【作者】 张本；

【导师】 栾荣生；

【作者基本信息】 四川大学 ， 流行病与卫生统计学， 2007， 博士

【摘要】 背景及目的：吸毒既是严重的健康问题又是严重的社会问题，据世界卫生组织的统计，现在世界上的吸毒人数已超过3亿，而我国的吸毒总人数估计为500万人左右并呈上升趋势。阿片类毒品成瘾性强，是非法交易的主要品种，对人类的危害亦是最大、最广泛的。目前主要依靠药物戒毒，但是药物治疗仅能暂时解除生理依赖，对心理依赖却无能为力，脱毒治疗一个月内复吸率即已高达80％，三个月内达95％，半年以上达97％，治疗成功的病人数远远低于新产生的病人数。寻找一种能够较好地解决心理依赖从而降低复吸率的疗法，成为全球科学工作者的攻关目标。现代神经科学的研究结果证实，阿片类毒品滥用所产生的成瘾和依赖与中脑边缘系统多巴胺通路密切相关。因此，采用定向手术的方法，毁损中脑边缘系统多巴胺通路中与阿片类药物心理依赖的产生密切相关的关键核团，阻断该通路以达到戒除患者对阿片类毒品心理依赖，这成为一种新的戒毒尝试方法。尽管上世纪70年代就有了采用立体定向手术治疗药物依赖的报道，但目前国外关于手术戒除阿片类毒品依赖的研究仅停留在动物试验的基础上。国内则于2000年7月开始了该项临床研究，到2004年10月止，国内共开展了1200多例手术。但是，国内这类手术共同的特点就是缺乏统一的规范和标准，手术病例较少，随访的时间尚比较短，难以评价手术的远期效果。因此，卫生部认为该项手术暂时不能作为临床服务项目向毒品依赖者提供，同时也认为此项手术有可能成为帮助毒品依赖者戒除毒瘾的技术手段之一，要求在严格的管理和监督下进行科学研究。开展此项手术的四川省的卫生行政部门组织专家研究制订科学的评价方案，对已接受手术的患者进行随访观察，以客观、科学地确定该项手术的适应症、安全性和有效性，从而提出该项手术的临床应用和深入研究的意见。本课题作为“四川地区手术戒毒科学评价研究”中的一部分，采用流行病学、心理学、社会医学、统计学以及临床医学等多学科相结合的方法，对立体定向手术治疗阿片类药物依赖近期与中期效果以及手术病人健康状况做出初步评估。主要研究目的如下：1．调查四川地区参加立体定向多靶点脑科手术治疗阿片类药物依赖（以下简称手术戒毒）患者的社会人口学特征、术前吸毒相关行为特征以及手术戒毒的基本资料，并对比手术前与术后半年时患者的复吸原因。2．初步分析四川地区手术戒毒人群在参加立体定向手术6个月后的疗效与躯体健康状况，探讨可能影响手术效果的因素。3．调查并总结手术戒毒病人在术后12个月的戒毒效果，探讨手术戒毒的疗效与美沙酮替代疗法的差异。4．评估手术戒毒患者在术后一年的生命质量、日常生活活动能力、认知功能、记忆力、心理、社会支持以及人格等健康状况相关指标，并分析术后一年复吸患者与未复吸患者的差异。5．探讨用综合评价的方法来评估研究对象健康状况的可行性，总结手术戒毒病人的健康状况。对象与方法：1．第一部分的研究对象为2004年6月至2004年11月在四川省参加脑科立体定向手术治疗阿片类药物依赖研究的所有患者，共计228人，其中208人完成了半年的随访，随访率为91.23％。第二部分研究对象为82名手术戒毒患者（手术组）和267名使用美沙酮替代疗法的阿片类药物依赖患者（未手术对照组）；两组在一年随访过程中分别有13人和27人脱落，随访率分别为84.15％和89.89％。第三部分中手术组与未手术对照组研究对象与第二部分相同，同时还设立了一个200人的健康对照组。2．在2004年11月至2005年6月期间，使用统一的调查表，采用面对面访谈、电话访谈以及信件访问的方法随访调查228名研究对象，并且辅助查阅患者的病案，随访所有的手术患者半年。运用双向随访研究，回顾性调查手术组与未手术对照组研究对象在基线调查前的复吸情况并前瞻性随访两组人群至2005年11月，以判断两组人群在接受不同戒毒疗法治疗一年后治疗效果的差异。采用吗啡胶体金检测尿液和纳络酮催瘾试验的方法来评估药物依赖者在接受治疗后的复吸情况。3．用健康体检与神经功能查体等方法评估手术戒毒患者术后半年的躯体健康状况。采用健康状况调查问卷（SF-36）、日常生活活动能力量表（ADL）、简易智能精神状态检查量表（MMSE）、韦克斯勒记忆力测验量表中文修订版（WMS-RC）、症状自评量表（SCL-90）、领悟社会支持量表（PSSS）及艾森克人格问卷（EPQ）评估手术组与未手术对照组吸毒人群接受不同治疗后一年时的健康状况。对比手术组的躯体、精神及总体健康与未手术对照组及健康人群对照组的差异；并且分析手术戒毒人群中复吸者与未复吸者健康状况的差异。4．把代表躯体健康状况的七个主要指标、精神健康状况的九个主要指标及总体健康的十六个指标用主成分分析分别拟合为各自的综合指标Q₁、Q₂、Q。根据拟合的结果对手术患者的躯体健康、精神健康、总体健康做出综合评价。5．采用成组t检验、x²检验与秩和检验分析基本资料，方差分析以及最小显著差法（LSD）法来分别处理多组资料间的比较以及有差异后的多重比较。使用生存分析计算手术戒毒患者在术后半年的累积复吸率，用非条件逐步logistic回归分析术后半年患者对非法药物的心理渴求的影响因素，可能影响术后患者复吸率的因素分析以及相对危险度的估计采用Cox比例风险回归模型。手术组与未手术对照组接受不同戒毒疗法治疗一年后的累积复吸率的计算用Log-Rank法，而两组人群累积复吸率的比较采用Kaplan-Meier法。用主成分分析拟和综合指标，使用方差分析、相关分析及x²检验处理与健康状况主观满意度有关的资料。运用SAS 9.1软件进行统计分析。结果：1．手术患者术前基本情况208名患者中男181人，女27人，平均年龄29.5岁，高中以上文化者占61.5％，主要来自四川及周边省区，职业多样。患者吸食阿片类毒品的历史平均为7.61年，吸毒剂量中位数为0.50g／次。患者均有自愿戒毒或强制戒毒史，平均戒毒13.89次，每次戒毒后均有复吸，平均操守时间为62.94天。患者术前复吸的主要原因是对毒品的心理渴求和无法忍受戒断症状。2．术后疗效半年随访术后82.67％（172／208）的患者无吸毒的欲望，84.62％（176／208）的患者无戒断症状。手术后6个月228名患者的累积戒毒概率为79.71％，其累积复吸率为20.29％（45／228）。复吸患者的平均操守时间为2.52月，复吸的高峰主要发生在术后前4个月，其复吸次数、复吸量、对毒品的主观感觉以及复吸的欣快感较术前均有明显的降低。患者复吸的主要原因是想通过吸最后一口来证明手术疗效和吸毒环境的诱发，复吸原因构成比与术前比较有统计学差异（P＜0.05）。手术并发症发生率为37.9％（79／208），多为一过性，在出院前消失或治愈。经多因素logistic回归分析，职业有无（OR=2.599）、吸烟与否（OR=7.908）、术前吸毒剂量（OR=3.427）、术前吸食毒品的频率（OR=2.453）、复吸次数（OR=0.690）以及术后戒断症状（OR=4.517）等6个因素与患者术后吸食毒品的欲望有统计学意义。多因素Cox回归分析表明，术前吸毒历史（RR=3.366）、术前吸毒频率（RR=1.835）、术后戒断症状（RR=11.091）、术后患者能否从事从前的工作或生活自理（RR=3.020），为患者发生复吸的危险因素。3．术后疗效一年随访一年随访研究中手术组男66人，女16人，招募时的平均年龄为30.67岁，术前平均吸毒7.6年；未手术对照组男206人，女61人，平均31.49岁，纳入时间前平均吸毒8.6年，两组人群在年龄、性别构成及吸毒年限无统计学差异（P＞0.05）。术后随访手术组82名患者一年，共有71名患者到达研究终点，在观察时间内有30名患者发生复吸，该组的累积戒毒概率为0.6202，其一年的累积复吸率为37.98％，对非法药物的心理渴求发生率为28.17％，复吸患者平均复吸3.43次，中位数操守时间为术后4个月。未手术对照组267名吸毒者接受美沙酮替代疗法治疗后一年，共有254人发生复吸，该组观察时间内的累积戒毒概率为0.0436，其一年的累积复吸率为95.64％，对非法药物的心理渴求发生率为91.22％，复吸患者平均复吸8.94次，中位数操守时间为接受治疗后1个月，两组人群在上述指标上的差异均有统计学意义（P＜0.05）。未手术对照组在接受美沙酮替代疗法治疗一年后，发生复吸的相对危险度是手术组的6.276倍。4．术后健康状况随访（1）生命质量：手术组在生命质量8个纬度的评分均高于未手术对照组，差异有统计学差异（P＜0.05）；手术组在生命质量的8个纬度的评分均低于健康对照组，除了情感职能纬度无统计学差异外，其它7个纬度的评分差异均有统计学意义（P＜0.05）；复吸者在术后一年时的生命质量各纬度的评分均低于未复吸者，在除情感职能外的7个纬度的评分与未复吸者相比较有统计学差异（P＜0.05）。（2）日常生活活动能力：手术组日常生活活动能力评分低于未手术对照组而高于健康对照组，评分差异均具有统计学意义（P＜0.05）；复吸者在术后一年的日常生活活动能力评分高于未复吸者，差异有统计学意义（P＜0.05）。（3）认知功能：手术组的认知功能评分高于未手术对照组而低于健康对照组，差异均有统计学意义（P＜0.05）；复吸者在术后一年的认知功能评分低于未复吸者，差异有统计学意义（P＜0.05）。（4）记忆力：手术组的记忆智商评分高于未手术对照组而低于健康对照组，差异均有统计学意义（P＜0.05）；复吸者在术后一年的记忆智商评分低于未复吸者，差异有统计学意义（P＜0.05）。（5）心理健康：手术组人群在SCL-90问卷的所有测评指标上的评分均低于未手术对照组的相应的评分，其中两组在总分，阳性项目，总均分，躯体化（f₁）、强迫症状（f₂）、忧郁（f₄）、焦虑（f₅）、敌对（f₆）、恐怖（f₇）、精神病质（f₉）和其它(f₁₀)等8个因子上的得分差异有统计学意义（P＜0.05）；而在人际关系敏感（f₃）和偏执（f₈）等两个因子上的得分与未手术对照组的差异无统计学意义（P＞0.05）；手术组在所有指标上的评分均高于健康对照组人群，差异均具有统计学意义（P＜0.05）。