though qualitative and quantitative differences exist. The most
common side effects include nausea, vomiting, constipation and drowsiness. Larger doses produce respiratory
depression and hypotension.
NPSA 2008/RRR05 Reducing dosing errors with opiates – July 2008
This guidance applies when the following opioid medicines are prescribed dispensed or administered: Buprenorphine,
diamorphine, dipipanone, fentanyl, hydromorphone, meptazinol, methadone, morphine, oxycodone, papaveretum,
pethidine
When opioid medicines are prescribed, dispensed or administered, in anything other than acute emergencies, the
healthcare practitioner concerned, or their clinical supervisor, should:
• Confirm any recent opioid dose, formulation, frequency of administration and any other analgesic medicines prescribed for
the patient. This may be done for example through discussion with the patient or their representative (although not in the
case of treatment for addiction), the prescriber or through medication records.
First line drugs
Second line drugs
Specialist drugs
24
Specialist only drugs
• Ensure where a dose increase is intended, that the calculated dose is safe for the patient (e.g. for oral morphine or
oxycodone in adult patients, not normally more than 50% higher than the previous dose).
• Ensure they are familiar with the following characteristics of that medicine and formulation: usual starting dose, frequency
of administration, standard dosing increments, symptoms of overdose, common side effects.
Morphine sulphate
except for oral solution 10mg in 5ml



4 hourly dosing
Oral solution 10mg in 5ml, 100mg in 5ml
Tablet 10mg, 20mg, 50mg
Injection 10mg in 1ml, 30mg in 1ml
12 hourly dosing
 Zomorph® m/r capsule 10mg, 30mg, 60mg,
100mg, 200mg
Diamorphine hydrochloride
Codeine phosphate
Dihydrocodeine
Tramadol
Oxycodone

Injection 5mg, 10mg, 30mg, 100mg, 500mg


Tablet 15mg, 30mg, 60mg
Oral solution 25mg in 5ml

Injection 60mg in 1ml

Tablets 30mg

Capsules 50mg

Capsules M/R 50mg, 100mg, 150mg, 200mg

Tablets M/R 100mg, 150mg, 200mg

Capsules 5mg, 10mg, 20mg


Oral solution 10mg in 1ml
Injection ▼ 10mg/ml
12 hourly dosing
 Longtec® M/r tablet 5mg, 10mg, 20mg, 40mg, 80mg
Notes:
1. In the post-operative period, patients should be closely monitored for adequate pain relief as well as for signs of
possible side-effects especially respiratory depression.
2. For peri-operative analgesia see separate anaesthesia formulary.
3. Morphine remains the most valuable opioid analgesic for severe pain although it frequently causes nausea and
vomiting. In addition to pain relief, morphine also confers a state of euphoria and mental detachment.
4. Following titration, except for stat doses, for example for dressing changes, morphine should be given regularly
every four hours, unless m/r preparations are required. If pain recurs because of prn dosing, it is likely that
increased dose or frequency of analgesia may be needed to regain pain control.
5. Modified-release morphine preparations should be prescribed as Zomorph®. MST® products have not been
included in the formulary as they are more expensive than Zomorph® and offer no further advantage. For those
with swallowing problems, Zomorph® capsules can be opened and the contents sprinkled on soft food or
dispersed in water.
6. ‘As required’ doses of immediate release product should be prescribed in case of breakthrough pain.
7. Opioid patches are expensive but there is a group of patients in whom their use is justifiable and appropriate e.g.
those with intolerable side effects to morphine, dysphagia, poor compliance or poor response to oral medication.
Patches provide constant plasma levels and can be useful for patients with early morning moderate to severe
pain. They should be reserved for patients requiring strong opioid analgesia who cannot tolerate large, oral,
regular doses or who are unable to comply with a frequent analgesia regimen. Patches are not suitable for
management of acute pain. Caution should be exercised in the elderly with regard to the slow onset and long
duration of action with the patches. Drowsiness can be a particular problem. There can be increased absorption
with febrile patients or with the use of electric blankets or heat pads.
8. Fentanyl patches: it is important to prescribe by brand e.g. Durogesic® D-Trans® as there are significant
differences in bioavailability. Available as 12 microgram/hour, 25 microgram/hour, 50 microgram/hour, 75
microgram/hour and 100 microgram/hour for 3 days (72 hours). Starting dose is 25 microgram/hour. The 12
microgram/hour is purely available as a titration dose for patients moving from 25 microgram to 50
microgram/hour patches.
9. Buprenorphine patches: available as Butrans® 5 microgram/hour, 10 microgram/hour and 20 microgram/hour
for 7-days and Transtec® 35 microgram/hour, 52.5 microgram/hour and 70 microgram/hour for 4 days. Neither
patch has been approved for use by the SMC. There are some situations where local specialists in pain
management may recommend use of these patches.
10. Pethidine tablets have been omitted from the formulary because the evidence favours the use of the
intramuscular route; there is a danger of the accumulation of nor-pethidine with repeated dosing especially in the
renally impaired. Stat doses of NSAID suppositories may be useful in renal and biliary colic (see Chapter 10).
First line drugs
Second line drugs
Specialist drugs
25
Specialist only drugs
11. Although tramadol has been included, the CSM have cautioned its use in patients with a history of epilepsy, as
there may be an increased risk of convulsions. Psychiatric reactions have been reported. It is used in secondary
care for acute post-operative pain short-term. In primary care tramadol should be limited to patients for whom cocodamol is not effective, when standard release formulations should be considered, although in some chronic pain
management cases, slow release analgesia may be an advantage.
Additional NICE Guidance
CG140 May 2012 (Rev Aug 2016): Palliative care for adults: strong opioids for pain relief
NG61 (Dec 2016): End of life care for infants, children and young people with life-limiting
conditions: planning and management
4.7.3
Neuropathic pain
Definition:
Neuropathic pain is pain secondary to a lesion or dysfunction of normal sensory pathways in either the peripheral or
central nervous system. Pain in ‘an area of numbness’ together with neuronal hyperexcitability causing continuous,
spontaneous or evoked pain e.g. allodynia, hyperpathia, stabbing pain, may be found.
Examples:
Many different types of pathology may cause neuropathic pain – this heterogeneity results in a wide variety of
mechanisms and presentations of pain, for example:
 infection: post-herpetic neuralgia;
 metabolic: diabetic neuropathy;
 trauma: phantom limb pain, some back pain and sciatica, complex regional pain syndrome;
 ischaemia: post-stroke central pain.
Treatment:
Up to 40% of patients may be refractory to drug treatment, so it is very important to avoid the development of
secondary ‘chronic pain disorder’ by:
Maintaining emotional and physical ‘fitness’ – explanation and advice about the pain, maintenance of normal
activities and exercise – treatment of secondary depression, support etc. There is a lot of information and self-help
resources that patients can access to support them to live with chronic pain:
http://www.nhs.uk/Livewell/Pain/Pages/Painhome.aspx
http://chronicpainscotland.org/patients-area/living-well-with-chronic-pain/
These resources include information on Exercise and Activity, Dealing with Stress and relaxation, and Workplace
issues/advice
 Physiotherapy – very important especially in Complex Regional Pain Syndrome to maintain function.
 TENS (transcutaneous nerve stimulation) – some patients find this method effective. Machines are available
to purchase. Patients will need to be taught how to use the TENS machine correctly. TENS is not suitable for
patients with pacemakers.
Referral to the pain clinic for multidisciplinary pain management if persistent distressing symptoms
NICE CG 173 Neuropathic pain – pharmacological management: The pharmacological management of
neuropathic pain in adults in non-specialist settings (Nov 2013) describes the recommended treatment pathway
for neuropathic pain in the non-specialist setting.
FOR ALL NEUROPATHIC PAIN EXCEPT TRIGEMINAL NEURALGIA
Unlicensed
 Tablet 10mg, 25mg, 50mg
Amitriptyline
Licensed for peripheral neuropathic pain
 Capsules 100mg, 300mg, 400mg
Gabapentin
only
Tablets 600mg
Duloxetine

