Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study. [Effect of suo quan pill for reducing clozapine induced salivation].
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. 40 Schizophrenic inpatients with clozapine induced salivation were divided into two groups randomly. They were treated with Suo Quan pill and a control study of the placebo (neutral pill) for reducing clozapine induced salivation. These cases were also classified by TCM Syndrome Differentiation and laboratory examinations were performed. Results: There was a significant difference in effect on salivation between the therapeutic group (21 cases) and the controlled group (19 cases), P < 0.01. According to their TCM subtypes two subtypes (Stagnation of Phlegm-Dampness and Yin Deficiency) showed the best results. No correlation between the peripheral clozapine level and salivation was found. No side effect was recorded.
There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified.