Chapter 4 Central Nervous System

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1 Chapter 4 page number 1 Chapter 4 Central Nervous System First line drugs Drugs recommended in both primary and secondary care Second line drugs Alternatives (often in specific conditions) in both primary and secondary care Specialist initiated drugs Secondary care, authorised independent prescribers or GPs with special interest initiation. Suitable for continuation by primary care. Shared care agreements may be applicable. Secondary care only drugs Drugs only suitable for secondary care use and initiated by appropriate team or specialist. Primary care prescribers should not be asked to prescribe. Primary & Secondary Care Notes Secondary Care Within this chapter drugs are listed under more than one section depending on their specific use. They may be colour coded differently and there may be different requirements for use. For the introduction of new drugs within Avon and Wiltshire Mental Healthcare Partnership (AWMHP), please refer to the formulary pages of AWMHP s internet site or hard copies are available on request. General Principles of drug therapy within the mental health setting. Use non-drug interventions where appropriate. Use the least number of drugs at lowest possible dose compatible with optimal well-being. Discuss in detail treatment goals and likely duration of therapy with patient. When more than one drug from the same class is considered clinically appropriate, the drug with the lowest cost should be prescribed. Choices in the formulary reflect this. Drugs with the higher cost should only be prescribed second line if patients are experiencing adverse effects. NICE has recommended this specifically for hypnotics and atypical antipsychotics. See NICE Appraisal TA77 (1) 4.1 Hypnotics and anxiolytics Short-term use while an inpatient may be appropriate but, in these instances, the patient should not be discharged on sleeping aids. Patients who have not responded to a particular hypnotic drug should not be prescribed alternatives. (1). CSM advice Hypnotics and anxiolytics are indicated for the short-term relief (two to four weeks) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress. Treatment may be solely for anxiety or anxiety in association with insomnia, short-term psychosomatic, organic or psychotic illness. The use of benzodiazepines to treat short-term mild anxiety is inappropriate and unsuitable, the only exception being in the palliative care setting. Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or causing the patient extreme distress. For management of management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder), see NICE CG 113 (2) Hypnotics

2 Chapter 4 page number 2 Zopiclone Zolpidem Temazepam Promethazine Hydrochloride Chloral Hydrate Melatonin Preferred in the elderly. See NICE TA77 See NICE TA77 Reserved for use in patients who wake in the night and require a hypnotic to get back to sleep. Review treatment after two weeks. ONLY for use in existing patients or, as liquid, in those unable to swallow other hypnotics. For treatment of side effects or to limit benzodiazepine use. Paediatrics only For epileptic adults with insomnia. Please note: ONLY licensed Circadin 2mg MR tablets may be prescribed. Melatonin in children ONLY for initiation and ongoing prescription by specialist in paediatrics/camhs patients. Please note Alimemazine has been removed from 3Ts Formulary, as it is prohibitively expensive. Prescribers are asked to utilise other formulary options Anxiolytics For use in epilepsy, see section 4.8 and, for use in palliative care, see Prospect Hospice Palliative Care Handbook (7 th Edition). Discuss treatment options with the patient and offer non drug interventions where appropriate. Use should be limited to short term as needed treatment when other methods (psychological and pharmacological) are proving ineffective. (2) NICE recommends that, when benzodiazepine are used for immediate management of anxiety, treatment should be for no longer than 2 4 weeks. See NICE guideline CG 113 (2) Some antidepressants are also licensed for use in anxiety (see SSRIs). Diazepam For short term use in anxiety or insomnia.. Max. 4-week course. For use as antispasmodic, see Musculoskeletal Chapter For substance misuse, see section Lorazepam Half the adult dose for elderly or debilitated patients. Buspirone For management of GAD Specialist initiation only Barbiturates these are not recommended for use as an anxiolytic 4.2 Drugs used in psychoses and related disorders

3 Chapter 4 page number Antipsychotic drugs (see section for treatments of drug induced parkinsonism) New psychotic illness should be referred to the appropriate assessment team promptly. Tel: (If > 16 years old but not for dementia patients) Swindon Crisis Team (Pager) or Devizes Crisis Team For inpatients within the acute trust, seek advice from the mental health liaison nurses (9am - 5 pm), tel: Out of hours, contact the crisis team as above. For further information regarding the Mental Health Liaison Team, please refer to the hospital intranet. See GWHNHSFT secondary care guidelines for Insomnia and Depression. For psychotic children and adolescents in the acute trust, the duty child and adolescent psychiatrist should be contacted on during normal working hours. Out of hours they can be contacted via GWH switchboard. See NICE clinical guideline CG82 (3) for detailed guidance on management of schizophrenia in primary and secondary care. Atypicals antipsychotics rarely give rise to drug induced parkinsonism, but are more likely to cause metabolic problems. For use as anti-emetics, see section 4.6. For short-term treatment of agitation and aggression in elderly patients, please see formulary- related guidelines.

4 Chapter 4 page number 4 Atypical Antipsychotics Olanzapine Quetiapine Risperidone Risperidone Aripiprazole Amisulpride Quetiapine XL For short-term treatment of agitation / aggression. ONLY for initiation on the advice of a specialist for treatment of psychosis or any other enduring mental illness. See Aripiprazole SCA. Please refer to NICE TA213 (Schizophrenia- Aripiprazole) and NICE TA292 (Bipolar disorder (adolescents)-aripiprazole). Please see NICE CG158 Conduct disorders in children and young people for further information To be initiated by consultant psychiatrist only. For use ONLY if patient has compliance issues or where twice daily dosing with immediate-release quetiapine could cause problems (e.g. supervised administration where twice daily dosing requires extra staff resources). In these circumstances, prescribers should review the need for the XL formulation at regular intervals and switch to the IR formulation as soon as clinically appropriate. See AWP letter, AWP PIL and AWP FAQs for further information. Clozapine- consultant psychiatrist initiation required. See MHRA Drug Safety Update Oct 17 for further information and advice on potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus Olanzapine Injection - for use in rapid tranquillisation (see AWMHP policy). Traditional Antipsychotics Haloperidol Caution in those with cardiac conditions. (SPC suggests carrying out an ECG before initiation) Do not use for patients suffering from Parkinson s Disease. Caution, risk of accumulation in the elderly:1.5mg starting dose. Haloperidol injection Zuclopenthixol (Clopixol Acuphase) Sulpiride Trifluoperazine Chlorpromazine tabs Please note all oral preparations of flupentixol and zuclopenthixol have been removed from formulary, but they may continue to be prescribed, as non-formulary medicines, for existing patients or in the exceptional circumstance that all other formulary options have been exhausted.