Cymbalta® Capsules 30mg, 60mg
Pregabalin

Capsules 25mg, 50mg, 75mg,
100mg, 200mg, 300mg
Capsaicin

Cream 0.075% (Axsain®)

Cream 0.025% (Zacin®)
First line drugs
Second line drugs
Licensed for diabetic peripheral neuropathic
pain only
Licensed for post-herpetic neuralgia and
painful diabetic peripheral polyneuropathy
Unlicensed
Specialist drugs
26
Specialist only drugs
1. Offer a choice of amitriptyline, gabapentin or capsaicin as initial treatment for neuropathic pain taking into
account individual patient factors (see table below) and the cost of treatment
2. When prescribing capsaicin, use the lower strength first (unlicensed). Consider the higher strength for patients
that have tolerated the lower strength but have had an inadequate response to it.
3. If the initial treatment is not effective or is not tolerated, offer one of the remaining drugs, and consider
switching again if the second and third drugs tried are also not effective or not tolerated.
4. Pregabalin should normally only be considered following a discussion of treatment options with a pain specialist
5. Consider tramadol only if acute rescue therapy is needed.
Amitriptyline
Gabapentin
Capsaicin cream
Duloxetine
Pregabalin
1st line
1st line
0.025%, 0.075%
2nd line
Specialist
1st line
recommendation
Helpful if patient
has problems with
sleep
Helpful where pain
described as
burning, shooting,
stabbing, pricking
Helpful for
localised pain
Helpful if
patient also
requires
antidepressant
Helpful where pain
described as
burning, shooting,
stabbing, pricking
Best taken in the
evening to reduce
‘hangover effect’ e.g.
6-8pm
Median effective
dose is 600mg three
times daily
Patients who do
not wish to take
oral medicine
Very low risk of
diversion/abuse,
therefore useful
in patients with
history of
substance
misuse
Median effective dose
is 150mg twice daily
Consider nortriptyline
if excess sedation
occurs
Reduce dose in renal
impairment
Patients who
cannot tolerate
oral medicines
No dose titration
necessary
Reduce dose in renal
impairment
Analgesic effect is
separate from
antidepressant effect
Avoid in patients with
memory problems
Lower strength
unlicensed for
neuropathic pain
Nausea common
on initiation
Avoid in patients with
memory problems
Median effective
dose is 25-50mg
daily
Some indications
unlicensed*
Some indications
unlicensed*
Some indications
unlicensed*
Unlicensed
indication*
Consider risk of falls
in elderly patients
Consider risk of falls in
elderly patients
Consider risk of falls
in elderly patients
Avoid in patients with
active history of
substance misuse
Avoid in patients with
active history of
substance misuse
**Risk of suicidal
ideation
**Risk of suicidal
ideation
Figure3. Prescriber Decision Aid
*NICE guidance re off label use. At the time of publication (November 2013), amitriptyline did not have a UK
marketing authorisation for this indication, duloxetine is licensed for diabetic peripheral neuropathic pain only, and
gabapentin is licensed for peripheral neuropathic pain only, so use for other conditions would be off-label. The
prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed
consent should be obtained and documented. See the General Medical Council's Good practice in prescribing
and managing medicines and devices for further information.
**Risk of suicidal ideation. Treatment with any anticonvulsant drug increases the risk of suicidal ideation and
behaviour in all patient groups, regardless of prescribed indication, as early as one week after starting treatment.
All patients should be monitored for signs of depression and/or suicidal ideation throughout treatment and
particular care should be taken when prescribing these drugs in those with a history of mental health disorder
and/or suicidal behaviour.
TRIGEMINAL NEURALGIA
First line drugs
Second line drugs
Specialist drugs
27
Specialist only drugs

Carbamazepine
Tablets, 100mg, 200mg,
400mg, SF Liquid 100mg in 5ml
MR Tablets, 200mg, 400mg
1. Offer carbamazepine as initial treatment for trigeminal neuralgia.
2. If initial treatment with carbamazepine is not effective, is not tolerated or is contraindicated, consider seeking
expert advice from a specialist and consider early referral to a specialist pain service or a condition-specific
service.
Other

Lidocaine (Versatis®)
medicated plaster 5%
Use outside of license by specialist palliative care team only.
Treatment of Headache
NICE Clinical Guideline 150: Headaches (Sept 2012) gives guidance on the diagnosis and management of
different types of headache.
Key priorities for implementation focus on:
 Correct diagnosis of tension type, migraine and cluster headache (see table below);
 The possibility of medication overuse headache in people whose headache developed or worsened while they
were taking the following drugs for 3 months or more:
o triptans, opioids, ergots or combination analgesic medications on 10 days per month or more or
o paracetamol, aspirin or an NSAID, either alone or any combination, on 15 days per month or more.
 The use of a headache diary
o to record the frequency, duration and severity of headaches;
o to monitor the effectiveness of headache interventions
o as a basis for discussion with the person about their headache disorder and its impact.
Diagnosis of tension-type headache, migraine and cluster headache
Headache
feature
Tension-type headache
Migraine (with or without aura)
Cluster headache
Pain
location1
Bilateral
Unilateral or bilateral
Unilateral (around the eye, above
the eye and along the side of the
head/face)
Pain quality Pressing/tightening (nonpulsating)
Pulsating (throbbing or banging in young people
aged 12–17 years)
Variable (can be sharp, boring,
burning, throbbing or tightening)
Pain
intensity
Mild or moderate
Moderate or severe
Severe or very severe
Effect on
activities
Not aggravated by routine
activities of daily living
Aggravated by, or causes avoidance of, routine
activities of daily living
Restlessness or agitation
Other
symptoms
None
Unusual sensitivity to light and/or sound or
nausea and/or vomiting
On the same side as the
headache:
Aura 2

