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4.1.1 Hypnotics
4.1.2 Anxiolytics
4.2.1 Antipsychotic drugs
Typical antipsychotics
Atypical antipsychotics
Prescribing guidelines for anti-psychotics
4.2.2 Antipsychotic depot injections
4.2.3 Mania
4.3 Depression
4.3.1 Tricyclic antidepressants
4.3.2 Monoamine oxidase inhibitors
4.3.3 SSRIs
4.3.4 Other antidepressants
4.4 Central Nervous System Stimulants
4.6.1 Nausea and vertigo
4.6.2 Anti-emetics and cytotoxic therapy
4.6.3 Adjunctive treatments for syringe drivers
4.7.1 Non-opioid analgesics
4.7.2 Opioid analgesics
4.7.3 Neuropathic pain
4.7.4.1 Acute migraine
4.7.4.2 Migraine prophylaxis
4.8.1 Anti-epileptics
4.8.2 Status epilepticus
4.9.1 Parkinson’s Diseases - Dopaminergics
4.9.2 Parkinson’s Disease - Antimuscarinics
4.9.3 Essential tremor, chorea and tics
4.10.1 Alcohol dependence
4.10.2 Opioid dependence
4.10.3 Nicotine replacement therapy
4.11 Drugs for Dementia

Link to GP Formulary

Link to Contents Page

Link to NICE guidance	Delerium. Clinical Guideline No. 103.
	Psychosis with coexisting substance misuse. Assessment and management in adults and young people. Clinical Guideline No. 120.
	Common mental health disorders. Clinical Guideline No. 123.

4.1.1 Hypnotics

Link to NICE guidance

Insomnia - newer hypnotic drugs. TAG 77.

Disturbed sleep patterns are common in hospital and often require no specific treatment. Simple measures are often satisfactory such as reassurance, pain relief, a hot drink, quiet and darkness. Benzodiazepines should be avoided.
Non-benzodiazepine hypnotics:
Cloral betaine tabs: (Welldorm^®) 707mg [14 tabs £5.65]. Dose: 1-2 tabs, max 5 daily, with water or milk at bedtime.
Chloral hydrate elixir: (Welldorm^®) 143mg in 5ml [150ml £8.70]. Dose: 15-45ml with water or milk at bedtime; 5ml initially for the elderly. Caution: chloral salts should be avoided in pregnancy, lactation, gastritis and in severe renal, hepatic or cardiac disease.
Also:
Clormethiazole caps: 192mg [14 caps £1.12]. Dose: 1-2 caps at bedtime.
Benzodiazepines should rarely be given for night sedation and their use should be minimised according to the Northern Devon Healthcare policy for hypnotics and sedatives. Alternatives should be satisfactory or most situations but benzodiazepines are justifiable for pre- and postoperative medication, terminal care, oncology and day-night reversal in psychogeriatric patients. If benzodiazepines started in hospital are prescribed on discharge the GP should be notified.
If a benzodiazepine is considered essential temazepam should be used but for no more than 3 consecutive nights. It has a short half-life and little hangover effect but, in comparison with longer acting benzodiazepines, withdrawal symptoms are more common after prolonged use. Nitrazepam has a prolonged action, repeated doses accumulate and hangover is a problem the next day. It should only be used if already taken before admission.
Benzodiazepine hypnotics:
Temazepam tabs: 10mg [7 tabs 69p]; 20mg [7 tabs 50p]; oral solution 10mg in 5ml [70ml £7.80] (CD). Dose: 10-30mg at bedtime.
Also:
Nitrazepam tabs: 5mg [7 tabs 23p]; oral suspension 2.5mg in 5ml [70ml £2.38]. Dose: 5-10mg at bedtime.
Zopiclone tabs: 3.75mg [7 tabs 40p]; 7.5mg [7 tabs 41p]. Dose: 7.5mg at bedtime, (elderly 3.75mg at bedtime).

4.1.2 Anxiolytics

Link to NICE guidance

Generalised anxiety disorder and panic disorder in adults Clinical Guideline No.113

Benzodiazepines relieve anxiety but should be given at the lowest effective dose for the shortest possible time and only if absolutely necessary. They may be used if anxiety is severe or disabling and even then for only 2-4 weeks. They should not be used to treat depression, phobic or obsessional states or chronic psychoses. In bereavement they may prevent the normal process of grieving. Short acting compounds, such as lorazepam, are preferable if there is hepatic impairment but they carry the risk of withdrawal symptoms. Benzodiazepines have a role to play should tranquillisation be needed in cases of Lewey body dementia.
Some antidepressants in low dose are effective anxiolytics. Antipsychotics, also in low dose, may relieve severe anxiety but the risk of tardive dyskinesia makes long term use undesirable (see 4.2.1).
First choice: Diazepam tabs: 2mg [21 tabs 62p]; 5mg [21 tabs 63p]; 10mg [21 tabs 65p]; oral solution: 5mg in 5ml [100ml £6.30]. Dose: 6-30mg daily in 3 divided doses.
Also:
Diazepam aqueous injection: 10mg in 2ml [45p].
Diazepam emulsion injection: 10mg in 2ml [91p].
Diazepam rectal solution: 2.5mg [£1.04]; 5mg [£1.25]; 10mg [£1.70].
Caution: To treat status epilepticus diazepam should be given as a rectal solution not as a suppository.
Also:
Chlordiazepoxide caps: 5mg [21caps £1.15]; 10mg [21 caps £2.39]. Dose: 30-100mg daily in 3 divided doses.
Lorazepam tabs: 1mg [14 tabs £2.01]; 2.5mg [14 tabs £2.93]. Dose: 1-4mg daily in divided doses.
Lorazepam injection: 4mg in 1ml [35p].

4.1.3 Barbiturates

With the exceptions of phenobarbital for epilepsy (see 4.8.1) , primidone for epilepsy or essential tremor (see 4.9.3) and thiopentone for anaesthesia (see 15.1.1), barbiturates should only be prescribed if already taken before admission.

4.2.1 Antipsychotic drugs

Link to NICE guidance	Schizophrenia - Clinical Guideline No.82
	Aripiprazole for the treatment of schizophrenia in people aged 15 to 17 years. TAG 213

4.2.2 Antipsychotic depot injects.

Long acting depots of antipsychotic drugs are given by deep im injection every 1-4 weeks for maintenance therapy and no more than 2-3ml should be injected into any one site. They are more convenient than oral preparations and ensure better compliance but they do cause more extrapyramidal reactions so treatment should be monitored carefully. Side effects may be prolonged so a small test dose should be given first. During transfer from oral to depot therapy the oral dose should be phased out gradually.
There are no major differences between depot preparations but zuclopenthixol may be more suitable for agitation and aggression which might otherwise be worsened by flupentixol. Pipothiazine can be given every 4 weeks.

Typical Preparations
Flupentixol oily injection: 20mg in 1ml [£1.27]; 40mg in 2ml [£2.49]; 100mg in 1ml [£1.84]; 200mg in 1ml [£3.01]. Dose: by deep im injection into the gluteal muscle, test dose of 20mg (10mg in the elderly), then after at least 7 days 20-40mg repeated at intervals of 2-4 weeks and adjusted according to response; max 400mg weekly; elderly initially quarter to half adult dose.
Fluphenazine oily injection: 25mg in 1ml [£2.26]; 100mg in 1ml [£8.75]. Dose: by deep im injection into the gluteal muscle, test dose of 12.5mg (6.25mg in the elderly), then after 4-7 days 12.5-100mg, repeated at intervals of 2-5 weeks and adjusted according to response.
Haloperidol decanoate oily injection: 50mg in 1ml [£3.81]; 100mg in 1ml [£5.05]. Dose: by deep im injection into the gluteal muscle, initially 50mg every 4 weeks, increased if needed by increments of 50mg to a max of 300mg every 4 weeks; elderly the initial dose should be 12.5-25mg every 4 weeks.
Pipothiazine injection: 50mg in 1ml [£16.29]; 100mg in 2ml [£26.65]. Dose: by deep im injection into the gluteal muscle, test dose of 25mg then a further 25-50mg after 4-7 days, then adjusted according to response at intervals of 4 weeks; maintenance usually 50-100mg (max 200mg); elderly the initial dose should be 5-10mg.
Zuclopenthixol oily injection: 200mg in 1ml [£1.99]; 500mg in 1ml [£3.64]. Dose: by deep im injection into the gluteal muscle, test dose of 100mg followed after at least 7 days by 200-500mg, repeated at intervals of 1-4 weeks adjusted according to response, mamimum 600mg weekly; elderly aquarter to half usual starting dose.

Atypical Preparations
Risperidone depot injection (Risperdal Consta^®): 25mg [£79.69], 37.5mg [£111.32], 50mg [£142.76]. Dose: By deep im injection into the gluteal muscle, patients taking oral risperidone up to 4mg daily, initially 25mg every 2 weeks; patients taking oral risperidone over 4mg daily, initially 37.5mg every 2 weeks; dose adjusted at intervals of at least 4 weeks in steps of 12.5mg to max. 50mg (elderly 25mg) every 2 weeks. NB During initiation risperidone by mouth may need to be continued for 4–6 weeks; risperidone by mouth may also be used during dose adjustment of depot injection.

