1

4. Central Nervous System

For further advice on mental health issues see NHS Fife website www.moodcafe.co.uk/ 4.1 - Hypnotics and anxiolytics 4.1.1 Hypnotics 1st Choice Non-drug treatment e.g. sleep hygiene 2nd Choice Drug treatment 1st Choice Zopiclone 2nd Choice Temazepam Nitrazepam

Prescribing Points

 Before a hypnotic is prescribed, the cause of the insomnia should be established and underlying factors be addressed. Non-drug management should be considered 1st e.g. sleep hygiene, avoiding caffeine intake close to bedtime.  A patient self help guide on sleep problems is available at http://www.moodcafe.co.uk/media/20236/tipsforbettersleep.pdf  Prescriptions for hypnotics should only be issued for short-term relief (1- 4 weeks) of severe insomnia that is disabling or causing unacceptable patient distress.  In new patients hypnotics should not be added as a repeat prescription. They should only be prescribed as „acutes‟.  Prescribers should exercise caution when starting a patient on a benzodiazepine or „z‟ drug as these medicines have a „street value‟.  Relative durations of action are: short-acting: lorazepam, temazepam, zopiclone intermediate-acting: nitrazepam long-acting: chlordiazepoxide, diazepam

 Short-acting hypnotics are preferable in patients with sleep onset insomnia, when sedation the following day is undesirable or when prescribing for elderly patients.  Short-acting hypnotics have a higher potential for abuse and withdrawal phenomena are more common.  Long-acting hypnotics are indicated in patients with poor sleep maintenance (e.g. early morning waking), when an anxiolytic effect is needed during the day or when sedation the following day is acceptable.  Longer acting hypnotics can increase the risk of falls in the elderly and may cause ataxia and confusion.  Patients who have been on a benzodiazepine for many years can be switched to diazepam and the diazepam then be slowly withdrawn (See withdrawal protocol BNF section 4.1.).  The sedating antihistamine promethazine is regarded as less suitable for prescribing in the BNF. However, it is sometimes used in patients for occasional insomnia when „z‟ drugs and benzodiazepines are considered inappropriate. Chloral and Derivatives - Chloral Hydrate

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Prescribing Points  Reserved for paediatric patients. Melatonin - Melatonin 3mg tablets

(Bio-melatonin®) (Unlicensed) Prescribing Points  Unlicensed, immediate release melatonin is used in treating sleep onset insomnia and also in delayed sleep phase syndrome in children in conditions such as ADHD.  Treatment with melatonin in children and adolescents should be initiated and supervised by a specialist. The need for continuing melatonin therapy should be reviewed at least annually.  Other formulations and strengths of unlicensed melatonin (including liquid preparations for younger children or in the presence of swallowing difficulties or the use of C/R melatonin in patients with learning difficulties) may be prescribed if Bio-Melatonin® is considered clinically unsuitable.  Circadin® (melatonin MR 2mg tablets) has not been approved by the SMC for the treatment of insomnia and should not be prescribed routinely in NHS Fife. Circadin® should only be prescribed if an Individual Patient Treatment Request has been approved. 4.1.2 Anxiolytics

For further advice on anxiety disorders see NHS Fife website http://www.moodcafe.co.uk/practitioners-resources/anxiety.aspx Acute anxiety 1st Choice Diazepam (long acting) 2nd Choice Lorazepam (short acting) Chlordiazepoxide(long acting)

Prescribing Points

 Patient self help guides on anxiety problems are available at http://www.moodcafe.co.uk/practitioners-resources/anxiety.aspx  Prescriptions for anxiolytics should only be issued for short-term relief (1- 4 weeks) of severe acute anxiety that is disabling or causing unacceptable patient distress.  The use of benzodiazepines to treat short–term “mild” anxiety is inappropriate and unsuitable.  Benzodiazepines should not be used as sole treatment for chronic anxiety.  Benzodiazepines should be used at the lowest possible dose for the shortest possible time. Dependence is particularly likely in patients with a history of alcohol or drug abuse and in patients with marked personality disorders.  Patients who have been on a benzodiazepine for many years can be switched to diazepam and the diazepam then be slowly withdrawn (See withdrawal protocol BNF section 4.1.).  The most common use for chlordiazepoxide is for alcohol withdrawal.  Lorazepam acts for a shorter period and does not accumulate with repeated doses but has greater potential for withdrawal phenomena, dependence and abuse. Lorazepam is useful in

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patients with impaired liver function and in the elderly.

Other drugs for acute anxiety

Propranolol (standard tablets)

Prescribing Points

 Used to relieve the physical symptoms of anxiety e.g. palpitations and tremor. Long acting propranolol preparations are more expensive than standard tablet formulations. Anxiety Disorders Also see - NICE CG 113 - Generalised Anxiety Disorder and Panic Disorder (with or without Agoraphobia), January 2011 http://www.nice.org.uk/guidance/cg113 NICE CG 31 - Obsessive-Compulsive Disorder, November 2005 http://www.nice.org.uk/guidance/CG31

NICE CG 26 - Post-Traumatic Stress Disorder, March 2005 http://www.nice.org.uk/guidance/cg26 1st Choice Citalopram +/- psychological Fluoxetine therapies Sertraline 2nd Choice Clomipramine +/- psychological Venlafaxine therapies 3rd Choice R - Pregabalin +/- psychological

therapies

Prescribing Points

 Psychological therapies should be considered along with pharmacological treatment in patients with anxiety disorders. Refer to NICE Clinical guidelines.  The choice of agent for the treatment of anxiety disorders will depend on licensed indications, patient preference, severity of the condition and cost. Also refer to NICE Clinical guidelines.  For further prescribing information on antidepressants see section 4.3.  R - Pregabalin is approved for restricted 3rd line use. For the treatment of GAD and anxiety associated with schizophrenia. Pregabalin is restricted to specialist initiation / specialist recommendation after failure with/intolerance to at least two different formulary SSRIs/SNRIs in patients unable to engage in or unresponsive to cognitive behavioral therapy. Treatment should be reviewed after a 12 week trial period and discontinued if found to be ineffective.  Prescribers should be alert to the misuse potential of pregabalin.  All strengths of pregabalin capsules are the same cost; therefore ensure the correct strength of capsule is prescribed i.e. 300mg rather than 2x 150mg.

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4.2 - Drugs used in psychoses and related disorders Also see :- Appendix 4A - Guidance on Drug Treatment of Schizophrenia in Patients 18 Years and Over http://www.fifeadtc.scot.nhs.uk/formulary/4-central-nervous-system/appendix-4a-treatment- of-schizophrenia-in-patients-18-years-over.aspx NICE Clinical Guidance 82 - Schizophrenia: Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care. March 2009. http://publications.nice.org.uk/schizophrenia-cg82 For prescribing in pregnancy refer to the UK Teratology Information Service http://www.uktis.org./index.html

4.2.1 Antipsychotic drugs

General Prescribing Points

 Patients should receive antipsychotic drugs for a minimum of 6 weeks before the drug is deemed ineffective.  Antipsychotics should be initiated with caution in the first episode (i.e. start with a low dose).  Patients should be reviewed regularly to monitor efficacy and development of side-effects.  Specialist advice should be sought before discontinuing antipsychotics due to the risk of relapse.  Prescribing of more than one antipsychotic drug at the same time is not recommended. See NHS Fife Policy M1-P3-MH - Regular Prescription of more than one antipsychotic drug at the same time - https://intranet.fife.scot.nhs.uk/uploadfiles/publications/MH3%20-%20(M1-P3- MH)%20%20More%20than%20one%20antipsychotic%20Approved%20June%202014.pdf  Antipsychotics vary in their side effect profile and this will influence choice of therapy. See Appendix 4A - Guidance on Drug Treatment of Schizophrenia. http://www.fifeadtc.scot.nhs.uk/media/2177/ff-appendix-4a.pdf

Antipsychotics in older people with dementia

 In elderly patients with dementia, all antipsychotic drugs are associated with a small increased risk of mortality and an increased risk of stroke or transient ischaemic attack. Elderly patients are also particularly susceptible to postural hypotension and to hyper- and hypothermia in hot or cold weather. It is recommended that: . Antipsychotic drugs should not be used in older patients to treat mild psychotic symptoms i.e. non-distressing symptoms. . Initial doses of antipsychotic drugs in elderly patients should be reduced (to half the adult dose or less), taking into account factors such as the patient‟s weight, co- morbidity, and concomitant medication. Doses used should be the lowest possible, titrated carefully and closely monitored. . Treatment should be reviewed regularly. . Patients/caregivers should be cautioned to immediately report signs and symptoms of potential cerebrovascular adverse events such as sudden weakness or numbness in the face, arms or legs, and speech or vision problems.  Antipsychotics may be prescribed with caution in the management of behavioural disorders associated with some types of dementia. It is important to remember that such behaviour can

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be a temporary phenomenon and that drugs should be prescribed on a short–term basis. Risperidone (for physical aggression) and olanzapine (off-label use) are the preferred antipsychotics for use in patients with dementia. 1st Choice - Chlorpromazine - Olanzapine - Risperidone 2nd Choice - Amisulpride - Aripiprazole (Abilify®) - Haloperidol – Quetiapine (standard tablets)

Prescribing Points

 Selection of an antipsychotic drug is influenced by relative adverse effects, the patient's susceptibility to adverse effects and variability in patient response. Choice should therefore be made jointly by the prescriber and the informed patient or carer where possible. Where more than one antipsychotic is appropriate, the drug with the lowest purchase cost should be prescribed.  In general, due to its side-effect profile chlorpromazine should not be initiated in the elderly. Chlorpromazine also has a high risk of photosensitivity.  Orodispersible formulations of olanzapine and risperidone are expensive compared to generic versions of the standards tablets. The orodispersible formulations should only be used in patients who have swallowing difficulties or when there are compliance problems with the standard tablets.  Haloperidol has a high risk of extrapyramidal side effects, especially in the elderly. The manufacturer of haloperidol recommends a baseline ECG before starting haloperidol and at regular intervals during treatment due to risk of QT prolongation /ventricular arrhythmias.  All antipsychotics can cause weight gain and can increase the risk of diabetes. – Clozapine (Zaponex®)

Prescribing Points

 Clozapine is the only drug with evidence for use in treatment resistant schizophrenia.  Clozapine must be initiated by and prescribed under the supervision of a Consultant Psychiatrist.  The patient, supplying pharmacist and consultant must be registered with the Clozapine (Zaponex®) Patient Monitoring Service. Patients are at risk of agranulocytosis and monitoring of white cell count is mandatory.  If a patient presents with signs of fever or infection then an urgent full blood count should be undertaken.  Patients who have not taken clozapine for 48 hours will require re-titration. Seek specialist advice.  Gastro–intestinal obstruction and paralytic ileus may also occur with clozapine. Patients should be advised to contact the prescriber if they develop abdominal pain or constipation.  Changes in smoking habit can significantly affect clozapine plasma levels increasing the risk

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of relapse (on starting or increasing smoking) or toxicity (on stopping or reducing smoking). 4.2.2 Antipsychotic depot injections First Generation - Flupentixol decanoate (Depixol®) – Fluphenazine decanoate - ®) - ®) - ®) Second Generation - ®) - ®) - ®)

Prescribing Points

 Depot injections should be used for the patient‟s convenience or to improve concordance.  First-generation antipsychotic depot injections are administered at intervals of 1-4 weeks dependent on patient requirements and drug half-life.  The BNF recommends that for 1st generation antipsychotics a test dose of the depot injection should be given first since some side–effects can be prolonged.  There is no evidence that there is a major difference in efficacy between depot injections. However, there may be differences in tolerability that are important which may affect choice on an individual basis.  Extrapyramidal reactions occur less frequently with second generation antipsychotic depot preparations.