5 Chapter 4 page number Antipsychotic depot injections Patients on depot anti-psychotic injections should be reviewed regularly. Flupentixol Decanoate (Depixol ) Fluphenazine Decanoate (Modecate ) Zuclopenthixol Decanoate (Clopixol ) Haloperidol Decanoate (Haldol ) Risperidone (Risperdal Consta ) Antimanic drugs /mood stabilising drugs See NICE clinical guideline CG38 (4) for detailed guidance on the management of bipolar disorder in adults, children and adolescents in primary and secondary care.

6 Chapter 4 page number 6 Lithium Carbonate Prescribe by brand. Priadel is 1 st line. Other available brands include Camcolit and Liskonum. Note Narrow therapeutic window, requires careful monitoring in stable patients levels should be monitored every 3 months. Weight, renal and thyroid function should be monitored every six months. Corrected serum calcium annually. Interacts with many medications including diuretics and NSAIDs. See Lithium interaction information for further details. The prescriber is responsible for ensuring that timely monitoring has taken place and that levels are in range. A lithium treatment pack should be given to patients intitiat ed on treatment with lithium. See Safer Lithium Therapy NPSA alert. Lithium Citrate Oral liquid Sodium Valproate If unable to swallow tablets. Prescribe by brand. Priadel is 1 st line. Other available brands include Li-liquid NB: 200mg Lithium Carbonate is equivalent to 509mg Lithium Citrate For use as a mood stabiliser and in bipolar disorder (off-label). See AWP Valproate Guidance for information on the initiation of valproate in bipolar disorder. See MHRA Drug Safety Update Feb 16 for further safety information and advice. See MRHA Drug Safety Update April 17 for further safety information and advice. Valproic acid (Depakote ) For existing bipolar patients only. See AWP Valproate Guidance for information on the initiation of valproate in bipolar disorder. See MRHA Drug Safety Update April 17 for further safety information and advice. Carbamazepine Lamotrigine See Lamotrigine SCA

7 Chapter 4 page number Antidepressant drugs If a patient has successfully responded to one antidepressant in the past and requires further treatment, consider using the same one at a similar dose this time. For new presentations of depression, prescribe a Selective Seretonin re-uptake Inhibitor as per NICE guideline CG90 (5). Assess response after 4 weeks. Positive effects may not be seen for at least 14 days. If there is no response to two courses of antidepressants, consider referral to specialist services. Remember older patients need lower doses of all antidepressant medications. When initiating antidepressant treatment in patients with ischaemic heart disease,note that sertraline has the best evidence base. See CG91 (6) for details on management of depression with chronic physical health problems Antidepressants should be discontinued between 6 to 12 months after recovery by negotiation with the patient. This needs to be discussed with the patient at the onset. Patients with recurrent depressive disorder may need extended prophylactic therapy. Withdrawal needs to be gradual over at least a 4-week period, with exception of Fluoxetine (see formulay guidelines, swapping & stopping). Do not stop abruptly unless a serious adverse effect has occurred. Remember washout period and cross tapering may be necessary (see formulay guidelines on swapping & stopping). Most antidepressants have been associated with hyponatraemia, the mechanism of this is probably SIADH. It is a rare but potentially serious adverse effect. It has been suggested that serotonergic drugs are relatively more likely to cause hyponatraemia. (7). Increased risk of GI bleed especially if co- prescribed with NSAID s and anti-platelet drugs. For more information on assessment and treatment in primary care of older treatment, see Depression Care Pathway Tricyclic and related antidepressant drugs See 3Ts Depression Treatment Pathway for information on place in therapy and 3Ts Guidance on Swapping and Stopping Antidepressants for information on how to safely swap and stop antidepressants. Consider the increased risk associated with tricyclic antidepressants in cardiovascular disease and elderly patients. For use of TCAs in neuropathic pain, see also section Neuropathic pain. Toxic in overdose. Amitriptyline Lofepramine Trazodone Clomipramine Imipramine Non-sedating. Prescribers to be aware of side effects. Sedating and useful in older patients with mild behavioural problems. Occasionally used in combination with an SSRI where sleep is a problem. Useful for patients with significant phobias and obsessional states.

8 Chapter 4 page number Monoamine-oxidise inhibitors Specialist initiation only See 3Ts Depression Treatment Pathway for information on place in therapy and 3Ts Guidance on Swapping and Stopping Antidepressants for information on how to safely swap and stop antidepressants. Phenelzine Interacts with indirect acting sympathomimetics present in many cough and Moclobemide decongestant preparations, and foods containing tyramine, causing dangerous rise in blood pressure. Effect may last for up to 2 weeks after stopping Selective serotonin reuptake inhibitors See 3Ts Depression Treatment Pathway for information on place in therapy and 3Ts Guidance on Swapping and Stopping Antidepressants for information on how to safely swap and stop antidepressants. Escitalopram Sertraline Citalopram First-line choice. See MHRA Safety Update (Dec 2011) Where patient unable to swallow 16mg (8 drops) of Citalopram oral drops may be considered to be equivalent in therapeutic effect to 20mg Citalopram tabs. See MHRA Safety Update (Dec 2011). See MHRA Drug Safety Update July 2016 for information and advice on serious drug interaction with cocaine Fluoxetine Suitable for under 18 s, patients with poor compliance and in pregnancy. Has a relatively long half-life so care if changing to another SSRI (see formulay guidelines on swapping & stopping). Paroxetine Initiation by specialist team only Other antidepressants See 3Ts Depression Treatment Pathway for information on place in therapy and 3Ts Guidance on Swapping and Stopping Antidepressants for information on how to safely swap and stop antidepressants.

