[Treatment options for drug-induced sialorrhea: Prescribing guidelines].

Objectives: Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been published. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation.

Methods: Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : « treatment », « hypersalivation », « induced », « drug », « clozapine »). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study.

Results: Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hypersalivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperidone (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hypersalivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63).

Conclusions: In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient response, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization.