Clozapine 引起過度流涎中西醫病機與治療的文獻回顧

Pathophysiology and Treatment of Clozapine Induced Hypersalivation by Chinese Medicine and Western Medicine

Clozapine 是第二代抗精神病藥物， 主要用於治療思覺失調症(Schizophrenia)。對於頑固型或其他抗精神病藥物無效時為最佳用藥。但是它的過度流涎副作用容易造成患者不適及可能引發吸入性肺炎，因而使用上受到限制。西醫認為Clozapine 使用所導致的過度流涎，與增加口水分泌或減少吞嚥反射有關。依上述理論，目前雖然有一些抗膽鹼藥物或交感神經活化劑被用來改善此副作用，但療效仍未獲得大規模的臨床試驗來證實。因此這個副作用還未有最佳改善方法。中醫認為口水屬於「五液」之一。人體津液的生成雖與五臟均有關聯，但口水過多主要與脾、胃、腎相關。由中醫生理及西醫對於服用Clozapine造成過度流涎的機轉來分析，我們認為此藥性味苦寒，服用後造成胃寒脾熱之證，久服更會導致腎虛。因此要以中醫輔助治療便擬定下列治療方針：初期服藥者以溫降胃氣搭配養脾陰之法治療，若久服者則需酌加溫腎之品。治療期間若有濕熱現象出現，則可配合辨證選用燥濕清熱、溫中化痰的藥物。

Clozapine is one of the second-generation antipsychotics (SGA) for schizophrenia. However, the use of Clozapine is limited due to the side effect of hypersalivation, which may result in aspiration pneumonia. In Western medicine, Clozapine induced hypersalivation is considered to be related to increase in saliva output or decrease in swallow reflex. Although some anticholinergic agents or alpha 2 agonists were applied to the treatment, there are currently insufficient data to confidently validate this clinical practice. In Chinese medicine, saliva is one of the “five humors”. Production of fluid and humor in the human body is related to the “five viscera”. Moreover, hypersalivation is mainly related to spleen, stomach, and kidney. As we think Clozapine is a bitter and cold drug, use of Clozapine causes “stomach cold and spleen heat pattern”, and “kidney deficiency pattern” if case of long-term use. For Clozapine-using patients, the solution lies in the use of traditional Chinese medicine as adjuvant therapy. At first, treatment policy include warming the stomach, directing qi downward and enriching spleen yin; then we can add drugs to tonify the kidney if need be. If dampness-heat is noted, we can treat the patient under the principle of “draining dampness and clearing heat”, as well as “warming the middle and resolving phlegm”.