9 Chapter 4 page number 9 Mirtazapine Venlafaxine (Prescribe the XL preparation as tablets in the community) Does not cause sexual dysfunction but sedation and weight gain is common. Useful for anxiety but beware of withdrawal, which can be problematic (see formulay guidelines on swapping & stopping). Using XL (once a day) may help minimise this. Do not initiate in patients with pre-existing unstable heart disease, hypertension or electrolyte disturbances. (7) Agomelatine - For use by AWP ONLY. AWP responsible for all prescribing and monitoring. See MHRA Drug Safety update (October 2012) - risk of dose-related hepatotoxicity and liver failure and letter to health care professionals (October 2013). Tryptophan AWP only. Duloxetine Vortioxetine To be used 3 rd line where SSRIs and mirtazapine have been ineffective or poorly tolerated and where co-morbidities make it a more suitable alternative than venlafaxine. To be used 3 rd line where SSRIs, SNRIs or mirtazapine have been ineffective or poorly tolerated. See NICE TA 367. General anxiety disorder (GAD) Sertraline Recommended as 1 st line by NICE CG113. (Please note that sertraline is not licensed for this indication). Escitalopram Venlafaxine Duloxetine Pregabalin Recommended as 1 st line by NICE CG113. See MHRA Safety Update (Dec 2011). To be used second line where SSRIs are ineffective or not tolerated. Has a short half life, so withdrawal effects are common. Only certain XL preparations are licensed for use in GAD. Venlalic is unlicensed in GAD. To be used third line where SSRIs and venlafaxine have been ineffective or poorly tolerated or where co-morbidities make it a more suitable alternative than venlafaxine. To be used third line where SSRIs, SNRIs have been ineffective or poorly tolerated or where comorbidities make it a more suitable alternative than duloxetine and venlafaxine. When prescribing pregabalin, please prescribe as a TWICE daily dosing regimen, as this is more convenient for the patient and much more cost effective. See Public Health England Advice Dec 2014 for further information on risk of misuse. See also Wiltshire Prescribing Guidance on Pregabalin in Neuropathic Pain, Generalised Anxiety Disorder and Fibromyalgia. Propranolol May be used short-term as an alternative to benzodiazepine for the physical symptoms of anxiety. Contraindicated in patients with asthma, bradycardia etc. 4.4 Central Nervous system stimulants Treatment should be in accordance with NICE guideline TA98 (8). For detailed guidance on management of ADHD in children, young people and adults, see NICE CG72 (9) For shared care agreement for the treatment of ADHD in children and adolescents, see 3Ts ADHD SCA. For shared care agreement for the treatment of ADHD in adults, see BNSSG Methylphenidate SCA. Methylphenidate Guanfacine Atomoxetine Lisdexamfetamine Second-line choice. See MHRA Drug Safety Update for further information. Second or third-line choice after methylphenidate and atomoxetine. Modafinil 4.5 Drugs used in the treatment of obesity.

10 Chapter 4 page number Anti-obesity drugs acting on the GI tract Prescribe according to NICE Clinical Guidance No 43. Use in conjunction with other lifestyle measures to manage obesity If BMI >50 consider immediate referral to specialist clinic to assess need for surgery. Orlistat ALWAYS advise patients to minimise fat intake to minimise side effects. Treatment with orlistat should be discontinued after 12 weeks if patients have been unable to lose at least 5 % of the body weight as measured at the start of therapy. Treatment should only be continued beyond 12 months after discussing potential benefits and risks with patient. Rarely tolerated or of benefit Centrally acting appetite suppressants The marketing authorisation for sibutramine has been suspended following review by the European Medicines Agency 4.6 Drugs used in nausea and vertigo See Trust guidelines for management of postoperative nausea and vomiting in adults (PONV) For use in Palliative care, see Prospect Hospice Palliative Care Handbook (7 th Edition). (10) Risk of occulogyric crisis particularly in adolescents and young adults with metoclopramide and prochlorperazine. Use with care in children and only under the supervision of the paediatricians. For drugs used to treat occulogyric reactions, see section Antimuscarinic drugs used in parkinsonism. For Hyoscine, see Anaesthetic chapter 15. Cyclizine Dexamethasone First choice for opioid induced vomiting and in the perioperative period. Beware of sedation. Prochlorperazine Betahistine Cinnarizine Domperidone Domperidone Levomepromazine Metoclopramide Metoclopramide Ondansetron I.M use. First choice post operatively for day cases. Consider Buccastem for short term use when tablets not tolerated. Used for treatment of dizziness, nausea and ear fullness in Menieres disease. Paediatric alternative to Betahistine which is un-licensed in children. For short term use. Very useful for older patients and patients where extrapyramidal side effects are best avoided. See MHRA Drug Safety Update for information on the risk of serious cardiac side-effects. See Wiltshire Domperidone Guidance for further information and advice. For long term use (off-label). See MHRA Drug Safety Update for information on the risk of serious cardiac side-effects. See Wiltshire Domperidone Guidance for further information and advice. For use in palliative care or oncology only. For short term use. No role in postoperative nausea and vomiting. Avoid use in children and young adults. For long term use (off-label). For licensed indications and paediatrics only.

11 Chapter 4 page number Analgesics Refer to the hospital trust guidelines on Treatment of Acute Pain in Adults (under review), Administration of I.V. Morphine in Recovery (under review) and Morphine as PCA (under review). Refer to the Musculoskeletal Chapter 10 for NSAIDs and Coxibs. Use the weakest analgesic that controls pain and avoid use of more than one opioid analgesic. eg. Co-codamol and Tramadol not to be co-prescribed. Co-proxamol has been withdrawn so new patients should not be commenced on it, and existing patients should be switched to formulary choices. In general, the use of concomitant opioids should be avoided. Advise patients to take regularly for chronic pain and check compliance. For use of analgesics in children, refer to the Trust Paediatric Analgesic Guidelines Non opioid analgesics Paracetamol First line at full dose for all patients in pain unless pain is severe or Paracetamol is contraindicated. Adults In view of recent reports of acute liver failure after administration of maximum doses of oral paracetamol, weight-adjusted dosing is recommended in adults (22). Children In primary care, prescribers should dose oral paracetamol in children in accordance with the latest MHRA guidance -po/documents/news/con pdf See Formulary Guidelines on appropriate weight-adjusted dosing of oral Paracetamol in adults and children Opioid analgesics For analgesia in palliative care, see Prospect Hospice Palliative Care Handbook (7 th Edition), Prospect Hospice Guide to Equivalent Opioid Doses in Palliative Care (GWH version) and Prospect Hospice Guide to Equivalent Opioid Doses in Palliative Care (GP version). Consider prescribing anti-emetics on a prn basis when initiating strong opioids. Co-prescribe regular prophylactic laxatives with any strong opioids. Starting doses for acute episodes will need to be higher for inpatients with chronic pain, particularly post operatively and those already taking opioids. See Trust guideline on acute pain management in adults. Dose of opioids may need to be adjusted individually according to the degree of analgesia and side effects; patients response to opioids varies widely. (11) Approximate oral analgesic equivalence to morphine. (12) Analgesic Conversion factor to oral morphine Duration of action Codeine 1/ hours Dihydrocodeine 1/ hours Pethidine 1/8 2 4 hours Tramadol 1/5 4 6 hours Oxycodone hours Methadone hours Buprenorphine immediate release (Temgesic) (sublingual) 200µg 12mg morphine 8 hours Buprenorphine patch (Transtec) 35µg/h 30-60mg morphine/24 hours(10) 3 days Buprenorphine patch (Butec or Reletrans) 20µg/h 18mg morphine/24 hours 7 days Fentanyl 25 patch (transdermal) is equivalent to Oral Morphine salt 90mg daily 1/2 x oral morphine is equivalent IM Morphine dose. 1/3 x oral morphine is equivalent IM / SC Diamorphine dose. IV Paracetamol Intravenous Paracetamol should ONLY be prescribed in line with Trust Policy. It is NOT for routine postoperative use. Intravenous Paracetamol is NOT generally recommended for use in children and, outside of Theatre, should ONLY be initiated in a child by a consultant. Vigilance is advised when prescribing and administering intravenous Paracetamol 10mg/mL solution for infusion, to ensure that the correct, weight-adjusted dose is ALWAYS given, as per MHRA Safety Update (13). See Formulary Guidelines on appropriate weight-adjusted dosing of Intravenous Paracetamol.

12 Chapter 4 page number 12 Codeine Phosphate Co-codamol Dihydrocodeine Please see MHRA Drug Safety Update (June 2013) regarding restrictions on use in children and breastfeeding mothers. Please see MHRA Drug Safety Update (April 2015) regarding restrictions on use for coughs and colds in children, adolescents and breastfeeding mothers. If compliance is an issue consider prescribing as Co-codamol 8/500 or 30/500. Note: - The strength must be specified. MST Continus granules - for NG tubes only. Tramadol Morphine (All except 10mg in 5ml solution are CDs) Diamorphine (CD) Injection Fentanyl Patch (CD) (Mezolar ) Consider if patient unable to tolerate Codeine. Caution in epileptics, can reduce the anticonvulsant threshold, particularly if coprescribed with TCA (11). Do not use MR preparation. Do not co-prescribe with codeine First line potent opioid. Prescribe SR as Zomorph. SR preparation not suitable for acute pain control. Initiate once approximate opiate requirements are known. More soluble, dose can be given in smaller volume. Use only when oral administration is inappropriate. Patch not suitable for acute pain control. Initiate once appropriate opiate requirements are known. See 3T s transdermal patch guidance. See MHRA Drug Safety Letter (July 2013) for information on risk of serotonin syndrome on co-administration of fentanyl with serotonergic drugs. See MHRA Drug Safety Update (July2014) for information on risk of life-threatening harm from accidental exposure to fentanyl patches Pethidine Injectable obstetrics use only. Oxycodone (CD) (Longtec & Shortec ) For use in the treatment of cancer pain. ONLY for patients intolerant of morphine despite interventions such as laxatives or antiemetics. See Trust guidelines. Significantly more expensive than morphine. Where indicated, prescribe MR as Longtec. and immediate-release as Shortec. Oxycodone M/R (Longtec ) For use as first-line opiate analgesia as part of post-operative enhanced recovery programmes, but ONLY in strict accordance with enhanced recovery protocols. No enhanced recovery patient may be discharged on Longtec unless on the advice of the GWH Pain Management team.

13 Chapter 4 page number 13 Oxycodone (CD) (Longtec & Shortec ) For use in the treatment of non-cancer pain. ONLY for patients intolerant of morphine despite interventions such as laxatives or antiemetics. See Trust guidelines. Significantly more expensive than morphine. Where indicated, prescribe MR as Longtec. and immediate-release as Shortec. Buprenorphine Patch (CD) (Butec or Reletrans 7-day patch and Transtec 4-day patch) Use only when oral administration is inappropriate. Patch not suitable for acute pain control. Initiate once appropriate opiate requirements are known. See 3T s transdermal patch guidance. Available as: Butec or Reltrans 7 day patches (5 micrograms / hr, 10 micrograms / hr, 15 micrograms / hr and 20 micrograms / hr) and Transtec 4 day (96 hour) patches (35 micrograms / hr, 52.5 micrograms / hr and 70 micrograms / hr) Please prescribe by BRAND but be particularly vigilant as BRAND NAMES are very SIMILAR Guidelines for approximate dose equivalents of Butec patches and other oral opioid analgesics: 5µg/hr patch 10µg/hr patch Tramadol 50mg/day mg/day Codeine 30 60mg 60- /day 120mg/day Dihydroco 60mg/day 60- deine 120mg/day 20µg/hr patch mg/day mg/day mg/day Fentanyl Tablets & Lozenges (CD) Methadone For palliative care use only. Where Oramorph is not appropriate. If pt requires >4 doses per 24hrs refer back to specialist team for advice. Tablets to be used in preference to lozenges where possible. See MHRA Drug Safety Letter (July 2013) for information on risk of serotonin syndrome on co-administration of fentanyl with serotonergic drugs. Used as part of the guidelines for withdrawal from substance abuse.

14 Chapter 4 page number Neuropathic pain Start with a low dose and titrate upwards until response is seen or maximum dose reached. Other anti-epileptic/antidepressant drugs are occasionally used under specialist supervision. See 3Ts Guidelines on Pharmacological Management of Neuropathic Pain. See also CG96 (14) for NICE recommendations on managment of neuropathic pain, but please note Gabapentin remains second-line formulary choice for neuropathic pain ahead of third- line Pregabalin. Amitriptyline Not licensed for neuropathic pain but a widely accepted treatment Imipramine Gabapentin capsules Not licensed for neuropathic pain but a widely accepted treatment See Public Health England Advice Dec 2014 for further information on risk of misuse. See MHRA Drug Safety Update Oct 17 for further information and advice on rare risk of severe respiratory depression. Carbamazepine Trigeminal neuralgia. Duloxetine Pregabalin Nortriptyline Consider in painful diabetic neuropathy only, where Amitriptyline and Gabapentin have either failed or are contraindicated. Consider as 3 rd line if amitripytline and gabapentin have failed. See Public Health England Advice Dec 2014 for further information on risk of misuse. See also Wiltshire Prescribing Guidance on Pregabalin in Neuropathic Pain, Generalised Anxiety Disorder and Fibromyalgia For those patients unable to tolerate amitriptylline or imipramine due to unacceptable side effects Antimigraine drugs Treatment of acute migraine attacks Adults (15) Prescribe a standard oral analgesic paracetamol, aspirin or ibuprofen for most people presenting with symptoms of migraine. Avoid opioid analgesics. Consider prescribing an alternative anti-inflammatory drug (NSAID) if standard analgesia has been tried unsuccessfully. Prescribe anti-emetics if nausea or vomiting are prominent symptoms (domperidone and metoclopramide are also effective for pain relief when combined with analgesics). Consider prescribing a triptan if first-line treatment has proved ineffective on three independent attacks of migraine. Consider admission or urgent referral if a serious cause of headache is suspected, or if the person is in severe, uncontrolled status migrainosus (migraine lasting for more than 72 hours).

15 Chapter 4 page number 15 Paracetamol Aspirin Sumatriptan injection Consider discontinuation in existing patients and discussion / referral to migraine clinic. Ibuprofen Sumatriptan Zolmitriptan See MHRA Drug Safety Update June 2015 for further information and advice on cardiovascular risk if using 2400mg/day or more. Seek expert advice if patient using for more than 2 episodes a week / 70 episodes a year as this can precipitate rebound headaches. If vomiting is a problem, consider melt/orodispersible formulation. Almotriptan Ergotamine Children If simple analgesics fail, children should be referred to rule out other causes. The younger the child the more significant the headache, particularly if under 5. Paracetamol Wherever possible, oral paracetamol for IV Paracetamol In all circumstances, IV children should be dosed according to the paracetamol must be dosed according to child s weight (Routine use: 15mg/kg 6 hourly). patient s weight. Please note doses and dose Please see revised paediatric dosing ranges in ranges are not interchangeable with oral MHRA communication. paracetamol. See Trust Guideline & MHRA Safety Update. Sumatriptan Zolmitriptan melt Migraleve (Pink tablets only) Second line in cbnf but unlicensed. Under 10 years, only under close medical supervision. Contains paracetamol and codeine, in addition the pink tablet contains buclizine Prophylaxis of migraine Occasionally other antiepileptic/antidepressant drugs. Adults Consider for: - three + attacks a month. - prolonged or severe headache. Amitriptyline Propranolol Unlicensed indication, but commonly used. Initiate with 10mg daily & increase to 160mg od (SR) over 2weeks. Intranasal sumatriptan Not recommended in children less than 12 years of age. Flunarizine (unlicensed drug) Consultant neurologists ONLY for supply from hospital pharmacy Topiramate Pizotifen Indometacin Children Pizotifen Propranolol Initiate at 0.5mg daily & increase slowly to 3mg daily. Consultant Neurologists ONLY 10mg tds. Clonidine Carbamazepine Topiramate