2nd Generation Antipsychotics

 2nd generation antipsychotic depot injections are substantially more expensive than and there is no evidence of better efficacy compared to 1st generation depot injections.  They may be considered if: . Patient has experienced unacceptable side-effects with typical antipsychotic depots. . Patient has responded favourably to oral risperidone but prefers a long-acting IM injection. . Patient has responded favourably to an oral atypical but there are concerns about long-term concordance.  Risperidone depot is administered at 2-week intervals. It has a delayed response therefore administration of oral medication should be continued for at least 4 - 6 weeks.  Paliperidone can be considered as an alternative to risperidone depot in patients where the use of a monthly depot would be advantageous.  Aripiprazole (Abilify Maintena®) is a monthly injection which is approved for use in patients requiring a depot who have been stabilised on oral aripiprazole.  The long-acting olanzapine injection (ZypAdhera®) for maintenance treatment of schizophrenia has not been accepted for use by the SMC and is non-formulary.

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4.2.3 Antimanic drugs

Also see

Lithium Shared Care Protocol and Information for GPs http://www.fifeadtc.scot.nhs.uk/shared- care-protocols/scps-fife/lithium.aspx SIGN Guideline No. 82. Bipolar Affective Disorder. May 2005. www.sign.ac.uk/pdf/sign82.pdf SIGN Guideline 127 – Management of Perinatal Mood Disorders, March 2012 www.sign.ac.uk/guidelines/fulltext/127/index.html NICE Clinical Guideline 38 - Bipolar disorder: The management of bipolar disorder in adults, children and adolescents, in primary and secondary care, July 2006 http://publications.nice.org.uk/bipolar-disorder-cg38 For prescribing in pregnancy refer to the UK Teratology Information Service http://www.uktis.org./index.html

– 1st Choice ®) 2nd Choice - ®) -

Prescribing Points

 Long-term treatment of bipolar disorder should continue for at least two years from the last manic episode and up to five years if the patient has risk factors for relapse.  For acute manic episodes, oral administration of an antipsychotic drug (see section 4.2.1), lithium or semisodium valproate should be considered.  The full prophylactic effect of lithium may not occur for six to twelve months after the initiation of therapy.  Due to differences in bioavailability, lithium products are not interchangeable therefore should be prescribed by brand name. The NHS Fife preferred brand is Priadel®.  Routine serum-lithium monitoring, monitoring of renal function and thyroid function are required in patients prescribed lithium. For further information see Lithium Shared Care Protocol and Information for GPs http://www.fifeadtc.scot.nhs.uk/shared-care- protocols/scps-fife/lithium.aspx.  The need for continued lithium therapy should be assessed regularly. Patients on continuous lithium treatment should be assessed by a secondary care specialist at least every 2 years.  Abrupt discontinuation of lithium increases the risk of relapse. If lithium is to be discontinued, the dose should be reduced gradually over a period of at least 4 weeks (preferably over a period of up to 3 months).  If treatment with valproate is to be stopped, reduce the dose gradually over at least 4 weeks.  There is an increased risk of teratogenicity associated with the use of lithium and valproate preparations. Women of child bearing potential should be informed of the possible H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use

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consequences and be provided with appropriate contraceptive advice. Valproate should not be prescribed routinely in women of child bearing potential.

4.3 - Antidepressant drugs Also see Appendix 4B: Guidance on the use of pharmacological agents for the treatment of depression http://www.fifeadtc.scot.nhs.uk/media/2180/ff-appendix-4b.pdf. http://sign.ac.uk/guidelines/fulltext/114/index.html SIGN guideline 114, Non-pharmaceutical management of depression in adults, January 2010 SIGN Guideline 127 – Management of Perinatal Mood Disorders, March 2012 www.sign.ac.uk/guidelines/fulltext/127/index.html http://www.nice.org.uk/guidance/cg90 NICE Clinical Guideline No. 90 Depression in Adults (Update) Oct 2009. http://www.nice.org.uk/guidance/cg91 NICE Clinical Guideline 91 (Oct 2009) The treatment and management of depression in adults with chronic physical health problems (partial update) for further advice. For prescribing in pregnancy refer to the UK Teratology Information Service http://www.uktis.org./index.html

General Prescribing Points

 Antidepressant drugs should not be used for initial treatment in mild depression as the risk- benefit ratio is poor. Psychological therapy should be considered initially; a trial of antidepressant therapy may be considered in cases refractory to psychological treatments or those associated with psychosocial or medical problems.  Ideally, patients with moderate to severe depression should be treated with psychological therapy in addition to drug therapy.  SSRIs are better tolerated and are safer in overdose than other classes of antidepressants and should generally be considered first-line for treating depression.  St John‟s wort (Hypericum perforatum) should not be prescribed or recommended for depression due to its limited evidence of efficacy and because St John‟s wort can interact with a number of other drugs (See BNF for further information).  Patients should be reviewed at least every 2-4 weeks at the start of antidepressant treatment. Treatment should be continued for at least 4 weeks (6 weeks in the elderly) before considering whether to switch antidepressant due to lack of efficacy. In cases of partial response, continue for a further 2-4 weeks (elderly patients may take longer to respond).  Following remission, antidepressant treatment should be continued at the same dose for at least 6 months (12 months in the elderly). Patients who have had 2 or more previous episodes of depression within the last 5 years may benefit from long-term antidepressants (at least 2 years) at therapeutic doses.  All antidepressants may be associated with a discontinuation syndrome and, if taken continuously for 6 weeks or longer, should be withdrawn gradually. The dose should preferably be reduced gradually over about 4 weeks, or longer if withdrawal symptoms emerge (6 months in patients who have been on long-term maintenance treatment). Drugs with a shorter half-life

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e.g. paroxetine or venlafaxine, are associated with a higher risk of withdrawal symptoms.  Hyponatraemia has been associated with all types of antidepressants, especially in the elderly, and should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant.  For Information on prescribing antidepressants during pregnancy and breastfeeding – see Appendix 4B: Guidance on the use of pharmacological agents for the treatment of depression. http://www.fifeadtc.scot.nhs.uk/media/2180/ff-appendix-4b.pdf

Depressive illness in children and adolescents

 The safety and efficacy of drugs used in the treatment of depression in children (under 18 years) has not been established. Long term safety information is also lacking. Depression in children should be managed by an appropriate specialist and treatment should involve psychological therapies. The CSM have issued advice on the treatment of depressive illness in children and adolescents - „Only fluoxetine has shown in clinical trials to be effective for treating children and adolescents but it is possible that it is associated with a small risk of self harm and suicidal thoughts. The balance of risk and benefit for the use of fluoxetine is considered favourable but careful monitoring for suicidal behaviour, self harm or hostility, particularly at the beginning of treatment should be undertaken.‟ 4.3.1 Tricyclic and related antidepressant drugs Amitriptyline (neuropathic pain) Clomipramine (phobia and obsessional states) Imipramine Lofepramine Nortriptyline (neuropathic pain) Trazodone

Prescribing Points

 Antimuscarinic and cardiovascular side-effects are common. Dose titration is essential to avoid risk of postural hypotension. Caution with use in elderly patients and those with cardiovascular disease.  Both amitriptyline and dosulepin (dothiepin) are not recommended in the treatment of depression due to their association with ischaemic heart disease, cardiac arrhythmias and fatalities following overdose. They should only be prescribed in new patients if initiated by a specialist.  Trazodone is more sedating and has fewer cardiovascular side-effects than tricyclics. Trazodone is often used in the elderly and as a hypnotic (off-label use). 4.3.2 Monoamine-Oxidase Inhibitors (MAOIs) Initiated by specialists only 4.3.3 Selective Serotonin Re-Uptake Inhibitors (SSRIs)

Citalopram Fluoxetine Sertraline

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Prescribing Points

 SSRIs are generally better tolerated than tricyclics. Tolerance to the main gastrointestinal side- effects usually develops within a short time. SSRIs have fewer cardiotoxic and antimuscarinic side-effects and are less sedating than the tricyclic and related antidepressants.  Due to the risk of gastrointestinal bleeding, SSRIs should be avoided if possible, or used with caution, in patients aged over 80 years, those with prior upper gastrointestinal bleeding, or in those also taking aspirin or another NSAID.  Citalopram has fewer drug interactions than other SSRIs, it has a relatively short half and is particularly useful in the elderly.  Due to the risk of a dose-dependent QT prolongation, citalopram should not be used in doses above 40mg a day in adults and not above 20mg a day in the elderly (>65 years) or in patients with reduced hepatic function. Citalopram is contra-indicated in patients with a known QT prolongation or congenital long QT syndrome and in patients who are taking other medicines known to prolong QT interval.  If a patient requires a dose of citalopram out with the above, an ECG should be performed and the reason for prescribing the unlicensed dose recorded in the patient‟s medical notes. Possibility of switching to an alternative antidepressant should be considered.  Fluoxetine, due to its long half-life, is less likely to cause a withdrawal reaction. Beware of drug interactions when switching to alternative antidepressants.  At higher doses it is more cost-effective to prescribe fluoxetine 3x20mg capsules rather than 60mg capsules.  Fluoxetine is also available as a 20mg dispersible tablet (Olena®). The tablet can be halved in order to administer a 10mg dose. The dispersible tablet should be used in preference to fluoxetine suspension in patients who are unable to swallow the capsule formulation. The dispersible tablets should also be used in patients requiring a 10mg dose instead of ordering a specially manufactured 10mg tablet formulation (costs up to £60 per month).  Patients who have had a recent cardiovascular event should be prescribed sertraline, it has less negative effects on the QT interval.  Escitalopram is non-formulary and should only be considered when formulary options have been ineffective, not tolerated or are considered unsuitable.  Escitalopram is contra-indicated in patients with known QT interval prolongation or congenital long QT syndrome and in patients who are taking other medicines known to prolong QT interval. 4.3.4 Other Antidepressant Drugs Mirtazapine Venlafaxine(standard tablets, M/R capsules)