4.2.3 Mania

Link to NICE guidance

Bipolar Disorder – Clinical Guideline No. 38

Lithium therapy is used for mania, hypomania, recurrent depression and bipolar affective disorder and should always be started by a psychiatrist. Preparations should always be prescribed by brand name because of major differences in bioavailability.
Carbamazepine is used for prophylaxis of manic-depressive illness in those unresponsive to lithium and is effective if there are rapid cycles of four or more affective episodes each year.
Valproic acid (as the semisodium salt) is licensed for the treatment of manic episodes associated with bipolar disorder. It may be useful in patients unresponsive to lithium. Sodium valproate has also been used, but it is unlicensed for this indication..
First choice: Lithium carbonate SR tabs (Priadel^®): 200mg [14 tabs 32p]; 400mg [14 tabs 47p]. Dose: for treatment and prophylaxis, 400-1200mg daily in 1-2 divided doses, adjusted according to plasma levels; in the elderly or if body weight is less than 50kg, 200mg daily.
Lithium citrate liquid: 520mg in 5ml (equivalent to 200mg lithium carbonate in 5ml) [150ml £5.61]. Dose: as for lithium carbonate SR tabs.
Caution: There is high risk of lithium intoxication unless great care is taken, especially if renal excretion is reduced by sodium depletion, thiazides, loop diuretics, ACE inhibitors or NSAIDs. The chance of lithium neurotoxicity is increased by drugs such as sumatriptan, methyldopa and (SSRIs) like fluoxetine. For other drug interactions see BNF Appendix 1.
Patients should be made aware of toxic symptoms such as anorexia, vomiting, diarrhoea, thirst and polyuria, muscle weakness, drowsiness and ataxia and they should carry the information card supplied by the ward.
Serum-lithium concentrations should be monitored between days 4 to 7 after initiation (or dose adjustment), then every week until dosage has remained constant for 4 weeks and every 3 months thereafter. The therapeutic range is 0.4-1.0mmol/l but in the elderly the levels should be kept to the lower part of the range. Levels above 1.2mmol/l may require emergency treatment (see BNF: Emergency treatment of poisoning).
Preparations vary widely in bioavailability; if a brand of lithium preparation is changed plasma levels should be checked as for starting treatment anew.
Renal, cardiac and thyroid function and serum calcium should be checked before and every 6 months during treatment.
Also:
Semi-sodium valproate tabs (Depakote^®): 250mg [28tabs £3.79], 500mg [28tabs £7.56]. Dose: initially 750mg daily in 2 or 3 divided doses, increased according to response, usual dose 1 to 2 g daily in divided doses.
Carbamazepine (see 4.8.1) . Dose: 400mg daily in divided doses increased until symptoms are controlled, usual to 400-600mg daily; max 1.6g daily.

4.3 Depression

Link to NICE guidance	Depression in children and young people – Clinical Guideline No.28
	Obsessive-compulsive disorder - Clinical Guideline No.31
	Depression in adults (update) – Clinical Guideline No. 90
	Depression with chronic physical health problem – Clinical Guideline No. 91

Antidepressants in current use are equally effective, each improving depression in about 60% of cases. Choice of drug is partly determined by safety, tolerability and other disorders or concurrent treatments. Drugs such as lofepramine and the SSRIs, are safer in overdose, and tend to cause less psychomotor impairment.

4.3.1 Tricyclic and related antidepressants

Tricyclics are effective antidepressants but no more than one type should be given at any one time. Anticholinergic side effects may limit their use, especially in the elderly, and they are cardiotoxic in overdose. Treatment should be started at low dose, especially in the elderly, and gradually increased for optimum effect.
Sedative tricyclics, eg amitriptyline, may be given as a single dose at night, thus avoiding the need for additional hypnotics. Sleep may improve immediately but the antidepressant effect may take 2-8 weeks to develop. Benefit on mood can be assessed at 4-6 weeks after which the dose can be increased gradually if necessary. After recovery, treatment may need to continue for a consolidation phase of about 1 year (and up to 2 years in the elderly) before it is slowly withdrawn. Amitriptyline is particularly dangerous in overdose. Clomipramine is used in phobic and obsessional states.
First choice: Lofepramine tabs: 70mg [14 tabs £1.36]. Dose: 140-210mg daily in divided doses; elderly may respond to lower doses.
Also:
Amitriptyline tabs: 10mg [14 tabs 43p]; 25mg [14 tabs 43p]; 50mg [14 tabs 48p]; syrup: 50mg in 5ml [150ml £16.82]. Dose: initially 75mg (elderly 30-75mg) daily in divided doses or as a single dose at bedtime, increased gradually as needed to a max of 150-200mg daily.
For expert use:
Clomipramine caps: 10mg [14 caps 83p]; 25mg [14 caps 96p]; 50mg [14 caps £1.24]. Dose: depression, 10mg daily initially, increased gradually as needed to 30-150mg daily in divided doses or as a single dose at bedtime; max 250mg daily; elderly initially 10mg daily increased carefully over approx 10 days to 30-75mg daily; phobic and obsessional states, 25mg daily initially (10mg daily in the elderly) increased over 2 weeks to 100-150mg daily, max 250mg daily.

4.3.2 Monoamine oxidase inhibitors

MAOIs are used much less than other antidepressants because of dangerous interactions with diet and other drugs. Caution: Great care must be taken to avoid the many foods and drugs which cause adverse interactions with MAOIs. A drug free interval, sometimes of several weeks, may be needed before starting or after stopping MAOIs (see 4.3.5). All patients should receive an MAOI warning card from the Pharmacy.
•Analgesics may show enhanced neurotoxicity: pethidine, other opioids and nefopam.
•Anticonvulsants are rendered less effective and the risk of fits is increased. Even so, carbamazepine is contraindicated within 2 weeks of taking MAOIs.
•Antihypertensives may cause severe hypotension because of enhanced effects.
•Food and drink may cause sudden severe hypertension: Bovril, Oxo, Marmite and other meat or yeast extracts, cheese, Complan, hung game, pickled herring, alcoholic and alcohol-reduced drinks.
•Serotonin reuptake inhibitors: CNS side effects of the SSRIs are increased. SSRIs should not be started until 14 days after MAOIs have been stopped. Conversely, MAOIs should not be started until 1 week after stopping sertraline and 5 weeks after stopping fluoxetine (see 4.3.5).
•Sumatriptan's neurotoxicity is enhanced.
•Sympathomimetics may cause sudden severe hypertension: amphetamines, dexfenflur-amine, diethylpropion, dopamine, ephedrine, fenfluramine, levodopa, phenylephrine, phenylpropanoloamine and pseudoephedrine.
•Tetrabenazine may cause dangerous CNS stimulation and severe hypertension.
•Tricyclics and related antidepressants may cause dangerous CNS stimulation and severe hypertension. They should not be given until 2 weeks after MAOIs have been stopped and should then be started at very low dose.
For other drug interactions see BNF App. 1.
Phenelzine is the safest MAOI but the most hepatotoxic. Tranylcypromine is the most hazardous because of its stimulant action. MAOIs should be withdrawn slowly over several months after prolonged use.
For expert use:
Phenelzine tabs: 15mg [21 tabs £3.94]. Dose: 15mg 3 times daily increased if needed to 4 times daily after 2 weeks, (hospital patients max 30mg 3 times daily) then reduce gradually to lowest possible maintenance dose (15mg on alternate days may be adequate).

4.3.3 SSRIs

Selective serotonin reuptake inhibitors are less sedative than tricyclics with fewer antimuscarinic effects and lower cardiotoxicity, but like tricyclics they may also aggravate epilepsy. They often cause nausea, especially in the first few weeks of treatment. For the elderly, sertraline is preferred to fluoxetine because of its shorter half-life. Caution: Neurotoxic effects of lithium and sumatriptan are enhanced by SSRIs. Anticonvulsants are antagonised, increasing the risk of fits, although fluoxetine also increases plasma levels of carbamazepine. For interactions with MAOIs see (see 4.3.2); for other drug interactions see BNF Appendix 1.
First choice: Fluoxetine: 20mg [7 caps 33p], syrup: 20mg in 5ml [70ml £4.77]. Dose: depression, 20mg once daily increased after 3 weeks if necessary, usual dose 20-60mg, max 80mg daily; bulimia nervosa 60mg once daily, max 80mg daily; obsessive-compulsive disorder, initially 20mg once daily increased after 2 weeks if necessary, usual dose 20-60mg daily, max 80mg daily.
Also:
Citalopram tabs: 10mg [7 tabs 50p]; 20mg [7 tabs 54p]; 40mg [39p]. Dose: depression, 20mg daily increased if necessary to a maximum of 40mg daily (elderly max 20mg daily); panic disorder, 10mg daily increased to 20mg after 7 days, usual dose 20-30mg daily, max 40mg daily (elderly max 20mg daily).

See also New Advice for the Safer Prescribing of Citalopram

Citalopram oral drops: 40mg/ml [15ml £12.75]. Dose: as above but 8mg (4 drops) equivalent to 10mg tablet.
Sertraline tabs: 50mg [7 tabs £2.14] 100mg [7 tabs £3.23]. Dose: depression, initially 50mg daily, increased if necessary by increments of 50mg over several weeks to max. 200mg daily; usual maintenance dose 50mg daily; obsessive-compulsive disorder, adults and adolescents over 13 years initially 50mg daily, increased if necessary in steps of 50mg over several weeks; usual dose range 50–200mg daily; post-traumatic stress disorder, initially 25mg daily, increased after 1 week to 50mg daily; if response is partial and if drug tolerated, dose increased in steps of 50mg over several weeks to max. 200mg daily