手术组术后一年复吸者在SCL-90所有指标的评分均高于未复吸者，评分差异均有统计学意义（P＜0.05）。对比手术前后三个不同阶段患者的心理健康指标后发现，总分、阳性项目、总均分、f₁～f₂、f₄～f₇、f₉等指标的值在术后1个月时较术前略有降低，其余3个因子在术后一月则略有升高后，所有指标到术后一年均有较大降低。（6）社会支持：手术组人群在社会支持的4个纬度评分均高于未手术对照组，差异有统计学意义（P＜0.05）；其在社会支持的4个纬度的评分均低于健康对照组人群，其中在家庭和其他人社会支持上无统计学差异（P＞0.05），在朋友社会支持及社会支持总分上有统计学差异（P＜0.05）；术后一年复吸患者的社会支持各纬度的评分均高于未复吸的患者，差异有统计学意义（P＜0.05）。（7）人格：手术组在人格测定的精神质（P分）和外向-内向（N分）上的评分均高于未手术对照组，而在神经质（E分）和掩饰（L分）的评分均低于未手术对照组，差异均有统计学意义（P＜0.05）；手术组的P分和N分均高于健康对照组，L分低于健康对照组，差异有统计学意义（P＜0.05），其E分低于健康对照组，但差异无统计学意义（P＞0.05）。术后复吸患者的P分和N分高于未复吸者，而在E分和L分则低于未复吸者，复吸与未复吸者在P分、N分、及L分上的差异有统计学意义（P＜0.05），而在E分上的差异没有统计学意义（P＞0.05）。手术患者术后一年时在人格测试的4个纬度的评分与术后一个月相比均有统计学意义（P＜0.05）；术后一个月时，其在人格测试的4个纬度的评分与术前相比均无统计学意义（P＞0.05）；术后一年与术前相比，其在P分与L分上的差异无统计学意义（P＞0.05），在N分与E分上的差异有统计学意义（P＜0.05）。5．术后健康随访综合评价（1）躯体健康综合评价：手术组术后一年躯体健康综合指标（Q₁）的评分为0.0849±3.9909，未手术对照组Q₁的评分为-4.0187±2.5494，健康对照组Q₁的评分为3.3331+1.9705；手术组术后一年Q₁的评分高于未手术组而低于健康对照组，差异均有统计学意义（P＜0.05）。术后一年时手术组的复吸者Q₁的评分为-2.8539±3.9633，未复吸者的Q₁评分为2.3379±2.1314，差异有统计学意义（P＜0.05）。（2）精神健康综合评价：手术组术后一年精神健康综合指标（Q₂）的评分为0.0493±3.7026，未手术对照组Q₂的评分为-3.0479±3.1344，健康对照组Q₂的评分为2.5320±2.7811；手术组术后一年Q₂的评分高于未手术组而低于健康对照组，差异均有统计学意义（P＜0.05）。术后一年时手术组的复吸者Q₂的评分为-3.0329±2.7003，未复吸者的Q₂评分为2.4123±2.3958，差异有统计学意义（P＜0.05）。（3）总体健康综合评价：手术组术后一年总体健康综合指标（Q）的评分为-0.3833±6.8589，未手术对照组Q的评分为-6.7713±4.2239，健康对照组Q的评分为5.7556±2.9593；手术组术后一年Q的评分高于未手术组而低于健康对照组，差异均有统计学意义（P＜0.05）。术后一年时手术组的复吸者Q的评分为-6.5977±5.0887，未复吸者的Q评分为4.3811±3.2560，差异有统计学意义（P＜0.05）。（4）健康状况主观满意度：手术组与未手术对照组及健康人群的健康主观满意度构成比均有统计学差异（P＜0.05），该人群对其健康满意的比例高于未手术对照组而低于健康对照组。结论：1．对228例手术戒毒患者的半年随访调查后发现，手术戒毒能去除75％以上患者对阿片类毒品的心理渴求、心理依赖及戒断症状。术后患者的20.29％累积复吸率与其术前全部复吸以及传统戒毒疗法治疗后半年约97％的复吸率相比降低较明显；复吸患者的复吸次数、复吸剂量、对毒品的主观感觉以及复吸的欣快感较术前均有明显的降低。相对于传统戒毒疗法而言，手术戒毒的近期戒毒效果比较满意。尽管戒毒手术对患者的躯体健康产生了一定的不良影响，但严重的特异性手术并发症发生率较低，并且术后不良反应多为一过性，在术后半年时多已恢复。2．对82例手术戒毒患者的回顾性及前瞻性随访调查发现，戒毒手术及其术后的辅助疗法治疗阿片类药物依赖有利于降低患者的复吸率、戒断症状以及对非法药物心理渴求发生率，延长复吸患者的操守时间，降低其复吸强度。与267名采用美沙酮替代疗法患者接受治疗后一年戒毒效果相比，手术戒毒获得了较满意的中期疗效，可以认为脑科立体手术治疗阿片类药物依赖与术后一年疗效之间存在可能的因果关联。3．术后半年的戒毒疗效与患者的术前吸毒行为、术后社会支持、所处社会环境以及精神心理特征等有关；躯体因素、精神心理因素以及社会支持则是影响手术患者术后一年疗效的主要因素。从总体上来看，术前脱毒效果、戒毒手术、患者所处的社会环境等因素与患者术后的短期疗效有更加直接的关系；而患者的躯体因素、精神心理因素及其社会支持则对手术的近期疗效、中期疗效甚至是远期疗效都有着不同程度的影响。术前彻底脱毒、成功的戒毒手术、患者良好的躯体与精神心理健康以及足够的社会支持，有利于其彻底戒毒。4．相对于未手术对照组人群而言，手术患者的生命质量、日常生活活动能力、认知功能以及社会支持在术后一年时得到了较大的改善；而其记忆力、心理健康以及人格的改善幅度不大；健康状况综合评价也显示无论其躯体健康与精神健康还是总体健康与正常水平仍有较大的差距；此外，手术患者对其自身的健康状况的主观满意度也不高。术后一年复吸的患者在生命质量的部分领域、日常生活活动能力、认知功能、记忆智商、心理健康、社会支持以及人格的部分领域与未复吸者尚有一定的差距，其健康状况总体评价与未复吸者相比较差。即使是未复吸的患者，其躯体健康、精神健康以及总体健康都没有达到正常水平。更多还原

【Abstract】 Background and Objectives:Drug abuse is a serious health problem and social problem, with an estimated 300 millions long-term users of drugs in the world and it was estimated that there were about 5 millions drug users in China. Opiate drugs, with stronger addiction, were the primary drugs in illegal trade, and the most dangerous drugs to human beings. At present time, drug abstinence relies mainly on medication and drug dependence can partly remove through physiological detoxification and elimination of abstinence syndromes for a while. However, psychological dependence and relapse after withdrawal have been treated ineffective. Relapse rates after detoxification are 80%-85%, 95% and 97% within one month, 3 months and half a year, respectively. The number of new patients was much more than that of patients with successful treatment. Exploring a new way to effectively alleviate psychological dependence, decline relapse rate and treat drug dependence becomes the common objective of scientists in the globe.Drug addiction and dependence induced by opiate abuse have revealed to be closely related to the mesocorticolimbic dopamine circuit, involving the ventral tegmental area, nucleus accumbency and ventral palladiums, among other regions according to modern neurosurgery. Therefore, drug abstinence by surgery, that is, ablating main nucleus in mesocorticolimbic dopamine circuit to treat opiate psychological dependence, becomes a new attempt. Nowadays, studies aboard on abstinence by making lesions in the encephalic nucleus are only limited to animal experiments in despite of there were already some reports about the surgery in the 1970s. Study domestically on abstinence by making lesions in the encephalic nucleus starting in Jul. 2000, more than 1200 