Prescribing Points

 These drugs are considered second-line agents for use when first line antidepressants have failed.  Mirtazapine has few antimuscarinic effects, but causes sedation during initial treatment. Lower doses of mirtazapine cause more sedation than higher doses.  Mirtazapine can be used as a first line option in patients who require sedation but are

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unsuitable for treatment with a tricyclic.  Mirtazapine is associated with a rare risk of white blood cell dyscrasias. Patients should be advised to report any fever, sore throat, stomatitis or other signs of infection. Weight gain is also frequently reported.  Treatment with venlafaxine is associated with a higher risk of withdrawal effects compared with other antidepressants.  Venlafaxine is contraindicated in patients with an identified high risk of cardiac arrhythmia and those with uncontrolled hypertension. Use with caution in patients with established cardiac disease.  Blood pressure should be reviewed periodically, after initiation of treatment and after dose increases. For patients who experience a sustained increase in blood pressure while receiving venlafaxine, either dose reduction or discontinuation should be considered.  The use of duloxetine in depression is restricted to patients with co-morbidities i.e. urinary incontinence, diabetic peripheral neuropathy.  Agomelatine (Valdoxan®) is not recommended by the Scottish Medicines Consortium (SMC). Agomelatine should not be prescribed unless an Individual Patient treatment Request has been approved by NHS Fife. 4.4 - CNS Stimulants and drugs used for ADHD Also see:- NHS Fife Shared Care Protocol - Children with Attention Deficit Hyperactivity Disorder (ADHD) - Atomoxetine, Methylphenidate http://www.fifeadtc.scot.nhs.uk/shared-care-protocols.aspx SIGN 112 - Management of attention deficit and hyperkinetic disorders in children and young people http://www.sign.ac.uk/pdf/sign112.pdf NICE Clinical Guidance 72 - Attention deficit hyperactivity disorder: Diagnosis and management of ADHD in children, young people and adults http://publications.nice.org.uk/attention-deficit-hyperactivity-disorder-cg72

Attention Deficit Hyperactivity disorder (ADHD) - Methylphenidate - standard tablet, M/R- M/R product should be prescribed by brand 1st Choice name Concerta® XL, Equasym XL®, Medikinet XL ® 2nd Choice - ®) - ®) 3rd Choice -

Prescribing Points

 Methylphenidate, atomoxetine and dexamfetamine are useful for some children with severe forms of ADHD as part of a comprehensive treatment programme when remedial measures alone prove insufficient. All 3 drugs are licensed for use in children aged 6 years and above.  Majority of children will persist with some degree of symptoms into adulthood (15-66% depending on the criteria used). Some individuals may be diagnosed with ADHD as adults, not having been diagnosed during childhood.  Use of methylphenidate, lisdexamfetamine or dexamfetamine in patients aged over 18 is an

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„off-label‟ use.  Atomoxetine is licensed for initiation in adults as well as children and adolescents.  Patient selection is important and therefore initiation and titration of treatment should be carried out by a child/adolescent psychiatrist, adult psychiatry or a paediatrician working in a dedicated specialist clinic.  Before initiation of drug therapy, and then at least every every 6 months thereafter, pulse, blood pressure, weight, and height should be measured. See NHS Fife Shared Care Protocols http://www.fifeadtc.scot.nhs.uk/shared-care-protocols.aspx.  The need to continue drug treatment for ADHD should be subject to specialist review at least annually.  Modified release preparations of methylphenidate (Concerta® XL, Equasym XL® or Medikinet XL®) can improve compliance and acceptability especially in adolescents and adults.  Due to differences in release profiles methylphenidate M/R preparations should be prescribed by brand.  Atomoxetine should normally be used 2nd line in patients who do not respond to methylphenidate or when methylphenidate is contraindicated or not tolerated e.g. because of significant anxiety, tic disorders or sleep difficulties. It may be used 1st line in patients where drug diversion is a concern or if substance misuse is also an issue.  Lisdexamfetamine is recommended 2nd line in patients who do not respond to methylphenidate as an alternative stimulant.  Dexamfetamine should normally be used 3rd line in patients where methylphenidate or atomoxetine are unsuitable. Melatonin - Melatonin 3mg (Bio-Melatonin ®)

(Unlicensed)

Prescribing Points

 Unlicensed, immediate release melatonin is used in treating sleep onset insomnia and also in delayed sleep phase syndrome in children in conditions such as ADHD.  Treatment with melatonin in children and adolescents should be initiated and supervised by a specialist. The need for continuing melatonin therapy should be reviewed at least annually.  Other formulations and strengths of unlicensed melatonin (including liquid preparations for younger children or in the presence of swallowing difficulties or the use of C/R melatonin in patients with learning difficulties) may be prescribed if Bio-Melatonin® is considered clinically unsuitable. Narcolepsy – ®)

Prescribing Points

 Due to risk of serious side-effects modafinil is only licensed for the treatment of narcolepsy. Modafinil is not recommended by the MHRA for use for any other off-label use. 4.5 - Drugs used in treatment of obesity Also see

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SIGN Clinical Guideline 115 - Management of Obesity www.sign.ac.uk/guidelines/fulltext/115/index.html 1st Choice 2nd Choice Orlistat (Xenical®)

Prescribing Points

 The main treatment for obesity is a suitable diet and increased physical activity. Orlistat should only be considered as an adjunct to lifestyle changes.  Before commencing drug therapy, patients should enter a minimum 3 month structured weight management programme to confirm that they can comply with dietary restriction.  Orlistat should be prescribed only as part of an overall plan for managing obesity in adults who meet one of the following criteria BMI ≥ 30kg/m2 or BMI ≥ 28kg/m2 plus associated risk factors e.g. type 2 diabetes, hypertension or hypercholesterolaemia.  Patients should have their body weight monitored and recorded on at least a monthly basis.  Orlistat should be discontinued after 3 months if patients fail to lose 5% of their initial body weight since starting drug treatment. (Less strict goals may be appropriate for people with type 2 diabetes.) Further courses should only be considered after a suitable period and patients should again demonstrate the ability to lose weight on a suitable diet.  Treatment should only be continued beyond 12 months after discussing potential benefits and risks with the patient. On stopping orlistat, there may be a gradual reversal of weight loss.  Patient experience of flatulence with loose stools may be limited by dietary compliance (decreased fat intake, <25g fat per meal).  Young people and adolescents who are severely obese should be referred to the specialist paediatric dietary clinic.  An over the counter version containing 60mg orlistat (Alli®) is available. 4.6 - Drugs used in nausea and vertigo Also see National Palliative Care Guidance http://www.palliativecareguidelines.scot.nhs.uk/documents/NauseaVomiting.pdf Cyclizine Domperidone* Haloperidol Hyoscine hydrobromide Levomepromazine Metoclopramide** Prochlorperazine H - Aprepitant (Emend®) - Choices for specific indications Chemotherapy Induced Highly emetogenic - H - Aprepitant (Emend®) Moderately emetogenic -

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Domperidone* Mildly emetogenic Domperidone*

Motion Sickness 1st Choice OTC treatment from pharmacy 2nd Choice Cyclizine N&V in Migraine 1st Choice Metoclopramide** 2nd Choice Domperidone* Opioid Induced 1st Choice Haloperidol (also see palliative care guidance, and PONV guidance) * For safety information regarding domperidone see prescribing note below. ** For safety information regarding metoclopramide see prescribing note below.

Prescribing Points

 Anti-emetics may only be necessary for short-term management of nausea & vomiting (N&V). Patients should be reviewed regularly and treatment discontinued when appropriate.  Metoclopramide can cause acute dystonic reactions, usually in the young (especially girls and young women) and the very old. Reactions usually occur shortly after starting treatment with metoclopramide and subside within 24 hours of stopping it.  Metoclopramide is preferred when patient sedation should be avoided. Prochlorperazine may be preferred when sedation is required.  ** Due to risk of neurological side-effects, metoclopramide is now only licensed for limited indications and the maximum duration of treatment is 5 days in all patients. For further advice, see http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON300404.  Prochlorperazine buccal tablets (Buccastem®) may be a suitable alternative formulation for patients who are vomiting.  Long-term use of haloperidol, levomepromazine, metoclopramide or prochlorperazine may cause tardive dyskinesia in the elderly.  Domperidone does not cross the blood brain barrier; it is less likely than metoclopramide and prochlorperazine to cause sedation or dystonic reactions. Domperidone is the preferred anti- emetic in patients with Parkinson‟s disease.  *Domperidone is associated with an increased risk of serious cardiac events especially in those aged over 60 or those who take more than 30mg daily. Domperidone should be only used for the shortest duration of time (normally no longer than 7 days) and the maximum licensed oral dose in adults is now 30mg daily. Domperidone is contraindicated in patients who are taking concomitant medication known to cause QT prolongation (such as erythromycin and ketoconazole), in patients with underlying cardiovascular disease or in conditions where cardiac conduction is, or could be, impaired and also in patients with severe hepatic impairment. (For further advice see http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON418518)  Domperidone and metoclopramide are no longer recommended as motility stimulants (See section 1.2).  Patients with prolonged N&V should be considered for administration of parenteral treatments (see palliative care guidance).