4.3.4 Other antidepressants

Flupentixol has antidepresent properties in low doses (1 to 3mg daily). It is also used for used for the treatment of psychoses.
Mirtazapine, a presynaptic alpha-2-antagonist increases central noradrenergic and serotonergic neurotransmission. It has few antimuscarinic effects, but causes sedation during initial treatment. It may reduce the incidence of insomnia, sexual dysfunction and nausea compared to SSRIs. In clinical trials excessive sedation and drowsiness, dry mouth & increased appetite and weight gain were more frequent with mirtazapine then placebo. Reversible neutropenia and agranulocytosis have been reported with mirtazapine. Treatment should be stopped and a blood count taken if fever, sore throat, stomatitis, or other signs of infection occur. Mirtazapine enhances the sedative effects of alcohol, antihistamines and other sedatives. It should be used cautiously with drugs that may cause neutropenia.
Trazodone is considered an atypical anti-depressant because it is neither a tricyclic nor an SSRI. At therapeutic doses it is thought to affect 5-HT reuptake and also noradrenergic transmission. Trazodone is a sedative anti-depressant, but the drowsiness experienced during the first days of treatment usually disappears on continued therapy.
Tryptophan is licensed as adjunctive therapy for depression resistant to standard antidepressants; it has been associated with eosinophilia-myalgia syndrome. Tryptophan should be initiated under specialist supervision.
Venlafaxine is a serotonin and noradrenaline re-uptake inhibitor (SNRI); it lacks sedative and antimuscarinic effects.
Nausea occurs in about one third of patients, especially in the first few weeks of treatment. Dizziness, sleep disturbances (insomnia & somnolence) dry mouth headache and nervousness are also common. Venlafaxine is contra-indicated in conditions associated with high risk of cardiac arrhymia and uncontrolled hypertension. Doses in excess of 300mg daily should only be prescribed under specialist supervision. In overdose there are accounts of cardiovascular toxicity, CNS depression and seizures. The data sheet states that there have been reports of fatalities in patients taking overdoses of venlafaxine, predominantly when in combination with alcohol, other drugs affecting the CNS, or both. Discontinuation effects can occur when patients stop venlafaxine abruptly, particularly after daily doses of 150mg or more. In some patients withdrawal is unpleasant and prolonged (4 weeks or more). Venlafaxine is associated with a higher risk of withdrawal effects compared with other antidepressants.

Flupentixol tabs:500microgram [14 tabs 61p]; 1mg [14 tabs 63p]. Dose: depression, initially 1mg each morning increased after 1 week to 2mg (half these doses in the elderly); max 3mg daily taken as 2mg in the morning, 1mg no later than 4pm (elderly max 1mg in the morning and 1mg no later than 4pm). Discontinue if no response after 1 week at maximum dosage.
Mirtazapine tabs: 15mg [7 tabs 76p]; 30mg [7 tabs 44p]; 45mg [7 tabs 85p]; orodispersible tabs: 15mg [7 tabs 57p]; 30mg [7 tabs 53p]; 45mg [7 tabs 59p]. Dose: initially 15mg at night increased according to response to 30mg at night; maximum 45mg at night.
Trazodone: 50mg [21 caps £1.14]; 100mg [21 caps £1.65]; 150mg tabs [14 tabs £2.18]; liquid: 50mg in 5ml [240ml £40.00]. Dose: initially 150mg daily (elderly 100mg daily) in divided doses after food or as a single dose at night; may be increased to 300mg daily; hospital patients up to a maximum of 600mg daily in divided doses.
Tryptophan: 500mg [42 tabs £11.74]. Dose: 1g three times a day; maximum 6g daily.
Venlafaxine tabs: 37.5mg [14 tabs 75p]; 75mg [14 tabs 89p]. Dose: depression, 37.5mg twice daily initially, increased if needed after at least 3-4 weeks to 75mg twice daily; severely depressed or hospitalised patients increase further if needed in steps of up to 75mg every 2-3 days; max 375mg daily.
Venlafaxine SR caps: 75mg [7 caps £5.52]; 150mg [7 caps £9.20]. Dose: 75mg daily as a single dose, increased if necessary after at least 2 weeks to 150mg once daily; max 225mg once daily.

4.4 Central Nervous System Stimulants

Link to NICE guidance	Attention deficit hyperactivity disorder (ADHD). TAG No.98
	Attention deficit hyperactivity disorder (ADHD). Clinical Guideline No. 72.

Central nervous system stimulants include amphetamines and related drugs (eg methylphenidate). They have very few indications and in particular should not be used to treat depression, obesity, senility, debility or for relief of fatigue.
The prescribing of methylphenidate is governed by shared care prescribing guidelines.
Methylphenidate tabs: 10mg [14 tabs £3.02] (CD) Dose: Child over 6 years, initially 5mg 1-2 daily, increased if necessary at weekly intervals by 5-10mg daily to a maximum of 60mg daily in divided doses; discontinue if no response after 1 month, also discontinue periodically to assess child’s condition.

4.5 Treatment of Obesity

Links to NICE guidance

Obesity. Clinical Guideline No.43

4.6.1 Nausea and vertigo

Anti-emetics are selected according to the cause of nausea and vomiting and are not used if symptoms will resolve with treatment of the underlying condition. Phenothiazines, eg prochlorperazine, are dopamine antagonists and block the trigger zone in the brain for nausea and vomiting. Metoclopramide, in addition to its effect on the brain, also has a direct action on the gut so it may be better for gastrointestinal diseases. It causes dystonic reactions, particularly in children and young women, and although these are less frequent than with phenothiazines it should be avoided in those under 20yrs.
Domperidone, causes fewer dystonic reactions than metoclopramide but it is more expensive and not injectable. Antihistamines, such as cinnarizine and cyclizine are relatively weak but are well tolerated. Cinnarizine is the drug of choice for motion sickness. Cinnarizine and betahistine are used for long term treatment of Meniere's disease but in the acute attack prochlorperazine may be given rectally or by im injection.

Anti-Emetics In Pregnancy
If anti-emetics are needed in pregnancy the National Teratology Information Service advises the following:
The first-line antiemetic drugs of choice in pregnancy are the antihistamines cyclizine and promethazine. Prochlorperazine and metoclopramide are considered second line agents because they may be associated with maternal dystonic reactions. The use of ondansetron can be considered in cases where first and second line anti-emetic therapies have proved unsuccessful, although the available safety data are still limited. Other drugs, including corticosteroids, should be used with caution as little human data are available. Domperidone and haloperidol are not recommended for this particular indication.

Anti-Emetics and Surgery
With the first dose or morphine, diamorphine or pethidine given parenterally consider the use of an anti-emetic.
Patients are at greater risk of developing postoperative nausea and vomiting (PONV) if they have had previous PONV, female, smokers, and increasing age.
For patients with problematic PONV the use of a combination of drugs with different modes of action is beneficial eg:
prochlorperazine (phenothiazine) 12.5mg by deep IM injection (adults only, reduce dose in the elderly) or; cyclizine (antihistamine) 50mg by IV or IM injection (may cause sedation in patients over 70 years but can cause temporary tachycardia) or; Metoclopramide (dopamine agonist) 10mg by IV or IM injection (should be avoided in patients under the age of 20 years because of the risk of dystonic reactions) or; ondansetron (5HT3 antagonist) 4mg by slow IV injection (caution in pregnancy & breast feeding);, for children above the age of 2 years ondansetron by slow IV injection, 100micrograms per Kg up to a maximum of 4mg.
If vomiting persists consider other causes.
Prochlorperazine plus cyclizine is more effective than ondansetron in established nausea and vomiting. Metoclopramide is probably the least effective antiemetic post surgery.

Antihistamines.
First choice: Cyclizine tabs: 50mg [21 tabs £1.71]. Dose: 50mg up to 3 times daily.
Cyclizine injection 50mg in 1ml [51p]: by im or iv injection, 50mg 3 times daily.

Prokinetic agents.
First choice: Metoclopramide tabs: 10mg [21 tabs 99p]; solution: 5mg in 5ml [150ml £12.00]. Dose: 10mg 3 times daily (5mg if aged 15-19years under 60kg).
Metoclopramide injection: 10mg in 2ml [26p]. Caution: it should be avoided in those under 20yrs because of risk of dystonic reactions.
Domperidone tabs: 10mg [28 tabs 99p]; suspension: 5mg in 5ml [200ml £12.00]. Dose: 10-20mg 3-4 times daily; max 80mg daily.
Domperidone suppositories: 30mg [31p]. Dose: 60mg twice daily.

Phenothiazines.
First choice: Prochlorperazine tabs: 5mg [21 tabs 86p]; syrup: 5mg in 5ml [100ml £3.34].Dose: for nausea and vomitingacute attack, 20mg initially then 10mg after 2 hours; prevention 5-10mg 2-3 times daily; for labyrinthine disorders 5mg 3 times daily gradually increased if needed to 10mg 3 times daily, then reduced after several weeks to 5-10mg daily.
Prochlorperazine injection: 12.5mg in 1ml [52p]. Dose: by deep im injection 12.5mg followed if needed after 6hrs by an oral dose as above.
Prochlorperazine buccal tabs: (Buccastem^®) 3mg [14 tabs £1.65]. Dose: 1-2 tabs twice daily; tabs should be placed high between upper lip and gum and allowed to dissolve.
Levomepromazine (BAN = methotrimeprazine) inj: 25mg in 1ml [£2.01]. Dose: adjuvant treatment in Palliative care (including management of pain and associated restlessness, distress or vomiting), 25 to 200mg by sc injection over 24 hours.

5HT₃ Antagonists
Ondansetron injection: 4mg in 2ml amp [£5.39]; 4mg tabs [£2.10], 8mg tabs [£4.71]; sugar-free syrup 4mg in 5ml [5ml £3.60].
Prevention of postoperative nausea and vomiting, by mouth, 16mg 1 hour before anaesthesia or 8mg 1 hour before anaesthesia followed by 8mg at intervals of 8 hours for 2 further doses
alternatively, by im or slow iv injection, 4mg at induction of anaesthesia; child over 2 years, by slow iv injection, 100micrograms/kg (max. 4mg) before, during, or after induction of anaesthesia
Treatment of postoperative nausea and vomiting, by im or slow iv injection, 4mg; child over 2 years, by slow iv injection, 100 micrograms/kg (max. 4mg)

Travel sicknes & vestibular disorders.
Cinnarizine tabs: 15mg [42 tabs £3.44]. Dose: for travel sickness, 30mg 2hrs before travel then 15mg every 8hrs during the journey if needed; for vestibular disorders 30mg 3 times daily.
Hyoscine hydrobromide tabs: 300microgram [12 tabs £1.67]. Dose: for motion sickness 300microgram 30mins before the start of a journey, followed by 300microgram every 6hrs if needed; max 3 doses in 24hrs.
Hyoscine hydrobromide injection: 400microgram in 1ml [£2.77].
Hyoscine hydrobromide patches: 1.5mg [£2.15]. Dose: apply one patch to hairless area of skin behind ear 5-6 hours before journey; replace if necessary after 72 hours, siting replacement patch behind other ear. NB patch releases approx 1mg hyoscine over 72 hours.
Betahistine tabs: 8mg [42 tabs 99p], 16mg [21tabs £1.01]. Dose: initially 16mg 3 times daily, preferably with food; maintenance 8-16mg 3 times daily.