red and/or watery eye
Symptoms can occur with or without headache
and:

nasal congestion and/or
runny nose

are fully reversible

swollen eyelid

develop over at least 5 minutes


last 5−60 minutes.
forehead and facial
sweating

constricted pupil and/or
drooping eyelid
Typical aura symptoms include visual symptoms
such as flickering lights, spots or lines and/or
partial loss of vision; sensory symptoms such as
numbness and/or pins and needles; and/or
speech disturbance.
Duration of
headache
30 minutes–continuous
Frequency < 15 days
of headache per month
First line drugs
4–72 hours in adults
15–180 minutes
1–72 hours in young people aged 12–17 years
≥ 15 days per < 15 days per month
month for more
than 3 months
Second line drugs
≥ 15 days per month for 1 every other day 1 every other
more than 3 months
to 8 per day3, with day to 8 per
remission4
day3,
Specialist drugs
28
Specialist only drugs
Diagnosis
1
Episodic
tensiontype
headache
Chronic
tension-type
headache 5
Episodic migraine
Chronic migraine
(with or without aura) (with or without aura)
> 1 month
with a
continuous
remission4
<1 month
in a
12-month
period
Episodic cluster
headache
Chronic
cluster
headache
Headache pain can be felt in the head, face or neck.
2 See
recommendations 1.2.2, 1.2.3 and 1.2.4 for further information on diagnosis of migraine with aura.
3
The frequency of recurrent headaches during a cluster headache bout.
4
The pain-free period between cluster headache bouts.
5
Chronic migraine and chronic tension-type headache commonly overlap. If there are any features of migraine, diagnose chronic
migraine.
4.7.4 Antimigraine drugs
4.7.4.1 Treatment of acute migraine
NICE Clinical Guideline 150: Headaches recommends:
1. Offering combination therapy with an oral triptan and an NSAID, or an oral triptan and paracetamol, for the acute
treatment of migraine
2. For young people aged 12–17 years consider a nasal triptan in preference to an oral triptan
3. If ineffective or not tolerated, offer a non-oral preparation of metoclopramide or prochlorperazine and consider
adding a non-oral NSAID or triptan if these have not been tried.
5HT1 agonists (triptans)
 Tablet 50mg, 100mg
Sumatriptan

Injection 6mg/0.5ml syringe

Nasal spray 10mg/0.1ml actuation
Naratriptan

Tablet 2.5mg
Zolmitriptan

Tablet 2.5mg

Nasal spray 5mg/0.1ml actuation

Orodispersible tablet 2.5mg, 5mg
Notes:
1. All 5HT1 agonists (triptans) are effective and well tolerated.
2. Headaches can recur within 24 hours in about 30-40% of patients treated with triptans.
3. Triptans are contraindicated in ischaemic heart disease, previous myocardial infarction and uncontrolled
hypertension.
4. If the first triptan fails, it is worth trying an alternative one.
Antiemetics
Refer to: Section 4.6 for antiemetic preparations
4.7.4.2
Prophylaxis of migraine
Propranolol

See section 2.4
Topiramate


Botulinum toxin
type A

Tablet 25mg, 50mg, 100mg
Sprinkle Capsule 15mg, 25mg,
50mg
Botox® Injection for
reconstitution 50 unit, 100 unit,
200 unit vial
First line drugs
Second line drugs
Specialist drugs
29
Specialist only drugs
Notes:
1. Where migraine attacks are frequent, consideration should be given to the avoidance of trigger factors such as
stress or diet (such as cheese, chocolate etc).
2. In patients with more than two attacks per month, prophylaxis should be tried.
3. Propranolol is first line choice for prophylaxis of migraine, unless contraindicated. It is useful where a co-existing
disease, e.g. hypertension or anxiety, is present.
4. Topiramate is indicated in adults for the prophylaxis of migraine headache.
5. Women and girls of childbearing potential should be informed that topiramate is associated with a risk of fetal
malformations and can impair the effectiveness of hormonal contraceptives. Ensure they are offered suitable
contraception.
6. The evidence for the use of pizotifen is limited and weight gain and sedation are often unacceptable side effects
of this drug.
7. Amitriptyline [unlicensed] may be useful when migraine coexists with tension-type headaches, insomnia or
depression. To minimise side effects, treatment should be started at a low dose (10-25mg ON) and increased to
a maintenance dose of 50-75mg ON.
8. Refer to this section of the BNF for more detailed guidance on prophylaxis. Details include the following
unlicensed alternatives: amitriptyline (also included in Section 4.3.1); sodium valproate 300mg bd (also included
in Section 4.8.1); verapamil [cluster headache] (also included in Section 2.6.2). Gabapentin has been used but is
unlicensed for this indication.
9. Botulinum toxin type A is recommended By NICE as an option for the prophylaxis of headaches in adults with
chronic migraine (defined as headaches on at least 15 days per month of which at least 8 days are with migraine)
see TA 260: Botulinum toxin type A for chronic migraine for more detail.
10. Patients should have failed to respond to at least three prior pharmacological prophylaxis therapies and have
been managed for headache medication overuse prior to being referred for this treatment.
11. For acute treatment of cluster headaches, offer oxygen and/or a subcutaneous or nasal triptan.
When using oxygen for the acute treatment of cluster headache:
 use 100% oxygen at a flow rate of at least 12 litres per minute with a non-rebreathing mask and a reservoir
bag and arrange provision of home and ambulatory oxygen.
4.8 Antiepileptics
4.8.1 Control of epilepsy
NICE CG 137: The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and
secondary care (January 2012) , NICE TA 76: Newer drugs for epilepsy in adults (Mar 2004) and NICE TA 79: Newer
drugs for epilepsy in children (April 2004) have been replaced by NICE CG 137: The epilepsies: the diagnosis and
management of the epilepsies in adults and children in primary and secondary care (Jan 2012)

The guidance recommends that all anti-epileptic drugs (AEDs) are initiated in children and adolescents by a
specialist. In adults AED therapy should be initiated by or on the recommendation of a specialist.

When possible, AED choice should be made on the basis of the presenting epilepsy syndrome. If the epilepsy
syndrome is not clear at presentation, the decision should be based on the presenting seizure type(s).

