丁丙诺啡舌下含片用于海洛因依赖者脱毒治疗临床评价

目的 :评价丁丙诺啡舌下含片对海洛因依赖者脱毒的效果及不良反应。方法 :采用多中心随机双盲双模拟对照试验及无对照开放试验设计。对照试验选择 2 39例中度海洛因依赖者 ,按照 1:1:2的比例随机分入丁丙诺啡10d组、丁丙诺啡 14d组和美沙酮 14d组。另外 4 9例重度海洛因依赖者使用丁丙诺啡进行 10 - 14d脱毒治疗 ,进行开放观察。结果 :丁丙诺啡舌下含片控制戒断症状总分和主要戒断症状评分与美沙酮比较差异无显著性 (P >0 .0 5 )。焦虑量表评分丁丙诺啡组与美沙酮组比较差异也无显著性 (P >0 .0 5 )。用药前 3d丁丙诺啡单次用量最大可达 6mg ,日剂量最大为 18mg。不良反应较少 ,主要为便秘。停药后无明显戒断症状。结论 :足量使用丁丙诺啡舌下含片用于海洛因依赖脱毒治疗安全有效     

Rapid heroin detoxification using a single high dose of buprenorphine

To test the effect of 32 mg of buprenorphine on the withdrawal process from heroin, 10 street-heroin using subjects were given 32 mg of sublingual buprenorphine, following heroin abstinence of 24 hours. Withdrawal symptoms were monitored during the first few hours, and followed for six days after buprenorphine administration, after which naltrexone (50 mg) was introduced to prevent future heroin use. Nine subjects completed detoxification with negligible withdrawal symptoms and a smooth transition to naltrexone. One subject was excluded from the study due to methadone ingestion prior to experiment. These results strongly suggest that painless detoxification from heroin can be obtained by a single high dose of buprenorphine.     

Opiate detoxification under anesthesia: no apparent benefit but suppression of thyroid hormones and risk of pulmonary and renal failure

INTRODUCTION: The new technique for opiate detoxification using anesthesia and high, repetitive doses of opiate-antagonists claims to detoxify addicts without withdrawal symptoms within 24-48 hours. We studied the method with 12 opiate addicts (5 L-polamidone, 4 dihydrocodeine, 3 heroin), using general anesthesia and the antagonists naloxone 0.5 mg/kg and naltrexone > 150 mg. Objective and subjective withdrawal symptoms were measured until urine was free of drugs and patients had no withdrawal symptoms. Thyroid hormones were measured before, during, and after the anesthesia period. RESULTS: All patients had moderate to severe opiate withdrawal symptoms. No detoxification was finished within 48 hours. The dihydrocodeine subjects were compared with conventionally detoxified controls; no difference was seen. The method suppressed thyroid hormones TT3, TT4, and TSH. The study was terminated because of side effects: 1 pulmonary failure and 2 renal failures. All patients survived without sequelae. CONCLUSION: There is no obvious benefit from this method, whereas the risks are high.     

Buprenorphine: an alternative to methadone for heroin dependence treatment.

Eighty-five heroin addicts who were unwilling to receive methadone maintenance or enter therapeutic communities were assessed, single-blind, for the lowest sublingual dose of buprenorphine that blocked heroin craving (8.0 mg max). All doses were administered daily under observation. After maintenance for 4 to 12 weeks, abstinent subjects (confirmed by urine drug screens) entered a double-blind discontinuation trial and were randomly assigned to receive dose reductions (10% twice weekly for 5 weeks to zero dose, then placebo for 2 weeks) or a stable dose for 7 weeks. Subjects were terminated from discontinuation if heroin was used or they had increased craving/symptoms. Subjects completed the trial if they did not use heroin and had no increase in craving/symptoms. A wide dose range (1.5-8.0 mg/day) was effective in reducing heroin craving and use. Of 73 subjects who received buprenorphine for 4 to 52 weeks, 40 had no prior treatment, despite high levels (mean $/day heroin = 70.5 +/- 94.7) and many years (mean years = 10.7 +/- 8.6) of dependence. Subjects who received dose reductions developed abstinence symptoms, low energy most commonly, associated with drug-seeking behavior. Discontinuation trial outcome (n = 51) shows a highly significant difference between 29 subjects who received dose reductions (28 terminated, 1 completed) and 22 subjects who received no dose reductions (3 terminated; 19 completed) (chi-square = 36.08; p less than .00001). The findings suggest that buprenorphine could be an important medication for reducing demand for heroin by many heroin addicts who remain outside the present health-care system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of buspirone in the treatment of opioid withdrawal