4.6.2 Anti-emetics and cytotoxic therapy

Chemotherapy induced nausea and vomiting should be prevented and also treated vigorously to maintain quality of life.
Cisplatin always causes nausea and vomiting but symptoms are rare with vinca alkaloids.
Other cytotoxic drugs can be placed between these two extremes according to the decreasing probability of causing symptoms:
1 cisplatin, 2 mustine, 3 dacarbazine, 4 carboplatin, 5 actinomycin,6 cyclophos-phamide iv, 7 doxorubicin, 8 cyclophosphamide orally, 9 epirubicin, 10 etoposide, 11 mitozantrone, 12 fluorouracil, 13 mito-mycin, 14 methotrexate, 15 bleomycin,16 melphalan (low dose), 17 vinblastine,18 vincristine.

A: moderately emetogenic chemotherapy
(i) Dexamethasone: 8mg by iv injection over 5mins at the start of chemotherapy; 4mg orally at the same time and repeated every 8hrs for 3 days.
(ii) Domperidone: 20mg orally 4 times daily for 5 days.

B: moderately emetogenic chemotherapy or radiotherapy,
Ondansetron injection: 8mg in 4ml amp [£10.79]; 8mg tabs [£4.71]. Dose: by mouth, 8mg 1–2 hours before treatment or by im inj or slow iv inj, 8mg immediately before treatment then by mouth, 8mg every 12 hours for up to 5 days.

C: severely emetogenic chemotherapy
Ondansetron injection: 8mg in 4ml amp [£10.79]; 8mg tabs [£4.71].
Dose: by im inj or slow iv inj, 8mg immediately before treatment, where necessary followed by 2 further doses of 8mg at intervals of 2–4 hours (or followed by 1mg/hour by continuous iv infusion for up to 24 hours), then by mouth, 8mg every 12 hours for up to 5 days; alternatively, by iv infusion over at least 15 minutes, 32mg immediately before treatment

Also where indicated on ChemoCare protocols:
Aprepitant caps: [3-day pack of one 125mg cap and two 80mg caps = £47.42]
Dose: 125mg 1 hour before chemotherapy, then 80mg daily as a single dose for the next 2 days; consult product literature for dose of concomitant corticosteroid and 5HT₃ antagonist.

4.6.3 Adjunctive treatments for syringe drivers

Anti-emetics, sedatives and other adjunctive treatments may be mixed with diamorphine and given subcutaneously via a syringe driver. The diluent should be water for injection or sodium chloride injection 0.9%, solutions should be freshly prepared and then changed within 24hrs of mixing.
Cyclizine (see 4.6.1) is a useful anti-emetic but it may cause local irritation. It may precipitate in the syringe if either cyclizine or diamorphine exceeds 25mg/ml. Dose: 50-150mg sc over 24hrs. Diluent must be water for injection.
Haloperidol (see 4.2.1) is effective for drug induced nausea, although extrapyramidal symptoms may occur, and it may be needed for only a few days if causative drugs have been stopped. It is non-irritant but may precipitate in the syringe if the concentration exceeds 10mg in 10ml. Dose: 2.5-10mg sc over 24hrs.
Hyoscine hydrobromide (see 4.6.1) is used to dry bronchial secretions. Dose: 0.6-2.4mg sc over 24hrs.
Levomepromazine (BAN = methotrimeprazine) (§4.6.1) is a very effective phenothiazine for agitation and terminal restlessness and is formulated for subcutaneous use. Dose: 25-200mg sc over 24hrs, higher doses if sedation is also required.
Metoclopramide (see 4.6.1) is sometimes irritant and should be avoided in intestinal obstruction where it increases peristalsis and causes colicky pain. Dose: 30-100mg sc over 24hrs.
Midazolam (see 15.1.4.1) is effective for terminal restlessness. It is a powerful sedative with anxiolytic and amnesic properties. It is non-irritant, in contrast to diazepam which is too irritant for subcutaneous use but which may be given rectally. Dose: 10mg sc over 24hrs.

4.7 Analgesics

4.7.1 Non-opioid analgesics

Paracetamol is equally effective for analgesia, it is less irritant to the stomach, but it has no anti-inflammatory activity. Anti-inflammatory analgesics are useful for chronic diseases with pain and inflammation and some are also useful for dysmenorrhoea, transient musculoskeletal symptoms and the pain of secondary bone tumours (see BNF: Prescribing in palliative care). Compound analgesics are rarely needed.
First choices:
Paracetamol tabs: 500mg [56 tabs 87p]; soluble tabs: 500mg [56 tabs £3.99]. Dose: 500mg-1g every 4-6hrs when needed, max 4g (8 tabs).
Also:
Paracetamol suspension: 120mg in 5ml [500ml £2.25]; Dose:
3 to 6 months, 2.5ml four times a day
6 to 24 months, 5ml four times a day
2 to 4 years,   7.5ml four times a day
4 to 6 years,    10ml four times a day

Paracetamol suspension: 250mg in 5ml [500ml £3.27]. Dose:
6 to 8 years,      5ml four times a day
8 to 10 years, 7.5ml four times a day
10 to 12 years, 10ml four times a day

Paracetamol iv infusion: 1g in 100ml [vial £1.25]. Dose: adults and adolescents over 50kg, 1g four times a day by iv infisusion over 15 mins, max 4g daily. Adults and adolescents under 50kg, 15mg/kg four times a day by iv infisusion over 15 mins, max 3g daily.
Paracetamol suppositories: 120mg [suppos £1.05]; 250mg [suppos £2.30]; 500mg [suppos £3.77].

Also:
Co-codamol 8/500 tabs: (codeine 8mg plus paracetamol 500mg) [56 tabs 87p]; effervescent tabs [56 tabs £2.64]. Dose: 1-2 tabs every 4-6hrs; max 8 tabs in 24hrs.
Co-dydramol 10/500 tabs: (dihydrocodeine 10mg plus paracetamol 500mg) [56 tabs 97p]. Dose: 1-2 tabs every 4-6hrs; max 8 tabs in 24hrs.

