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Anticholinergic Discontinuation for Antipsychotic-Induced Extra-Pyramidal Symptoms

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Anticholinergic Discontinuation for Antipsychotic-Induced Extra-Pyramidal Symptoms Anticholinergic discontinuation for antipsychotic- induced extra-pyramidal symptoms Item Type Article Authors Albert, Michael Citation Pereira, S. R. & Albert, M. (2017). Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms. Cochrane Database of Systematic Reviews, -(3), pp.14. Download date 25/09/2021 03:40:14 Link to Item http://hdl.handle.net/20.500.12904/9804 Cochrane Database of Systematic Reviews Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms (Protocol) Pereira SR, Albert M Pereira SR, Albert M. Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD012525. DOI: 10.1002/14651858.CD012525. www.cochranelibrary.com Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms (Protocol) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 BACKGROUND .................................... 1 OBJECTIVES ..................................... 2 METHODS ...................................... 3 ACKNOWLEDGEMENTS . 9 REFERENCES ..................................... 10 CONTRIBUTIONSOFAUTHORS . 11 DECLARATIONSOFINTEREST . 11 SOURCESOFSUPPORT . 12 Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms (Protocol) i Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Protocol] Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms Simi R Pereira1, Michael Albert2 1General Adult Psychiatry, Norfolk and Suffolk NHS Foundation Trust, Norwich, UK. 2Department of Psychiatry, Highbury Hospital, Nottingham, UK Contact address: Simi R Pereira, General Adult Psychiatry, Norfolk and Suffolk NHS Foundation Trust, Drayton High Road, Norwich, Norfolk, NR5 6BE, UK. [email protected], [email protected]. Editorial group: Cochrane Schizophrenia Group. Publication status and date: New, published in Issue 3, 2017. Citation: Pereira SR, Albert M. Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD012525. DOI: 10.1002/14651858.CD012525. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of discontinuation compared with continued use of anticholinergic drugs prescribed for antipsychotic-induced extrapyramidal symptoms in people with schizophrenia and related disorders including schizophreniform disorder, delusional disorder, psychosis and schizoaffective disorder. BACKGROUND ing antipsychotics. Parkinsonism is a group of symptoms, usually emerging within a few days after starting antipsychotic treatment or a dose increase, which resemble idiopathic Parkinson’s disease, including tremor, bradykinesia (slow movement), rigidity (limb Description of the condition stiffness), mask-like face, hypersalivation and postural instability. People with severe mental illness are often prescribed antipsy- The chronic EPSEs such as tardive dyskinesia are more commonly chotics to treat their symptoms. Such medications exert their ther- seen after years of antidopaminergic (e.g. antipsychotic) therapy apeutic effects by blocking the dopamine receptors. However, and the pathophysiology is uncertain. Tardive dyskinesia symp- one of the side effects of blocking the dopamine receptors is the toms include restlessness and involuntary movement of groups of emergence of extrapyramidal side effects (EPSEs) due to the anti- muscles in the tongue, lips, face, trunks and extremities. Unlike dopaminergic effects of antipsychotics on the basal ganglia. EPSEs the acute EPSEs, it may not be resolved by withdrawing the treat- can be acute and chronic. Acute EPSEs are dystonias, parkinson- ment. ism and akathisia, and those classified as chronic include tardive Although most antipsychotics can induce EPSEs, the prevalence dyskinesia and tardive dystonia (American Psychiatric Association and incidence varies between antipsychotics. It is difficult to state 2006). an exact figure for prevalence of EPSEs, the cumulative incidence Dystonia is an acute involuntary muscle contraction or spasm and ranges from 7.7% (olanzapine) to 32.8% (depot typical drugs) akathisia is a feeling of inner restlessness and the urge to move. (Novick 2010). The incidence of tardive dyskinesia ranges from They are both often seen within a few hours to a few weeks of start- Anticholinergic discontinuation for antipsychotic-induced extra-pyramidal symptoms (Protocol) 1 Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 2.8% (olanzapine) to 11.1% (depot typical drugs) (Novick 2010). How the intervention might work Both typical and atypical antipsychotics are included in the World Dopamine normally suppresses acetylcholine activity; therefore Health Organization (WHO) Model List of Essential Medicines removal of dopamine inhibition causes an increase in release (WHO 2015); however, people living in low and middle income of acetylcholine and therefore cholinergic activity (Stahl 2008). countries have a limited choice of medication, which necessitates Acetylcholine is an excitatory neurotransmitter which can cause the use of older, cheaper drugs such as haloperidol, chlorpromazine EPSEs if it is in excess. This is a possible explanation of how and fluphenazine, with a higher potency for EPSE. antipsychotics, whose main action is dopamine blockade, cause People with parkinsonism report slowness of thinking or ‘feeling EPSEs: by removing the dopamine inhibition and thereby in- like a zombie’, while those with akathisia describe inner restlessness creased cholinergic activity and subsequent EPSEs. Anticholiner- and unease. While individuals are often unaware of the movements gic drugs block the acetylcholine receptors thereby overcoming the caused by tardive dyskinesia and are usually not distressed by them, excessive cholinergic activity. Discontinuation of anticholinergics relatives often find them distressing. These movements can be very may cause re-emergence of EPSEs as the acetylcholine receptors obvious to onlookers and can set people apart socially, possibly cease to be blocked, resulting in excessive cholinergic activity. adding to the stigma of severe psychiatric illness. Extrapyramidal symptoms result in social and functional disability; the suffering and stigmatisation associated with them is likely to remain with Why it is important to do this review us for a long time to come (Gervin 2000). There is no current evidence from systematic reviews to support prescribing anticholinergic drugs in the absence of extrapyrami- dal side effects, and they have various undesirable side effects. This review aims to assess whether anticholinergic medications are required for long-term treatment of extrapyramidal symptoms Description of the intervention by reviewing the effect of discontinuation. There are no previous Cochrane reviews comparing the discontinuation of anticholin- Anticholinergic (antimuscarinic) drugs are prescribed alongside ergic medication to continued use. The clinical relevance of this antipsychotic drugs to help prevent unwanted extrapyramidal side review is to assess if we are making people worse by possible emer- effects often associated with antipsychotics. Anticholinergics li- gence or re-emergence of EPSE(s) by stopping adjunct anticholin- censed for use in the United Kingdom are orphenadrine, procycli- ergic medication, or if adjunct anticholinergic medication needs dine and trihexyphenidyl (BNF 2015). Biperiden is the anticholin- to be continued long term. geric drug on the World Health Organization (WHO) Model List There are several Cochrane reviews on anticholinergic med- of Essential Medicines (WHO 2015). There are other anticholin- ication for extrapyramidal side effects: these include ’Anti- ergic medications available, for example benztropine, dexetemide, cholinergics versus placebo for neuroleptic-induced parkinson- etybenzatropine and profenamine (also known as ethopropazine). ism’ (Dickenson 2014a); ’Anticholinergics (various) for neurolep- Anticholinergic drugs can aggravate the anticholinergic side ef- tic-induced parkinsonism’ (Dickenson 2014b); ’Anticholinergics fects of antipsychotic drugs which can precipitate glaucoma, dry for neuroleptic-induced akathisia’ (Rathbone 2006); and ’Anti- mouth or urinary retention. They can also cause constipation and cholinergic medication for neuroleptic-induced tardive dyskine- drowsiness and have been associated with an increase in ’positive’ sia’ (Soares-Weiser 1997). A recommendation which stems from psychotic symptoms (Johnstone 1983), cognitive decline (Bottiggi ’Anticholinergic versus placebo for neuroleptic-induced parkin- 2006), and with worsening of tardive dyskinesia (Yassa 1988). An- sonism’ is to review the effect of discontinuation of anticholinergic ticholinergic medications can be abused for their stimulating and medication, which has not previously been studied in a Cochrane euphoriant effects (Pullen 1984), with one study showing that systematic review. The reason for this is that many studies cur- 33% of people prescribed anticholinergic medication had abused rently being excluded from the parkinsonism reviews (Dickenson them
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