16 Chapter 4 page number Cluster Headaches Treatment Sumatriptriptan injection Oxygen Indometacin Prophylaxis Verapamil Consultant initiation only for Indomethacin Responsive Headaches syndrome. Methysergide Consultant only, maximum duration 3months. See MHRA Drug Safety Update March 2014 for information on risk of serious fibrotic reactions. 4.8 Antiepileptics All patients with suspected epilepsy should be referred to specialists. Anti-epileptics interact with many drugs including each other - see BNF for details. Remember most anti-epileptic drugs are teratogenic; women wanting to conceive should be referred. Phenytoin has a narrow therapeutic index. Serum levels need to be monitored regularly. Phenobarbitone supplies for patients to use at home need to be written as a controlled drug prescription. Children should be treated with a single anti-epileptic drug (monotherapy) wherever possible. It is recommended in adults and children that combination therapy (adjunctive or add-on therapy) should only be considered when attempts at monotherapy with anti-epileptic drugs (as above) have not resulted in seizure freedom. If trials of combination therapy do not bring about worthwhile benefits, treatment should revert to the regimen (monotherapy or combination therapy) that has proved most acceptable to the child, in terms of the balance between effectiveness in reducing seizure frequency and tolerability of side effects. Refer to NICE guidance documents Nos 76 and 79. (16,17) Control of epilepsy Adults See MHRA Drug Safety Update Nov17 for updated information and advice on switching between different branded, branded- generic or generic preparations.

17 Chapter 4 page number 17 Sodium Valproate Carbamazepine Oxcarbazepine Lamotrigine Phenytoin Levetiracetam Topiramate Clonazepam Clobazam Gabapentin Pregabalin Phenobarbitone Retigabine Brivaracetam Lacosamide Use with caution in females of childbearing age - risk to unborn child. See MHRA Drug Safety Update Feb 16 for further safety information and advice. See MRHA Drug Safety Update April 17 for further safety information and advice. Please note Oxcarbazepine (Mylan) will be initiated in all new patients with Oxcarbazepine (Trileptal) reserved for existing patients only. Interacts with Valproate reduced dose required refer to SPC. Mainly used for prophylaxis following head trauma although limited evidence for effectiveness. Has a narrow therapeutic index. Endorse FP10s with SLS prescribeable on the NHS for epilepsy only. See Public Health England Advice Dec 2014 for further information on risk of misuse. See MHRA Drug Safety Update Oct 17 for further information and advice on rare risk of severe respiratory depression. May be useful in those refractory to established treatments or who are unable to tolerate Gabapentin. Consultant initiation only. See Public Health England Advice Dec 2014 for further information on risk of misuse. For adjunctive treatment of partial onset seizures with or without secondary generalisation ONLY when previous treatment with carbamazepine, clobazam, gabapentin, lamotrigine, levetiracetam, sodium valproate and topiramate has not provided adequate response, has not been tolerated or would be contraindicated. See NICE TA232 for further details. See EMA safety update and MHRA Drug Safety Update (July 2013). As adjunctive therapy in the treatment of refractory partial-onset seizures with or without secondary generalisation in adult and adolescent patients from 16 years of age with epilepsy. Not licensed for children < 16 years of age. On consultant neurologist advice: Vigabatrin Perampanel For use in patients aged 12 years and over. See 3Ts Perampanel Prescribing Information for further information. Eslicarbazepine For the adjuvant treatment of partial onset seizures with or without secondary generalisation in patients over 18 years of age, in line with NICE Clinical Guideline 137. See 3Ts Eslicarbazepine SCA. Zonisamide

18 Chapter 4 page number Control of epilepsy Children See MHRA Drug Safety Update Nov17 for updated information and advice on switching between different branded, branded- generic or generic preparations. First Line Sodium Valproate Use with caution in girls likely to need treatment into their childbearing years. See MHRA Drug Safety Update Feb 16 for further safety information and advice. Steroids - refractory infantile spasm. Biotin Pyridoxine See MRHA Drug Safety Update April 17 for further safety information and advice. Folinic Acid Lamotrigine Phenobarbitone Carbamazepine Second Line Phenytoin Clonazepam Clobazam Clomipramine Levetiracetam Topiramate Ethosuximide Acetazolamide Rufinamide Piracetam Interacts with Valproate reduced dose required refer to SPC. Drug of choice for neonatal seizures and used occasionally for older children. Contraindicated in some childhood epilepsies. i.e. absence seizures, myoclonic seizures. Second line drugs can be used as monotherapy or in combination. Lacosamide unlicensed use for chidren < 16 years of age. Vigabatrin - On consultant paediatrician approval.

19 Chapter 4 page number Drugs used in status epilepticus Most intravenous anti-epileptics have very specific administration requirements; see SPCs for details. Respiratory depression is more likely to occur with intravenous medication. Resuscitation facilities must be available. Adults Diazepam rectal Diazemuls IV injection only. Midazolam Maleate (Epistatus) Note: Midazolam is a controlled drug. For Buccal administration Lorazepam injection Phenytoin infusion Sodium Valproate injection Midazolam injection If no IV access, use as IM injection Paraldehyde rectally - consultant neurologist advice only. Phenobarbitone injection Levetiracetam injection Clonazepam injection - consultant approval required, /use on ICU only. Children Children should be treated if seizure is longer than 4 minutes or recurrent. Diazepam rectal Paraldehyde rectal Midazolam Maleate (Epistatus) Please note: Injection supplied as a ready mixed preparation (50%). Dose in mls of 50% preparation is TWICE that stated in C-BNF. Can be problems with availability. Very effective in children with recurrent prolonged seizures. Contact Dr Chinthapalli (consultant paediatrician) for advice on prescribing in children. See Shared Care Agreement. For Buccal administration Diazemuls IV injection only Lorazepam injection Phenytoin infusion Phenobarbitone injection treatment of choice for neonatal seizures. Clonazepam injection consultant paediatrician approval required. ICU and SCBU only. Midazolam injection - consultant paediatrician approval required. ICU only. 4.9 Drugs used in parkinsonism and related disorders Dopaminergic drugs used in parkinsonism Avoid treatment if possible and consider referral. Treatment choice depends on biological age rather than chronological age. In patients who are otherwise fit and active, consider commencing treatment with an agonist (less likelihood of motor complications). (11) L-Dopa can be problematic and cause long-term side effects, but is better at improving motor disability. (14) Consider controlled release L-dopa preparations as they give smoother symptom control. If early morning symptoms are problematic, the patient may require initial dispersible Co-beneldopa. Within the Acute Trust, expert advice should be sought from Dr Mukherjee. See NICE CG35 (18) and SIGN guideline 113 (19) for details on management of parkinsons disease.

20 Chapter 4 page number 20 Co-Beneldopa Co-Careldopa Ropinirole Ropinirole MR Selegiline Pramipexole Pramipexole MR Bromocriptine Entacapone Sastravi (co-careldopa + entacapone) Rotigotine (patches) Amantadine Dopamine agonist of first choice. For use ONLY when treatment with plain Ropinirole has failed due to poor compliance. Please note Spirico XL is currently the most costeffective preparation in primary care. For use ONLY when treatment with Ropinirole/Ropinirole MR has proved ineffective. For use ONLY when treatment with Ropinirole/Ropinirole MR has proved ineffective and treatment with plain Pramipexole has failed due to poor compliance. Please note Pipexus is currently the most costeffective preparation in primary care. For use ONLY in patients with swallowing difficulties. For use in patients with Parkinson s Disease - consultant initiation only. For use (off-label) in patients with Multiple Sclerosis, in line with NICE Clinical Guidance consultant initiation only. Apomorphine - See MHRA Drug Safety Update April 2016 for further information on, and advice of ways to minimise the risk of, serious adverse effects. Dopaminergic drugs used in restless leg syndrome (RLS) All other possible causes of symptoms should be excluded before prescribing for restless leg syndrome. In patients with a serum ferritin of less than 50mcg/l, prescribing oral iron supplements resolves symptoms in approx. 50% of cases. Where all other causes have been excluded, plain ropinirole may be considered for moderate to severe idiopathic RLS. Where plain ropinirole is prescribed, the patient should be reviewed after 3 months and ropinirole discontinued if no effect has been seen. A PCT Individual Funding Request should be made prior to initiation of any other treatment for RLS e.g. pramipexole or rotigotine. Ropinirole Plain ONLY not modified-release Antimuscarinic drugs used in parkinsonism Prescribe on a prn basis, not regularly. Long-term use can increase the risk of tardive dyskinesia. Orphenadrine is least likely to be abused. Can be used for extra pyramidal side-effects/ occulogyric reactions. New prescriptions to control extrapyramidal effects in Parkinson s patients requires consultant initiation.

21 Chapter 4 page number 21 Procyclidine Can be used for reactions to Metoclopramide and Prochlorperazine. Orphenadrine Trihexyphenidyl Benhexol Drugs used in essential tremor, chorea, tics and related disorders Propranolol (unlicensed indication). Haloperidol Clonidine Metoprolol Baclofen Clonazepam (unlicensed indication) (unlicensed indication) Sulpiride Pimozide (unlicensed indication) Tetrabenazine Primidone Motor Neurone Disease Riluzole As per NICE guidance No 20. (20) Drugs To Reduce Spasicity Baclofen Dantrolene See MHRA Drug Safety Update for information on risk of skin and injection site reactions with injection Botulinum Toxin Type A Restricted to use by certain consultants. There are various preparations available and doses are not equivalent. Tizanidine Should be used third line only when baclofen and dantrolene have not been tolerated due to severe side effects Drugs used in substance dependence Patients in the community with substance dependence problems should be referred to one of the following agencies: Alcohol Swindon & Wilts Alcohol & Drug Service (SWADS), 13 Milton Road, Swindon. SN1 5JE. Tel: Drugs and Homeless Initiative (DHI), Old School House, Maxwell Street, Swindon. SN1 5DR. Tel: Inclusion Community Drug Services, 47 Victoria Road, Swindon. SN1 3AY. Tel: Fastest method of referral is through the Joint Assessment Clinic for all substance misuse, including alcohol. Facilitated by all three organisations at the SWADS address. Monday am, Tuesday 1-3pm, Thursday 1-3pm. Open access no letter of referral necessary. Clients must have been seen, assessed and have ongoing support by one of the above agencies before commencing any of the medications in this section. Patients admitted to the acute trust with substance dependence problems should be urgently referred to Inclusion Community Drug Services. Before a patient on Substitute Medication is discharged, contact must be made with Inclusion Community Drug Services to ensure proper arrangements are in place for appropriate support in the community. Remember appropriate vitamin supplementation.

22 Chapter 4 page number 22 Alcohol Dependance Nalmefene Acamprosate Disulfiram Naltrexone Diazepam Chlordiazepoxide Opioid Dependance Buprenorphine Methadone Naloxone Naltrexone For use in reduction of alcohol consumption in line with NICE TA 325. See also Wiltshire Prescribing Information on Nalmefene for GPs. Maintain abstinence in alcohol-dependent patients. It should be combined with counselling. See SCA for use in alcohol misuse. Alcohol deterrent compound; an adjuvant in the treatment of carefully selected and co-operative patients with drinking problems. Its use must be accompanied by appropriate supportive treatment. See SCA and signature sheet for use in alcohol and Naltrexone for Alcohol pathway. NICE approved: CG 115 For the symptomatic treatment of acute alcohol withdrawal Symptomatic relief of acute alcohol withdrawal (short term use 4 weeks) Substitution treatment for opioid drug dependence, and psychological treatment. NICE approved: management of opioid dependence Drug misuse: opioid detoxification CG 52 For use in the treatment of opioid drug addictions. NICE approved: management of opioid dependence Drug misuse: opioid detoxification CG 52 Complete or partial reversal of CNS and especially or synthetic opioids See SCA and signature sheet for use in opioid depe NICE approved: TA 115 Smoking Cessation Products Refer to Swindon NHS Stop Smoking Service Tel: or go to: Refer to Wiltshire Stop Smoking Service Tel: , or visit: Should not be initiated by secondary care unless required for medical reasons. Limited preparations available in Acute Trust. Appropriate motivational support is essential. Nicotine Replacement Therapy Varenicline Bupropion (Zyban ) Not available within the Acute Trust. Note: May impair performance of skilled tasks

