4. Central Nervous System

Transcription

1 4. Central Nervous System 1 For further advice on mental health issues see NHS Fife website Hypnotics and anxiolytics Hypnotics Non-drug treatment e.g.sleep hygeine Drug treatment Zopiclone Temazepam Nitrazepam 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 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 Patients who have been on a benzodiazepine for many years can be switched to diazepam and the diazepam then be slowly withdrawn (See withdrawal protocol BNF section 4.1.).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 S - Chloral Hydrate

2 2 Reserved for paediatric patients. Melatonin S - Melatonin 3mg tablets (Bio-melatonin ) (Unlicensed) 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 Anxiolytics For further advice on anxiety disorders see NHS Fife website Acute anxiety Diazepam (long acting) Lorazepam (short acting) Chlordiazepoxide(long acting) Patient self help guides on anxiety problems are available at 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

3 3 patients with impaired liver function and in the elderly. Other drugs for acute anxiety Anxiety Disorders Also see - Propranolol (standard tablets) Used to relieve the physical symptoms of anxiety e.g. palpitations and tremor. Long acting propranolol preparations are more expensive than standard tablet formulations. NICE CG Generalised Anxiety Disorder and Panic Disorder (with or without Agoraphobia), January NICE CG 31 - Obsessive-Compulsive Disorder, November NICE CG 26 - Post-Traumatic Stress Disorder, March Citalopram +/- psychological Fluoxetine therapies Sertraline Clomipramine +/- psychological Venlafaxine therapies 3rd Choice Pregabalin +/- psychological therapies 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. Pregabalin is approved for restricted 3 rd line use in 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. 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.

4 Drugs used in psychoses and related disorders Also see :- Appendix 4A - Guidance on Drug Treatment of Schizophrenia in Patients 18 Years and Over NICE Clinical Guidance 82 - Schizophrenia: Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care. March For prescribing in pregnancy refer to the UK Teratology Information Service Antipsychotic drugs General 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 - MH)%20%20More%20than%20one%20antipsychotic%20Approved%20June% pdf Antipsychotics vary in their side effect profile and this will influence choice of therapy. See Appendix 4A - Guidance on Drug Treatment of Schizophrenia. 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 hyperand 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, comorbidity, 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

5 5 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. S - Chlorpromazine S - Olanzapine S - Risperidone S - Amisulpride S - Aripiprazole (Abilify ) S - Haloperidol S Quetiapine (standard tablets) 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. S Clozapine (Zaponex ) 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

6 6 of relapse (on starting or increasing smoking) or toxicity (on stopping or reducing smoking) Antipsychotic depot injections First Generation S - Flupentixol decanoate (Depixol ) S Fluphenazine decanoate S - Haloperidol decanoate (Haldol ) S - Pipotiazine palmitate (Piportil Depot ) S - Zuclopenthixol decanoate (Clopixol ) Second Generation S - Risperidone (Risperdal Consta ) S - Paliperidone (Xeplion ) S - Aripiprazole (Abilify Maintena ) 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 1 st 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. 2 nd Generation Antipsychotics 2nd generation antipsychotic depot injections are substantially more expensive than and there is no evidence of better efficacy compared to 1 st 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.

7 Antimanic drugs Also see Lithium Shared Care Protocol and Information for GPs SIGN Guideline No. 82. Bipolar Affective Disorder. May SIGN Guideline 127 Management of Perinatal Mood Disorders, March NICE Clinical Guideline 38 - Bipolar disorder: The management of bipolar disorder in adults, children and adolescents, in primary and secondary care, July For prescribing in pregnancy refer to the UK Teratology Information Service S Lithium (Prescribe by brand name only, preferred brand is Priadel ) S - Semisodium valproate (Depakote ) S - Sodium valproate (off label use) 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 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

8 8 consequences and be provided with appropriate contraceptive advice. Valproate should not be prescribed routinely in women of child bearing potential Antidepressant drugs Also see Appendix 4B: Guidance on the use of pharmacological agents for the treatment of depression SIGN guideline 114, Non-pharmaceutical management of depression in adults, January 2010 SIGN Guideline 127 Management of Perinatal Mood Disorders, March NICE Clinical Guideline No. 90 Depression in Adults (Update) Oct 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 General Antidepressant drugs should not be used for initial treatment in mild depression as the riskbenefit 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

9 9 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. 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 Tricyclic and related antidepressant drugs Amitriptyline (neuropathic pain) Clomipramine (phobia and obsessional states) Imipramine Lofepramine Nortriptyline (neuropathic pain) Trazodone 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) Monoamine-Oxidase Inhibitors (MAOIs) Initiated by specialists only Selective Serotonin Re-Uptake Inhibitors (SSRIs) Citalopram Fluoxetine Sertraline

10 10 SSRIs are generally better tolerated than tricyclics. Tolerance to the main gastrointestinal sideeffects 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 Other Antidepressant Drugs Mirtazapine Venlafaxine(standard tablets, M/R capsules) 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

11 11 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 CNS Stimulants and drugs used for ADHD Also see:- NHS Fife Shared Care Protocol - Children with Attention Deficit Hyperactivity Disorder (ADHD) - Atomoxetine, Methylphenidate SIGN Management of attention deficit and hyperkinetic disorders in children and young people NICE Clinical Guidance 72 - Attention deficit hyperactivity disorder: Diagnosis and management of ADHD in children, young people and adults Attention Deficit Hyperactivity disorder (ADHD) S - Methylphenidate - standard tablet, M/R- M/R product should be prescribed by brand name Concerta XL, Equasym XL, Medikinet XL S Atomoxetine (Strattera ) S Lisdexamfetamine (Elvanse ) 3rd Choice S - Dexamfetamine 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

