| 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.
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