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 Cyclizine is the recommended 1st line agent for treatment of PONV.  Cyclizine has potential for abuse.  Cyclizine, haloperidol, levomepromazine and metoclopramide are used for management of nausea and vomiting in palliative care and can be added to morphine or diamorphine in a syringe driver for continuous subcutaneous administration (off-label use). The choice of agent will depend on the underlying cause of the nausea and vomiting.  Ondansetron is the recommended 1st line agent for chemotherapy induced N&V; it may also be used peri-operatively to prevent PONV as per the PONV Guidelines and also for constant, intractable nausea in patients with Parkinson‟s disease. st  Ondansetron and other 5HT3 antagonists are prescribed in the 1 week after chemotherapy but thereafter if N&V are difficult to control without use of 5HT3 antagonist, the GP should contact the hospital for further advice.  The „Melt‟ formulation of ondansetron is relatively expensive compared to standard tablets and should only be considered when patients are continuously vomiting and are unable to take the standard tablets.  Domperidone and dexamethasone (section 6.3.2) are also routinely used in the management of cytotoxic chemotherapy-induced nausea and vomiting.  Aprepitant is restricted to use in the prevention of acute and delayed nausea and vomiting with highly emetogenic cisplatin-based chemotherapy in adults after failure with ondansetron. It is not approved for use in the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. Other Vestibular Disorders Acute treatment Cinnarizine or Prochlorperazine Maintenance Betahistine or Cinnarizine

Prescribing Points

 Cinnarizine or prochlorperazine are effective for the acute treatment of vestibular disorders.  Prochlorperazine buccal tablets (Buccastem®) may be a suitable alternative for patients who are vomiting.  Prochlorperazine is best avoided in the elderly due to the risk of postural hypotension, confusion and drug-induced parkinsonism.  Long-term use of prochlorperazine is not recommended as it can hinder recovery. Betahistine or cinnarizine are preferred as maintenance therapy.  Betahistine should be reserved for prophylaxis in patients with a proven diagnosis of Ménière‟s disease. Betahistine can be used to reduce the frequency and severity of attacks of hearing loss, tinnitus and vertigo. 4.7 - Analgesics Also see:- Appendix 4C - Management of Chronic Non-Malignant Pain http://www.fifeadtc.scot.nhs.uk/media/2183/ff-appendix-4c.pdf Acute Pain Guidelines http://intranet.fife.scot.nhs.uk/atoz/index.cfm?fuseaction=service.display&objectid=67947A94- 5056-8C6F-C0B9209FE8095FC2 SIGN 136 –Management of Chronic pain http://sign.ac.uk/pdf/SIGN136.pdf

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SIGN 107 - Diagnosis and Management of Headache in Adults www.sign.ac.uk/guidelines/fulltext/107/index.html British Pain Society’s Opioids for persistent pain: Good Practice www.britishpainsociety.org/book_opioid_main.pdf 4.7.1 Non- Opioid analgesics and compound analgesic preparations The WHO ladder was designed to aid cancer pain and is useful in acute pain. It was not designed for chronic pain but may give guidance to aid patients to manage symptoms whilst trying to implement self-help strategies. When considering titrating to strong opioids, refer to NHS Fife Chronic Non-Malignant Pain Strong Opioid Prescribing Guideline and the British Pain Society‟s Guidance on Good Practice (see links above). The objective of treatment in all types of pain, irrespective of origin, is to achieve symptom control, and improve the patient‟s quality of life. At any stage in the ladder, the addition of an appropriate Formulary NSAID can be considered for the treatment of short term exacerbation of pain or where there is an inflammatory component.

Non-Opioid analgesics Paracetamol Ibuprofen (low dose <1.2g daily) Naproxen R - Nefopam (Acupan®) Prescribing Points  Paracetamol tablets or caplets are the preferred formulation not capsules.  Dispersible and effervescent formulations of paracetamol are considerably more expensive and should be restricted to patients with swallowing difficulties. Their high sodium content (the equivalence of up to 8g daily of salt) exceeds the WHO daily salt intake recommendation of 6g daily.  In patients with a low body weight (>33kg to<50kg) the max. daily dose of paracetamol is 60mg/kg and not exceeding 3g. Patients > 50kg with risk factors for hepatotoxicity the max. dose per administration is 1g (i.e 2 x 500mg ). Maximum daily dose is 3g.  Paracetamol infusion is restricted to short term treatment of moderate pain following surgery and fever, when administration by intravenous route is clinically justified and other routes are

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not available.  R - Nefopam is relatively expensive and is approved for restricted use only in patients intolerant of opioids. Nefopam has significant anticholinergic side-effects and should be used VERY cautiously, if at all, in frail older people especially those with cognitive impairment. Compound analgesic preparations 1st Choice Co-codamol 30/500 Co-codamol 15/500 (restricted to patients unable to tolerate 30/500 or unable to cope with combining 30/500 with paracetamol) 2nd Choice Co-dydramol 20/500, 30/500

Prescribing Points

 The use of low strength compound analgesics, e.g. co-codamol 8/500 and co-dydramol 10/500, in chronic pain is not generally encouraged. There is no evidence that they are more effective than paracetamol in relieving acute pain, they produce more side-effects and can complicate treatment of overdosage.  Co-codamol 15/500 is more expensive to prescribe than the generic co-codamol 30/500. Use of co-codamol 15/500 should be restricted to patients unable to tolerate the 30/500 strength or unable to cope with combining co-codamol 30/500 with paracetamol.  Dispersible and effervescent formulations of co-codamol are considerably more expensive and should be restricted to patients with swallowing difficulties. Their high sodium content (the equivalence of up to 8g daily of salt) exceeds the WHO daily salt intake recommendation of 6g daily.  Co-dydramol is approved for patients in whom codeine/co-codamol is ineffective and for patients who are known to be poor metabolisers of codeine (10% of the population). 4.7.2 Opioid analgesics Weak Opioids 1st Choice Codeine 2nd Choice Compound analgesic preparations (see above) 3rd Choice Tramadol oral Strong Opioids Morphine sulphate (including parenteral 1st Choice preparations) (Zomorph® is preferred M/R preparation) Oxycodone (Shortec® - immediate release, 2nd Choice Longtec® M/R are preferred oral preparations) - Fentanyl patches (Matrifen®) – 3rd Choice Palliative care initiation only - ®) -

Palliative care initiation only - ®) –

Palliative care initiation only Diamorphine Tramadol injection

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R- Oxycodone 50mg/ml inj (Oxynorm®) R- Cyclimorph® R- Pethidine

Prescribing Points

Weak opioids

 Up to 10% of the population have poor or absent metabolism of codeine resulting in a reduced or absent analgesic effect. Co-dydramol or tramadol may be more effective in this patient group.  Tramadol is a Schedule 3 Controlled Drug and should be considered 3rd line after codeine and co-codamol/co-dydramol and may also be useful in patients with neuropathic pain.  Modified release tramadol preparations should only be prescribed for use in night time breakthrough pain, to aid compliance or if there are side-effects with immediate release tramadol. Modified release tramadol preparations are available as both 12-hour and 24-hour release formulations. The appropriate dose for the formulation should be prescribed. 12 hour formulations should be prescribed twice daily. 24 hour formulations once daily.  The combination product Tramacet® should not be prescribed as there is insufficient paracetamol in each tablet. Strong opioids  In chronic non–malignant pain the long–term use of opioids has many implications. Complete analgesia is rarely achievable and then only at the expense of side-effects such as cognitive impairment. Extensive guidance is given in the NHS Fife Chronic Non-Malignant Pain Strong Opioid Prescribing Guideline and on the Pain Society website www.britishpainsociety.org/book_opioid_main.pdf.  Patients prescribed a strong opioid should also be prescribed paracetamol to be used regularly.  In cancer pain or in a palliative care setting, modified release preparations of strong opioids should be prescribed in combination with an immediate release preparation to allow treatment of breakthrough pain.  In chronic, non-malignant pain, immediate–release preparations should not be prescribed routinely and should only be considered for short-term flare-ups.  Patients prescribed a strong opioid should have access to regular prophylactic laxatives. Combination of a stimulant and softening laxative is recommended.  Post operative patients may be discharged on an appropriate short-term analgesic regimen which may include potent opioids. These should not be automatically continued beyond this period.  Elderly patients are particularly susceptible to side effects of opioids e.g. respiratory depression and constipation.  Transdermal preparations are not suitable for acute pain or in those patients whose analgesic requirements are changing rapidly because the long time to steady state prevents rapid titration of the dose.  Care should be taken to avoid unintentional changes to brand of modified release morphine preparations or fentanyl patches.  Oxycodone is the 2nd line choice strong opioid for patients with severe non-malignant pain in

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whom morphine is ineffective or not tolerated.  Oxycodone preparations should always be prescribed by brand name. Shortec® is the preferred immediate release preparation and Longtec® is the preferred modified release preparation.  Targinact® (oxycodone/naloxone combination) is not currently approved for use in NHS Scotland by the SMC - an individual patient treatment request form (IPTR) should be submitted and approved before prescribing.  Fentanyl is the 3rd line choice strong opioid, it should be reserved for patients whose pain has been stabilised on oral opioids. Therapy with transdermal fentanyl is restricted to palliative care or for chronic intractable pain in patients intolerant of morphine and oxycodone.  Matrifen® is the preferred brand of fentanyl patches.  There are important differences between matrix and reservoir formulations of fentanyl patches and they are not interchangeable.  Fentanyl buccal tablets (Abstral®) or nasal spray (Pecfent®) is reserved for breakthrough pain in palliative care patients. They should only be used when immediate release morphine and oxycodone is ineffective or unsuitable. Prescribers should be aware of the differing absorption and elimination characteristics of available oral fentanyl preparations; doses are not interchangeable and should be titrated in individual patients. (See SPC‟s for further information).  Transdermal buprenorphine (either as Butrans® 7 day patch or Transtec® 4 day patch) are not currently approved for use in NHS Scotland by the SMC - an individual patient treatment request form (IPTR) should be submitted and approved before prescribing.  R- Cyclimorph® and pethidine are approved for restricted use only in patients undergoing endoscopy  R- Oxycodone injection 50mg/ml is approved for restricted use in cancer patients with moderate to severe pain who are unable to tolerate morphine or diamorphine who require a high dose of oxycodone via syringe driver. 4.7.3 Neuropathic Pain/ Adjuvants See Appendix 4C: Guidance on Chronic Pain Management: Neuropathic Pain http://www.fifeadtc.scot.nhs.uk/media/2183/ff-appendix-4c.pdf 1st Choice Amitriptyline (off label use) Imipramine (If amitriptyline is not tolerated)

(off label use) Nortriptyline (If patient at increased risk of

seretonergic syndrome) (off label use) 2nd Choice Gabapentin 3rd Choice Pregabalin Fibromyalgia 1st Choice Amitriptyline (off label use) Imipramine (If amitriptyline is not tolerated)

(off label use) Nortriptyline (If patient at increased risk of

seretonergic syndrome) (off label use) 2nd Choice Gabapentin (off label use) 3rd Choice – Duloxetine (Cymbalta®) Trigeminal neuralgia H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use

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1st Choice Carbamazepine 2nd Choice Gabapentin (off label use) 3rd Choice Oxacarbazepine (off label use)

Post herpatic neuralgia 1st Choice Amitriptyline (off label use) Imipramine (If amitriptyline is not tolerated)

(off label use) Nortriptyline (If patient at increased risk of

seretonergic syndrome) (off label use) 2nd Choice Gabapentin 3rd Choice R - Lidocaine patches (Versatis®) Diabetic peripheral neuropathic pain 1st Choice Amitriptyline (off label use) Imipramine (If amitriptyline is not tolerated)

(off label use) Nortriptyline (If patient at increased risk of

seretonergic syndrome) (off label use) 2nd Choice Gabapentin +/- TCA 3rd Choice – Duloxetine (Cymbalta®) Prescribing Points  Neuropathic symptoms are characterised by a description of tingling, burning or shooting pains, there may also be allodynia (pain elicited by a non–noxious stimulus e.g. light touch) and hyperalgesia (pain that is of inappropriate severity to a noxious stimulus).  Titration should be made up to the most effective dose with consideration given to the occurrence of side effects. (See Appendix 4C). http://www.fifeadtc.scot.nhs.uk/media/2183/ff-appendix-4c.pdf  After a minimum trial period of 6-8 weeks at maximum tolerated dose the patient should be reviewed to ascertain benefits produced. Treatment should be withdrawn gradually if ineffective. Tricyclic Antidepressants (TCAs)  There is evidence that tricyclic antidepressants have analgesic efficacy in a variety of chronic pain syndromes and their use should be considered where conventional analgesics are proving of limited benefit in the chronic situation.  Tricyclic antidepressants (TCAs) appear to be more effective than other classes of antidepressants. Amitriptyline has been the most studied but nortriptyline has similar benefits and may be chosen in an attempt to avoid side–effects such as sedation.  Patients should be warned of likely side–effects with TCAs and that unlike conventional analgesics, the TCAs may have to be taken regularly for 4–6 weeks before the full analgesic effect may be apparent.  The analgesic effect of amitriptyline is attained at a lower dose (<75mg) than that required to treat depression.  Laxatives should be considered for patients receiving regular amitriptyline.