4.7.2 Opioid analgesics

Controlled drugs marked CD are covered by schedules 2-3 of the Misuse of drugs regulations 1985 (BNF: Controlled drugs and drug dependence).
All discharge and outpatient prescriptions for controlled drugs are required to state: (i) the name and address of the patient; (ii) the formulation, strength and dose of the preparation; (iii) the total quantity in words and figures.
Opioids relieve moderate to severe pain, particularly of visceral origin. Side effects include nausea, vomiting, constipation and drowsiness, larger doses causing respiratory depression and hypotension.
Morphine is the most valuable opioid for severe pain, it gives a state of euphoria and mental detachment but it frequently causes nausea and vomiting. It is the drug of choice for patient controlled analgesia (PCA) given intravenously. It is the oral treatment of choice for severe pain in terminal care when it is best started as a liquid preparation every 4hrs (BNF: Prescribing in terminal care). When pain is controlled the daily dose can then be given as 2 equal doses of morphine sulphate slow release tabs every 12hrs.
Diamorphine is a powerful opioid and may cause less nausea and hypotension than morphine. Its greater solubility makes it the parenteral opioid of choice for terminal care. It is commonly given by subcutaneous or intravenous infusion via a syringe driver (§4.6.3). Diamorphine can also be used in epidural infusions and intrathecal injections.
Oral morphine 3mg is equivalent to oral diamorphine 2mg or parenteral diamorphine 1mg.
Pethidine gives prompt, short lasting analgesia and is less potent than morphine, even in high doses. It is used for analgesia in labour because it causes less respiratory depression in the neonate. It can also be used in iv PCA as an alternative to morphine.
Buprenorphine has a much longer duration of action than morphine and sublingually is effective for 6-8hrs. Vomiting may be a problem, it may cause dependence and unlike most opioid analgesics its effects are only partially reversed by naloxone. Because of its combined agonist and antagonist properties it may cause withdrawal symptoms, including pain, in those addicted to opioids.
Pentazocine also has agonist and antagonist properties and thus can precipitate withdrawal symptoms in the addicted. It should not be used after myocardial infarction as it may increase pulmonary and systemic blood pressure. It can cause hallucinations and thought disturbance if given by injection.
Codeine is effective for the relief of mild to moderate pain but is too constipating for long term use.
Dihydrocodeine has an analgesic efficacy similar to that of codeine.
Fentanyl is used by injection for intra-operative analgesia (see 15.1.4.3), in epidural PCA, transdermally for palliative care, and occasionally in IV PCA.
First choice (orally):
Morphine sulphate solution: 10mg in 5ml [100ml £1.78] (CD). Dose: 5-20mg every 4hrs.
Morphine sulphate concentrate solution 20mg in 1ml [30ml £4.98, 120ml £18.59] (CD).
Morphine sulphate SR tabs: 5mg [14 tabs £0.77]; 10mg [14 tabs £1.20]; 15mg [14 tabs £2.24]; 30mg [14 tabs £2.90]; 60mg [14 tabs £5.65]; 100mg [14 tabs £8.95]; 200mg [14 tabs £18.98] (CD). Dose: initially 10-30mg every 12hrs, increased to 60mg every 12hrs then by further increments of 25-50% if needed.
Also:
Morphine sulphate injection: 10mg in 1ml [94p]; 15mg in 1ml [84p]. 50mg in 50ml IV PCA vial [£1.70] (CD). Dose: for acute pain, by sc or im injection, 10mg every 3hrs if needed (15mg for heavier or muscular patients).
Morphine sulphate tablets (Sevredol^®): 10mg [28 tabs £2.65]; 20mg [28 tabs £5.28]; 50mg [28 tabs £14.01] (CD).
Morphine hydrochloride suppositories: 15mg [12 suppos £11.56]; 30mg [12 suppos £13.70] (CD). Dose: 15-30mg every 4hrs.
First choice (parenterally):
Diamorphine injection: 5mg [£2.93]; 10mg [£3.73]; 30mg [£3.96]; 100mg [£10.66]; 500mg [£46.84] (CD). Dose: for acute pain, by sc or im injection, 5mg repeated every 4hrs if needed (up to 10mg for heavier or muscular patients);
• for myocardial infarction 5mg by slow iv injection (1mg/min), followed by a further 2.5-5mg if needed (half these doses in the frail or elderly);
• for acute pulmonary oedema 2.5-5mg by slow iv injection (1mg/min);
• for chronic pain, by continuous sc or iv injection via a syringe driver (§4.6.3), 10mg over 24hrs initially or the dose calculated from oral therapy.
OR
Oxycodone injection: 10mg in 1ml [£1.60], 50mg in 1ml [£14.02] (CD). Dose: slow iv injection 1 to 10mg every 4 hours when necessary; by sc injection initially 5mg every 4 hours when necessary; by sc infusion initially 7.5mg over 24 hours adjusted according to response.
Also:
Codeine phosphate tabs: 15mg [28 tabs £1.04]; 30mg [28 tabs £1.22]; oral solution 25mg in 5ml [300ml £2.92]. Dose: 30-60mg every 4hrs when needed; max 240mg daily.
Codeine phosphate injection: 60mg in 1ml [£2.44] (CD). Dose: by im injection, 30-60mg every 4hrs when needed.
Dihydrocodeine tabs: 30mg [28 tabs £1.49]; syrup 10mg in 5ml [420ml £9.80]. Dose: 30mg every 4 to 6 hours when needed.
Dihydrocodeine injection: 50mg in 1ml [£3.17] (CD). Dose: by deep sc or im, 50mg every 4 to 6 hours when needed.
Tramadol caps: 50mg [28 caps 55p]. Dose: 50 to 100mg every four hours, max. 400mg daily.
Buprenorphine sublingual tabs: 200microgram [42 tabs £4.23] (CD). Dose: initially 200-400microgram sublingually every 8hrs, increased if needed to 200-400microgram every 6hrs.
Buprenorphine injection: 300microgram in 1ml [48p] (CD). Dose: by im or slow iv injection 300-600microgram every 6-8hrs.
Fentanyl 2 microgram/ml and levobupivacaine 0.1% Epidural PCA. [100ml £7.09]. (CD)
Fentanyl 2 microgram/ml and bupivacaine 0.1% Epidural PCA. [500ml £9.58]. (CD)
Fentanyl patches: 12microgram/hr [1 patch £2.74]; 25microgram/hr [1 patch £3.92]; 50microgram/hr [1 patch £7.32]; 75microgram/hr [1 patch £10.20]; 100microgram/hr [1 patch £12.58] (CD).
Dose: 1 patch applied to dry, hairless, non-irritated or irradiated skin on torso or upper arm, then replaced after 72hrs. The same area should be avoided for several days. Initial dose: 25 mcg/hr for those who have not previously received a strong opioid analgesic; dose estimated from previous requirement in those who have (check with pharmacy). Additional analgesia may be needed for the first 24hrs because of slow onset of action.
Pentazocine tabs: 25mg [56 tabs £41.58] (CD). Dose: 25-50mg every 3-4hrs after food.
Pentazocine injection: 30mg in 1ml [£1.67] (CD). Dose: by sc, im or iv injection, 30-60mg every 3-4hrs when needed.
Pethidine injection: 50mg in 1ml [43p]; 100mg in 2ml [45p] (CD).
Dose: by sc or im injection, 25-100mg, repeated after 2 to 3hrs; by slow iv injection, 25-50mg repeated after 2 to 3hrs.
For obstetric analgesia, by sc or im injection, 50-100mg, repeated 1-3hrs later if needed, max 400mg in 24hrs.
Pethidine tabs: 50mg [84 tabs £37.36] (CD). Dose: 50-150mg every 4hrs.

4.7.3 Neuropathic pain

Link to NICE guidance

Neuropathatic pain – pharmacological management. Clinical Guideline No. 96

Neuropathic pain is generally managed with a tricyclic antidepressant and certain antiepileptic drugs. Neuropathic pain may respond only partially to opioid analgesics. Amitriptyline is prescribed most frequently, initially 10 to 25mg each night. Gabapentin is licensed for the treatment of neuropathic pain. Capsaicin (see 10.3.2) is licensed for neuropathic pain, but the intense burning sensation during initial treatment may limit use.

Effective Practice Committee Statement July 2005
Pregabalin may have a limited place in the management of neuropathic pain but should be reserved for third or fourth line use after amitriptyline (see 4.3.1), carbamazepine (see 4.8.1) and gabapentin (see 4.8.1). Until more data is available its use should be limited to initiation in the pain clinics.

See also Effective Practice Committee guidance on the Management of Painful Diabetic Neuropathy

Pregabalin caps: 25mg [28 caps £32.20]; 50mg [28 caps £32.20]; 75mg [28 caps £32.20]; 100mg [28 caps £32.20]; 150mg [28 caps £32.20]; 200mg [28 caps £32.20]; 225mg [28 caps £32.20]; 300mg [28 caps £32.20]. Dose: initially 150mg daily in 2-3 divided doses, increased if necessary after 3-7 days to 300mg daily in 2-3 divided doses; increased further if necessary after 7 days to a maximum of 600mg daily in 2-3 divided doses.

4.7.4.1 Acute migraine

Treatment of a migraine attack should be guided by response to previous treatment and the severity of the attacks. A simple analgesic such as paracetamol (see 4.7.1) (preferably in a soluble or dispersible form) or a NSAID is often effective; concomitant anti-emetic treatment (see 4.6.1) may be required. If treatment with an analgesic is inadequate, an attack may be treated with a specific antimigraine compound such as a 5HT₁ agonist (‘triptan’). Ergot alkaloids are rarely required now.

Analgesics.
First choice: Paracetamol soluble tabs 500mg
plus:
metoclopramide tabs 10mg (if anti-emetic needed)
Also:
Migraleve^® pink tabs: (buclizine 6.25mg plus paracetamol 500mg plus codeine 8mg) and Migraleve^® yellow tabs: (paracetamol 500mg plus codeine 8mg). Dose: 2 pink tabs during prodrome or at onset of the attack then 2 yellow tabs every 4hrs if needed; max 2 pink and 6 yellow tabs in 24hrs [12 tabs £2.93].

5HT₁ agonists.
First Choice: Sumatriptan tabs: 50mg [28p each]. Dose: 50mg as soon as possible after onset (patients not responding should not take a second dose for the same attack); dose my be repeated once after not less than 2 hours if migraine recurs; max 300mg in 24hours.

4.7.4.2 Migraine prophylaxis

Migraine may be triggered by stress, exercise, chocolate, cheese, alcoholic drinks, oranges, oral contraceptives and other factors, so changes in life style may reduce the number of attacks. If they occur more than once or twice monthly prophylaxis may be tried using aspirin, beta blockers, pizotifen or tricyclic antidepressants. The need for continuing therapy should be reviewed every 6 months. Propranolol is the most commonly used beta blocker but caution is needed because of interaction with ergotamine. Pizotifen affords good prophylaxis but may cause weight gain. To avoid undue drowsiness treatment may be started at 500 micrograms at night and gradually increase to 3mg.
First choices:
Propranolol tabs: 10mg [28 tabs 88p]; 40mg [28 tabs 90p]. (see 2.4). Dose: 20-40mg 2-3 times daily.
Pizotifen tabs: 500microgram [28 tabs £1.43]; 1.5mg [28 tabs £2.52]. Dose: initially 500microgram at night to avoid drowsiness and increased slowly if needed to a max of 3mg at night.
Also:
Amitriptyline tabs: 10mg [28 tabs £1.07]; 25mg [28 tabs 86p]. (see 4.3.1). Dose: initially 10mg at night increased according to response; maintenance usually 50-75mg at night.

4.8 Anticonvulsants

4.8.1 Control of epilepsy

Links to NICE guidance	Epilepsy (adults) - newer drugs. TAG 76.
	Epilepsy (children) - newer drugs. TAG 79.
	Epilepsy - Clinical Guideline No.20
	Retigabine for the adjunctive treatment of partial onset seizures in epilepsy. TAG 232.