It is recommended that children, young people and adults should be treated with a single AED (monotherapy)
wherever possible. If the initial treatment is unsuccessful, then monotherapy using another drug can be tried.
Caution is needed during the changeover period.

Combination therapy (adjunctive or 'add-on' therapy) should only be considered when attempts at monotherapy
with AEDs have not resulted in seizure freedom. If trials of combination therapy do not bring about worthwhile
benefits, treatment should revert to the regimen (monotherapy or combination therapy) that has proved most
acceptable to the child, young person or adult, in terms of providing the best balance between effectiveness in
reducing seizure frequency and tolerability of side effects.

Consistent supply to the child, young person or adult with epilepsy of a particular manufacturer's AED preparation
is recommended, unless the prescriber, in consultation with the child, young person, adult and their family and/or
carers as appropriate, considers that this is not a concern.

Different preparations of some AEDs may vary in bioavailability or pharmacokinetic profiles and care needs to be
taken to avoid reduced effect or excessive side effects.

When prescribing sodium valproate to women and girls of present and future childbearing potential, the possible
risk of malformation and neurodevelopmental impairments in an unborn child should be discussed, particularly
with high doses of this AED or when using as part of polytherapy.

CSM advice has been issued for the following drugs:
Carbamazepine
Ethosuximide
Lamotrigine
Oxycarbazepine
First line drugs
Phenytoin
Sodium valproate
Topiramate
Vigabatrin
Please refer to the individual drug entries in the
BNF, section 4.8.1.
Second line drugs
Specialist drugs
30
Specialist only drugs
Choice of antiepileptic drug (listed alphabetically)
Seizure type
First-line AEDs
Adjunctive AEDs
Generalised tonic–clonic
Carbamazepine
Lamotrigine
Oxcarbazepinea
Sodium valproate
Tonic or atonic
Sodium valproate
Clobazama
Lamotrigine
Levetiracetam
Sodium valproate
Topiramate
Lamotriginea
Absence
Ethosuximide
Lamotriginea
Sodium valproate
Ethosuximide
Lamotriginea
Sodium valproate
Myoclonic
Levetiracetama
Sodium valproate
Topiramatea
Levetiracetam
Sodium valproate
Topiramatea
Focal
Carbamazepine
Lamotrigine
Levetiracetam
Oxcarbazepine
Sodium valproate
Carbamazepine
Clobazama
Gabapentina
Lamotrigine
Levetiracetam
Oxcarbazepine
Retigabine
Sodium valproate
Topiramate
Other AEDs that may be
considered on referral to
tertiary care
Rufinamidea
Topiramatea
Clobazama
Clonazepam
Levetiracetama
Topiramatea
Zonisamidea
Clobazama
Clonazepam
Piracetam
Zonisamidea
Eslicarbazepine acetate
Lacosamide
Phenobarbital
Phenytoin
Pregabalina
Tiagabine
Vigabatrin
Zonisamidea
a At
the time of publication of guidance (January 2012) this drug did not have UK marketing authorisation for this indication
and/or population. Informed consent should be obtained and documented.
Notes:
1. Controlled release preparations of carbamazepine are preferable to standard release formulations.
2. MHRA advice (April 2017): Children exposed in utero to valproate are at a high risk of serious developmental
disorders (in up to 30-40% of cases) and/or congenital malformations (in approximately 10% of cases)
o
do not prescribe valproate medicines for epilepsy or bipolar disorder in women and girls unless other
treatments are ineffective or not tolerated; migraine is not a licensed indication
o
ensure women and girls taking valproate medicines understand the 30–40% risk of neurodevelopmental
disorders and 10% risk of birth defects and are using effective contraception
o
valproate use in women and girls of childbearing potential must be initiated and supervised by
specialists in the treatment of epilepsy or bipolar disorder .
3. Lamotrigine and oral contraceptives: The Faculty of Family Planning and Reproductive Health Care Clinical
Effectiveness Unit could find no evidence that lamotrigine reduces the effectiveness of hormonal contraception,
but there is evidence that seizure control worsens in some women when starting a combined oral contraceptive
pill (COC) containing ethinylestradiol and desogestrel, and that side effects associated with lamotrigine can
increase when women using lamotrigine discontinue COC.
4. Phenytoin has a narrow therapeutic index and the relationship between dose and plasma concentration is nonlinear; a small dose increase in some patients may produce large rises in plasma concentration with acute toxic
side effects.
5. On the basis of single dose tests, there are no clinically relevant differences in bioavailability between available
phenytoin sodium tablets and capsules, but there may be a pharmacokinetic basis for maintaining the same
brand in some patients.
6. 90mg of phenytoin (chewable tablets or suspension) is considered to be equivalent to 100mg of phenytoin
sodium (capsules or tablets), so care is needed if patients are transferred from one preparation to another.
7. Retigabine has been approved by NICE as adjunctive treatment of partial onset seizures in adults. For guidance
see: NICE TA 232: Retigabine as adjunctive treatment for the control of partial onset seizures (July 2011)
8. The CSM have issued a warning regarding vigabatrin and visual field defects. Patients need monitoring, with
visual field assessment carried out every 6 months. See Current Problems in Pharmacovigilance November 1999 for details.
9. The risk of serious skin-related adverse drug reactions, including Stevens-Johnson syndrome, occurring with
First line drugs
Second line drugs
Specialist drugs
31
Specialist only drugs
carbamazepine may be increased in the presence of the HLA-A*3101 allele in patients of European descent or
Japanese origin. However, there are currently insufficient data to support screening for this allele before starting
carbamazepine treatment. Patients of European descent or Japanese origin who are known to be positive for
this allele should only receive carbamazepine, oxcarbazepine or eslicarbazepine (not formulary) after careful
consideration of the benefits and risks. Full Drug Safety Update (December 2012)
10. Epanutin Capsules (phenytoin) have been discontinued; all other presentations of Epanutin continue to be
available. Phenytoin Sodium Flynn Hard Capsules are available which are identical to Epanutin capsules.
Prescriptions should be written as ‘Phenytoin Sodium Flynn xmg Hard Capsules’, See Flynn Pharma Ltd
Announcement
11. Perampanel is available on the formulary as adjunctive treatment for refractory epilepsies. The dose requires
titration upwards according to response and tolerability over a period of at least 3 months. Titration upwards to
a stable maintenance dose should be undertaken by the specialist. Once the patient is on a stable dose
(at least 3 months after starting treatment) prescribing responsibility can be passed over to GPs under
shared care arrangements.
Antiepileptic drug formulations
 See section 11.6
Acetazolamide






Tablet 100mg, 200mg, 400mg
Tegretol® m/r tablet 200mg, 400mg
Chewable tablet 100mg, 200mg
SF Liquid 100mg/ml
Suppository 125mg, 250mg
Tablet 10mg
Clonazepam


Tablet 500microgram, 2mg
Injection see 4.8.2
Ethosuximide











Capsule 250mg
Syrup 250mg/5ml
Capsule 100mg, 300mg, 400mg.
Tablets 600mg 800mg
Tablet 25mg, 50mg, 100mg, 200mg
Dispersible tablet 2mg, 5mg, 25mg, 100mg
Tablets 250mg, 500mg, 1g
Oral solution SF 100mg/ml
Tablets 150mg, 300mg, 600mg
Oral suspension SF 300mg/5ml
Fycompa® Tablets 2mg, 4mg, 6mg, 8mg, 10mg 12mg
Phenytoin sodium




Epanutin® Capsule 25mg, 50mg, 100mg, 300mg
Tablet 100mg
Chewable tablet 50mg (scored)
Suspension 30mg in 5ml
Pregabalin

Capsules 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 300mg
Retigabine▼

Tablets 50mg, 100mg, 200mg, 300mg, 400mg
Sodium valproate






Crushable tablet 100mg
E/c tablets 200mg, 500mg
Epilim Chrono® m/r tablet 200mg, 300mg, 500mg
SF Liquid 200mg/5ml
Intravenous injection 400mg
Tablets 5mg, 10mg, 15mg
Topiramate


Tablet 25mg, 50mg, 100mg, 200mg
Sprinkle capsules 15mg, 25mg, 50mg
Vigabatrin


Tablet 500mg
SF Powder 500mg
Carbamazepine
Clobazam
SLS
Gabapentin
Lamotrigine
Levetiracetam
Oxcarbazepine
Perampanel▼
Tiagabine
MHRA advice: Antiepileptic products – changing brands
First line drugs
Second line drugs
Specialist drugs
32
Specialist only drugs
In November 2013 the Commission of Human Medicines issued advice on the suitability of switching between
different manufacturer’s products of antiepileptic drugs (AEDs). They have grouped the AEDs into categories
depending on their suitability for switching (see table below). Further information can be found here.
Category 1
Category 2
Category 3
Phenytoin, carbamazepine,
phenobarbital, primidone
Doctors are advised to ensure that
their patient is maintained on a
specific manufacturer’s product.
Valproate, lamotrigine,
perampanel, retigabine,
rufinamide, clobazam,
clonazepam, oxcarbazepine,
eslicarbazepine, zonisamide,
topiramate.
Levetiracetam, lacosamide,
tiagabine, gabapentin, pregabalin,
ethosuximide, vigabatrin.
It is usually unnecessary to ensure
that patients are maintained on a
specific manufacturer’s product
unless there are specific concerns
such as patient anxiety, and risk of
The need for continued supply of a
particular manufacturer’s product
should be based on clinical
judgement and consultation with
patient and/or carer taking into
account factors such as seizure
frequency and treatment history
confusion or dosing errors.
4.8.2 Status epilepticus
 Buccolam® single dose oral syringe 2.5mg, 5mg, 7.5mg, 10mg
Buccal midazolam
Diazepam


Rectal solution 2.5mg, 5mg, 10mg
Intravenous injection (emulsion) (Diazemuls®) 5mg/ml
Lorazepam

Intravenous injection (into large vein) 4mg/ml
Phenytoin sodium

Intravenous injection 250mg/5 ml
Clonazepam

Intravenous injection 1mg/ml or infusion of 1mg
Paraldehyde

Rectally administered 5ml ampoule. For doses in children see BNF.
Replaces
unlicensed
product (Epistatus)
Notes:
1. Buccal midazolam (first line) or rectal diazepam (second line) should only be prescribed in the community for
children, young people and adults who have had a previous episode of prolonged or serial convulsive seizures .
2. Buccal midazolam (as Buccolam®) is available in single use oral syringes colour coded by age
3. A single dose of buccal midazolam should be administered in accordance with the table below. Administration in
children aged 3 to 6 months must be carried out in a hospital setting.
Age range
3 to 6 months (hospital setting )
Dose
2.5mg
Label colour
Yellow
> 6 months to < 1 year
1 year to < 5 years
5 years to < 10 years
10 years to < 18 years
2.5mg
5 mg
7.5 mg
10 mg
Yellow
Blue
Purple
Orange
4. Unlicensed versions of buccal midazolam should no longer be prescribed
5. In the community, treatment of status epilepticus with rectal diazepam should be considered if preferred by the
patient or where buccal midazolam is not available
6. Major status epilepticus should be treated initially with i.v lorazepam. Intravenous diazepam may also be used
but lorazepam has a longer duration of action.
7. Diazepam i.v is associated with a high risk of venous thrombophlebitis, which is reduced by using an emulsion
(Diazemuls®).
8. Absorption from intramuscular injection or from suppositories is too slow for the treatment of status epilepticus.
9. Paraldehyde is also included for paediatric use in prolonged or recurrent seizures
First line drugs
Second line drugs
Specialist drugs
33
Specialist only drugs
4.9 Drugs used in parkinsonism and related disorders
For guidance on the management of Parkinson’s disease refer to NICE Clinical Guideline CG35: Parkinson's
disease: quick reference guide (June 2006)
Notes:
1. Parkinson’s disease is classically determined by the triad of rest tremor (usually starting in one arm) with
bradykinesia (slowing of movement) and rigidity (which may manifest as cogwheel rigidity particularly in the
arms).
2. Patients often display a generalised lack of movement both in terms of facial expression and general body
movement. They often have reduced arm swing (usually asymmetrical at the beginning) with festinant gait. They
may have impaired ability to correct their balance.
3. All patients with a suspected diagnosis of Parkinson’s disease should be referred for a specialist opinion
prior to initiating any treatment.
4. There is currently no treatment that has been definitely proven to slow down the progression of Parkinson’s
disease and therefore patients will not be adversely affected by waiting to commence treatment particularly if
there is any doubt about the diagnosis.
5. Current drug therapy aims simply to correct the chemical imbalance. Although this approach fails to prevent the
progression of the disease, it greatly improves the quality and expectancy of life of most patients.
6. It is important to eliminate the possibility of anti-dopaminergic drugs causing parkinsonian symptoms, for example
prochlorperazine, metoclopramide, chlorpromazine, trifluoperazine, haloperidol and thioridazine.
7. Elderly: Antiparkinsonism drugs carry a special risk of inducing confusion in the elderly. It is particularly
important to initiate treatment with low doses and to use small increments.
4.9.1 Dopaminergic drugs used in parkinsonism
Levodopa plus peripheral decarboxylase inhibitor preparations
Notes:
1. Levodopa in combination with a dopa-decarboxylase inhibitor is the treatment of choice for patients disabled by
idiopathic Parkinson’s disease. It should not be used for neuroleptic-induced Parkinsonism.
2. Sudden onset of sleep: Excessive daytime sleepiness and sudden onset of sleep can occur with co-careldopa,
co-beneldopa, and the dopamine receptor agonists. Patients starting on treatment with these drugs should be
warned of the possibility of these effects and of the need to exercise caution when driving or operating
machinery. Patients who have suffered excessive sedation or sudden onset of sleep, should refrain from driving
or operating machines, until those effects have stopped.
Co-beneldopa
(Madopar®)