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 Amitriptyline should be used with caution in the elderly and be avoided in patients with cognitive impairment. It should also be avoided in patients with cardiac disease, glaucoma or prostatic hypertrophy. Gabapentin  Gabapentin tablets are substantially more expensive than the capsules. When prescribing use the most cost effective strength and formulation.  Amitriptyline and gabapentin can be used as a combination if pain is severe and refractory.  Patients should be warned of likely side–effects and that, unlike conventional analgesics, gabapentin may have to be taken regularly for 4–6 weeks before the full analgesic effect is appreciated.  Prescribers should be alert to the abuse potential of gabapentin. Trigeminal neuralgia  Trigeminal neuralgia is a very painful condition and may require rapid titration of dose. At a 1st presentation, patients should be referred to neurology for assessment. Lidocaine Patches  R - Lidocaine 5% plaster (Versatis®) is approved for restricted use when initiated/recommended by a pain specialist in post herpetic neuralgia or for other localised neuropathic pain. Versatis® is more expensive than other products used in post herpetic neuralgia. Restricted to patients who are intolerant of first line therapies or where these therapies have been ineffective. Versatis® should be discontinued if there is no evidence of response after 4 weeks of treatment. Pregabalin  Pregabalin may be prescribed for peripheral neuropathic pain, if first and second line treatments have failed or the patient is unable to tolerate them. Discontinue if there is no therapeutic benefit after an eight week trial. All strengths of capsules are the same cost; therefore ensure the correct strength of capsule is prescribed i.e. 300mg rather than 2x 150mg.  R - Pregabalin oral solution can be used as an alternative to capsules in patients with swallowing problems. The oral solution can be considered for 2nd line use only in patients unable to swallow gabapentin tablets/capsules.  Prescribers should be alert to the abuse potential of pregabalin. Duloxetine  3rd line treatment option for patients with fibromyalgia, particularly in patients with low mood where1st and 2nd line choices (tricyclics, gabapentin respectively) have been ineffective, not tolerated or are considered inappropriate. Initiation would be restricted to/or on the advice of a specialist. 4.7.4 Antimigraine drugs Also see SIGN 107 - Diagnosis and Management of Headache in Adults. www.sign.ac.uk/guidelines/fulltext/107/index.html 4.7.4.1 Treatment of acute migraine attack Step 1 Aspirin Ibuprofen Naproxen Paracetamol H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use

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Anti-emetic 1st Choice Metoclopramide 2nd Choice Domperidone Prescribing Points  Any analgesic product used for a prolonged period of time has the potential to cause chronic overuse headache.  Treatment of a migraine attack should be guided by response to previous treatment, the severity and frequency of the attacks, other symptoms and patient preference.  An early stepped approach should be used starting with an analgesic +/- antiemetic and escalating to 5HT1 receptor antagonist (triptan) as required.  Simple oral analgesics such as aspirin, ibuprofen, naproxen or paracetamol are suitable first line agents. This medication is better taken early in the attack when absorption will be least inhibited by gastric stasis.  For rapid effect, dispersible or effervescent preparations are preferred. However, they may contain relatively large quantities of sodium chloride and are more expensive than standard preparations. They should be reserved for patients with gastric stasis or swallowing difficulties.  Suppositories may be useful for pain relief if vomiting occurs during migraine.  Opioid analgesics should not be used for acute migraine, due to the potential for development of medication overuse headache. Migraleve® products contain codeine and should not be prescribed.  Aspirin should not be given to patients under 16 years due to the risk of Reye‟s syndrome, unless specifically indicated.  Metoclopramide or domperidone tablets or suppositories may be necessary to relieve nausea, and have the advantage of promoting gastric emptying and normal peristalsis.  Metoclopramide can cause acute dystonic reactions especially in the young and the very old.  Due to risk of neurological side-effects, metoclopramide is now only licensed for limited indications and the maximum duration of treatment is 5 days in all patients. For further advice, see MHRA Drug Safety Update, August 2013 www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON300404  Domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death especially in those aged over 60 or those who take more than 30mg daily. Domperidone should be taken at the lowest effective dose, avoided in patients who are taking concomitant medication known to cause QT prolongation (such as erythromycin and ketoconazole) and used with caution in patients with underlying cardiovascular disease. (For further advice see MHRA Drug Safety Update, May 12. www.mhra.gov.uk/home/groups/dsu/documents/publication/con152742.pdf)

Step 2 5HT1-receptor agonists 1st Choice Sumatriptan 2nd Choice Rizatriptan Prescribing Points  Triptans should be reserved for patients resistant to simple analgesics +/- antiemetic therapy.  Ensure the diagnosis of migraine is correct as triptans are expensive and can be ineffective in

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other types of headache.  Patient‟s characteristics and preferences vary and individual responses to a triptan cannot be predicted. Finding the most suitable therapy may involve trial and error and if the first triptan fails then switch to another. Other triptans can be used if the formulary options are not found to be effective or tolerated.  If a patient fails to responds to one triptan which has been tried for three separate migraine attacks, then an alternative triptan should be considered.  Medication should be taken as early as possible after migraine headache starts, but not during the aura phase. Headache recurrence within the first 24 hours can be treated with a second dose. If the first dose of a triptan fails to help, alternative (analgesic) medication should be considered.  Triptans are not recommended for use in those aged over 65 and are contraindicated in those with a history of cardiac disease.  Nasal zolmitriptan or subcutaneous sumatriptan should be considered in severe migraine, where vomiting precludes oral treatment or where oral triptans have been ineffective.  Overuse of triptans (more than 2 days use per week) should be discouraged due to the risk of medication overuse headache.

4.7.4.2 Prophylaxis of migraine Pizotifen Propranolol - Sodium Valproate (off label use) - Topiramate

Prescribing Points

 The aim of prophylactic therapy is to reduce the frequency, severity and duration of attacks and improve responsiveness to treatment. Acute treatment will still be required  Prophylaxis should be considered for patients who suffer at least two attacks per month, suffer an increasing frequency of headaches, suffer significant disability despite suitable treatment for migraine attacks or cannot take suitable treatment for migraine attacks.  Evidence suggests that standard release preparations of propranolol are superior to modified release preparations.  Topiramate and sodium valproate may be effective for migraine prophylaxis if other treatments fail.  Sodium valproate should be avoided in women of child bearing potential due to its teratogenic risk.  Prophylaxis should be given for 6 months, then consideration given to gradual withdrawal if there has been a good response. If symptoms recur the preventive treatment should be recommenced.  Botox® is not recommended by the Scottish Medicines Consortium (SMC) for the prophylaxis of headaches in adults with chronic migraine

4.7.4.3 Cluster headache and the trigeminal autonomic cephalalgias 1st Choice Sumatriptan injection (Imigran®)

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2nd Choice Zolmitriptan nasal spray (Zomig®)(off label use)

Prescribing Points

 Oral medication is usually ineffective for acute attacks.  During a cluster headache, patients may suffer more than one attack daily and require up to 2 doses of sumatriptan in a 24 hour period.  In secondary care, patients may get rapid relief of the cluster headache by the use of oxygen. Patients should receive 100% oxygen at a flow rate of 10-12 litres/min. for 15 minutes.  Prophylaxis of cluster headache can be considered if the attacks are frequent, last for more than 3 weeks, or if the attacks cannot be treated effectively. Refer for specialist advice. 4.8 - Antiepileptics

Also see SIGN 70 - Diagnosis and Management of Epilepsy in Adults www.sign.ac.uk/pdf/qrg70.pdf Also see SIGN 81 - Diagnosis and management of Epilepsies in Children and Young People www.sign.ac.uk/pdf/qrg81.pdf Also see NICE Clinical Guidance 137 - The Epilepsies: the Diagnosis and Management of the Epilepsies in Adults and Children in Primary and Secondary Care http://www.nice.org.uk/guidance/cg137

4.8.1 Control of Epilepsies - Carbamazepine - for partial seizures and 1st Choice secondary generalised tonic-clonic seizures - Lamotrigine - for primary generalised epilepsy (including absences and myoclonus),

partial seizures, secondary generalised tonic– clonic seizures - Leviteracetam - for mycolinic seizures, focal

seizures - Sodium Valproate- for primary generalised epilepsy (including absences and myoclonus),

partial seizures, secondary generalised tonic- clonic seizures 2nd Choice

(Restricted use when 1st line choices have failed or in combination with a 1st line

choice): - Clobazam (Schedule 11 - requires ‘SLS’

endorsement on prescription) - Eslicarbazepine -Lacosamide -Topiramate 3rd Choice* (Restricted use for treatment resistant seizures or as adjuncts to other therapy): - Ethosuximide

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- Oxcarbazepine - Perampanel (Fycompa®) - Phenobarbital - Phenytoin - Primidone – Rufinamide (Inovelon®) (Lennox-Gastaut

syndrome) – Retigabine (Trobalt®) – Vigabatrin (Sabril®) (infantile spasms) – Zonisamide (Zonegran®) *may be used earlier in certain seizure types or patient groups For appropriate prescribing of anti-epileptic drugs see section below on switching between different manufacturers’ products

