PPT-PGN-05 Appendix 16

Clozapine-related hypersalivation

Incidence is variably reported as 10-80%, with poorly understood mechanism, and few evidence based studies. Aspiration is the most serious consequence of hypersalivation as it may lead to coughing, hoarseness, difficulty speaking, choking, bronchitis or pneumonia

Assess:  Onset - most common in early months of treatment, may wear off or persist for years  Frequency - occasional or daily  Timing – daytime/ night (most frequently)  Degree of distress caused (e.g. night time ‘choking sensation’, social stigma, non-compliance, disturbed sleep, skin chafing)  Consider that this side effect may not require any treatment?  Degree of patient sedation  Other possible causes (drugs, physical illness)/ aggravating factors.

Non-pharmacological options:  Use SF chewing gum (or other methods), to encourage regular swallowing, daytime  Place towel over pillow at night  Prop head up with extra pillows  Purchase special pillows/ cases.

Modification of existing drug therapy:  Divide dose throughout day, if predominantly troublesome at night.  Clozapine dose-reduction, mental state permitting (this may be a dose related side effect). A clozapine plasma level may guide this.  Review any other medication which may contribute this side effect (e.g. sedative agents).  Care if any agents (especially centrally acting) are co- prescribed, as this may potentiate the anticholinergic action of clozapine. Observe for: constipation, confusion, memory impairment and other cognitive deficits.

Pharmacological management:  All drug treatments are off-label for this indication. Refer to section 9 of the Prescribing Medicines policy (UHM-PGN-02) for further guidance on off-label prescribing. Multiple drug options are available, however most have very limited evidence for use. Some of the most commonly used options are detailed below:

 Hyoscine hydrobromide (Kwells) 300 – 900 micrograms/day in divided doses. This is the most widely used drug and should be used first line. These should be sucked slowly /chewed prior to swallowing (thought to act Northumberland, Tyne and Wear NHS Foundation Trust Appendix 16 – Clozapine-related hypersalivation – V03-Apr 19 Part of PPT-PGN-05 – Safe Prescribing of Clozapine – (NTW(C) 38 - Policy on Pharmacological Therapies)

PPT-PGN-05 Appendix 16

locally, on salivary glands. May exacerbate anticholinergic side effects of clozapine.  Hyoscine transdermal patch: 1mg/24 hour (Scopaderm TTS), one fresh patch applied to the skin behind the ear, every 72hrs. Expensive option, but useful for poor compliance with tablets.  Trihexyphenidyl (benzhexol): 5-15mg at night. A centrally acting M1 antagonist. May impair cognitive function. Lower doses (e.g. 2mg) may be effective.  Propantheline: suggested dose 7.5mg at night. Peripheral anticholinergic drug, theoretically less likely to produce central anticholinergic side effects. Note that tablets only available as 15mg strength and cannot be easily halved as are coated.  Pirenzepine: 50-150mg daily. A selective M1/M4 antagonist. Unlicensed in the UK and must be imported on a named patient basis. Has been widely used with anecdotal benefit although the only RCT suggested no benefit.

There is varying levels of evidence for several other treatment options including (but not limited to) , metoclopramide, sulpiride, nasal ipratropium and sublingual drops. Further information is available in the reference sources listed below.

References UKMI https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Fwww.sps.nhs.uk%2Fw p-content%2Fuploads%2F2015%2F11%2FQA54_8_Hypersalivationdruginduced.doc

Maudsley ‘Prescribing Guidelines in Psychiatry’ 13th Edition, 2018 pp189-190

P. Hardy, Pinderfields Hosp ‘Drug Treatment Options for Clozapine-Induced Hypersalivation’ July 2003

Northumberland, Tyne and Wear NHS Foundation Trust Appendix 16 – Clozapine-related hypersalivation – V03-Apr 19 Part of PPT-PGN-05 – Safe Prescribing of Clozapine – (NTW(C) 38 - Policy on Pharmacological Therapies)