In an attempt to develop a new opiate detoxification approach, the authors assessed the efficacy of buspirone in the treatment of acute heroin withdrawal. Buspirone, a drug interacting with the serotonergic system, was selected because there is evidence that a decrease in serotonergic neurotransmission may be involved in opiate withdrawal symptoms. Twenty-nine hospitalized heroin addicts were randomized to 4 groups: (1) placebo; (2) methadone; (3) buspirone 30 mg daily; (4) buspirone 45 mg daily. The double-blind trial started in all patients with a 5-day methadone stabilization period ending with a 30-mg dose. This was followed from days 6 through 12 by placebo in group 1 and by a methadone taper in group 2. Because of its delayed action, buspirone was started on day 1 in groups 3 and 4 and was continued, after methadone discontinuation, through day 12. On day 13, drugs and placebo were discontinued and patients were observed through day 14. Withdrawal symptoms were assessed with the "Subjective Opiate Withdrawal Scale" (SOWS) and the "Objective Opiate Withdrawal Scale" (OOWS). The SOWS and OOWS scores were significantly higher in the placebo group than in the methadone, buspirone 30 mg, and buspirone 45 mg groups. There were no significant differences in SOWS or OOWS scores when the methadone group was compared with each of the two buspirone groups or when the two buspirone groups were compared with one another. In conclusion, buspirone, a nonopiate drug with no abuse potential, a safe side effect profile and no withdrawal symptoms, at doses of 30 and 45 mg, was as effective as a methadone taper in alleviating the withdrawal symptoms of heroin addicts stabilized for 5 days with, and then withdrawn from, methadone. The use of buspirone could be particularly helpful in outpatient settings where the duration of the methadone taper recommended for detoxification can be lengthy.     

Plasma concentrations of buprenorphine 24 to 72 hours after dosing.

BACKGROUND: This study evaluated plasma buprenorphine concentrations 24-72 h following sublingual administration of a dose of buprenorphine solution, ranging from 16 mg/70 kg to 44 mg/70 kg, administered on a daily or thrice-weekly schedule. Additionally, this study evaluated the effects of different thrice-weekly buprenorphine dose schedules on opiate use and withdrawal symptoms. METHODS: Opiate dependent subjects (n = 10) were maintained in an outpatient clinic for two 3-week periods at each of three thrice-weekly buprenorphine dose schedules (providing a weekly total buprenorphine dose of 64, 84 and 112 mg) and for 1 week of a daily buprenorphine dose of 16 mg/70 kg. Plasma samples were obtained 24, 48 and 72 h following administration of buprenorphine. Urine samples were also collected and opiate withdrawal symptoms, agonist effects and the use of heroin, cocaine, alcohol and other drugs, were assessed. RESULTS: Plasma levels showed a wide range of intra- and inter-subject variability. Nonetheless, higher doses of buprenorphine resulted in higher plasma concentrations at each time point and plasma concentration decreased with time. There were no significant differences in heroin use across dosing. Rates of withdrawal symptoms were low and did not differ across dosing schedules. CONCLUSIONS: In the two highest dose schedules, plasma levels 72 h following the administration of the highest dose and at 48 h after the lower dose, were comparable to plasma concentrations at 24 h following daily administration of 16 mg/70 kg of buprenorphine.     

丁丙诺啡舌下含片用于治疗阿片类依赖首次给药时机的探讨

本文通过７３例海洛因依赖者在选用丁丙诺啡给药时机和首次剂量条件下进行的临床观察，显示用丁丙诺啡舌下含片进行脱毒治疗是行之有效的。提出了特别引起重视的用药环节即丁丙诺啡的首次剂量及给药时间问题。同时本试验的结果提示，采用盲法治疗可避免心理因素和人为因素的干扰。     

Effects of buprenorphine in heroin addicts

Twelve heroin addicts on the 8th day after withdrawal, and 8 healthy volunteers were given a single i.m. injection of buprenorphine 0.6 mg and their subjective response rated on 10 psychological variables. Pre-injection rating differed significantly between addicts and controls on 7 variables out of 10. Following buprenorphine more subjective changes were noted in the control group which became more calm, depressed, more aware of the environment, sleepy, tired, intoxicated, dizzy and nauseated. The drug addicts reported changes only in 2 variables (less tense and dysphoric) but otherwise showed no significant changes. These findings support the notion that buprenorphine induces low or normalizing effects in heroin addicts. This drug might thus be suitable for maintenance therapy in opiate addiction.     