patients participated in this clinical study before Oct. 2004. The common characteristics of this surgery were lack of unified criterion and standard, less cases, shorter follow-up period and difficulty in evaluating long-term effect. Consequently, Health Ministry of China halted the surgery urgently and considered that this surgery could not be provided for drug users in clinical practice owing to above reasons. At the same time, they also considered that this surgery maybe become one of way for drug abstinence. Therefore, the Ministry demanded that Sichuan Health Administration organize experts in related domains to draw scientific evaluation plan to follow up patients who accepted the surgery and assess indication, safety and validity of the surgery disinterestedly. An attitude on clinical practice and profound research for this surgery will be provided in the later on the base of assessment and follow-up. As a part of scientific evaluation study on drug abstinence by stereotactic neurosurgery in Sichuan Province, this study plan to utilize theories and methods involved in epidemiology, psychology, social medicine, biostatistics, as well as clinical medicine to evaluate the therapeutic effect of stereotactic surgery for opioid dependence and the health statuses of opiate users in postoperation more than one year primarily. The mainly study objectives are as follows.1. To investigate the social and demographic characteristics of opiates dependent users with stereotactic surgery for drug abstinence in Sichuan Province, China, as well as drug-taking related behavioral characteristics of them in preoperation, and to compare relapse reasons of these patients in preoperation with those of them in postoperation.2. To analyze the therapeutic effect of stereotactic surgery for drug abstinence and the physical health of patients in postoperation more than six months elementarily, and to explore possible factors to impact on the therapeutic effect of stereotactic surgery for treating the opiates dependence of patients in Sichuan.3. To investigate and summarize the therapeutic effect of opioid dependent users with stereotactic surgery for drug abstinence in the postoperation more than 12 months, and to compare the differences of therapeutic effect between surgery for drug abstinence and methadone substitute therapy for drug abstinence.4. To assess the health statuses involved in quality of life （QOL）, activity of daily living （ADL）, cognitive function, memory ability, psychology, social supporting, and personality for the patients with stereotactic surgery for treating their opioid dependence and compare the differences of health statuses between patients relapsed and patients unrelapsed in postoperation more than 12 months. 5. To explore the feasibility of multi-dimensional and comprehensive evaluation on the health statuses among patients with stereotactic surgery for treating their opioid dependence and to summarize their physical health, mental health and overall health.Populations and Methods:1. Study populations in the first part were 228 patients who participated in a clinical study performed by two hospitals from Jun. to Nov. 2004 in Sichuan Province; and with response rate of 91.23%, totally 208 patients finished the six-month follow-up. Study populations in the one-year follow-up investigation were 82 patients with surgery （surgical group） and 267 opiate users with methadone maintenance therapy （nonsurgical control group）. After one-year follow-up, there were 13 patients and 27 opiate users fall-up in two groups; accordingly, response rate of two groups was 84.15% and 89.89%, respectively. Study populations in surgical group and nonsurgical control group in health assessment study were same with those in the second part. Besides, we also recruited 200 healthy persons to take as a comparative group in this part （healthy person group）.2. A six-month follow-up study, using a uniform self-designed questionnaires by face-to-face and telephone interview, as well as gaining data from medical records of patients, was conducted from Nov. 2004 to Jun. 2005 in Sichuan Province. 