A systematic chart review of pharmacological interventions in patients with clozapine-induced hypersalivation

Schizophr Res. 2024 Jun:268:138-144. doi: 10.1016/j.schres.2023.08.004. Epub 2023 Aug 17.


Objectives: To investigate the efficacy and tolerability of medications, such as mouthwash use of 1 % atropine sulfate and tropicamide drops, oral amitriptyline and amisulpride used for clozapine-induced hypersalivation (CIH).

Methods: The medical charts of inpatients with psychotic disorders between 2010 and 2022 were reviewed retrospectively. We detected 161 patients with eligible data who received or commenced clozapine. Primary outcome was defined as the percentage change in the diameter of a wet patch on the pillow (DWP) for improvements in CIH.

Results: The frequency of CIH was 42 % (n = 68). The first step medications for CIH were tropicamide drops (49 %), atropine drops (43 %) and amitriptyline (3 %). After the first step, the median DWP significantly decreased by -33 %. During the index hospitalization, in 18 patients with persistent CIH, the median DWP significantly decreased by -42 % with the second step medications which also included amisulpride. There were no reported serious adverse events. The change in DWP was significantly correlated with the duration of clozapine treatment (r = 306) and clozapine serum level at discharge (r = 0.294). A linear regression model showed a link between the change in DWP and reduced Positive and Negative Syndrome Scale scores.

Conclusions: Our findings emphasize that mouthwash use of atropine or tropicamide drops has a satisfying and tolerable effect in treating CIH. Switching medications for CIH seems to be effective when CIH persists despite a first step agent. Controlled follow-up studies are needed to understand the relationship between CIH, clozapine serum levels, illness severity, and functioning.

Keywords: Atropine; Psychosis; Schizophrenia; Sialorrhea; Tropicamide.

MeSH terms

  • Adult
  • Antipsychotic Agents* / administration & dosage
  • Antipsychotic Agents* / adverse effects
  • Clozapine* / administration & dosage
  • Clozapine* / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychotic Disorders / drug therapy
  • Retrospective Studies
  • Sialorrhea* / chemically induced
  • Sialorrhea* / drug therapy
  • Young Adult


  • Clozapine
  • Antipsychotic Agents