Treatment strategies for clozapine-induced sialorrhea in France: A systematic review

Clozapine-induced hypersialorrhoea (or hypersalivation) is a common side effect, and at present there is no therapeutic strategy with a validated indication to treat it. The corrective strategies proposed in the scientific literature have varying degrees of validity. As a result, it is important to regularly update the available data and to make proposals that are in line with the specialties available in each country.

A systematic review of the literature respecting PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statements was carried out using the PubMed, Embase and Cochrane databases with the keywords "Clozapine", "induced", "hypersalivation" or "sialorrhea". Only articles dealing with substances marketed in France and written in French or English were selected.

64 articles were included in this review. The various strategies identified corresponded mainly to treatments with regulatory actions on the cholinergic, noradrenergic and dopaminergic neurotransmission systems. This selection of drug strategies available in France for clozapine-induced hypersalivation identified 17 substances.

The level of evidence concerning treatments for clozapine-induced hypersialorrhoea remains limited. As a first option, and if clinically feasible (benefit-risk ratio), a cautious, gradual reduction in dosage is preferred. If this fails, local anticholinergic treatment may be initiated and evaluated following pharmaco-practical recommendations based on the drugs available in France and their level of evidence.