228 patients were visited to gather information about their drug-taking and the surgery in order to obtain the socidemographic and drug-taking related behavioral characteristics of them. Then, an ambispective follow-up study was applied. In this part, we investigated the relapse of 82 patients in surgical group and 267 opiate users in nonsurgical control group before baseline investigation, retrospectively, and visited the objective populations in two groups from baseline investigation to our study termination prospectively to estimate the difference of relapse rate between two groups after they accepted different therapies one year later. Lab tests including morphine testing in urine and naloxine test were used to evaluate the therapeutic effect for drug users in follow-up.3. The physical health statuses of patients in postoperation more than six months were evaluated by physical examination and nervous function examination. In the following, we selected the MOS 36-item Short Form Health Survey （SF-36）, Activity of Daily Living Scale （ADL）, the Mini-Mental State Examination （MMSE）, Wechsler Memory Scale-Revised for Chinese （WMS-RC）, the Self-report Symptom Inventory Symptom Check-List 90 （SCL-90）, Perceived Social Supporting Scale （PSSS）, and Eysenck Personality Questionnaire （EPQ） to evaluate the health statuses of populations in surgical and nonsurgical control group after they accepted different therapies one year later. Besides, we also compared the difference of physical and mental health, as well as overall health among populations in surgical group, nonsurgical control group and healthy person group, and compared the difference of physical and mental health, as well as overall health between patients relapsed and unrelapsed.4. Seven indexes that represented physical health, nine indexes that represented mental health, and sixteen indexes that represented overall health, were integrated into their comprehensive indexes, that is, Q₁、Q₂、Q, respectively. Afterward, we evaluated the physical health, mental health, and overall health for the patients with surgery according to the score of comprehensive indexes.5. Statistical methods to analyze basic data in the study involved in this part included t-rest, x² test and rank-sum test. ANOVA and LSD were used to analyze the data among multiple groups and post multiple comparisons after significant difference occurred, respectively. We used survival analysis to calculate the cumulative relapse rate of patients in postoperation more than 6 months, unconditional stepwise logistic regression to analyze the influencing factors on patient’s desire to illegal drugs after surgery, and Cox regression to explore the influencing factors on relapse in postoperation. Survival analysis was also utilized to calculate and compare the cumulative relapse rate of populations in two groups. Furthermore, we used principal component analysis to integrate comprehensive indexes, used ANOVA, correlation analysis, and x² test to analyze the data related to subjective satisfaction to health statuses. All the data in the study were analyzed by software SAS 9.1.Results:1. Common Characteristics of Patients in PreoperationOne hundred and eighty-one male patients and twenty-seven female patients participated in this study, and their mean age was 29.5 years. Most of the respondents were in Sichuan and some peripheral province, 61.5 percent of them graduated from senior high school and over, and with various occupations. All patients abused opioid drugs before the surgery, and with the median drug-taking dose of 0.50g each time, the average duration of drug-taking was 7.6 years. All patients were detoxified by unconstraint or compulsory abstinence before surgery, with mean drug abstinent time of 13.9. However, with the average abstinent duration of 62.94 days, all patients relapsed after each detoxification. The relapse reasons of patients in preoperation centralized in drug-taking psychological desire and abstinence syndrome.2. Six-Month Follow-up of the Therapeutic Effect on Surgery for Opioid DependenceWith no drug-taking psychological desire of 82.7% （172/208）, 84.6 percent （176/208） of the patients had no any abstinence syndrome. The cumulative abstinent probability of 228 patients was 79.71% in postoperation more than 6 months, so the corresponding cumulative relapse