硫必利聯(lián)合可樂(lè)定對(duì)比硫必利、可樂(lè)定單藥用于兒童抽動(dòng)障礙有效性和安全性的隊(duì)列研究

楊春松 張伶俐 俞丹 楊亞亞 吳小芳

中圖分類(lèi)號(hào) R748;R969.3 文獻(xiàn)標(biāo)志碼 A 文章編號(hào) 1001-0408（2021）20-2514-06

DOI 10.6039/j.issn.1001-0408.2021.20.13

摘 要 目的：比較硫必利、可樂(lè)定、硫必利聯(lián)合可樂(lè)定等3種用藥方案用于兒童抽動(dòng)障礙（TD）的療效和安全性。方法：連續(xù)性收集2019年1-12月于四川大學(xué)華西第二醫(yī)院門(mén)診部就診的312例TD患兒的資料，按用藥方案的不同分為可樂(lè)定組、硫必利組、硫必利聯(lián)合可樂(lè)定組，每組104例。硫必利組患兒給予鹽酸硫必利片，初始劑量為每天50～100 mg，根據(jù)耐受情況和臨床經(jīng)驗(yàn)逐步增加劑量至每天150～500 mg?？蓸?lè)定組患兒給予可樂(lè)定透皮貼片，初始劑量為每周1 mg，維持劑量為每周1～2 mg，每周1次。硫必利聯(lián)合可樂(lè)定組患兒給予鹽酸硫必利片（用法用量同硫必利組）+可樂(lè)定透皮貼片（用法用量同可樂(lè)定組）。3組患兒用藥療程均為3個(gè)月，療程結(jié)束后每3個(gè)月隨訪(fǎng)1次（隨訪(fǎng)時(shí)間均以治療24、36、48周表示）。觀(guān)察3組患兒治療前和治療4、8、12、24、36、48周時(shí)的耶魯綜合抽動(dòng)嚴(yán)重程度量表（YGTSS）評(píng)分，并記錄各隨訪(fǎng)時(shí)間點(diǎn)的不良反應(yīng)發(fā)生情況。結(jié)果：治療前3組患兒的YGTSS評(píng)分比較，差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）。治療4、8、12、24、36、48周時(shí)，3組患兒的YGTSS評(píng)分均顯著低于同組治療前（P<0.05）。治療4、8、12周時(shí)，硫必利聯(lián)合可樂(lè)定組患兒的YGTSS評(píng)分均顯著低于硫必利組和可樂(lè)定組（P<0.05），而硫必利組和可樂(lè)定組比較差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）;治療24周時(shí)，硫必利聯(lián)合可樂(lè)定組患兒的YGTSS評(píng)分顯著低于硫必利組（P<0.05），而硫必利聯(lián)合可樂(lè)定組與可樂(lè)定組、硫必利組與可樂(lè)定組比較差異均無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）;治療36、48周時(shí)，3組患兒的YGTSS評(píng)分比較差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）。治療12周時(shí)，經(jīng)Bonferroni法校正P值后的結(jié)果顯示，硫必利聯(lián)合可樂(lè)定組患兒的YGTSS評(píng)分均顯著低于硫必利組和可樂(lè)定組（P<0.016 7），而硫必利組和可樂(lè)定組比較差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.016 7）。3組患兒的不良反應(yīng)總發(fā)生率比較，差異無(wú)統(tǒng)計(jì)學(xué)意義（P>0.05）。結(jié)論：可樂(lè)定、硫必利、硫必利聯(lián)合可樂(lè)定等3種用藥方案均能顯著改善TD患兒的抽動(dòng)癥狀，且安全性較好。

關(guān)鍵詞 抽動(dòng)障礙;兒童;可樂(lè)定;硫必利;有效性;安全性;隊(duì)列研究

Cohort Study on the Effectiveness and Safety of Tiapride Combined with Clonidine versus Tiapride and Clonidine Alone for Children with Tic Disorders

YANG Chunsong1，2，ZHANG Lingli1，2，YU Dan3，YANG Yaya1，2，WU Xiaofang1，2（1. Dept. of Pharmacy/Evidence-based Pharmacy Center， West China Second Hospital， Sichuan University， Chengdu 610041， China; 2. Key Laboratory of Birth Defects and Related Diseases of Women and Children， Sichuan University， Ministry of Education， Chengdu 610041， China; 3. Dept. of Genetics， Metabolism and Endocrinology， West China Second Hospital， Sichuan University， Chengdu 610041， China）

ABSTRACT? ?OBJECTIVE： To compare the effectiveness and safety of three regimens of tiapride， clonidine and tiapride combined with clonidine in the treatment of tic disorder （TD） in children. METHODS： A sequential collection of 312 children with TD from the outpatient department of West China Second Hospital of Sichuan University were conducted during Jan.-Dec. 2019. They were divided into clonidine group， tiapride group， tiapride combined with clonidine group， with 104 cases in each group. Tiapride group was given Tiapride hydrochloride tablets with initial dose of 50-100 mg per day， and the dose was gradually increased to 150-500 mg per day according to tolerance and clinical experience. Clonidine group was given Clonidine transdermal patches， once a week， with initial dose of 1 mg each week， maintenance dose of 1-2 mg each week， once a week. Tiapride combined with clonidine group was given Tiapride hydrochloride tablets （same usage and dosage as tiapride group）+Clonidine transdermal patches （same usage and dosage as clonidine group）. The treatment course of 3 groups was 3 months. After the treatment， they were followed up every 3 months （the following were expressed as 24， 36 and 48 weeks after treatment）. Yale global tie severity scale （YGTSS） scores of 3 groups were observed before treatment， after 4， 8， 12， 24， 36， 48 weeks of treatment， and the occurrence of ADR was recorded at different follow up time points. RESULTS： Before treatment， there was no statistical significance in YGTSS scores among 3 groups （P>0.05）. After 4， 8， 12， 24， 36 and 48 weeks of treatment， YGTSS scores of 3 groups were significantly lower than those before treatment （P<0.05）. After 4， 8 and 12 weeks of treatment， YGTSS scores of tiapride combined with clonidine group were significantly lower than tiapride group and clonidine group （P<0.05）， while there was no statistical significance between tiapride group and clonidine group （P>0.05）. At 24 weeks of treatment， YGTSS score of children in tiopride combined with clonidine group was significantly lower than tiopride group （P<0.05）， but there were no significant differences between tiopride combined with clonidine group and tiopride group， and between tiopride group and clonidine group （P>0.05）. After 36 and 48 weeks of treatment， there was no significant difference in YGTSS scores among 3 groups （P>0.05）. After 12 weeks of treatment， the results of P value corrected by Bonferroni method showed that YGTSS score of tiopride combined with clonidine group was significantly lower than those of tiopride group and clonidine group （P<0.016 7）， while there was no statistical significance in the difference between tiopride group and clonidine group （P>0.016 7）. There was no statistically significant difference in the total incidence of ADR among 3 groups（P>0.05）. CONCLUSIONS： Clonidine， tiapride and tiapride combined with clonidine can significantly improve the tic symptoms of TD children with good safety.