Prescribing Points

 All drugs for control of epilepsy should be initiated by hospital specialists only.  Antiepileptic medication should be commenced after two or more clinically definite seizures or after one seizure in a patient with a clearly epileptiform EEG or causative lesion on brain imaging. Treatment may also be considered after a single attack if the risk of a second seizure is considered to be high.  If a second seizure occurs before the patient is seen by a specialist then start an appropriate first choice agent. Phone the specialist for advice if required.  The choice of agent is determined by the epilepsy syndrome, type of seizure, other medication, co-morbidities and the age and sex of the patient.  Treatment with a single agent is preferred. A combination of drugs may be used in refractory patients.  In order to minimise side-effects It is essential to initiate anti-epileptic drugs at a low dose and titrate the dose gradually as per BNF.  When switching patients from one drug to another the dose should be reduced /increased gradually. Seek specialist advice.  Therapeutic drug monitoring should only be considered in patients where non-compliance or patient toxicity is suspected or when managing drug interactions.  In new patients, the use of M/R carbamazepine is recommended instead of standard tablets to aid compliance and minimise side-effects.  There is an increased risk of teratogenicity associated with the use of all antiepileptic drugs. This risk is increased with the use of high doses or the use of a combination of antiepileptic drugs. Women taking antiepileptic drugs who may become pregnant should be informed of the possible consequences. The risk is particular high with sodium valproate especially at high doses (>800mg daily) or when used in combination with lamotrigine.  The effectiveness of hormonal contraceptives may be considerably reduced by some antiepileptics. This should be considered when discussing choice of contraception. Switching Between Different Manufacturers’ Products for a Particular Anti-Epileptic Drug  The MHRA have divided anti-epileptic drugs into 3 categories in order to determine whether it is necessary to maintain continuity of supply of a specific manufacturer‟s products.

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 The following categories relate only to the treatment of epilepsy, it does not apply to the use of these drugs for other indications e.g. mood stabilisation, neuropathic pain.  If a patient has to be maintained on a particular product this should be prescribed by brand name or the name of the manufacturer should be stated on the prescription.  In order to maintain continuity of supply, when a specified product is unavailable, pharmacists may dispense a product from a different manufacturer if discussed and agreed with both the prescriber and patient/carer.

Category Anti-epileptic drug

Category 1 – Ensure patient is maintained on Carbamazepine, phenobarbital, phenytoin, a specific manufacturer‟s product primidone

Category 2 – Need for continued supply of a Clobazam, clonazepam, eslicarbazepine, particular manufacturer‟s product should be lamotrigine, oxcarbazepine, perampanel, based on clinical judgement and consultation retigabine, rufinamide, sodium valproate, with patient and/or carer. Taking into topiramate, zonisamide account factors such as seizure frequency and treatment history.

Category 3 – Usually unnecessary to ensure Ethosuximide, gabapentin, lacosamide, patients are maintained on a specific levetiracetam, pregabalin, tiagabine, manufacturer‟s product unless specific vigabatrin patient reason e.g. patient anxiety and risk of confusion or dosing errors.

Neuropathic Pain For the use of gabapentin and pregabalin in neuropathic pain refer to section 4.7.3. 4.8.2 Drugs used in status epilepticus Also see Paediatric Department Guideline on ‘Emergency Management of Status Epilepticus in Children’ - http://intranet.fife.scot.nhs.uk/uploadfiles/publications/Status%20Epilepticus.pdf

- Midazolam (Preferred brand Epistatus® - 1st Choice buccal, intranasal- both are unlicensed routes)

Alternative Choices - Diazepam Rectal tubes - Paraldehyde rectal (unlicensed) H - Fosphenytoin injection H - Lorazepam Injection H - Paraldehyde injection (unlicensed) H - Phenytoin injection Community setting The preferred midazolam product in NHS Fife is Epistatus®. Patients and carers are trained on the use of this product. Alternative formulations e.g. Buccolam® pre-filled syringes should not be prescribed.

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Prescribing Points

Community Setting

 Where possible, treatment should be initiated in the community prior to hospital.  A possible underlying cause (e.g. hypoglycaemia, hypoxia etc) must be considered.  The first episode of status epilepticus should be treated with buccal midazolam if available, and an ambulance should be called.  Treatment should be given if convulsion lasts longer than 5 minutes. Rectal diazepam is an alternative to buccal midazolam.  Buccal midazolam should only be initiated on the advice of a specialist in accordance with agreed local guidelines and following appropriate training of the parent or carer. It may, however, be continued to be prescribed in primary care  The preferred midazolam product in NHS Fife is Epistatus®. Patients and carers are trained on the use of this product. Alternative formulations e.g. Buccolam® pre- filled syringes should not be prescribed.  In some cases, rectal paraldehyde may be administered in the community for prolonged seizures, according to individual patient protocol.

Hospital

 If still fitting at 10 minutes and, if not already in hospital, call an ambulance. A second dose may be given sooner if resuscitation facilities are available.  If convulsion continues beyond 30 minutes (status epilepticus), patient will need hospitalisation and preferably admission to ITU.  Clobazam may be prescribed to prevent status epilepticus in patients with a previous history of status or who are known to be at risk if their seizures accelerate or begin to cluster. It may also be prescribed for those whose seizures occur or accelerate at certain times e.g. during menstruation or intercurrent infections. Prescriptions should be endorsed „SLS‟.

4.8.3 Febrile convulsions

Also see

NICE Clinical Guidance update 160 - Feverish illness in children: Assessment and initial management in children younger than 5 years http://guidance.nice.org.uk/CG160/ Midazolam (Preferred brand Epistatus® - buccal 1st Choice - unlicensed route) 2nd Choice Diazepam (rectal)

Prescribing Points

 See prescribing points above under section 4.8.2

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4.9 - Drugs used in parkinsonism and related disorders Also see SIGN guideline No. 113, Diagnosis and Pharmacological Management of Parkinson’s Disease www.sign.ac.uk/guidelines/fulltext/113/index.html ALL PATIENTS WITH SUSPECTED PARKINSON’S DISEASE SHOULD BE REFERRED FOR SPECIALIST ASSESSMENT BEFORE TREATMENT IS INITIATED. (See referral pathway on the intranet public folders - parkinsons).

General Prescribing Points

 Therapy is usually initiated with levodopa. However in younger patients (aged <70 years) dopamine receptor agonists may be used initially.  Dopamine receptor agonists, and less commonly levodopa, may cause compulsive behaviours or impulse control disorders (binge eating, pathological gambling/shopping, sexual deviancy/hypersexuality) (14-17% of patients). Patients and carers should be advised in advance of these potential adverse effects. If the patient develops an impulse control disorder, the dopamine-receptor agonist should be discontinued or the dose titrated downwards slowly, until the symptoms resolve or are manageable in the context of their overall motor control.  Patients who have suffered excessive sedation or sudden onset of sleep with dopaminergic drugs (levodopa and dopamine receptor agonists) should refrain from driving or operating machines until those effects have stopped recurring. In some individuals, these drugs may cause wakefulness and should be avoided in the evening.  Older patients are more susceptible to adverse drug effects, and thus treatment should be initiated at low doses, and increased with caution. Treatment should not be withdrawn abruptly.  Patients with PD must be encouraged to take their medication as regularly as possible, and this is particularly relevant in situations where they are not self medicating (e.g. hospital admission). Medication regimens should only be adjusted after discussion with a specialist.  In hospital settings, drugs regimes should be administered at the correct prescribed times even if they are out with normal drug rounds.  Not all strengths of drugs for Parkinson‟s disease are stocked in hospital pharmacies. Patients should be advised to bring in their own medication when being admitted to ensure continuity of treatment. 4.9.1 Dopaminergic drugs used in parkinsonism Levodopa - Co-beneldopa (Madopar®) - Co-careldopa (Sinemet®)

Prescribing Points

 To reduce the risk of nausea, levodopa therapy should be taken with food. Patients with more advanced disease may be encouraged to take before food to aid absorption and reduce motor fluctuations. Levodopa should be initiated at a low dose and increased in small steps. Dosing intervals should be chosen to suit the needs of the individual patient.  Reduction in dose of levodopa should only occur after specialist consultation and levodopa should not be withdrawn abruptly as this may lead to potentially fatal neuroleptic type syndrome.

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 Levodopa may colour urine red.  Dispersible Madopar® may be useful for patients with swallowing difficulties, or where rapid absorption is desired, for example first thing in the morning.  Modified–release formulations of levodopa are not routinely recommended. They are reserved only for nocturnal immobility and rigidity.  Co-careldopa intestinal gel (Duodopa®) is not recommended by the Scottish Medicines Consortium (SMC) for the treatment of advanced levodopa-responsive Parkinson‟s disease. An Individual Patient Treatment Request needs to be approved before prescribing. Dopamine agonists Also see :- Shared Care Protocol for Apomorphine http://www.fifeadtc.scot.nhs.uk/shared-care- protocols/scps-fife/apomorphine.aspx - Apomorphine - Pramipexole - Ropinirole – Rotigotine (Neupro®) Prescribing Points

 When prescribing pramipexole, ensure the correct dose and strength are prescribed. Pramipexole dose and strengths are stated in terms of base. See BNF.  Sudden onset of sleep can occur with dopamine-receptor agonists.  Rotigotine patches are expensive compared to tablets but may be prescribed in patients when oral therapy is unsuitable, to reduce the burden of oral medicines or when patients have significant motor fluctuations especially overnight.  Patients taking dopaminergic drugs who require an antiemetic must not be prescribed metoclopramide, prochlorperazine or cyclizine. Domperidone is the antiemetic of choice in this patient group.

 Domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death especially in those aged over 60 or those who take more than 30mg daily. Domperidone should be taken at the lowest effective dose, avoided in patients who are taking concomitant medication known to cause QT prolongation (such as erythromycin and ketoconazole) and used with caution in patients with underlying cardiovascular disease. (For further advice see MHRA Drug Safety Update, May 12 www.mhra.gov.uk/home/groups/dsu/documents/publication/con152742.pdf).  Apomorphine is a potent dopamine-receptor agonist used in patients experiencing unpredictable „off‟ periods with levodopa treatment or motor fluctuations. Patients on apomorphine should be co-prescribed long-term domperidone. Other dopaminergic agents - Selegiline - Stalevo® – COMT inhibitor) (normally prescribed as Stalevo®, but may be used as entacapone when co- prescribed with other levodopa therapy) -

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Prescribing Points

 These agents have complex drug interactions. Caution should be taken when co-prescribing with other drugs. See BNF.  Selegiline and entacapone are used in Parkinson‟s disease to reduce „end-of-dose‟ deterioration.  Selegiline should be administered in the morning as it may cause insomnia.  A buccal formulation of selegiline, (Zelapar®), produces less side effects but is considerably more expensive than the oral formulation. It should only be considered in patients with swallowing problems or intolerance of standard selegiline.  Entacapone must be used in combination with levodopa and both drugs must be taken at the same time. A combination product, Stalevo®, is available to aid concordance.  Stalevo® is only available in fixed component doses. When increasing the dose, multiple tablets can not be used. The strength of Stalevo® needs to be increased instead.  Amantadine may be useful for control of dyskinesia.