rate of them was 20.29% （45/228）. Relapse of the patients occurred in 1 to 4 month in postoperation mainly, and the average abstinent duration of relapsed patients was 2.52 months. A significant decrease of relapse time, relapse dose, subjective feel on drugs and relapse euphoria appeared in patients who relapsed after surgery when compared with those before surgery. The relapse reasons of patients in postoperation were mainly in validating the effect of the treatment and temptation by drug-taking surroundings. There was significant difference of relapse reason ratio of these patients between preoperation and postoperation （P<0.05）. The complication rate was 37.3 %, no too many severe complications occurred in patients, and most of the complications disappeared or were healed before they discharged. The multivariate logistic regression showed potential significant predictors of drug-taking desire of patients in postoperation to involve in occupation （OR=2.599）, smoking （OR=7.908）, drug-taking dose in preoperation （OR=3.427）, drug-taking frequency in preoperation （OR=2.453）, relapse times in preoperation （OR=0.690） and abstinent syndrome in postoperation （OR=4.517）. The multivariate Cox regression indicated that possible factors to impact relapse rate after surgery included drug-taking duration in preoperation （RR - 3.366）, drug-taking frequency in preoperation （RR = 1.835）, abstinent syndrome in postoperation （RR = 11.091） and doing former work and self-living （RR = 3.020）.3. One-Year Follow-up of the Therapeutic Effect on Surgery for Opioid DependenceSixty-six male patients and sixteen female patients were enrolled in surgical group, and with average drug-taking duration of 7.6years, their mean age was 30.67 years. As saying the nonsurgical control group, 206 male and 61 female opiate users with average drug-taking duration of 8.6 years were enrolled, and their mean age was 31.49 years. There was no significant difference of age, sex, and drug-taking duration between populations in surgical group and nonsurgical control group （P>0.05）. Totally 71 patients in surgical group arrived at the study termination after 12 months visit. With relapse of 30 patients and average relapse time of 3.43 from their surgery to the last visit, the cumulative drug abstinent probability and relapse rate, and the rate of drug-taking psychological desire of 82 patients in surgical group were 0.6202,37.98%, and 28.17%, respectively. Two hundred and fifty-four drug users in nonsurgical control group relapsed after they were treated by methadone substitute therapy more than 12 months. With average relapse time of 8.94 after they accepted methadone substitute therapy more than 12 months, the cumulative drug abstinent probability and relapse rate, and the rate of drug-taking desire of 267 patients in nonsurgical control group were 0.0436,95.64%, and 91.22%, respectively. The median drug abstinent duration of study populations in surgical group and nonsurgical control group who relapsed was four months and one month, respectively, after they accepted different therapy. There was significant difference of cumulative relapse rate, the rate of drug-taking psychological desire, relapse time and drug abstinent duration between populations in surgical group and nonsurgical control group （P<0.05）. The relapse risk of opiate users in nonsurgical control group from detoxification to the last visit was 5.276 times than that of patients in surgical group after they accepted different therapy.4. One-Year Follow-up of the Health Statuses of Patients with Surgery for Opioid Dependence（1） QOL: The score on eight dimensions of QOL evaluated for patients in surgical group was higher than that for opiate users in nonsurgical control group, and significant difference was found in each comparison （PO.05）. The score on eight dimensions of QOL evaluated for patients in surgical group was lower than that for healthy person group, and other than the score role-emotional, there was significant difference in seven dimensions of QOL between two groups （P<0.05）. Also, the score on eight dimensions of QOL evaluated for patients unrelapsed was higher than that for patients relapsed, and other than the score role-emotional, there was significant difference in seven dimensions of QOL between patients unrelapsed and relapsed （P<0.05）.