注射用利培酮微球与口服利培酮对精神分裂症血浆催乳素及社会功能的影响

目的比较两种不同剂型的利培酮（注射用长效利培酮微球与口服利培酮）对精神分裂症患者血浆催乳素及社会功能的影响。方法 74例口服利培酮≤4mg/d达6周且病情稳定的门诊精神分裂症患者,被随机分为注射长效利培酮微球组（注射组,利培酮剂量每2周为25～50mg）和口服利培酮组（口服组,利培酮剂量≤4mg/d）。于分组前及分组后4周、8周、16周检测患者的血浆催乳素水平,于分组前和分组后8周、16周以个人和社会功能量表（Personal and Social Performance,PSP）评定患者的社会功能,以阳性和阴性症状量表（PANSS）、临床疗效总评量表中的病情严重程度（GGI-SI）及Simpson锥体外系副反应评定量表（SEPS）评定疗效和不良反应。结果注射组37例患者中,有30例（82.1%）完成研究,口服组37例患者中,有32例（85.7%）完成研究,将完成全部研究的患者的资料纳入统计分析。分组前两组的PNASS、CGI-SI及SEPS评分比较均无统计学差异。分组治疗16周后,两组的PANSS评分及CGI-SI评分均下降,但两组间比较无统计学差异;注射组、口服组的SEPS评分的均数（标准差）为3.7（2.5）和5.1（2.8）,（t=2.12,P=0.037）。分组治疗8周后,注射组与口服组的血浆催乳素均数（标准差）分别为48.2（15.7）μg/L及54.2（18.8）μg/L,（t=2.59,P=0.012）,两组的PSP评分的均数（标准差）分别为70.9（9.7）及65.3（11.1）,（t=2.01,P=0.049）;分组16周后,注射组与口服组的血浆催乳素浓度的均数（标准差）分别为31.5（17.1）μg/L及58.5（16.8）μg/L,（t=6.24,P〈0.001）,两组的PSP评分的均数（标准差）分别为79.3（6.0）及66.1（9.6）,（t=6.44,P〈0.001）。两组血浆催乳素水平的差异有统计学意义（F=4.79,P=0.033）,两组PSP分值的差异有统计学意义（F=8.70,P=0.005）。结论与口服利培酮相比,注射长效利培酮微球后患者出现的锥体外系不良反应较轻,高催乳素血症的程度较低,社会功能恢复较好。

Randomized controlled trial comparing the effect of long-acting risperidone microsphere injection versus oral risperidone on plasma prolactin level and on social functioning in patients with schizophrenia

Background：The effect of long-acting risperidone on serum prolactin levels and on patients＇ social functioning has not been fully assessed in Chinese schizophrenic patients. Methods： Seventy-four schizophrenic out-patients whose illness was stable and who had been maintained on oral risperidone treatment for 6 weeks or longer were randomly assigned to continued treatment with oral risperidone （≤4 mg/d） or biweekly treatment with injections of long-acting risperidone microspheres. Plasma prolactin concentrations were assessed pre-randomization and 4, 6, and 8 weeks post-randomization. Social functioning was evaluated using the Personal and Social Performance （PSP） pre-randomization and 8 weeks and 16 weeks after randomization. Clinical effectiveness and side effects were evaluated by comparing pre-randomization and 16-week post-randomization values of the Positive And Negative Symptoms Scale （PANSS）, the Severity Index of the Clinical Global Inventory （CGI-SI） and the Simpson Extrapyramidal Scale （SEPS）. Results： 30 （82.1%） of the 37 patients in the long-acting injection group and 32 （85.7%） of the 37 patients in the oral administration group completed the 16-week trial. There were no statistical differences between groups in the pre-treatment values of PANSSS, CGI-SI or SEPS. After 16 weeks of treatment the PANSS and CGI-SI showed significant improvement in both groups, but there was no significant difference between the two groups. However, the mean （sd） post-treatment SEPS score was significantly lower in the injection group than in the oral treatment group 3.7 （2.5） vs 5.1（2.8） , t=2.12,P=0.037]. After 8 weeks of treatment mean serum prolactin levels in the injection and oral administration groups were 48.2 （15.7） and 54.2 （18.8） μg/L, respectively （t=2.59, P=0.012）; and the mean PSP scores were 70.9 （9.7） and 65.3 （11.1）, respectively （t=2.01, P=0.049）. After 16 weeks of treatment serum prolactin concentrations were 31.5 （17.1） and 58.5 （16.8） μg/L, respectively （t=6.24, P0.001）; and mean PSP scores were 79.3 （6.0） and 66.1 （9.6）, respectively （t=6.44, P0.001）. The pre-post change in prolactin concentration was significantly smaller in the injection group （F=4.79, P=0.033） and the pre-post change in PSP scores was significantly greater in the injection group （F=8.70, P=0.005）. Conclusion： Compared to schizophrenic patients treated with oral risperidone, those treated with long-acting risperidone microsphere injections for 16 weeks had less extra-pyramidal side effects, less hyperprolactinemia and better social functioning.