12 12 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 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 2 nd 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 1 st line in patients where drug diversion is a concern or if substance misuse is also an issue. Lisdexamfetamine is recommended 2 nd line in patients who do not respond to methylphenidate as an alternative stimulant. Dexamfetamine should normally be used 3 rd line in patients where methylphenidate or atomoxetine are unsuitable. Melatonin S - Melatonin 3mg (Bio-Melatonin ) (Unlicensed) 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 S Modafinil (Provigil ) 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 Drugs used in treatment of obesity Also see

13 13 SIGN Clinical Guideline Management of Obesity Diet and lifestyle changes Orlistat (Xenical ) 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 Drugs used in nausea and vertigo Also see National Palliative Care Guidance Cyclizine Domperidone* Haloperidol Hyoscine hydrobromide Levomepromazine Metoclopramide** Prochlorperazine H - Aprepitant (Emend ) S - Ondansetron Choices for specific indications Chemotherapy Induced Highly emetogenic S - Ondansetron H - Aprepitant (Emend ) Moderately emetogenic S - Ondansetron

14 14 Mildly emetogenic Domperidone* Domperidone* Motion Sickness N&V in Migraine Opioid Induced OTC treatment from pharmacy Cyclizine Metoclopramide** Domperidone* 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. 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 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 antiemetic 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 in patients with severe hepatic impairment. (For further advice see 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

15 15 (see palliative care guidance). Cyclizine is the recommended 1 st 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 1 st 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. Ondansetron and other 5HT 3 antagonists are prescribed in the 1 st week after chemotherapy but thereafter if N&V are difficult to control without use of 5HT 3 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 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 Analgesics Also see:- Appendix 4C - Management of Chronic Non-Malignant Pain Acute Pain Guidelines

16 16 SIGN Diagnosis and Management of Headache in Adults NICE Clinical Guidance 88 - Low back pain NICE Clinical Guidance 59 - Osteoarthritis British Pain Society s Opioids for persistent pain: Good Practice Non- Opioid analgesics and compound analgesic preparations The WHO Analgesic Ladder is widely regarded as being the best approach to the medical management of pain, whether it is acute, chronic non-malignant or chronic malignant pain. When considering titrating to strong opioids, refer to the British Pain Society s Guidance on Good Practice. 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 ) 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

17 17 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 (See restricted list on ADTC website). Compound analgesic preparations 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) Up to 10% of the population have poor or absent metabolism of codeine resulting in a reduced or absent analgesic effect. The use of low strength compound analgesics, e.g. co-codamol 8/500, 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 Opioid analgesics Weak Opioids Strong Opioids 3rd Choice Codeine Phosphate (as co-codamol 15/500, 30/500) Tramadol oral Morphine sulphate (including parenteral preparations)(zomorph is preferred M/R preparation) Oxycodone (Oxynorm -immediate release,oxycontin M/R are preferred oral preparations) S - Fentanyl patches (Matrifen ) Palliative care initiation only S - Fentanyl sublingual tablets (Abstral )- Palliative care initiation only S - Fentanyl nasal spray (Pecfent ) Palliative care initiation only Diamorphine

18 18 Tramadol injection R- Oxycodone 50mg/ml inj (Oxynorm ) R- Cyclimorph R- Pethidine Weak opioids Strong opioids Up to 10% of the population have poor or absent metabolism of codeine resulting in a reduced or absent analgesic effect. Tramadol may be more effective in this patient group. Tramadol should be considered 2 nd line after co-codamol 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. 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 on the Pain Society website, 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 2 nd line choice strong opioid for patients with severe non-malignant pain in whom morphine is ineffective or not tolerated.

19 19 Oxycodone preparations should always be prescribed by brand name. Oxynorm is the preferred immediate release preparation and Oxycontin 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 3 rd 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 Neuropathic Pain/ Adjuvants See Appendix 4C: Guidance on Chronic Pain Management: Neuropathic Pain 3rd Choice Trigeminal neuralgia 3rd Choice Post herpatic neuralgia Amitriptyline (off label use) Nortriptyline (If amitriptyline is not tolerated) (Off label use) Gabapentin Pregabalin Carbamazepine Gabapentin (off label use) Oxacarbazepine (off label use) Amitriptyline (off label use) Nortriptyline (If amitriptyline is not tolerated) (off label use) Gabapentin 3rd Choice Lidocaine patches (Versatis )

20 20 Diabetic peripheral neuropathic pain Amitriptyline (off label use) Nortriptyline (If amitriptyline is not tolerated) (off label use) Gabapentin +/- TCA 3rd Choice S Duloxetine (Cymbalta ) 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). 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. 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 1 st presentation, patients should be referred to neurology for assessment.

21 21 Lidocaine Patches Pregabalin Lidocaine 5% medicated plaster may be used topically for the treatment of post-herpetic neuralgia, in those patients who are intolerant of 1 st /2 nd -line systemic therapies or where these therapies have been ineffective. Benefits of lidocaine patches are apparent within the 1 st week. If there is no patient benefit within one week then the patches should be stopped and the patient reviewed. 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. Prescribers should be alert to the abuse potential of pregabalin Antimigraine drugs Also see SIGN Diagnosis and Management of Headache in Adults Treatment of acute migraine attack Step 1 Aspirin Ibuprofen Naproxen Paracetamol Anti-emetic Metoclopramide Domperidone 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 5HT 1 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.