（2） ADL: The score of ADL evaluated for patients in surgical group was higher than that for opiate users in nonsurgical control group, was lower than that for healthy person group, and significant difference was found in each comparison （P<0.05）. The score of ADL evaluated for patients unrelapsed was lower than that for patients relapsed, and there was significant difference in score of ADL between patients unrelapsed and relapsed （P<0.05）.（3） Cognitive Function: The score of cognitive function evaluated for patients in surgical group was higher than that for opiate users in nonsurgical control group, was lower than that for healthy person group, and significant difference was found in each comparison （P<0.05）. The score of cognitive function evaluated for patients unrelapsed was lower than that for patients relapsed, and there was significant difference in score of cognitive function between patients unrelapsed and relapsed （P<0.05）.（4） Memory Ability: The score of Memory Quotient （MQ） evaluated for patients in surgical group was higher than that for opiate users in nonsurgical control group, was lower than that for healthy person group, and significant difference was found in each comparison （P<0.05）. The score of MQ evaluated for patients unrelapsed was lower than that for patients relapsed, and there was significant difference in score of MQ between patients unrelapsed and relapsed （P<0.05）.（5） Psychological Health: All the scores tested by SCL-90 evaluated the psychological health for the patients in surgical group were lower than that for populations in nonsurgical group. There was significant difference of positive items, general average, somatization （f₁）, obsessive-compulsive （f₂）, depression （f₄）, anxiety （f₅）, hostility （f₆）, phobia （f₇）, psychotism （f₉）, as well as dining and sleeping (f₁₀) between surgical group and nonsurgical control group （P<0.05）; hoverer, significant difference of interpersonal sensitivity （f₃） and paranoid ideation （f₈） was not found in populations in two groups （P>0.05）. All the scores tested by SCL-90 evaluated for the patients in surgical group were higher than that for populations in healthy person group, and the significant difference was found in each comparison （PO.05）. Moreover, all the scores tested by SCL-90 evaluated for the patients relapsed in surgical group were higher than that for patients unrelapsed, and the significant difference was found in each comparison （P<0.05）. After compared the index of psychological health for patients in preoperation, one month after surgery and in postoperation more than twelve months, we found that the score of sum, positive items, general average, f₁ -f₂、f₄-f₇、and f₉ decreased a little, and the other three factors increased a little in one month after surgery when compared with that in preoperation, and that all the scores evaluated for the patients in postoperation more than 12 months decreased a lot when compared with that in preoperation. （6） Social Supporting: All the scores tested by PSSS evaluated the social supporting for the patients in surgical group were higher than that for populations in nonsurgical group, and the significant difference was found in each comparison （P<0.05）. Significant difference of family and someone else social supporting was found when we compared them in populations between surgical group and healthy person group （P<0.05）; however, we did not find any significant difference of friend and overall social supporting in populations between surgical group and healthy person group （P>0.05）. Besides, All the scores tested by PSSS evaluated the social supporting for the patients unrelapsed were higher than that for patients relapsed, and the significant difference was found in each comparison （P<0.05）.（7） Personality: The score of psychoticism and extrovertion-introvertion tested by EPQ evaluated for patients in surgical group was higher than that for nonsurgical control group （P<0.05）, and the score of neuroticism and concealment tested by EPQ evaluated for patients in surgical group was lower than that for nonsurgical control group （P<0.05）. The score of psychoticism and extrovertion-introvertion tested by EPQ evaluated for patients in surgical group was higher than that for healthy person group （P<0.05）, and the score of concealment tested by EPQ evaluated for patients in surgical group was lower than that for nonsurgical control group （P<0.05）. Although the score of neuroticism tested by EPQ evaluated for patients in surgical group was lower than that for nonsurgical control group, there was no significant difference （P>0.05） in this comparison. The score of psychoticism and extrovertion-introvertion tested by EPQ evaluated for patients relapsed was higher than that for patients unrelapsed （P<0.05）, and the score of neuroticism and concealment tested by EPQ evaluated for patients relapsed was higher than that for patients unrelapsed （P<0.05）. Significant difference was just found in comparison of psychoticism, neuroticism, extrovertion-introvertion between patients relapsed and those unrelapsed （P<0.05）. There was significant difference of psychoticism, neuroticism, extrovertion-introvertion and concealment evaluated for patients in postoperation more than 12 months when compared with those evaluated for them in one month after surgery （P<0.05）. Whereas, there was no significant difference of psychoticism, neuroticism, extrovertion-introvertion and concealment evaluated for patients in one month after surgery when compared with those evaluated for them in preoperation （P>0.05）. Furthermore, when we compared the personality for patients in postoperation more than 12 months and one month after surgery, we found that significant difference of neuroticism and extrovertion-introvertion occurred （P<0.05）, and on the contrary, we did not find any significant difference in psychoticism and concealment （P>0.05）.5. Comprehensive Evaluation of Health Statuses（1） Comprehensive Evaluation of Physical Health: The score of Q₁ evaluated for populations in surgical group, nonsurgical control group and healthy person group was 0.0849±3.9909, -4.0187±2.5494, and 3.3331±1.9705, respectively. The score of Q₁ evaluated for patients in surgical group was higher than that for populations in nonsurgical control group （P<0.05）, and was lower than that for populations in healthy person group （P<0.05）. Besides, the score of Q₁ evaluated for patients unrelapsed in postoperation more than one year was higher than that for patients relapsed （P<0.05）, and the average score of them was 2.3379±2.1314 and -2.8539±3.9633, respectively.（2） Comprehensive Evaluation of Mental Health: The score of Q₂ evaluated for populations in surgical group, nonsurgical control group and healthy person group was 0.0493±3.7026, -3.0479±3.1344, and 2.5320±2.7811, respectively. The score of Q₂ evaluated for patients in surgical group was higher than that for populations in nonsurgical control group （P<0.05）, and was lower than that for populations in healthy person group （P<0.05）. Moreover, the score of Q₂ evaluated for patients unrelapsed in postoperation more than one year was higher than that for patients relapsed （P<0.05）, and the average score of them was 2.4123±2.3958 and -3.0329±2.7003, respectively.（3） Comprehensive Evaluation of Overall Health: The score of Q evaluated for populations in surgical group, nonsurgical control group and healthy person group was -0.3833±6.8589, -6.7713±4.2239, and 5.7556±2.9593, respectively. The score of Q evaluated for patients in surgical group was higher than that for populations in nonsurgical control group （P<0.05）, and was lower than that for populations in healthy person group （P<0.05）. Moreover, the score of Q evaluated for patients unrelapsed in postoperation more than one year was higher than that for patients relapsed （P<0.05）, and the average score of them was 4.3811±3.2560 and -6.5977±5.0887, respectively.