Capsule 62.5mg, 125mg, 250mg
Disp tablet 62.5mg, 125mg
Madopar CR® m/r capsule 125mg
Co-careldopa
(Sinemet®)



Tablet 62.5mg, 125mg (Sinemet Plus®) 275mg
Half Sinemet CR ® m/r tablet 125mg
Sinemet CR ®m/r tablet 250mg
Co-careldopa/ entacapone
(Stalevo)






Tablets 50mg/12.5mg/200mg
Tablets 75mg/18.75mg/200mg
Tablets 100mg/25mg/200mg
Tablets 125mg/31.25mg/200mg
Tablets 150mg/37.5mg/200mg
Tablets 200mg/50mg/200mg
Notes:
1. The co-careldopa (10/100) formulation (Sinemet 110) should not generally be used as the dose of carbidopa
may be insufficient to achieve full inhibition of extracerebral dopa-decarboxylase; co-careldopa 25/100 should
therefore be used so that the daily dose of carbidopa is at least 75mg.
2. Levodopa therapy should be initiated with low doses and gradually increased, by small increments, at intervals of
2-3 days. The final dose is usually a compromise between increased mobility and dose-limiting side effects.
3. Modified release preparations may help with “end-of-dose” deterioration or nocturnal immobility and rigidity.
4. The triple combination product Stalevo is a useful aid to compliance in patients requiring treatment with L-dopa
and the COMT inhibitor entacapone and facilitates the requirement for entacapone to be taken at the same time
as L-dopa.
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34
Specialist only drugs
Dopamine receptor agonists
Pramipexole


Tablets 88microgram, 180microgram, 700microgram,
Prolonged release tablets 260microgram, 520microgram, 1.05mg, 2.1mg, 3.15mg
Ropinirole




Tablets 1mg, 2mg, 5mg
Starter pack (250microgram, 500microgram and 1mg tablets)
Follow-on pack (500micrograms, 1mg and 2mg tablets)
Rotigotine▼


Patches 2mg/24 hours, 4mg/24 hours, 6mg/24 hours, 8mg/24 hours
28 day Starter pack (7x2mg/24hr, 7x4mg/24hr, 7x6mg/24hr, 7x8mg/24hr patches)
Apomorphine



Injection 20mg in 2ml, 50mg in 5ml
Injection 30mg in 3ml pen injector
50mg in 10ml pre-filled syringes
MR▼ tablets 2mg, 4mg, 8mg
For use in hospital only
For intermittent s/c injection
For continuous s/c infusion in the community
Notes:
1. Doses of dopamine receptor agonists should be increased slowly according to response and tolerability. As
doses are increased the strength should be increased as appropriate, rather than the number of tablets.
2. Ergot-derived dopamine receptor agonists: the CSM has advised that ergot-derived dopamine receptor
agonists, bromocriptine, cabergoline, lisuride and pergolide have been associated with pulmonary,
retroperitoneal, and pericardial fibrotic reactions. The ergot derivatives have therefore not been included in the
formulary. However, many patients have been taking these drugs for years, with good symptom control and
without side effects. Such patients should be monitored and the potential side effects discussed and only
discontinued if the patient wishes. These patients should be treated under specialist supervision. No new patients
should be initiated on these drugs. The CSM guidelines are that these agents should only be considered in
patients who are intolerant of or fail to respond to non-ergot agonists.
3. Ropinirole MR and rotigotine formulations all have black triangle status (▼) and any suspected adverse reactions
must be reported using the Yellow Card Scheme.
4. Ropinirole is likely to be most useful as an adjunct to levodopa. It can be used as monotherapy in younger
patients who are at risk of developing disabling dyskinesia with long-term levodopa therapy.
5. The Scottish Medicines Consortium (SMC) advises that rotigotine is suitable for use as monotherapy in early
stage disease (June 2007) but recommends restricted use in advanced Parkinson’s disease with levodopa where
the transdermal route would facilitate treatment (July 2007)
6. Apomorphine is sometimes helpful in stabilising patients experiencing unpredictable “off” periods with levodopa
treatment and can be given either by intermittent s/c injection or by continuous s/c infusion. It is essential to
stabilise patients on domperidone for at least 2 days before starting treatment with apomorphine. All initiations
must take place in secondary care under the direct supervision of the Parkinson’s Specialist Nurses.
7. Once assessment for suitability and response is undertaken in secondary care and patient has been stabilised on
a tailored apomorphine schedule, patients are suitable for shared care. Details of shared care guidelines can be
obtained from the Parkinson’s Specialist Nurses at both sites.
Catechol-O-methyltransferase inhibitors (COMT inhibitors)
Entacapone

Tablets 200mg
Tolcapone

Tablets 100mg
Notes:
1. The current guidance is that entacapone should be the first COMT inhibitor to be used, and tolcapone should only
be used in cases of entacapone intolerance or failure.
2. Tolcapone is black triangle status (▼) and any suspected adverse reactions must be reported using the Yellow
Card Scheme.
3. Tolcapone is associated with potentially life-threatening hepatotoxicity hence regular monitoring of liver function is
necessary.
MAO type B antagonist
 Tablet 5mg, 10mg
Selegiline
Rasagilene
First line drugs



Syrup 10mg in 5ml
Oral lyophilisate 1.25mg
Tablets 1mg
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35
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Notes:
1. Selegiline is used in severe Parkinsonism in conjunction with levodopa to reduce “end-of-dose” deterioration.
2. The oral lyophilisate formulation of selegiline is significantly more expensive than standard tablets or syrup but
allows once-daily dosing.
3. 1.25mg of selegiline oral lyophilisate is approximately therapeutically equivalent to 10mg selegiline tablets
Mixed action
Amantadine


Capsules 100mg
Syrup 50mg in 5ml
Note:
Amantadine has a modest effect on dyskinesias and only a small proportion of patients derive much benefit.
Tolerance to its effect occurs.
4.9.2 Antimuscarinic drugs used in parkinsonism
 Tablets 50mg
Orphenadrine

