Clozapine Induced Hypersalivation (Sialorrhoea) – Clinical Importance and Pharmacological Options for Management
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Clozapine is an evidence-based treatment in treatment-resistant schizophrenia. It is known to reduce all-cause mortality in schizophrenia and also has anti-suicidal effects. Clozapine’s efficacy has to be weighed up against rare serious side effects such as agranulocytosis, myocarditis, cardiomyopathy and thromboembolic phenomenon. [Cardiac complications of clozapine]
Common side effects such as weight gain and hypersalivation can affect compliance and therefore should be proactively managed.
Approximately 30%-80% of patients report hypersalivation as a side effect. One study reported a rate of 91%. [Maher S et al., 2016]
Day time drooling is reported as the top three adverse effects with clozapine.
It is associated with significant distress, social embarrassment, low self-esteem, insomnia and in severe cases can lead to aspiration pneumonia. It is one of the important factors associated with non-adherence to clozapine. [Gupta s et al., 2020]
MECHANISMS OF CLOZAPINE INDUCED HYPERSALIVATION
- M4 muscarinic receptor agonism
- Alpha-2 receptor antagonism
- Unopposed beta-adrenoceptors activity secondary to alpha-1 and alpha-2 antagonism
- Decreased laryngeal peristalsis
- Decreased swallowing via reduction of GI motility
Rating Scales:
- Nocturnal Hypersalivation Rating Scale
- Drooling Severity and Frequency Scale
MANAGEMENT OF CLOZAPINE INDUCED HYPERSALIVATION
Non-Pharmacological Interventions:
Day time:
- Chewing sugarless gums may reduce hypersalivation as it promotes swallowing.
Nighttime:
- Covering the pillow with a towel
- Elevating the head and sleeping on the side reduces sleep disruption and risk of aspiration.
Pharmacological management
1.Wait and watch:
- Clozapine-induced hypersalivation occurs in the early stage of treatment and can reduce in severity over time.
2. Review clozapine dose as hypersalivation may be dose-related
3. Clozapine level:
- Consider medications that may increases levels of clozapine e.g CYP1A2 inhibitors.
4. Reduce dose if possible with close monitoring for relapse.
5. Augmentation strategies:
- There are a range of augmentation strategies indicated with evidence derived from case reports, series and few RCTs.
- Common clinical strategies include the addition of anticholinergic agents e.g atropine, hyoscine. Clinicians, however, should be mindful of worsening of anticholinergic effects of clozapine such as constipation, cognitive issues and blurred vision.
- Sub-lingual atropine drops are less likely to have systemic anticholinergic effects.
- Amisulpride (100mg-400 mg/day) has been proposed as an effective alternative to anticholinergic agents. It may also allow for clozapine dose reduction.
SUMMARY OF PHARMACOLOGICAL MANAGEMENT FOR CLOZAPINE INDUCED HYPERSALIVATION (SIALORRHOEA)
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