Restless Legs Syndrome

Treatments for restless leg syndrome should only be initiated by a Consultant Physician/Neurologist running Movement Disorder clinics. They can be considered in moderate to severe idiopathic restless legs syndrome (RLS) i.e. when symptoms result in significant disruption to sleep and impairment of daily living. 4.9.2 Antimuscarinic drugs used in parkinsonism - -

Prescribing Points

 These drugs should not be prescribed for idiopathic Parkinson‟s disease.  Antimuscarinic drugs should not be used in drug-induced parkinsonism. If possible, the offending drug should be discontinued instead.  Tardive dyskinesia is not improved by antimuscarinic drugs and may be made worse.  Procyclidine can be given parenterally and is effective emergency treatment for acute drug- induced dystonic reactions.  Abrupt withdrawal of antimuscarinics must be avoided as this can pose significant clinical risk. 4.9.3 Drugs used in essential tremour, chorea, tics and related disorders Essential Tremor 1st Choice Propranolol (standard tablets) 2nd Choice - Primidone

Prescribing Points

 Propranolol is the drug of choice for tremor associated with anxiety or thyrotoxicosis.  Primidone is a suitable alternative where a beta blocker is contraindicated or not tolerated.

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Intractable Hiccups

Also see:-

NHS Fife Palliative Care Guidelines http://www.fifeadtc.scot.nhs.uk/guidance-documents/fife- wide-palliative-care.aspx

Chlorpromazine Haloperidol

Prescribing Points

 Chlorpromazine has a high risk of photosensitivity Torsion dystonias and other involuntary movements - Botulinum A toxin (Botox®)

Prescribing Points

 There are several brands of botulinum A toxin available. They are not interchangeable and doses are specific to individual preparations. The NHS Fife preferred brand is Botox®.  Botox® is not recommended by the Scottish Medicines Consortium (SMC) for the prophylaxis of headaches in adults with chronic migraine, for use in focal lower limb spasticity associated with stroke nor for the temporary improvement in the appearance of moderate to severe vertical lines between the eyebrows seen at frown (glabellar lines).

4.10 - Drugs used in substance dependence Also see :- NHS Fife Addiction Service Guidelines http://www.fifeadtc.scot.nhs.uk/guidance-documents.aspx

4.10.1 Alcohol dependence Also see :-

SIGN 74 - Management of Harmful Drinking and Alcohol Dependence in Primary Care www.sign.ac.uk/guidelines/fulltext/74/index.html

NICE Clinical Guidance 100 - Alcohol-use disorders: Diagnosis and clinical management of alcohol-related physical complications http://publications.nice.org.uk/alcohol-use-disorders-diagnosis-and-clinical-management-of- alcohol-related-physical-complications-cg100 NICE Clinical Guidance 115 - Alcohol Dependence and Harmful Alcohol Use www.nice.org.uk/guidance/CG115

Alcohol detoxification

Also see:- NHS Fife Addiction Service Guideline A5 http://www.fifeadtc.scot.nhs.uk/media/7041/a5- guidelines-for-detoxification-of-people-with-alcohol-dependence-in-the-community-final-april- 2011.pdf H – Hospital Use Only S – Specialist Initiation or Recommendation R – Restricted Use

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Chlordiazepoxide

Prescribing Points

 Alcohol dependent patients exhibiting moderate to severe withdrawal features or those assessed at high risk of developing severe withdrawal symptoms should be prescribed benzodiazepines for detoxification.  Chlordiazepoxide in a tapered dosing regime over a period of 5 to 10 days is recommended (See Guideline A5).  For short term use only - there is no role for long term prescribing of chlordiazepoxide in alcohol dependence.  Benzodiazepines should not be prescribed if the patient is likely to drink alcohol concomitantly.

Vitamin Supplementation Also see:- NHS Fife Addiction Service Guideline A9 http://www.fifeadtc.scot.nhs.uk/media/7038/a9- alcohol-dependence-inpatient-management-of-alcohol-withdrawal-final-april-2011-.pdf - Pabrinex® Thiamine Prophylaxis of Wernicke–Korsakoff syndrome: Pabrinex® Treatment of patients with Wernicke–Korsakoff syndrome (hospital in–patients): Pabrinex® Poor diet in patients who are alcohol dependent but not at risk of Wernicke-Korsakoff syndrome: Thiamine

Prescribing Points

 Patients with any sign of Wernicke–Korsakoff syndrome must be given treatment doses of Pabrinex® in hospital. Signs include confusion, ataxia, ophthalmoplegia/nystagmus, memory disturbance, hypothermia and hypotension, coma/unconsciousness.  Prophylactic doses of Pabrinex® should be given to patients at any risk of Wernicke–Korsakoff syndrome e.g. those with recent diarrhoea, vomiting, poor diet, other physical illness or signs of weight loss or malnutrition.  Patients with a chronic alcohol problem and whose diet is deficient should be given oral thiamine 50mg three times daily indefinitely.  Vitamin B compound strong tablets are not recommended for use in alcohol misuse patients due to lack of evidence of efficacy.

Alcohol relapse prevention Also see:- NHS Fife Addiction Service Guideline A11 http://www.fifeadtc.scot.nhs.uk/guidance- documents/addiction-services/guidance-for-the-use-of-unlicensed-and-off-label-medication- within-nhs-fife-addiction-services.aspx - Acamprosate (Campral EC®) + counselling

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- Disulfiram (Antabuse®)+counselling - Naltrexone +counselling R - Nalmefene (Selincro®) +psychosocial

support

Prescribing Points

 Relapse prevention medication should be considered only after the patient has been fully assessed, undergone alcohol detoxification and are motivated to prevent relapse with psychosocial interventions assisted by medication.  Acamprosate reduces the risk of relapse by suppressing the “urge to drink” in response to learned triggers. It should be initiated as soon as possible after detoxification and if assessed to be effective (i.e. there is a major reduction in drinking) continued for a minimum of 6 months. Treatment with acamprosate should not be stopped if there is a minor relapse. Treatment may be continued longer term with regular reviews every six months.  Disulfiram is used as a deterrent by triggering an unpleasant reaction if alcohol is consumed. It is only effective if taken daily. Even small amounts of alcohol which may be included in liquid medicines or mouthwashes may precipitate a reaction. Alcohol should be avoided for at least 1 week after stopping treatment.  For patients successfully maintaining abstinence with disulfiram treatment should be continued for a minimum of 6 months but may be continued longer-term with regular reviews every 6 months.  Consumption of disulfiram should be witnessed or supervised by a spouse, friend, healthcare or support worker. There is no evidence supporting unsupervised consumption.  Naltrexone is used as an adjunct in patients to prevent relapse, after successful withdrawal. Use is restricted to patients with no history of liver problems, substance misuse or opioid dependence. Patients should be reviewed at least every 6 months. (See Guideline A11 for further advice).  For the use of oral baclofen in relapse prevention - See Guideline A11. http://www.fifeadtc.scot.nhs.uk/guidance-documents/addiction- services/guidance-for-the-use-of-unlicensed-and-off-label-medication-within-nhs- fife-addiction-services.aspx Nalmefene  R – Nalmefene is approved for restricted use by addiction services only for the reduction of alcohol consumption in patients who have a high drinking risk level without physical withdrawal symptoms, and who do not require immediate detoxification. It should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption.  Before initiating treatment, prescribers should evaluate the patient‟s clinical status, alcohol dependence, and level of alcohol consumption. Nalmefene should only be prescribed for patients who continue to have a high drinking risk level two weeks after the initial assessment.  During treatment, patients should be monitored regularly and the need for continued treatment assessed. Caution is advised if treatment is continued for more than 1 year.

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4.10.2 Nicotine Dependence Also see Appendix 4D - NHS Fife Stop Smoking Guidance – http://www.fifeadtc.scot.nhs.uk/media/2273/4d-smoking-cessation-guidance.pdf Smoking cessation "A Guide to Smoking Cessation in Scotland 2010" - www.healthscotland.com/documents/4661.aspx. 1st Choice - Nicotine Replacement Therapy 1st Choice Nicotine Patches + specialist support* Nicotine Gum, Inhalator, Lozenges and Oral 2nd Choice spray 2nd Choice - Varenicline (Champix®) + specialist support** * For NRT, specialist support = NHS Fife stop smoking services, community pharmacists, specialist GP clinics. ** For varenicline, specialist support = NHS Fife stop smoking services, specialist GP clinics

Prescribing Points

General Points

 If client/patient consents, they should always be referred to specialist services for behavioural support.  Available evidence suggests that clients/patients are up to four times more likely to quit with the right combination of support and products. The client/patient must be committed and motivated to stop smoking.  Therapy to aid smoking cessation is chosen according to the smoker‟s preference; previous experience of smoking-cessation products; contra-indications and adverse effects of the products and product costs.  Initial prescriptions should be sufficient to last two weeks.  NRT/ varenicline should be prescribed as acute prescriptions and must not be added to repeats.  Smokers with diabetes should be advised to monitor their blood sugar levels more closely than usual when attempting to quit smoking.

Nicotine Replacement Therapy (NRT)

 The aim of NRT is to reduce usage over 8-12 weeks as per product information. If clients/patients require treatment beyond 12 weeks they should be referred to specialist stop smoking services for further support and advice.  NRT prescribing should not start until the client/patient has agreed to a „stop date‟.  "Cutting down to quit" using NRT is not supported by NHS Fife. Clients/patients wishing to reduce smoking in this manner should purchase their own NRT.  The nicotine patch should be considered the 1st line choice in patients with a stable smoking pattern.  Immediate -release NRT formulations e.g. gum, inhalator, lozenges or oral spray should only

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be prescribed - . if the client/patient has an irregular smoking pattern . the patch is unsuitable . previous failure with the patch . the patch is not preferred by the client/patient . if the client/patient wishes to actively take control of the nicotine cravings . where appropriate, as part of combination therapy  The use of immediate release NRT, as monotherapy, in patients with high nicotine dependence (>20 cigs. /day) can be relatively expensive.  Clients/patients with a high level of nicotine dependence or those who have failed with NRT previously may benefit from using a combination of a patch + an immediate release NRT formulation.  Combination therapy should be reviewed at least every 4 weeks post-quit to see if both products are still required. Combination therapy should not be continued long-term.  NRT is not licensed to be used in combination with varenicline or bupropion.  NRT should be prescribed as 4 week prescriptions. Consider annotating prescription either as “Dispense weekly” or as “Dispense fortnightly”.

