Drooling or saliva spillage has been explored widely among children with neurodevelopmental conditions. Yet, the approach to drooling in an otherwise developmentally normal child remains unexplored, as it is regarded as self-limiting. Nonetheless, drooling beyond age 4 in the awake stage should raise concern.

This narrative review aims to shed light on drooling in developmentally normal children, also known as ‘healthy droolers’, and the available evidence on its management.

Most notable factors causing saliva spillage include poor oral-motor control and impaired oral sensation. Delayed saliva acquisition may be an early indicator of developmental or intellectual delay. Drooling impairs both the children's and parents' overall quality of life significantly.

Healthy droolers can be managed by simple behavioural therapy and reassurance.

Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes.

The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients.

Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p = 0.013) and use of other antipsychotics (p = 0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p = 0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p = 0.029).

Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.

Clozapine is the first atypical antipsychotic. It is used in refractory schizophrenia. It has a heavy side effect burden, including weight gain, dizziness, blurred vision, and sialorrhea. Not only is sialorrhea bothersome, but it can also have with serious consequences, such us aspiration pneumonia, neutropenia, agranulocytosis, myocarditis, and may be responsible for low self-esteem, leading to low treatment compliance and discontinuation.

Identifying the mechanism behind clozapine-induced sialorrhea. Finding how frequent clozapine-induced sialorrhea is compared to other antipsychotics. Finding effective ways to prevent clozapine-induced sialorrhea.

PubMed database search, with “clozapine sialorrhea” keyword expression. 12 Articles published in the last ten years were selected among the 112 best matches. Reference lists of articles were reviewed to identify additional articles.

Clozapine is a muscarinic M1-5 receptor antagonist, explaining its anticholinergic effects. Due to its strong anticholinergic action, sialorrhea is a paradoxical side effect. To prevent it, several drugs can be used, such us scopolamine, pirenzepine, sublingual atropine solutions, clonidine, botulinum neurotoxin, and others. Sialorrhea was relatively more frequently reported in clozapine (1.1%) compared with other antipsychotics (0.31%). Mubaslat and Lambert (2020) found that drops of atropine reduce the rate of saliva secretion significantly better than placebo. Uzun, et al. (2019) observed the adjunction of N‐acetylcysteine allowed a significant decrease of the severity of sialorrhea and was well tolerated.

Although effective in refractory schizophrenia, clozapine side effects, namely sialorrhea, can be bothersome and may affect treatment adherence. Fortunately, we have tools at our disposal to help patients better handle it.

No significant relationships.