Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study

Abstract

The beneficial effect of sulpiride augmentation of clozapine therapy for treatment-resistant schizophrenia patients is enhanced by its antisalivatory effect on clozapine-induced hypersalivation (CIH). Amisulpride, similar to sulpiride, is a substitute benzamide derivative with higher selective binding to the D2/D3 dopamine receptor. We hypothesized that add-on amisulpride would also be beneficial in controlling CIH. In a randomized, double-blind, placebo-controlled cross-over study, 20 clozapine-treated schizophrenia (DSM-IV criteria) inpatients with CIH were randomly initially assigned to add-on amisulpride (nine patients; 400 mg/day up-titrated from 100 mg/day over 1 week) or placebo (11 patients). Primary outcome was change in the five-point Nocturnal Hypersalivation Rating Scale (NHRS). Other measures included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale (CGI) and Simpson-Angus Scale (SAS). Mean NHRS indices were considerably lower with amisulpride (1.79 +/- 1.25) than with placebo (2.63 +/- 1.33) [F(1,38) = 5.36, P < 0.05]. With amisulpride treatment, there was a significant improvement on the negative symptoms subscale of the PANSS [F(3,57) = 3.76, P < 0.05], but not on the SAS, CGI or other subscales of the PANSS (all F < 1). Short-term amisulpride augmentation has a strong ameliorating effect on CIH. A long-term, large-scale study with a broader dose range is warranted to evaluate the stability of this effect across time.

Amisulpride versus moclobemide in treatment of clozapine-induced hypersalivation

“…Our study and some other publications have demonstrated that substitute benzamide derivatives both with higher selective binding to the D 2 /D 3 dopamine receptors (such as sulpiride or amisulpride) and a reversible selective monoamine oxidase inhibitor-A (moclobemide) may be effective as treatment of CIS (Croissant et al 2005;Kreinin et al 2005Kreinin et al , 2006Kreinin et al , 2009Praharaj et al 2009). …”

“…Previous studies (Kreinin et al 2005(Kreinin et al , 2006(Kreinin et al , 2009) demonstrated effi cacy of three medications from group of substitute benzamide derivatives in treatment of CIS. We suggest that the antisalivation activity of this group of medications is most likely related to its peripheral activity for reducing gastric acid secretion.…”

Amisulpride Improved Debilitating Clozapine-Induced Sialorrhea

“…10 The effective dose ranged from as low as amisulpride 50 mg/d 9 to 400 mg/d used in Kreinin et al 10 study. In our case, response was noted after 150 mg/d which resulted in significant reduction in daytime sialorrhea and improvement in speech.…”

Augmenting Clozapine With Sertindole

“…In contrast, amisulpride, a potent D 2 and D 3 antagonist, reduces clozapine-induced hypersalivation, but the mechanism remains unknown. 51 The mechanism of clozapine-induced hypersalivation needs to be clarified further to find effective treatment for this adverse effect.…”