If possible a single drug should be used to control fits and the frequency of administration should be kept low to help with compliance. Sudden dose reduction or withdrawal of anticonvulsants may precipitate fits. The changeover from one antiepileptic drug to another should also be cautious, withdrawing the first drug only when the new regimen has largely been established.
Pregnancy: There is an increased risk of teratogenicity associated with the use of antiepileptic drugs (reduced if treatment is limited to a single drug). In view of the increased risk of neural tube and other defects associated, in particular, with carbamazepine, oxcarbazepine, phenytoin and valproate women taking antiepileptic drugs who may become pregnant should be informed of the possible consequences. Those who wish to become pregnant should be referred to an appropriate specialist for advice. Women who become pregnant should be counselled and offered antenatal screening (alpha-fetoprotein measurement and a second trimester ultrasound scan).
To counteract the risk of neural tube defects adequate folate supplements are advised for women before and during pregnancy; to prevent recurrence of neural tube defects, women should receive folic acid 5mg daily. This dose may also be appropriate for women receiving antiepileptic drugs.
The concentration of antiepileptic drugs in the blood can change during pregnancy, particularly in the later stages. The dose of antiepileptics should be monitored carefully during pregnancy and after birth, and adjustments made on a clinical basis. Routine injection of vitamin K at birth effectively counteracts any antiepileptic-associated risk of neonatal haemorrhage.
Tonic-clonic seizures (grand mal): The drugs of choice for tonic-clonic seizures are carbamazepine, lamotrigine, sodium valproate, and topiramate. Clobazam, levetiracetam, and oxcarbazepine are second-line drugs.
Absence seizures (petit mal): Ethosuximide and sodium valproate are the drugs of choice in simple absence seizures; alternatives include clobazam, clonazepam, and topiramate. Sodium valproate is also highly effective in treating the tonic-clonic seizures which may co-exist with absence seizures in primary generalised epilepsy. Lamotrigine may also be effective [unlicensed indication].
Myoclonic seizures: occur in a variety of syndromes, and response to treatment varies considerably. Sodium valproate is the drug of choice and clonazepam or lamotrigine may be used. Alternatives include clobazam, levetiracetam, and topiramate.
Atypical absence, atonic, and tonic seizures: These seizure types are usually seen in childhood, in specific epileptic syndromes, or associated with cerebral damage or mental retardation. They may respond poorly to the traditional drugs. Sodium valproate, lamotrigine, and clonazepam may be tried. Second-line drugs that are occasionally helpful include acetazolamide, clobazam, ethosuximide, levetiracetam, phenobarbital, phenytoin, and topiramate.
Vigabatrin: Important advice has recently been issued regarding the prescribing of vigabatrin. Use of vigabatrin should be restricted to combination therapy after all other appropriate combinations have proven inadequate or have not been tolerated, except in the case of infantile spasms, where vigabatrin can continue to be used in monotherapy.
Plasma levels of sodium valproate are of little clinical value and are not monitored routinely.
Clearance of phenytoin by the liver is limited so a small increase in dose may produce a large rise in plasma levels. The dose should therefore be increased slowly, plasma levels should be monitored and doses should be reduced if there is clinical evidence of toxicity.
Carbamazepine, phenytoin, phenobarbital and primidone interact with a large number of other drugs, partly because of hepatic enzyme induction, so BNF Appendix 1 should be checked before additional drugs are prescribed.
First choice:
Carbamazepine tabs (Tegretol^®): 100mg [28 tabs £0.69]; 200mg [28 tabs £1.28]; 200mg MR [28 tabs £2.60]; 400mg [28 tabs £2.51]; 400mg MR [28 tabs £5.12]; sugar free liquid: 100mg in 5ml [300m1 £6.12]. Dose: epilepsy, initially, 100–200mg 1–2 times daily, increased slowly (see notes above) to usual dose of 0.8–1.2g daily in divided doses; in some cases 1.6–2g daily in divided doses may be needed, elderly reduce initial dose; trigeminal neuralgia, initially 100mg 1–2 times daily (but some patients may require higher initial dose), increased gradually according to response; usual dose 200mg 3–4 times daily, up to 1.6g daily in some patients.
Plasma concentration for optimum response 4–12mg/litre (20–50micromol/litre).
Carbamazepine suppositories: 125mg; 250mg [28 supps £59.98]. Dose: epilepsy, as above for short-term use (max. 7 days) when oral therapy temporarily not possible but final adjustment should always depend on clinical response (plasma concentration monitoring recommended); max. 1g daily in 4 divided doses. NB 250mg rectal = 200mg oral.
Also:

Phenytoin
NPSA –Preventing Fatalities from Medication Loading Doses
Phenytoin has been identified as a drug where particular care needs to be exercised on initiation of therapy.
Prescribers who are unfamiliar with the prescribing of this drug are strongly advised to read the full SPC.
ORAL
Loading dose: 3 to 4mg/kg daily or 150 to 300mg daily (as a single dose or in 2 divided doses, increased gradually as necessary (with plasma-phenytoin concentration monitoring).
Maintenance dose: Usually 200 to 500mg daily (exceptionally higher doses may be used). Plasma concentration for optimum response 10–20mg/litre (40–80micromol/litre).
Phenytoin sodium caps (Epanutin^®): 25mg [28 caps 66p]; 50mg [28 caps 67p]; 100mg [28 caps 94p]; 300mg [28 caps £2.83].
Phenytoin suspension: 30mg in 5ml [300ml £2.56]. Dose: as above. NB 90mg (15ml) is equivalent to one 100mg capsule.
PARENTERAL
(see 4.8.2).

Sodium valproate tabs (Epilim^®): 100mg [28 tabs £1.57]; 200mg EC [28 tabs £2.16]; 500mg EC [28 tabs £5.39]: Epilim Chrono: 200mg CR [28 tabs £3.26]; 300mg CR [28 tabs £4.89]; 500mg CR [28 tabs £8.15]; sugar free liquid: 200mg in 5ml [300ml £9.33]. Dose: initially 600mg daily in 2 divided doses, preferably after food, increased by 200mg daily every 3 days to max. 2.5g daily, usual maintenance dose 1–2g daily (20–30mg/kg daily.
Sodium valproate injection: 300mg in 3ml [£7.00]. Dose: by iv injection (over 3–5 minutes) or by iv infusion, continuation of valproate treatment, same as current dose by oral route; initiation of valproate therapy, by iv injection (over 3–5 minutes), 400–800mg (up to 10mg/kg) followed by intravenous infusion up to max. 2.5g daily. For use in status epilepticus (see 4.8.2).

Phenobarbital tabs: (BAN = phenobarbitone) 15mg [28 tabs £1.59]; 30mg [28 tabs 95p]; 60mg [28 tabs 71p]. Dose: 60-180mg at night. Plasma concentration for optimum response 15-40mg/l (60-180 micromols/l).
Phenobarbital liquid (alcohol-free): 15mg in 5ml [250ml £11.08].
Phenobarbital sodium injection: 60mg in 1ml [£2.41], 200mg in 1ml [£2.46]. For use in status epilepticus (see 4.8.2).
For expert use:
Clobazam tabs: 10mg [28 tabs £4.37]. Dose: epilepsy 20-30mg daily; max 60mg daily.
Clonazepam tabs: 500microgram [28 tabs £1.04]; 2mg [28 tabs £1.39]. Dose: initially 1mg (elderly 500microgram) at night for 4 nights, increasing over 2-4 weeks; maintenance usually 4-8mg usually at night but may be given in 3-4divided doses if necessary.
Gabapentin caps: 100mg [21 caps £1.93]; 300mg [21 caps £2.84]; 400mg [21 caps £2.02]. Dose (epilepsy): 300mg on day one, 300mg twice daily on day two, then 300mg three times daily on day three, increased thereafter according to response in steps of 300mg daily (in 3 divided doses) to a max 2.4g daily; usual range 0.9-1.2g daily.
Dose (neuropathic pain): 300mg on day 1, then 300mg twice daily on day 2, then 300mg three times a day on day 3, then increased in steps of 300mg daily (in 3 divided doses) to a max 1.8g daily.
Lamotrigine tabs: 25mg [28 tabs £1.04]; 50mg [28 tabs £1.37]; 100mg [28 tabs £1.98]; 200mg [28 tabs £3.40]. Dispersible tabs: 2mg [28 tabs £9.75]; 5mg [28 tabs £2.18]; 25mg [28 tabs £1.39]; 100mg [28 tabs £2.60]. Dose: varies depending on whether being used as monotherapy, with sodium valproate or with other anticonvulsant drugs see BNF.
Levetiracetam tabs: 250mg [14 tabs £6.93]; 500mg [14 tabs £12.20]; 750mg [14 tabs £20.79]; oral solution 100ml per ml [300ml £71.00]. Dose: adult and adolescent over 12 years, body-weight over 50kg, initially 500mg twice daily, adjusted in steps of 500mg twice daily every 2 to 4 weeks; max. 1.5g twice daily;
Oxcarbazepine tabs: 150mg [14 tabs £3.82]; 300mg [14 tabs £6.18]; 600mg [14 tabs £12.35]. Dose: initially 300mg twice daily increased according to response in steps of up to 600mg daily at weekly intervals; usual dose range 600mg to 2.4g daily in divided doses.
Tiagabine tabs: 5mg [14 tabs £5.73]; 10mg [14 tabs £11.46]; 15mg [14 tabs £17.19]; Dose: adjunctive therapy, adult and child over 12 years, with enzyme-inducing drugs, 5mg twice daily for 1 week, then increased at weekly intervals in steps of 5–10mg daily; usual maintenance dose 30–45mg daily (doses above 30mg given in 3 divided doses); in patients receiving non-enzyme-inducing drugs, initial maintenance dose 15–30mg daily.
Topiramate: 25mg [14 tabs 98p]; 50mg [14 tabs £1.28]; 100mg [14 tabs £1.23]; 200mg [14 tabs £5.78]; 15mg sprinkle caps [14caps £4.30]; 25mg sprinkle caps [14caps £5.78]; 50mg sprinkle caps [14caps £9.49]. Dose: monotherapy, initially 25mg at night for 1 week then increased in steps of 25–50mg daily at intervals of 1–2 weeks taken in 2 divided doses; usual dose 100mg daily in 2 divided doses; max. 400mg daily; adjunctive therapy, initially 25mg at night for 1 week then increased in steps of 25–50mg daily at intervals of 1–2 weeks taken in 2 divided doses; usual dose 200–400mg daily in 2 divided doses; max. 800mg daily.
NB If patient cannot tolerate titration regimens recommended above then smaller steps or longer interval between steps may be used.

4.8.2 Status epilepticus

Status epilepticus should be treated with intravenous diazepam emulsion injection (Diazemuls^®) or diazepam rectal solution. Diazepam by im injection or suppository works too slowly. Phenytoin or sodium valproate may then be given by slow iv injection to prevent recurrence.
Thiopentone anaesthesia is used for resistant status epilepticus.
First choices:
Diazepam emulsion injection: (Diazemuls^®) 10mg in 2ml [91p]. Dose: by iv injection, 10mg at a rate of 1ml (5mg) per minute, repeated once after 10 minutes if necessary; child under 12 years, 300–400micrograms/kg [unlicensed dose], repeated once after 10 minutes if necessary.
Diazepam rectal solution: 2.5mg [£1.04]; 5mg [£1.25]; 10mg [£1.70]. Dose: adult and child over 12 years, 10–20mg, repeated once after 10–15 minutes if necessary (max. 30mg); elderly 10mg (max. 15mg); neonate [unlicensed] 1.25–2.5mg; child 1 month–1 year [unlicensed] 5mg; 1–2 years 5mg; 2–12 years 5–10mg.
Also:

Phenytoin
NPSA –Preventing Fatalities from Medication Loading Doses
Phenytoin has been identified as a drug where particular care needs to be exercised on initiation of therapy.
Prescribers who are unfamiliar with the prescribing of this drug are strongly advised to read the full SPC and the UCL’s Injectable Medicines Administration Guide.
PARENTERAL

Phenytoin sodium can be given by slow intravenous injection, followed by the maintenance dosage if appropriate; monitor ECG and blood pressure and reduce rate of administration if bradycardia or hypotension occurs. Intramuscular phenytoin should not be used (absorption is slow and erratic).
If given by iv infusion phenytoin should be diluted in 50 to 250ml of 0.9% sodium chloride, concentration should not exceed 10mg per ml. Administration should commence immediately and must be completed within one hour. An in-line filter (0.2 micron) should be used. Inspect infusion regularly and disconnect if haziness or a precipitate forms. Do not refrigerate. To avoid local venous irritation each injection or infusion should be preceded and followed by an injection of sterile physiological saline through the same needle or catheter. Phenytoin sodium doses in BNF may differ from those in product literature.
Caution: infusion-related adverse events include hypotension, arrhythmias, dizziness, confusion, tingling sensation in the limbs, respiratory and CNS depression.
Loading dose: by slow intravenous injection or infusion (with blood pressure and ECG monitoring), 20mg/kg at a rate not exceeding 1mg/kg/minute (max. 50mg per minute). child 1 month–12 years, 20mg/kg at a rate not exceeding 1mg/kg/minute (max. 50mg per minute). neonate 20mg/kg at a rate not exceeding 1mg/kg/minute.
Maintenance dose: maintenance doses of about 100mg, by mouth or by intravenous administration, should be given thereafter every 6–8 hours, adjusted according to plasma-phenytoin concentration. child 1 month–12 years, 5–10mg/kg daily (max. 300mg daily) in 2 divided doses. neonate 5–10mg/kg daily in 2 divided doses.
Phenytoin sodium injection: 250mg in 5ml [£3.40].
ORAL (see 4.8.1)

Phenobarbital sodium injection: (BAN = phenobarbitone) 200mg in 1ml [£2.46]. Dose: by intravenous injection (dilute injection 1 in 10 with water for injections), 10mg/kg at a rate of not more than 100 mg/minute; max. 1g.

4.9 Parkinsonism

All effective treatments for parkinsonism may have undesirable side effects, notably dyskinesia, confusion and postural hypotension.

4.9.1 Dopaminergics for parkinsonism

Levodopa with a dopa decarboxylase inhibitor, eg co-beneldopa or co-careldopa, increases brain dopamine. It is the treatment of choice for disabling idiopathic Parkinson's disease. It should not be used for neuroleptic induced parkinsonism. It is usually ineffective in vascular or other degenerative parkinsonian syndromes, although a degree of improvement may occur in some cases. It should be started at low dose, increased gradually over days or weeks and the intervals between doses adjusted to individual need. Modified release preparations may help with end of dose deterioration and nocturnal immobility. The maintenance dose is usually a compromise between mobility and side effects.
Caution: Excessive daytime sleepiness and sudden onset of sleep can occur with co-careldopa, co-beneldopa, and the dopamine receptor agonists. Patients starting 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 recurring.
Selegiline, is a monoamine oxidase B inhibitor used in conjunction with levodopa to reduce ‘end-of-dose’ deterioration in advanced Parkinson’s disease. When combined with levodopa, selegiline should be avoided or used with great caution in patients with postural hypotension.
Entacapone, a COMT inhibitor, is used as an adjunct to levodopa therapy for those patients who experience "end of dose" deterioration and cannot be stabilised. A combination product of entacapone with co-careldopa, Stalevo^®, is available to improve patient concordance.
Pramipexole, ropinirole and rotigotine, non-ergot dopamine, are preferable to ergot dopamine antagonists which are no longer recommended due to their serious adverse effects. They are likely to be most useful as aN adjunct to levodopa. However, they are often used as monotherapy, particularly in younger patients who are at risk of developing disabling dyskinesia with long-term levodopa therapy. Rotigotine is available as a transdermal patch which may be of particular use where they are compliance issues.
Apomorphine, a dopamine agonist given by infusion or sc injection, may give benefit when motor fluctuations become a problem. Responsiveness to treatment must be assessed by inpatient trial under expert supervision. Domperidone 20mg 3 times daily is given for the preceding 48hrs to prevent vomiting.
Amantadine has modest antiparkinsonian effects. It improves mild bradykinetic disabilities as well as tremor and rigidity. It may also be useful for dyskinesias in more advanced disease. Tolerance to its effects may develop and confusion and hallucinations may occasionally occur. Withdrawal of amantadine should be gradual irrespective of the patient’s response to treatment.
First choice:
Co-beneldopa: 62.5mg (levodopa 50mg) [28caps £1.39]; 125mg (levodopa 100mg) [28caps £1.93]; 250mg (levodopa ) [28caps £3.30]; disp tabs 62.5mg (levodopa 50mg) [28tabs £1.65]; disp tabs 125mg (levodopa 100mg) [28tabs £2.93]. Dose: see BNF. Tablets may be dispersed in water or orange squash (but not orange juice) or swallowed whole.
Co-beneldopa controlled release caps: 125mg (levodopa 100mg) [28caps £3.58]. Dose: see BNF.
or:
Co-careldopa tabs : 62.5mg (levodopa 50mg) [28tabs £1.95]; 110mg (levodopa 100mg) [28tabs £2.04]; 125mg (levodopa 100mg) [28tabs £6.95]; 275mg (levodopa) [28tabs £10.07].
Dose: see BNF.
Also:
Co-careldopa controlled release tabs: 125mg (Half Sinemet^® CR) [28 tabs £5.41]; 250mg (Sinemet^® CR) [28 tabs £5.41]. Dose: see BNF.
For expert use:
Selegiline tabs: 5mg [14 tabs £1.28]. Dose: 10mg in the morning or 5mg at breakfast and midday, elderly initial dose 2.5mg daily. Caution: the dose of levodopa may need to be reduced by 20-50% to avoid side effects.
Pramipexole tabs: 88microgram [21 tabs £2.67]; 180microgram [21 tabs £3.82]; 350microgram [21 tabs £26.74]. 700microgram [21 tabs £29.06]. Dose: see BNF.
Ropinirole tabs: 250mcrogram [21 tabs £4.18]; 500mcrogram [21 tabs £4.75]; 1mg [21 tabs £5.44]; 2mg [21 tabs £11.12]; 5mg [21 tabs £23.23]. Dose: see BNF.
Rotigotine patches: 2mg/24hrs [7 = £19.31]; 4mg/24hrs [7 = £29.43]; 6mg/24hrs [7 = £35.70]; 8mg/24hrs [7 = £35.70]. Dose: see BNF.
Entacapone tabs: 200mg [28 tabs £16.09]. Dose: 200mg with each dose of levodopa/dopa-decarboxylase inhibitor; max. 2g daily.
Stalevo^® (levodopa/carbidopa/entacapone): 50/12.5/200 [21tabs £14.56]; 75/18.75/200 [21tabs £14.56]; 100/25/200 [21tabs £14.56]; 150/37.5/200 [21tabs £14.56]; 200/50/200 [21tabs £14.56]. Dose: see BNF.
Apomorphine injection: 20mg in 2ml [£7.59 per amp]; 50mg in 5ml [£14.62 per amp]; 30mg in 3ml pen [£24.78 per pen]. Dose: under specialist supervision only.
Amantadine caps: 100mg [14 caps £2.84]. Dose: see BNF.

4.9.2 Antimuscarinics for parkinsonism

Antimuscarinic drugs (incorrectly termed anticholinergics) are less effective than levodopa for idiopathic Parkinson's disease. They may be used initially, either alone or with selegiline, in mild disease if tremor predominates. They also reduce symptoms of drug induced parkinsonism but should not be used prophylactically. Tardive dyskinesia is not improved and may be worsened by antimuscarinic drugs.
First choice: (Parkinson's disease): Trihexyphenidyl tabs: (BAN = Benzhexol) 2mg [21 tabs £4.85]; 5mg [21 tabs £5.21]. Dose: 1mg daily gradually increased; maintenance usually 5-15mg daily in 3-4 divided doses; max 20mg daily.
Also:
Orphenadrine tabs: 50mg [21 tabs 72p]; oral solution 50mg in 5ml [200ml £8.48]. Dose: 50mg 3 times daily gradually increased in steps of 50mg every 2-3 days according to response; max 400mg daily in divided doses.
First choice (drug induced parkinsonism): Procyclidine tabs: 5mg [21 tabs £1.89]; syrup: 5mg in 5ml [150ml £7.54]. Dose: 2.5mg 3 times daily gradually increased as needed; max 30mg daily (60mg daily in exceptional circumstances).
Procyclidine injection: 10mg in 2ml [£1.49]. Dose: for acute dystonia 5mg-10mg by im or iv injection (usually effective in 5-10mins but may need 30 mins for relief); elderly preferably lower end of range.