Use of NRT during Pregnancy/Breastfeeding

 Ideally, pregnant women should stop smoking without using NRT but if this is not possible, NRT may be recommended to assist a quit attempt. The aim should be to discontinue NRT use after 2-3 months.  Intermittent forms of NRT are preferable during pregnancy although a patch may be appropriate if nausea and/or vomiting are a problem. If patches are used then the 16 hour patch is preferred. Referral to Quit 4 Life is recommended.  NRT can be used by women who are breastfeeding. NRT products taken intermittently are preferred as their use can be adjusted to allow the maximum time between their administration and feeding of the baby, to minimize the amount of nicotine in the milk. Referral to Quit 4 Life is recommended.

Varenicline

 Varenicline should only be used as part of a programme of behavioural support following a comprehensive assessment. Clients/patients wishing to use varenicline should be referred to specialist support if they consent.  Varenicline has been associated with suicidal behaviour. Clients/patients should be advised to discontinue varenicline and seek prompt medical attention if they develop signs of agitation, depressed mood or suicidal thoughts. Clients/patients with a history of psychiatric illness should be monitored closely while taking varenicline.  Varenicline is not licensed for use in those aged less than 18 years of age and should also be avoided in pregnancy and during breastfeeding.  Varenicline is a „black triangle‟ drug, all adverse drug reactions should be reported to the MHRA.  Varenicline is only recommended in clients/patients who have previously failed at least one

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recent quit attempt (within the last 12 months) with appropriate use of NRT.  Varenicline should be prescribed as 4 week prescriptions, consider annotating “Dispense Fortnightly”. Set target stop date within the first two weeks of treatment, preferably in the second week.  Clients/patients who have been taking varenicline for greater than 21 days and are still smoking should be re-assessed for their motivation to stop smoking. Varenicline should be discontinued.  Varenicline should only be prescribed for a maximum of 12 weeks. The benefits of treatment beyond 12 weeks appear modest (Scottish Medicines Consortium).  Based on average usage figures, a 12-week course of varenicline is more expensive than NRT monotherapy.  Varenicline is not licensed for use in combination with NRT. 4.10.3 Opioid dependence Also see NHS Fife Addiction Service Guidelines http://www.fifeadtc.scot.nhs.uk/guidance- documents.aspx

Also see Royal College of General Practitioners Guidance - Guidance for the use of Methadone for the Treatment of Opioid Dependence in Primary Care. www.smmgp.org.uk/download/guidance/guidance015.pdf

Also see Drug Misuse and Dependence UK Guidelines on Clinical Management. http://www.nta.nhs.uk/uploads/clinical_guidelines_2007.pdf

Also see NICE Clinical Guidance 52 - Drug Misuse – Opioid Detoxification http://publications.nice.org.uk/drug-misuse-opioid-detoxification-cg52 Opioid detoxification Also see NHS Fife Addiction Service Guideline A2, A3 http://www.fifeadtc.scot.nhs.uk/media/7020/a2- procedure-for-community-detoxification-using-lofexidine-final-april-2011.pdf http://www.fifeadtc.scot.nhs.uk/media/7017/a3-guidelines-for-detoxification-using-buprenorphine-final-april- 2011.pdf

Buprenorphine/naloxone (Suboxone®) - Lofexidine (BritLofex®) Methadone 1mg/ml oral solution

Prescribing Points

 Patients with specific symptoms of opioid withdrawal, such as diarrhoea, nausea/vomiting or colic can be treated with loperamide, metoclopramide, hyosine butylbromide, mebeverine and non steroidal anti-inflammatory drugs (NSAIDs) if required.

Opioid maintenance prescribing Also see NHS Fife Addiction Service Guideline A7, A8 http://www.fifeadtc.scot.nhs.uk/media/12771/a7-guidelines-for-the-titration-on-to-buprenorphine-for-opioid- dependence-final-april-2011.pdf http://www.fifeadtc.scot.nhs.uk/media/7035/a8-guideline-for-methadone-titration-in-opioid- dependence-final-april-2011.pdf

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Buprenorphine/naloxone (Suboxone®) Methadone 1mg/ml oral solution

Prescribing Points

 Prescriptions should be considered only after the patient has been fully assessed and has shown evidence of opioid dependence and motivation to address their opioid misuse.  Titration of methadone or buprenorphine should be undertaken as per Guidelines A7 and A8. Tolerance testing (Guideline A1) should be undertaken by the specialist service only.  An ECG should be undertaken before dose titration above 100mg of methadone.  Methadone and buprenorphine should be taken daily, under supervision, generally for at least the first 3 months.  Take-home doses should not normally be prescribed where: . a patient has not reached a stable dose . the patient shows a continued and unstable pattern of drug misuse, including a significant increase in alcohol intake, the use of illicit drugs, benzodiazepines or other tranquillisers . the patient has a significant, unstable psychiatric illness or is threatening self-harm . there is continuing concern that the prescribed medicine is being, or may be, diverted or used inappropriately . there are concerns about the safety of medicines stored in the home and possible risk to children.  Sugar-free methadone should only be prescribed in individuals with confirmed diabetes. Syrup based methadone is not the primary cause of dental caries.  Buprenorphine/naloxone (Suboxone®) should only be prescribed if heroin or other opioid intake is equivalent to 30mg methadone or less.  For patients prescribed buprenorphine preparations, liver function tests should be undertaken at baseline and at regular interval throughout treatment.  Naloxone is an opioid-receptor antagonist used to reverse opioid overdose. Patients dependant on opioids and their carers may be given a supply of naloxone to be used in case of accidental overdose. Patients and carers should undergo overdose recognition, basic life support and naloxone training in advance of receiving supply.

Missed doses

 Patients who miss 3 days or more of their regular prescribed dose of opioid maintenance therapy are at risk of overdose because of loss of tolerance. Consider reducing the dose in these patients.  If the patient misses 5 or more days of treatment, an assessment of illicit drug use is also recommended before restarting substitution therapy; this is particularly important for patients taking buprenorphine, because of the risk of precipitated withdrawal. Opioid relapse prevention - Naltrexone

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Prescribing Points

 Liver function tests should be checked prior to initiation and monitored during treatment.  Patient should carry an emergency medical card with them.

Reversal of Opioid Overdose S – Naloxone (Prenoxad®)

Prescribing Points

 Naloxone (Prenoxad®) is approved for emergency use in the home or other non-medical settings for the complete or partial reversal of respiratory depression due to a suspected opioid overdose. Patients /carers must receive adequate training in the use of Prenoxad®.

 To arrange suitable training for patients/carers GPs should contact the Naloxone Co-ordinator on 01592 716446.

Acute benzodiazepine detoxification symptoms Also see:- NHS Fife Addiction Service Guideline A12 http://www.fifeadtc.scot.nhs.uk/media/7023/a12- guidelines-for-benzodiazepine-prescribing-in-benzodiazepine-dependence-final.pdf

Diazepam

Prescribing Points

 Long term benzodiazepine prescribing is discouraged. There are no licensed indications for the prescribing of benzodiazepines for more than 2-4 weeks.  Patients prescribed other benzodiazepines should be converted to diazepam using the benzodiazepine dose equivalent chart (see Guideline A12, appendix 5). Only diazepam 5mg and 2mg tablets should be prescribed to minimise diversion (10mg diazepam tablets have a higher street value). No combination benzodiazepine prescribing should be offered (e.g. nitrazepam + diazepam).  There is no role for the use of the „z drugs‟ e.g. zopiclone, zolpidem in benzodiazepine detoxification. Benzodiazepine Maintenance prescribing Also see:- NHS Fife Addiction Service Guideline A12 http://www.fifeadtc.scot.nhs.uk/media/7023/a12- guidelines-for-benzodiazepine-prescribing-in-benzodiazepine-dependence-final.pdf

Diazepam Prescribing Points

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 Routine prescribing of benzodiazepines in substance misuse is not recommended. Specialist advice should be sought.  The use of benzodiazepines to treat short term mild anxiety is inappropriate and unsuitable. Benzodiazepines may be used short-term to treat anxiety or insomnia that is severe, disabling or subjecting the individual to unacceptable distress.  Only diazepam 5mg and 2mg tablets should be prescribed to minimise diversion (10mg diazepam tablets have a higher street value.  No combination benzodiazepine prescribing should be offered (e.g. nitrazepam + diazepam).  There is no role for the use of the „z drugs‟ e.g. zopiclone, zolpidem as an alternative to benzodiazepine maintenance prescribing. 4.11 - Drugs for dementia Also see:- Fife Shared Care Protocol - Acetylcholinesterase Inhibitors and Memantine http://www.fifeadtc.scot.nhs.uk/media/8535/cholinesterase-guidlines.pdf NICE MTA 217 - Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease http://publications.nice.org.uk/donepezil-galantamine-rivastigmine-and- memantine-for-the-treatment-of-alzheimers-disease-ta217

Mild to moderate 1st Choice - Donepezil - Galantamine 2nd Choice - Rivastigmine Moderate only if Acetylcholinesterase (AChE) inhibitors are not tolerated or

contraindicated) - Memantine Severe - Memantine Prescribing Points

 A patient self help guide on memory problems is available at http://www.moodcafe.co.uk/media/24604/Coping%20with%20Memory%20Problems.pdf  Benefit is assessed by repeating the cognitive assessment at around 6 months. If the drug has not been effective then it should be discontinued and an alternative considered instead.  Patients who continue on treatment should be reviewed regularly by the patient‟s GP. The GP should seek specialist advice if there any concerns about the patient‟s care or if there are concerns about ongoing benefit with the medication.  Acetylcholinesterase (AChE) inhibitors (donepezil, galantamine or rivastigmine) may be prescribed for the management of mild to moderate Alzheimer‟s disease and for people with dementia with Lewy bodies who have non-cognitive symptoms that cause significant distress to the individual.  If prescribing an AChE inhibitor, treatment should normally be started with the drug with the lowest acquisition cost. However, an alternative AChE inhibitor could be prescribed if it is considered appropriate when taking into account adverse event profile, expectations about adherence, medical comorbidity, possibility of drug interactions and dosing profiles.  Donepezil is available as an orodispersible tablet for patients who experience difficulty in

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swallowing oral tablets.  Galantamine is available as an oral solution for those with swallowing difficulties or as a modified release capsule for once daily administration to aid compliance.  Rivastigmine may also be used in the treatment of dementia in Parkinson‟s disease. It is available as a liquid preparation and as a transdermal patch for patients who have difficulty with oral administration.

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