Oral solution 50mg/5ml
Procyclidine



Tablet 5mg
Syrup 2.5mg/5ml, 5mg/5ml
Injection 10mg in 2ml
Trihexphenidyl


Tablet 2mg, 5mg
Syrup 5mg in 5ml
Notes:
1. Patients with mild symptoms of Parkinson’s disease, particularly where tremor predominates, may be treated
initially with antimuscarinic drugs (alone or with selegiline), levodopa being added or substituted as symptoms
progress.
2. They have value in post-encephalitic Parkinsonism.
3. They reduce tremor and rigidity but have little effect on bradykinesia. They are useful in reducing sialorrhoea.
4. The antimuscarinic drugs reduce the symptoms of drug-induced Parkinsonism.
5. Tardive dyskinesia is not improved by the antimuscarinic drugs and may be made worse.
6. Trihexphenidyl is the antimuscarinic of choice particularly in younger patients
7. Orphenadrine has been included for patients who may misuse procyclidine.
4.9.3 Drugs used in essential tremor, chorea, tics, and related disorders
Note:
BNF Section 4.9.3 gives information on choice of medication. See the current edition of the BNF for dose guidelines.
Essential tremor
Notes:
1. Propranolol (section 2.4) may be useful for tremors, or tremors associated with anxiety or thyrotoxicosis.
2. Primidone and clonazepam are alternatives.
Tics etc
Notes:
1. Haloperidol may be useful in improving motor tics and symptoms of Gilles de la Tourette syndrome and related
choreas.
2. Pimozide (N.B. CSM warnings; see section 4.2.1), clonidine (section 4.7.4.2) and sulpiride (section 4.2.1) are
also used in Gilles de Tourette syndrome.
3. Chlorpromazine and haloperidol (section 4.2.1) are used to relieve intractable hiccups.
Huntington’s Chorea
 Tablet 25mg
Tetrabenazine
Notes:
1. Tetrabenazine has a useful action for movement disorders, only in the latter stage of the disease.
2. Tetrabenazine may cause depression and excessive sedation. It may also precipitate extrapyramidal side
effects. It is therefore important to initiate treatment on the minimum effective dose and increase dosage no
more frequently than on a weekly basis.
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Second line drugs
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36
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Myoclonus
Piracetam


Tablet 800mg, 1.2g
Oral solution 333.3mg/ml
Amyotrophic Lateral Sclerosis (Motor Neurone Disease)
 Tablet 50mg
Riluzole
Notes:
1. Riluzole is used to extend life or the time to mechanical ventilation in patients with motor neurone disease who
have amyotrophic lateral sclerosis.
2. NICE guidance TA 20 (January 2001): Riluzole is recommended for the treatment of individuals with the
amyotrophic lateral sclerosis (ALS) form of Motor Neurone Disease (MND). A neurological specialist should
initiate therapy with expertise in the management of MND. Routine supervision of therapy should be managed by
locally agreed shared care protocols undertaken by general practitioners.
Torsion dystonias and other involuntary movements
 Injection 500 unit vial
Botulinum A toxin
(Dysport®)
Notes:
1. Dysport® is indicated for the treatment of spasmodic torticollis, blepharospasm and hemifacial spasm in adults.
2. Please refer to product literature for further information.
4 .1 0
Drugs used in substance dependence
Alcohol dependence
Chlordiazepoxide

See section 4.1.2
Disulfiram
Acamprosate
Nalmefene▼



Tablet 200mg
Tablet e/c 333mg
Selincro® Tablets 18ng
Notes:
NICE CG100 Alcohol use disorders (June 2010) gives guidance on the diagnosis and management of symptoms
caused by alcohol dependence.
1. Acamprosate should only be prescribed in combination with counselling, when it may be helpful in maintaining
abstinence in alcohol dependent patients.
2. Diazepam or oxazepam may be considered as alternatives to chlordiazepoxide
3. NICE TA 325 offers nalmefene in conjunction with psychosocial support for dependent drinkers who do not need
immediate detoxification. Patients should be referred to the STAR service (East Sussex Drug and Alcohol
service) who will assess for suitability, prescribe nalmefene where appropriate and provide psychosocial support.
All prescribing will remain with the STAR service. Nalmefene should not be prescribed in primary care.
Cigarette smoking:
Nicotine replacement therapy (NRT), varenicline and bupropion are all proven to help patients quit smoking.
Guidance on how they can be used is given in NICE guidance PH10: Smoking cessation services (August 2008)

Offer NRT, varenicline or bupropion, as appropriate, to people who are planning to stop smoking.

NRT, varenicline or bupropion should normally be prescribed as part of an abstinent-contingent treatment, in
which the smoker makes a commitment to stop smoking on or before a particular date (target stop date). The
prescription of NRT, varenicline or bupropion should be sufficient to last only until 2 weeks after the target stop
date. Normally, this will be after 2 weeks of NRT therapy, and 3–4 weeks for varenicline and bupropion, to allow
for the different methods of administration and mode of action. Subsequent prescriptions should be given only to
people who have demonstrated on re-assessment that their quit attempt is continuing.

Varenicline or bupropion may be offered to people with unstable cardiovascular disorders, subject to clinical
judgement.

Consider offering a combination of nicotine patches and another form of NRT (such as gum, inhalator, lozenge or
nasal spray) to people who show a high level of dependence on nicotine or who have found single forms of NRT
inadequate in the past.

Do not favour one medication over another. The clinician and patient should choose the one that seems most
likely to succeed.

Neither varenicline or bupropion should be offered to young people under 18 nor to pregnant or breastfeeding
First line drugs
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37
Specialist only drugs
women.

If a smoker’s attempt to quit is unsuccessful using NRT, varenicline or bupropion, do not offer a repeat
prescription within 6 months unless special circumstances have hampered the person’s initial attempt to stop
smoking, when it may be reasonable to try again sooner.

Do not offer NRT, varenicline or bupropion in any combination.