（4） Subjective Satisfaction of Patients to Health Statuses: The ratio of subjective satisfaction of patients in surgical group to their health statuses was significant difference when compared with than that of populations in nonsurgical control and healthy person group （P<0.05）. The proportion of patients satisfied with their health statuses was higher than that of populations in nonsurgical control group and lower than that of populations in healthy person group.Conclusions:1.A six-month follow-up of 228 patients indicated that the stereotactic surgery could eliminate psychological desire to drug-taking, psychological dependence and abstinence syndrome among most of the patients. Substantial decline in relapse rate that was 20.29% appeared in these patients when compared with that of 100% among them in preoperation and that of about 97% among drug users with traditional drug abstinent therapy. The relapse time, relapse dose, subjective feel on drugs and relapse euphoria of patients relapsed decreased distinctly when compared with those of patients in preoperation. Therefore, an acceptable short-term therapeutic effect of the surgery was obtained when compared with that of traditional drug abstinent therapy. Although the side effect of the surgery affected the physical health of some patients a lot, lower rate of severe complication appeared and most of patients got well after surgery more than six months.2. The retrospective and prospective follow-up of 82 patients with surgery found that the stereotactic surgery and its assistant therapy could be helpful to decrease the rate of relapse, abstinent syndrome, and psychological desire to drug-taking among these patients, could extend the drug abstinent duration of patients relapsed, and could reduce their relapse intensity. Compared with the one-year therapeutic effect of methadone substitute therapy on 267 opiate users, the stereotactic surgery and its assistant therapy achieved much more satisfactory intermediate-stage therapeutic effect. Thereby, we could consider that potential cause and effect association existed between drug abstinence by stereotactic surgery and the therapeutic effect in postoperation more than 12 months.3. The therapeutic effect of stereotactic surgery on patients with opioid dependence in postoperation more than 6 months was relevant to drug-taking related behaviors in preoperation, social supporting in postoperation, social surroundings, as well as mental and psychological factors. Physical factors, psychological and mental factors, as well as social supporting were the main factors to impact on the therapeutic effect of patients in postoperation more than 12 months. As a whole, factors including detoxification effect in preoperation, stereotactic surgery, social surroundings, etc, were easier to influence the short-term therapeutic effect of patients in postoperation. And that, physical factors, neuropsychological and mental factors, as well as social supporting will impact on the short-term and mediate-stage, even on the long-term therapeutic effect of patients in postoperation. Therefore, complete detoxification in preoperation, successful stereotactic neurosurgery on patients, excellent physical, mental and psychological health, as well as sufficient social supporting benefited these patients to break away from the control of addiction and psychological dependence of drugs and to abstain from drugs completely.4. The QOL, ADL, cognitive functioning, and social supporting of patients in surgical group in postoperation more than 12 months improved a lot, and the memory ability, psychological health and personality of them were just ameliorated a little, when compare with those of populations in nonsurgical control group. The comprehensive evaluation of health statuses also showed that there were much more disparity on the physical health, mental health and overall health of patients to compare with the standard level. In addition, these patients in surgical group were unsatisfied with their health subjectively. Much more differences involved in part dimension of QOL, ADL, cognitive functioning, MQ, psychological health, social supporting, and personality were still found between patients relapsed and those unrelapsed. The comprehensive evaluation of health statuses also indicated that there were much more disparity on the physical health, mental health and overall health of patients relapsed when compare with those of patients unrelapsed. Furthermore, we found that the comprehensive evaluation of their physical health, mental health, as well as overall health did not arrive at the common level even though we assessed the patients unrelapsed.更多还原