吸烟与精神分裂症患者药物疗效、副反应及血药浓度的关系

Association of smoking with the therapeutic effects of the drug, side effects and plasma level of drug in patients with schizophrenia

目的:探讨吸烟对精神分裂症患者服用氯氮平、氯丙嗪后血药浓度、治疗效应以及药物副反应的影响。方法:选择2003-10/2005-01在上海市精神卫生中心及其分部、徐汇区及卢湾区精神卫生中心住院的精神分裂症患者74例,患者家属知情同意。按入院先后顺序分为氯丙嗪组37例(吸烟者14例,非吸烟者23例),氯氮平组37例(吸烟者16例,非吸烟者21例),分别给予氯氮平及氯丙嗪治疗,一二周内逐渐达到治疗剂量。于治疗后第4周末、第8周末分析氯氮平、氯丙嗪血药浓度采用高效液相色谱法,于治疗前、治疗第4周末、治疗第8周末用阴性、阳性症状量表评定精神症状,应用副反应量表、不自主运动量表评定药物副反应。结果:1例患者因服用氯丙嗪过敏而脱落,2例患者因服用氯氮平严重影响白细胞水平而脱落,进入结果分析氯丙嗪组和氯氮平组分别为36例和35例。①血药浓度:第8周末氯丙嗪组吸烟者显著低于非吸烟者犤(73.50±35.53),(106.82±48.38)μg/L,(t=2.219,P<0.05)犦。在第4周末、第8周末氯氮平组吸烟者均显著低于非吸烟者犤(248.19±104.62),(273.06±120.52)μg/L;(521.68±275.30),(500.74±198.21)μg/L,(t=4.001,4.008,P<0.01)犦。氯氮平组女性非吸烟者在第8周末显著高于男性犤(621.50±199.44),(414.00±158.84)g/L,(t=2.461,P<0.05)犦。②副反应量表评分:氯丙嗪组、氯氮平组非吸烟者在第4周末、第8周末显著高于吸烟者(t=2.034～2.637,P<0.05)。③不自主运动评分:氯氮平组非吸烟者在第4周末、第8周末显著高于吸烟者(t=2.093,2.101,P<0.05)。结论:吸烟可降低氯氮平、氯丙嗪在患者体内的血药浓度,对氯氮平血药浓度的影响出现的更快更明显,但能够减轻氯氮平和氯丙嗪的副反应及由药物引起的不自主运动。氯氮平的血药浓度变化还具有有性别差异特征,女性的用药剂量应较低一些,避免因药物浓度过高而增加药物副反应。

AIM： To investigate the effects of smoking on the plasma concentration of drug, therapeutic effects and side effects in patients with schizophrenia after treatment of clozapine and chlorpromazine.METHODS： Seventy-four patients with schizophrenia, who were hospitalized in Shanghai Mental Health Center and its branch department from October 2003 to January 2005 and the mental health centers of Xuhui district and Luwan district, took part in this study with the permission of their relatives. According to the order of admission, they were divided into chlorpromazine group （n=37, 14 smokers and 23 nonsmokers） and clozapine group （n=37, 16 smokers and 21 nonsmokers）. They were treated withclozapine and chlorpromazine respectively, and the therapeutic dosages were gradually reached within one or two weeks. The plasma levels of clozapine and chlorpromazine were measured with high performance liquid chromatograpy （HPLC） at the ends of the 4^th and 8^th weeks after treatment;Their psychiatric symptoms were evaluated with the positive and negative syndrome scale, and the side effects of the drugs were assessed with the treatment emergent symptom vale and abnormal involuntary movement scale before treatment and at the ends of the 4^th and 8^th weeks.RESULTS： One patient.lost for allergic reaction to chlorpromazine, and 2 patients lost because that their leucocyte levels were seriously affected by the treatment of clozapine, finally 36 and 35 cases in the clozapine group and chlorpromazine group respectively were involved in the analysis of resuits. ① Plasma level of drugs： At the end of the 8^th week in the chlorpromazine group, it was significantly lower in smokers than in nonsmokers[（73.50±35.53）, （106.82±48.38） μg/L, （t=2.219, P 〈 0.05）]; At the ends of the 4^th and 8^th weeks in the clozapine group, it was all significantly lower in smokers than in nonsmokers [（248.19 ±104.62）, （273.06±120.52） μg/L;（521.68±275.30）, （500.74±198.21）μg/L, （t=4.001, 4.008，P 〈 0.01）]; At the end of the 8^th week in the clozapine group, it was significantly.lower in female nonsmokers than in male ones [（621.50±199.44）, （414.00±158.84） μg/L,（t=2.461, P 〈 0.05）]. ② Score of treatment emergent symptom scale： At the ends of the 4^th and 8^th weeks, it was all significantly higher in nonsmokers than in smokers in both the chlorpromazine group and clozapinegroup （t=2.034 to 2.637, P 〈 0.05）. ③ Score of abnormal involuntary movement scale： At the ends of the 4^th and 8^th weeks in the clozapine group, it was significantly higher in smokers than. in nonsmokers （t=2.093,2.101, P 〈 0.05）.CONCLUSION： Smoking can decrease the plasma levels of clozapine and chlorpromazine in patients with schizophrenia, and the effect on the plasma level of clozapine is more obvious and faster, but it can relieve the side effects and the involuntary movement caused by clozapine and chlorpromazine. There is gender difference in the plasma level of clozapine in patients with schizophrenia, and the dosage for female patients should be lower so as to avoid the increase of side effects caused by higher concentration of the drugs.