Buprenorphine dosing regime for inpatient heroin withdrawal: a symptom-triggered dose titration study

The study aimed to identify the range of buprenorphine doses required to comfortably alleviate symptoms in patients undergoing inpatient heroin withdrawal using a symptom-triggered titration dosing regime, and to identify the patient characteristics that impact upon the buprenorphine dose requirements. The study was conducted in two Australian inpatient withdrawal units, recruiting 63 dependent, injecting heroin users with no recent methadone treatment, dependence on other drugs, or other active medical or psychiatric conditions. In a single (patient) blinded case series, placebo or 2 mg sublingual buprenorphine tablets was administered four times a day according to severity of withdrawal (assessed with Subjective Opiate Withdrawal Scale). Up to 16 mg buprenorphine was available over the first 4 days of the admission, up to 8 mg on day 5, and placebo continued until day 6. Thirty-two subjects completed the dosing regime, with mean (±S.D.) daily doses of 3.8±2.8 on day 1, 5.8±3.2 on day 2, 4.8±3.3 on day 3, 2.3±2.6 on day 4, 0.8±1.3 on day 5, and a total dose of 17.4±9.7. Higher buprenorphine doses were required by those patients with more severe psychosocial dysfunction, women, those with more frequent heroin use, and those with more severe dependence on heroin at intake. A dosing regime using sublingual buprenorphine tablets for short inpatient heroin withdrawal is proposed.     

A Preliminary Investigation of Outcome Following Gradual or Rapid Buprenorphine Detoxification

Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient detoxification schedules under double-blind, double-dummy conditions. The two detoxification schedules were buprenorphine gradual (36 days; N = 3) or buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and observer-ratings of opioid withdrawal, treatment retention and illicitopioid use. Outcome measures were similar for the two groups during buprenorphine maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use, and a drop in treatment retention occurred during rapid detoxification. Stable subject-rated opioid withdrawal and treatment retention, and less illicit-opioid use occurred during gradual detoxification. These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification.     

Intimate relationship characteristics associated with condom use among drug users and their sex partners: a multilevel analysis

This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.     

Buprenorphine maintenance treatment of heroin dependence: the first experience from Iran

The aim of this study was to assess the efficacy of 1-, 2-, and 4-mg-per-day sublingual doses of buprenorphine in the maintenance treatment of heroin-dependent patients over a 17-week treatment period. Subjects were randomized to three dosage groups. Participants consisted of 105 heroin addicts (102 men and 3 women) who met the DSM-IV criteria for opioid dependence and were seeking treatment. Subjects received buprenorphine at a dose of 1, 2, or 4 mg per day and were treated in an urban outpatient clinic, including a weekly 1-hour individual counseling session. Days retained in treatment were measured. Overall, 49 patients (46.7%) completed the 17-week study. Completion rates by dosage group were 34.3% for the 1 mg dose group, 42.9% for the 2 mg dose group, and 62.9% for the 4 mg dose group. Retention in the 4 mg dose group was significantly better than in the 1 mg dose group (P = .017). None of the other comparisons was significant. The results support the efficacy and safety of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (4 mg) of buprenorphine was the best of the three doses for Iranian heroin addicts to increase their retention in treatment.     

Tramadol versus buprenorphine for the treatment of opiate withdrawal: a retrospective cohort control study

Various drugs have been used for the treatment of opioid withdrawal, e.g., methadone, buprenorphine, and clonidine. Tramadol is a centrally acting synthetic analgesic agent with opiate activity due to low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mu opioid receptors. As a consequence, there may be a role for the use of tramadol in the treatment of opiate withdrawal. We attempt to assess the efficacy of tramadol in treating moderate heroin withdrawal through a retrospective cohort control study, conducted in a detoxification unit in a community teaching hospital. Out of 100 heroin abusers admitted for detoxification during the review period, 64 patients who were treated either with buprenorphine or tramadol, were included in this study, with 20 participants in the buprenorphine group and 44 in the tramadol group. Both groups were matched for age, sex, and self-reported average quantity of heroin used per day. In the tramadol group, the average CINA maximum was 9.0, and in the buprenorphine group it was 11.2 (P = 0.07). The use of oral clonidine per patient in the tramadol group was 1.6 tablets, and in the buprenorphine group 0.1 tablets (P = 0.002). The length of stay was 3.7 days in the tramadol group and 4.1 days in the buprenorphine group (P = 0.5). Four participants in the tramadol group received three or more doses of buprenorphine because their symptoms were not controlled, and were considered as treatment failures. These preliminary data suggest that tramadol may be comparable to buprenorphine in the management of mild to moderately severe heroin withdrawal. These findings, if reproduced in larger studies with stronger research designs, have potentially great implications for the management of opioid withdrawal in both the inpatient and outpatient setting.     

Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine

Buprenorphine and naloxone sublingual (s.l.) dose formulations may decrease parenteral buprenorphine abuse. We evaluated pharmacologic interactions between 8 mg s.l. buprenorphine combined with 0, 4, or 8 mg of naloxone in nine opiate-dependent volunteers stabilized on 8 mg s.l. buprenorphine for 7 days. Combined naloxone and buprenorphine did not diminish buprenorphine's effects on opiate withdrawal nor alter buprenorphine bioavailability. Opiate addicts stabilized on buprenorphine showed no evidence of precipitated opiate withdrawal after s.l. buprenorphine-naloxone combinations. Buprenorphine and naloxone bioavailability was approximately 40 and 10%, respectively. Intravenous buprenorphine and naloxone produced subjective effects similar to those of s.l. buprenorphine and did not precipitate opiate withdrawal.     

A comparative clinical study of the effect of WeiniCom, a Chinese herbal compound, on alleviation of withdrawal symptoms and craving for heroin in detoxification treatment

WeiniCom is a Chinese herbal compound. The purposes of this double blind study were to evaluate (1) the efficacy of WeiniCom in reducing acute opioid withdrawal symptoms and craving, and (2) the side effects of WeiniCom, in each instance by comparing WeiniCom with buprenorphine, an established opioid detoxification treatment agent. Forty-two heroin addicts meeting the criteria of dependence in DSM-IV were randomly assigned to two treatment groups: a WeiniCom group (21 cases), and a buprenorphine group (21 cases). The Withdrawal Symptom Rating Scale and the Craving Rating Scale were employed to assess acute withdrawal symptoms and craving for heroin, and the Side Effects Rating Scale was used to measure side effects in the 14-treatment period. Both the WeiniCom and buprenorphine treatments are well-tolerated and very safe. Overall, the relief from opioid withdrawal symptoms and craving was better in the WeiniCom group than in the buprenorphine group. The rate of reduction in the severity of the withdrawal symptoms was faster in the WeiniCom group than in the buprenorphine group. By day nine to 10, the WeiniCom group showed very few withdrawal symptoms. In contrast, from day five on, the buprenorphine group continued to report relatively high scores for withdrawal symptoms and craving. WeiniCom demonstrated positive effects quickly, and required a shorter treatment period to achieve a desired degree of elimination of acute withdrawal symptoms and craving.     

海洛因对人体食物摄入量及营养状况的影响

本文对１８４例海洛因成瘾者做了饮食生活习惯调查，并分别于戒毒治疗前和治疗后期采用５ｄ连续称重法做了膳食调查及体检和血、尿生化指标检测。结果表明：成瘾者在滥用毒品期间除了各种食物营养素和热能摄入量显著低于非滥用期外，体检情况及血尿生化指标变化较大。戒毒治疗后期血清蛋白含量、血红蛋白含量及体重均有明显增加，机体营养状况大为改善．调查中亦证实海洛因滥用可影响睡眠习惯及性功能．     

益安回生口服液联合丁丙诺啡治疗海洛因依赖疗效观察

目的:观察丁丙诺啡 益安回生口服液在海洛因依赖脱瘾治疗中的疗效,探索疗效好,不造成新药瘾的脱毒脱瘾方案。方法:将90例海洛因依赖患者随机分为A、B两组。A组给予丁丙诺啡舌下片 益安回生口服液。B组给予丁丙诺啡舌下片 安慰剂,对照组观察两组的脱瘾疗效。结果:两组戒断症状记分差异有非常显著性意义(P<0.01)。A组在焦虑、肌肉骨骼疼痛、失眠的分级明显优于B组。结论:益安回生口服液与丁丙诺啡舌下片联用能更有效的缓解戒断症状。     

Buprenorphine dosing regime in the management of out-patient heroin withdrawal

This study aimed to establish a buprenorphine regime suitable for the short-term management of out-patient heroin withdrawal using an open-label, single-group case series. Eighteen dependent injecting heroin users underwent an 8-day withdrawal episode with supervised dosing of sublingual Subutex tablets. Buprenorphine doses were titrated daily over a 5-day period. Fifteen subjects (83%) completed the 5-day regime, and 14 (78%) completed the 8-day withdrawal episode. The mean doses ((SD) were 6.1 (1.2) mg on day 1; 9.6 (1.7) mg on day 2; 10.1 (1.9) mg on day 3; 8.9 (2.0) mg on day 4; 4.1 (1.5) mg on day 5; and a total regime dose of 38.9 (5.8) mg. Withdrawal severity was mild, with minimal rebound upon the cessation of dosing. Five subjects reported no heroin use, and five subjects reported using on only one occasion during the 8 days. An out-patient buprenorphine regime is recommended.     

海洛因依赖者脱毒后稽延性戒断症状与渴求的关系

目的··:探讨海洛因依赖者脱毒后造成复吸的重要因素。方法··:采用海洛因稽延性戒断症状自评量表对封闭式戒毒病房的151例海洛因依赖者进行调查,了解稽延性戒断症状与渴求等因素的关系。结果··:稽延性戒断症状与渴求、脱毒时间及吸毒方式有密切关系,与渴求关系最密切的是稽延性戒断症状的睡眠障碍及焦虑项目。结论··:稽延性戒断症状与渴求紧密相关。