Schneider B, Weigmann H, Hiemke C, Weber B, Fritze J
Center of Psychiatry, Department of Psychiatry and Psychotherapy I, Johann Wolfgang Goethe-University of Frankfurt/Main, Germany.
Pharmacopsychiatry. 2004 Mar;37(2):43-5. doi: 10.1055/s-2004-815523.
Hypersalivation is known as a frequent, disturbing, and socially stigmatizing side effect of therapy with the atypical antipsychotic clozapine. It has been shown that the addition of the anticholinergic pirenzepine is able to reduce clozapine-induced hypersalivation, probably by blocking M4-receptors. Nevertheless, a pharmacokinetic interaction between both compounds cannot be excluded.
In this pilot study, 29 schizophrenic patients (ICD-10; 51.7 % female; age: 36.7 +/- 8.7 years [mean +/- SD]) were included. Serum concentrations of clozapine and its pharmacologically active metabolite N-desmethylclozapine were determined under steady-state conditions by automated HPLC with UV detection before and after addition of pirenzepine for 3 days.
Significantly fewer patients reported hypersalivation after addition of pirenzepine (69 % vs. 34.5 %, P = 0.002). No significant differences of clozapine and N-desmethylclozapine serum levels before (329 +/- 181 ng/ml and 218.0 +/- 123.4 ng/ml, respectively) and 3 days after (336 +/- 215 ng/ml and 235.9 +/- 164.4 ng/ml, respectively) addition of pirenzepine were found. In three patients, however, clozapine serum levels increased; this was probably unrelated to pirenzepine.
In conclusion, treatment of clozapine-induced hypersalivation with pirenzepine is a recommendable combination with low risk of additional side effects.
流涎过多是使用非典型抗精神病药物氯氮平治疗时常见、令人困扰且会带来社会污名化的副作用。研究表明，添加抗胆碱能药物哌仑西平能够减少氯氮平引起的流涎过多，可能是通过阻断M4受体实现的。然而，不能排除这两种化合物之间存在药代动力学相互作用。
在这项初步研究中，纳入了29名精神分裂症患者（国际疾病分类第十版；51.7%为女性；年龄：36.7±8.7岁[均值±标准差]）。在添加哌仑西平3天前后，通过自动高效液相色谱法结合紫外检测，在稳态条件下测定氯氮平及其药理活性代谢物N-去甲基氯氮平的血清浓度。
添加哌仑西平后，报告流涎过多的患者显著减少（69%对34.5%，P = 0.002）。添加哌仑西平前（分别为329±181纳克/毫升和218.0±123.4纳克/毫升）和3天后（分别为336±215纳克/毫升和235.9±164.4纳克/毫升）氯氮平和N-去甲基氯氮平的血清水平未发现显著差异。然而，有3名患者的氯氮平血清水平升高；这可能与哌仑西平无关。
总之，用哌仑西平治疗氯氮平引起的流涎过多是一种值得推荐的联合用药，额外副作用风险较低。
