Berkshire West Integrated Care System Representing Berkshire West Clinical Commisioning Group Royal Berkshire NHS Foundation Trust Berkshire Healthcare NHS Foundation Trust Berkshire West Primary Care Alliance
Anticholinergic (Antimuscarinic) Guidelines
Treatment of Antipsychotic Induced Extra Pyramidal Side Effects (EPSE)
[APC ClinDoc 036]
For the latest information on interactions and adverse effects, always consult the latest version of the Summary of Product Characteristics (SPC), which can be found at: http://www.medicines.org.uk/
Approval and Authorisation
Approved by Job Title Date Area Prescribing APC Chair September 2015 Committee
Change History
Version Date Author Reason v.1.0 01/10/2018 unknown Updated APC Category
This prescribing guideline remains open to review considering any new evidence
This guideline should only be viewed online and will no longer be valid if printed off or saved locally
Author Unknown Date of production: Sept 2015 Job Title Unknown Review Date unknown Protocol Lead Unknown Version v.1.0
ANTICHOLINERGIC (ANTIMUSCARINIC) GUIDELINES
TREAMENT OF ANTIPSYCHOTIC INDUCED EXTRA PYRAMIDAL (EPSE) SIDE EFFECTS
Authors (Original Contributor) Ms former Chief Pharmacist, Diane Booth BHFT Mrs Kiran Hewitt Lead Clinical Pharmacist, BHFT Mrs Katie Sims Senior Clinical Pharmacist, BHFT Version 7.0 Reviewed 09/2015 Document History 6.0 updated in line with recent references Date of Next Review 09/2017 (or sooner if there are changes to national guidelines) Approved by Drug and Therapeutics 13/11/2015 Committee, BHFT
MI = Medicines Information service at Prospect Park Hospital Tel: 0118-960-5075, Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015
Page 1 of 8
Acknowledgements:
The authors would like to thank the members of the pharmacy department, Prospect Park Hospital and the Drug & Therapeutics Committee representatives of Berkshire Healthcare NHS Foundation Trust who provided help, advice and constructive feed back during the compilation of these guidelines and for future revisions.
Any enquiries regarding these guidelines or other medication related queries should be forwarded to the MIS (Medicines Information Service), pharmacy department, Prospect Park Hospital, on 0118 960 5075, or your ward/locality pharmacist.
MI = Medicines Information service at Prospect Park Hospital Anticholinergic Guidelines Tel: 0118-960-5075 Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015 Page 2 of 8 CONTENTS
ANTICHOLINERGIC (ANTIMUSCARINIC) GUIDELINES TREAMENT OF ANTIPSYCHOTIC INDUCED EXTRA PYRAMIDAL (EPSE) SIDE EFFECTS Page Treatment Choices 4 General Treatment Principles 4 Side Effects 5 Movement Disorders 5 Toxicity 5 Discontinuation 6 Prescribing Information 6 Treatment of Special Patient Populations 7
References 8
MI = Medicines Information service at Prospect Park Hospital Anticholinergic Guidelines Tel: 0118-960-5075 Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015 Page 3 of 8 ANTICHOLINERGIC FORMULARY
FIRST LINE TREATMENT CHOICE Procyclidine
ALTERNATIVE Trihexyphenidyl (formerly benzhexol)
If no improvement after a routine adequate trial of medication, Refer to secondary care
General Treatment Principles
Procyclidine has been chosen as first line treatment choice based on cost and usage within Berkshire Healthcare NHS Foundation Trust. There is no clear evidence that one anticholinergic is more efficacious than another; individual patients may respond better to, or tolerate one drug over another.1 Anticholinergics should only be prescribed if other measures for reducing extrapyramidal side effects are not possible, such as lowering the dose of the antipsychotic, or changing to a lower risk antipsychotic e.g. an atypical agent. 2,3 Anticholinergics interact with and therefore should not be routinely used in combination with other drugs with anticholinergic/antimuscarinic properties (eg antihistamines, TCAs, MAOIs), clozapine) due to an increased risk of side effects and anticholinergic burden The lowest effective dose should be used where possible. Do not prescribe these agents prophylactically in anticipation of EPSE. Not all patients develop these side effects. Prescribe on a “PRN” basis if possible. The recommended dosage of procyclidine is 5mg up to three times a day. Older patients should be prescribed 2.5mg up to twice daily, initially. Most patients do not require anticholinergics on a regular basis. If regular treatment is necessary, use at the lowest effective dose. Attempts should be made to withdraw anticholinergics after three months of therapy and restarted only if symptoms re-emerge. Treatment is rarely needed long term.4
MI = Medicines Information service at Prospect Park Hospital Anticholinergic Guidelines Tel: 0118-960-5075 Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015 Page 4 of 8 Abuse potential warning: Abuse of anticholinergics, particularly procyclidine and trihexyphenidyl is possible, and all these drugs have a potential street value. Alleged effects with relatively low doses include euphoria, reduced anxiety and psychotic effects.5
Hence it is important that all anticholinergic consumption and prescribing is carefully monitored.
Side Effects
Adverse effects are related to the ability of anticholinergic agents to block acetylcholine at muscarinic receptors (and some possible dopamine agonistic activity). All anticholinergics can produce the following effects to varying degrees: 6,7,8
Gastro-intestinal: constipation, dry mouth, nausea and vomiting
Ophthalmologic: blurred vision, increased intra-ocular pressure in angle closure glaucoma
Cardiovascular: tachycardia, dizziness
Genito-urinary: urinary retention, delayed micturition, sexual dysfunction
Allergic: hypersensitivity, rash
Central Effects: memory and cognitive impairment, nervousness, confusion, drowsiness, sedation, insomnia, euphoria, anxiety, agitation, paranoid delusions, hallucinations
Movement disorders
It is unclear whether anticholinergic use increases the risk of tardive dyskinesia (TD); much of the literature is conflicting. However, use of these drugs in patients with existing TD can exacerbate the movement disorder and may unmask any latent TD.9,10
Toxicity
It is important to consider a patient’s total anticholinergic load from other drugs with an intrinsic anticholinergic activity, for example antipsychotics and tricyclic antidepressants.
MI = Medicines Information service at Prospect Park Hospital Anticholinergic Guidelines Tel: 0118-960-5075 Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015 Page 5 of 8 Some evidence suggests that orphenadrine may be more toxic in overdose than the other agents (with trihexyphenidyl possibly the safest and least toxic).11 The manufacturers of orphenadrine (Disipal®) will be discontinuing it in December 2015 because of manufacturing issues. It will no longer be available as a treatment choice within BHFT.
Discontinuation
If withdrawn abruptly, anticholinergic agents can cause a discontinuation syndrome, characterised by rebound EPSE, cholinergic rebound, myalgia, depression, anxiety, insomnia, headaches, gastric intestinal distress, nausea, vomiting and malaise.
Withdrawal should be slow and gradual, over 1-2 weeks. High doses of medication should be withdrawn even more gradually over a period of weeks.12
Prescribing Information
Drug Form Strength Equivalent Av. BNF Max. Dosages Daily Daily Dose Dose procyclidine tablets 5mg 2mg 5mg up 30mg injection 5mg per 1ml to three liquid 2.5mg per 5ml times a (60mg in day exceptional 10mg per 5ml circumstances) trihexyphenidyl tablets 2mg, 5mg 2mg 1-2mg 20mg liquid 5mg per 5ml up to three times day *
4,13 * 1mg daily initially (5-15mg per day to be given in three to four divided doses).6
MI = Medicines Information service at Prospect Park Hospital Anticholinergic Guidelines Tel: 0118-960-5075 Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015 Page 6 of 8 Treatment of Special Patient Populations
Condition/ Population Considerations Pregnancy Information is extremely limited. Use near term has been associated with neonatal withdrawal symptoms. Consult MIS for advice (0118 960 5075)
Lactation No information readily available (may inhibit lactation) Consult MIS for advice Cardio-vascular Use with caution due to potential tachycardia Disease Glaucoma Contra-indicated in angle closure glaucoma Liver Manufacturers advise caution Disease Renal Impairment Manufacturers advise caution Old Age Use with great care due to anticholinergic burden. Side effects are common and problematic, e.g. confusion. Use cautiously in patients with prostatic hypertrophy. Start with a low dose and stop treatment if/when ineffective or no benefit seen and as part of routine medication rationalisation. Procyclidine can be given twice daily as clearance is reduced.
MI = Medicines Information service at Prospect Park Hospital Anticholinergic Guidelines Tel: 0118-960-5075 Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015 Page 7 of 8
References
1. Raja M. Managing antipsychotic induced acute and tardive dystonia. Drug Safety 1998; 19(1): 57-72 2. Holloman L, Marder S. Management of acute extrapyramidal effects induced by antipsychotic drugs. Am J Health Syst. Pharm 1997, 1;54(21): 2461-2477 3. Kalish S et al. Antipsychotic prescribing patterns and the treatment of extrapyramidal symptoms in older people. J Am Geriatr Soc 1995; 43(9): 967- 973 4. Bazire S. Psychotropic Drug Directory 2014, Lloyd-Rheinhold Communications LLP, Dorsington, Warwickshire, UK. 5. Dose M, Tempel HD. Abuse potential of anticholinergics. Pharmacopsychiatry 2000; 33(suppl 1): 43-46 6. SPC for trihexyphenidyl (Last Updated on eMC 03-Feb-2015, Genus Pharmaceuticals – www.emc.medicines.org.uk) 7. SPC for procyclidine (Kemadrin®) Last Updated on eMC 06-Nov-2014, Aspen - www.emc.medicines.org.uk) 8. SPC for orphenadrine (Disipal®). Discontinued 01/12/2015 www.emc.medicines.org.uk 9. Awouters F et al. Tardive dyskinesia: etiology and therapeutic aspects. Pharmacopsych 1990; 23(1): 33-37 10. Alphs L, Davis JM. Non catecholaminergic treatments of tardive dyskinesia. J Clin Psychopharmacol 1982; 2(6): 380-385 11. Slordan L, Gjerden P. Orphenadrine. Br J Psych 1999;174: 275-276 12. Marken PA et al. Anticholinergic drug abuse and misuse: Epidemiology and therapeutic implications. CNS Drugs 1996;5(3): 190-199 13. Monthly Index of Medical Specialities, March 2004 edition. Haymarket Medical Publications LTD., London, UK
MI = Medicines Information service at Prospect Park Hospital Anticholinergic Guidelines Tel: 0118-960-5075 Monday – Friday 9am – 5pm Email: [email protected]
Berkshire Healthcare NHS Foundation Trust Edition 7.0 September 2015 Page 8 of 8