Smokers not wishing to quit straight away but wishing to follow the nicotine assisted reduction to stop (NARS)
strategy should not be offered NRT until they are ready to fully quit.
Nicorette®
NiQuitin CQ®





Gum 2mg, 4mg (Freshfruit and Icy White)
Invisi Patch 10mg, 15mg, 25mg
Inhalator 15mg cartridge
Nasal Spray 500 micrograms per spray
QuickMist® oromucosal spray 1mg per
spray
30 and 105 pack sizes available


Patch 7mg,14mg 21mg
Minis Lozenge 1.5mg, 4mg
24 hour application. Packs of 7
16 hour application (take off at night) packs of 7
Available as starter pack and refil
Available as a single or double pack
20 and 60 pack sizes available
Notes:
1. Patches are first choice for most patients. The 16-hour patch (Nicorette®) is preferable as nicotine can cause
sleep disturbances. However, if the patient has the first cigarette within 30 minutes of waking, the 24-hour patch
(NiQuitin CQ®) would be more appropriate.
2. All listed products are licensed for use in children aged 12 and over.
3. All products are contra-indicated in the under 12’s
4. All the listed products can be used in pregnancy and lactation. However, patients should be advised to try and
give up without the use of NRT due to the harmful effects of nicotine on the foetus and the fact that it also passes
freely into breast milk.
Bupropion

Tablet m/r, f/c 150mg
Notes:
1. Bupropion should be started 1-2 weeks before target stop date. The dose is initially 150mg DAILY for the first 6
days, only increasing to 150mg TWICE DAILY on day 7. Maximum period of treatment is 7 – 9 weeks.
2. Patients should only be prescribed bupropion if they are motivated to stop and (ideally) are receiving support
from a Smoking Cessation Adviser.
3. GPs must assess the client’s suitability for bupropion.
4. In order to promote compliance and prevent wastage, the following prescribing schedule is recommended:
 2 weeks
 2 weeks dependent on continued abstinence
 3 – 5 weeks as appropriate (Total course = 7 – 9 weeks)
5. Prescriptions should be linked to an appointment with a Smoking Cessation Adviser to check for continued
abstinence.
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Second line drugs
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38
Specialist only drugs
6. Bupropion is not recommended for smokers under the age of 18 years, as its safety and efficacy have not been
evaluated in this group. Women who are pregnant or breastfeeding or those with a current or history of bipolar
disorder should not be prescribed bupropion.
7. CSM advice: Bupropion is associated with a dose-related risk of seizure. In approximately 50% of cases, the
patients had either a past history of seizure(s) and/or risk factors for their occurrence. Bupropion is therefore
contraindicated in patients:
- with a current seizure disorder or any history of seizures;
- current or previous diagnosis of bulimia or anorexia nervosa;
- with a known central nervous system (CNS) tumour;
- experiencing abrupt withdrawal from alcohol or benzodiazepines
Bupropion should not be prescribed in patients with other risk factors for seizures unless there is compelling
justification for which potential benefit outweighs the increased risk of seizure. Such risk factors include:
- concomitant administration of any drug known to lower the seizure threshold (e.g. antipsychotics,
antidepressants, antimalarials, theophylline, systemic steroids, tramadol, quinolones and sedating
antihistamines).
- Alcohol abuse.
- History of head trauma.
- Diabetes treated with hypoglycaemics or insulin.
- Use of stimulants or anorectic products.
In such patients a lower dose of 150 mg daily throughout the entire treatment period should be considered.
8. Bupropion has considerable potential for interaction with other medicines. Further details can be found in the
Summary of Product Characteristics (SPC).
9. Details of other side effects associated with bupropion can be found in the SPC. Doctors and pharmacists are
asked to continue to report all suspected adverse reactions.
 Tablets 500 microgram, 1mg
 Starter pack containing 500mcg and 1mg tablets
NICE guidance (TA123) July 2007
1. Varenicline is recommended within its licensed indications as an option for smokers who have expressed a
desire to quit smoking.
2. Dose titration is necessary – see below
Varenicline
Days 1 – 3:
0.5 mg once daily
Days 4 – 7:
0.5 mg twice daily
Day 8 – End of treatment:
1 mg twice daily
3. Treatment should be started 1-2 weeks prior to the agreed quit date and continued for 12 weeks.
4. Varenicline is contra-indicated in the under 18’s during pregnancy and lactation.
5. The MHRA has recently issued a reminder in its Drug Safety Update (November 2008) of safety issues
associated with varenicline.
Psychiatric disorders are the most commonly reported suspected adverse reactions for varenicline in the UK.
Depression and suicide-related events have been reported in patients using varenicline who are trying to stop
smoking.
Patients who are taking varenicline who develop suicidal thoughts or who develop agitation, depressed mood, or
changes in behaviour that are of concern for the doctor, patient, family, or caregiver should stop their treatment
and contact their doctor immediately.
4.11 Drugs for dementia
NICE guidance: NICE TA 217 (March 2011) Donepezil, galantamine, rivastigmine, and memantine for the
treatment of Alzheimer's Disease (rev May 2016)
The acetylcholinesterase (AChE) inhibitors donepezil, galantamine and rivastigmine are recommended as options for
managing mild to moderate Alzheimer’s disease under all of the conditions specified in below (1-4)
Memantine is recommended as an option for managing Alzheimer’s disease for people with:
• moderate Alzheimer’s disease who are intolerant of or have a contraindication to AChE inhibitors
or
• Severe Alzheimer’s disease.
Treatment should be under the conditions specified below (1-3).
Treatment should be in accordance with the following conditions:
1. Only specialists in the care of patients with dementia (that is, psychiatrists including those specialising in learning
disability, neurologists and physicians specialising in the care of older people) should initiate treatment. Carers’
First line drugs
Second line drugs
Specialist drugs
39
Specialist only drugs
views on the patient’s condition at baseline should be sought.
2. Treatment should be continued only when it is considered to be having a worthwhile effect on cognitive, global,
functional or behavioural symptoms.
3. Patients who continue on treatment should be reviewed regularly using cognitive, global, functional and
behavioural assessment. Treatment should be reviewed by an appropriate specialist team, unless there are
locally agreed protocols for shared care. Carers’ views on the patient’s condition at follow-up should be sought.
4. If prescribing an AChE inhibitor (donepezil, galantamine or rivastigmine), treatment should normally be started
with the drug with the lowest acquisition cost (taking into account required daily dose and the price per dose once
shared care has started).
Donepezil hydrochloride
Galantamine
Rivastigmine
Memantine



Tablet 5mg, 10mg
Tablet 8mg, 12mg
Capsules M/R Reminyl® XL 8mg, 16mg, 24mg





Oral solution 4mg/ml
Capsule 1.5mg, 3mg, 4.5mg, 6mg
Oral solution 2mg/ml
Patches 4.6mg in 24 hours, 9.5mg in 24 hours
10mg, 20mg, 10mg/ml oral soln
Notes:
Behavioural and psychological symptoms can be part of the dementing process, but it is important to exclude any
intercurrent illness. Behavioural and psychological approaches are important and the use of medication has a lower profile.
If medication is used, the rule of start low, go slow, monitor effects frequently applies. It is important to review any drug
at regular intervals and assess whether it can be stopped as the treatment symptoms may have remitted.
Other Guidance: NICE CG42: Dementia: supporting people with dementia and their carers in health and social care
First line drugs
Second line drugs
Specialist drugs
40
Specialist only drugs