23 Chapter 4 page number Drugs for dementia Early referral is desirable. Therapy is most effective when started early in the course of disease and is continued longer term with appropriate assessment every 6 months as per NICE guideline TA111. (21) Memantine is now recommended as an option for managing moderate Alzheimer s disease for people who cannot take AChE inhibitors, and as an option for managing severe Alzheimer s disease. Donepezil Wiltshire ONLY - GPs may prescribe in patients Donepezil with a clear diagnosis with no unusual features in GWH GWH is not funded to prescribe accordance with local enhanced service (LES) donepezil (or any other memory drug). agreement and Wiltshire Dementia Care Pathway. Funding sits with AWP and primary care, Patients in whom diagnosis is unclear, who are and so GWH should not routinely initiate or complex, who deteriorate or who require donepezil supply donepezil (or other memory drugs). oro-dispersible tablets should be referred to local AWP memory services. Donepezil Swindon ONLY - For initiation by AWP specialist ONLY with potential for transfer of care to GP in line with shared care agreement. In some situations, donepezil may be initiated by a Care of the Elderly or Neurology consultant at GWH but patients must then be referred to AWP Memory Services for ongoing prescribing. Galantamine Rivastigmine Memantine See Donepezil (Swindon) SCA & signature sheet. Wiltshire ONLY - For initiation by AWP specialist ONLY with potential for transfer of care to GP in line with shared care agreement. See Dementia Drugs (Wiltshire) SCA Wiltshire ONLY - For initiation by AWP specialist ONLY with potential for transfer of care to GP in line with shared care agreement. See Dementia Drugs (Wiltshire) SCA Please note the Alzest brand of rivastigmine patch is currently the most cost-effective in both primary care & secondary care. Swindon ONLY For initiation by AWP specialist ONLY with potential for transfer of care to GP in line with shared care agreement. Galantamine & Rivastigmine Swindon & GWH These drugs should be ONLY be prescribed by AWP, as funding to supply them sits wholly with AWP. Please note the Alzest brand of rivastigmine patch is currently the most cost-effective in both primary care & secondary care. Memantine - Wiltshire & GWH Only AWMHP memory clinics may routinely prescribe / provide memantine as the budget for this drug sits solely with AWMHP. Where patients are admitted on memantine, the patient s own supply from AWMHP should be utilised wherever possible. GWH should only provide memantine where an inpatient is unable to obtain their own supplies from home. Refer to Memantine (Swindon) SCA Miscellaneous Please see MHRA Drug Safety Update Aug 2017 for information and advice on the rare risk of central serous chorioretinopathy with local and systemic administration of corticosteroids. Methylprednisolone Used for Multiple Sclerosis relapse as indicated 100mg tablets by NICE CG008. NHS Swindon, NHS Wiltshire and Great Western Hospitals NHS Foundation Trust in collaboration with Avon & Wilts Mental Healthcare Partnership Trust. References: 1. Zalepon, Zolpidene and Zopiclone for the short-term management of insomnia. NICE Technology Appraisal Guidance No TA77. April Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults Management in primary, secondary and community care.nice clinical guideline 113 Issue date: January Schizophrenia. Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care.nice clinical guideline 82. Issue date: March 2009

24 Chapter 4 page number Bipolar disorderthe management of bipolar disorder in adults, children and adolescents, in primary and secondary care. NICE clinical guideline 38. Issue date: July Depression.The treatment and management of depression in adults. NICE clinical guideline 90 Issue date: October Depression in adults with a chronic physical health problem Treatment and management. NICE clinical guideline 91. Issue date: October Professor Gordon Duff. CEM/CMO/2004/11 Safety of selective serotonin reuptake inhibitor antidepressants. 06/12/ Methylphenidate, atomoxetine and dexamfetamine for attention deficit hyperactivity disorder (ADHD) in children and adolescents (review)technology Appraisal 98. Issue date: March Attention deficit hyperactivity disorder Diagnosis and management of ADHD in children, young people and adults NICE clinical guideline 72 Issue date: September Prospect Hospice Palliative Care Handbook (7 th Edition) 11. BNF No 60 September Twycross et al. Palliative Care Formulary. 2 nd Edition Intravenous paracetamol (Perfalgan ): risk of accidental overdose, especially in infants and neonatesdrug Safety Update. Volume 3, Issue 12 July 2010 from MHRA and CHM 14. Neuropathic pain. The pharmacological management of neuropathic pain in adults in non-specialist settingsnice clinical guideline 96 Issue date: March CKS Topic Migraine Newer drugs for epilepsy in adults Technology Appraisal 76 March Newer drugs for epilepsy in children. NICE Technology Appraisal Guidance 79. April Parkinson s disease Diagnosis and management in primary and secondary careissue date: June 2006 NICE clinical guideline Diagnosis and pharmacologicalmanagement of Parkinson s disease Scottish Intercollegiate Guidelines Network 113 January Guidance on the Use of Riluzole (Rilutek) for the Treatment of Motor Neurone Disease. January Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer s disease NICE technology appraisal guidance 111 (amended) Issue date: November 2006 (amended September 2007, August 2009) 22.Claridge, LC. BMJ Lesson of the week: Acute liver failure after administration of paracetamol at maximum recommended daily dose. BMJ 2010; 341: c6764

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