Editing Clozapine (section)

===Hypersalivation===
Hypersalivation, or the excessive production of saliva, is one of the most common adverse effects of clozapine (30–80%).<ref name="Syed Cochrane 2008" /> The saliva production is especially bothersome at night and first thing in the morning, as the immobility of sleep precludes the normal clearance of saliva by swallowing that occurs throughout the day.<ref name="Syed Cochrane 2008" /> While clozapine is a [[muscarinic]] antagonist at the [[Muscarinic acetylcholine receptor M1|M<sub>1</sub>]], [[Muscarinic acetylcholine receptor M2|M<sub>2</sub>]], [[Muscarinic acetylcholine receptor M3|M<sub>3</sub>]], and [[Muscarinic acetylcholine receptor M5|M<sub>5</sub>]] receptors, clozapine is a full agonist at the [[Muscarinic acetylcholine receptor M4|M<sub>4</sub>]] subset. Because M<sub>4</sub> is highly expressed in the [[salivary gland]], its M<sub>4</sub> agonist activity is thought to be responsible for hypersalivation.<ref>{{cite web |url=http://www.medscape.com/viewarticle/409612_2 |title=Treatment of Clozapine-Induced Sialorrhea |access-date=8 February 2010 |url-status=live |archive-url=https://web.archive.org/web/20120209042338/http://www.medscape.com/viewarticle/409612_2 |archive-date=9 February 2012}}</ref> clozapine-induced hypersalivation is likely a dose-related phenomenon, and tends to be worse when first starting the medication.<ref name="Syed Cochrane 2008" /> Besides decreasing the dose or slowing the initial dose titration, other interventions that have shown some benefit include systemically absorbed anticholinergic medications such as [[Scopolamine|hyoscine]],<ref>{{cite journal | vauthors = Segev A, Evans A, Hodsoll J, Whiskey E, Sheriff RS, Shergill S, MacCabe JH | title = Hyoscine for clozapine-induced hypersalivation: a double-blind, randomized, placebo-controlled cross-over trial | journal = International Clinical Psychopharmacology | volume = 34 | issue = 2 | pages = 101–107 | date = March 2019 | pmid = 30614850 | doi = 10.1097/YIC.0000000000000251 | s2cid = 58554168 | url = https://kclpure.kcl.ac.uk/portal/en/publications/hyoscine-for-clozapineinduced-hypersalivation(0575f794-ce85-4b57-81aa-14fb64045b3c).html }}</ref> [[diphenhydramine]]<ref name="Syed Cochrane 2008">{{cite journal | vauthors = Syed R, Au K, Cahill C, Duggan L, He Y, Udu V, Xia J | title = Pharmacological interventions for clozapine-induced hypersalivation | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD005579 | date = July 2008 | pmid = 18646130 | pmc = 4160791 | doi = 10.1002/14651858.CD005579.pub2 | veditors = Syed R }}</ref> and topical anticholinergic medications like [[ipratropium bromide]].<ref name="Bird et al 2011 Review" /> Mild hypersalivation may be managed by sleeping with a towel over the pillow at night.<ref name="Bird et al 2011 Review">{{cite journal | vauthors = Bird AM, Smith TL, Walton AE | title = Current treatment strategies for clozapine-induced sialorrhea | journal = The Annals of Pharmacotherapy | volume = 45 | issue = 5 | pages = 667–675 | date = May 2011 | pmid = 21540404 | doi = 10.1345/aph.1P761 | s2cid = 42222976 }}</ref>