4.9.3 Essential tremor, chorea, tics and related disorders

Link to NICE guidance

Motor Neurone disease - riluzole. TAG 20

Propranolol may benefit benign essential tremor and primidone may give relief in some cases.
Tetrabenazine is used for movement disorders in Huntington's chorea and related disorders. It is ineffective in some patients and may cause depression.
Haloperidol and chlorpromazine (see 4.2.1) are used to relieve intractable hiccup. Botulinum A Toxin-Haemagglutinin Complex may be used for refractory blepharospasm and hemifacial spasm.
Tetrabenazine tabs: 25mg [28 tabs £25.00]. Dose: initially 12.5mg twice daily (12.5mg once daily in the elderly) gradually increased to 12.5-25mg 3 times daily; max 200mg daily in divided doses.
Propranolol tabs: 40mg [28 tabs 90p]. Dose: 40mg 2-3 times daily.
For expert use:
Botulinum A Toxin-Haemagglutinin Complex: Botox^® [1 vial £138.20]; Dysport^® [1 vial £154.00].

4.10 Substance dependence

4.10.1 Alcohol dependence

Link to NICE guidance	Alcohol-use disorders: physical disorders Clinical Guideline No. 100.
	Alcohol-use disorders. Diagnosis, assessment and management of harmful drinking and alcohol dependence. Clinical Guideline No. 115.

Long acting benzodiazepines such as Chlordiazepoxide are now considered to be the first choice drug in attenuating alcohol withdrawal symptoms. To minimise the risk of dependence administration should be for a limited period only. Benzodiazepines should not be prescribed if the patient is likely to continue drinking alcohol. Clormethiazole has fallen out of favour because it is potentially addictive and it may cause respiratory failure if taken with alcohol. Disulfiram is an adjunct to the treatment of alcohol dependence and is rarely used. After only small amounts of alcohol it causes unpleasant symptoms: facial flushing, throbbing headache, palpitations, tachycardia, nausea and vomiting. With larger doses of alcohol it causes dysrhythmias, hypotension and collapse.
First choice:
Chlordiazepoxide caps: 5mg [28 caps £1.53]; 10mg [28 caps £3.19]. Dose: 20mg four times daily for 2 days, then 15mg four times daily for 2 days then 10mg four times daily for 2 days then 5mg twice a day for 2 days (this can be supplemented on an as required basis by an additional 20mg up to four times a day. In severe dependency a starting dose of 60mg four times a day may be warranted. In this case the duration of the withdrawal regimen might exceed from 8 to 14 days.
For expert use:
Disulfiram tabs: 200mg [7 tabs £3.47]. Dose: 800mg as a single dose on the first day, reduced over 5 days to 100-200mg daily and continued for up to one year if needed.

4.10.2 Opioid dependence

Link to NICE guidance	Drug misuse – methadone & buprenorphine TAG 114
	Drug misuse – naltrexone TAG 115
	Drug misuse: psychosocial interventions. Clinical guideline No. 51.
	Drug misuse: opioid detoxification. Clinical guideline No. 52.

Methadone (CD), an opioid agonist, can be substituted for opioids such as diamorphine (heroin) to prevent withdrawal symptoms in the addicted . It can cause addiction itself but the aim of treatment is gradual dose reduction titrated against withdrawal symptoms. As a guideline 1mg methadone can be substituted for 2mg pure heroin, 4mg morphine or 30mg codeine.
The purity of street heroin varies so widely that equivalent doses cannot be stated.
Lofexidine alleviates symptoms of opioid withdrawal. Like clonidine it acts centrally to reduce sympathetic tone but the fall in blood pressure is less marked.
Naltrexone, also an opioid antagonist, is given to former addicts as an aid to prevent relapse. It blocks the action of opioids such as diamorphine and precipitates withdrawal symptoms in the dependent.
First choice: Methadone mixture (sugar free): 1mg in 1ml (CD). Dose: initially 10-20mg daily given as a single or 2 divided doses then increased by 10-20mg daily until there is no signs of withdrawal or intoxication; max usually 40-60mg daily [100ml £2.08].
NB The methadone equivalence to street heroin cannot accurately be estimated because street drugs vary in purity. 1g of street heroin is roughly equivalent to 50 to 80mg of methadone. Titrate dose against withdrawal symptoms starting with the lower dose. Liason with the Quay Centre (01271 344454) is a good idea the next working day. Unless advised otherwise, patients should be issued with no more than one day’s dose to take home.
For expert use:
Buprenorphine sublingual tablets (CD). 400microgram [7 tabs £1.97]; 2mg [7 tabs £7.64]; 8mg [7 tabs £21.32]. Dose: according to preprinted dosing schedules.
Lofexidine tabs: 200microgram [60 tabs £61.79]. Dose: as per printed regimen.
Naltrexone tabs: 50mg [7 tabs £5.59]. Dose: 25mg initially then 50mg daily. The total weekly dose may be divided and given on 3 days of the week to improve compliance, eg 100mg on Monday and Wednesday, 150mg on Friday.

4.10.3 Nicotine replacement therapy (NRT)

Link to NICE Guidance	Smoking cessation services. PH10
	Smoking cessation – varenicline. TAG 123

From 1^st January 2007 there will be no smoking on NDHCT’s premises. This maylead to an increase in demand for NRT for in-patients, relatives who are sleeping in the hospital and staff. The Pharmacy will supply NRT on prescription to in-patients and for sale to relatives and staff.
NRT will be supplied free of charge to in-patients who need help to cease smoking whilst in hospital. This must be prescribed on their in-patient chart by a member of the medcal staff. The appropriate product should be selected (see guide based on Fagerstrom Test and NICE guidance – available from the Pharmacy). A limited stock of NRT will be held on the Medical Admissions Unit for use when the Pharmacy is closed.
Patients can be divided into two categories:
(i) Those who do not intend to give give up smoking on discharge: supply NRT whilst in hospital but do not supply on discharge.
(ii) Those who intend to give up smoking: supply NRT whilst in hospital and for 14 days on discharge. Ward staff should refer the person to the Smoking Cessation service.
Nicorette^® patches: 5mg [7 patches £9.07]; 10mg [7 patches £ £9.07]; 15mg [7 patches £9.07]. Dose: apply patch for 16 hours per 24 hour period.
Nicotinell^® patches: 10 [7 patches £9.12]; 20 [7 patches £9.40]; 30 [7 patches £9.97]. Dose: apply patch for 24hours per day.
Nicorette^® chewing gum: 2mg [30pieces £3.25]; 4mg [30pieces £3.99]. Dose: see BNF.
Nicorette^® inhalator: 10mg [6 = £4.46]. Dose: see BNF.

4.11 Drugs for Dementia

Link to NICE guidance	Dementia. Clinical Guideline No. 42.
	Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease. TAG 217.

Acetylcholinesterase inhibiting drugs are used in the treatment of Alzheimer’s disease, specifically for mild to moderate disease. Rivastigmine is also licensed for mild to moderate dementia associated with Parkinson’s disease. The evidence to support the use of these drugs relates to their cognitive enhancement. Treatment with acetylcholinesterse inhibitors should be initiated and supervised only by specialist experienced in the management of dementia.
Donepezil is a reversible inhibitor of acetylcholinesterase that can be given once daily. Rivastigmine is a reversible non-competitive inhibitor of acetylchloinesterase. Galantamine is a reversible inhibitor of acetylcholinesterase and also has nicotinic receptor agonist properties. It can be given twice daily.

Donepezil tabs: 5mg [7 tabs £14.96]; 10mg [7 tabs £20.97]. Dose: 5mg at night, incresing after one month to 10mg at night; maximum 10mg daily.
Galantamine tabs: 8mg [14 tabs £17.08]; 12mg [14 tabs £21.00]. Dose: 4mg twice daily for 4 weeks, increased to 8mg twice daily for 4 weeks; maintenance 8 to 12mg twice daily.
Galantamine MR caps: 8mg [7 caps £12.97]; 16mg [7 caps £16.23]; 24mg [7 caps £19.95]. Dose: 8mg once daily for 4 weeks, increased to 16mg once daily for 4 weeks; maintenance 16 to 24mg once daily.
Rivastigmine caps: 1.5mg [14 caps £16.63]; 3mg [14 caps £16.63]; 4.5mg [14 caps £16.63]; 6mg [14 caps £16.63]. Dose: 1.5mg twice daily increased in steps of 1.5mg twice daily at intervals of at least two weeks according to response and tolerance; usual range 3 to 6mg twice daily.
Rivastigmine transdermal patches: 4.6mg/24hours [7 patches £18.19]; 9.5mg/24hours [7 patches £18.19]. Dose: initially apply 4.6mg/24 hours patch to clean, dry, non-hairy, non-irritated skin on back, upper arm, or chest, removing after 24 hours and siting a replacement patch on a different area (avoid using the same area for 14 days); if well tolerated increase to 9.5mg/24 hours patch daily after no less than 4 weeks; if patch not applied for more than several days, treatment should be restarted with 4.6mg/24 hours patch.
NB When switching a patient from oral to transdermal therapy, patients taking 3–6mg daily should be prescribed the 4.6mg/24 hours patch; patients taking 9mg daily who do not tolerate the dose well should be prescribed the 4.6mg/24 hours patch, while those taking 9mg daily who tolerate the dose well should be prescribed the 9.5mg/24 hours patch; patients taking 12mg daily should be prescribed the 9.5mg/24 hours patch. The first patch should be applied on the day following the last oral dose