Lofexidine versus clonidine in rapid opiate detoxification

The aim of the present study is to evaluate lofexidine and clonidine, in an accelerated opiate detoxification procedure (3 days), without anaesthesia. Forty heroin-dependent individuals were detoxified, evaluating withdrawal symptoms, craving levels, mood changes, urine toxicologic screens, and dropout during therapy with either (1) clonidine, oxazepam, baclofen, and ketoprofene, with naloxone and naltrexone for 3 days (20 subjects) or (2) lofexidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone for 3 days (20 subjects).Both clonidine and lofexidine rapid detoxifications were found effective. The subjects treated with lofexidine showed significantly lower levels of withdrawal symptoms, fewer mood problems, less sedation and hypotension. No significant differences in craving levels, morphine metabolites in urine, or dropout rate were evidenced between the two groups. The early use of naltrexone during detoxification in combination with either alpha-2-agonist facilitated the acceptance for long-term naltrexone treatment. Lofexidine appeared to be more useful than clonidine in a 3-day accelerated opiate detoxification, not only to counteract withdrawal symptoms, but also in the treatment of dysphoria and mood changes. Because lofexidine does not produce hypotension, safe outpatient treatment, without hospital support, could be possible.     

Clonidine and opiate receptor antagonists in the treatment of heroin addiction

Good results in detoxification methods have been reached using both together clonidine and opiate receptors antagonists. One hundred fifty-two heroin-abusing patients were studied evaluating withdrawal symptoms after therapy with (a) clonidine only, (b) clonidine and naltrexone, (c) clonidine and naloxone, and (d) placebos. Treatment results, emotional and behavioral changes, and involvement in psychosocial programs were evaluated after a 6-month follow-up. Although opiate antagonists were able to induce slight and transient withdrawal signs and symptoms, there was, in the group of patients treated with clonidine and naltrexone together, a low percentage of catabolites in urine and an improvement in mood and family relationships. Furthermore, the patients that underwent longer naltrexone treatment showed a stronger involvement in psychosocial programs, and even their relatives demonstrated more interest in the recovery program. A decrease in the difficulties of accepting an opiate antagonists treatment and a different evaluation of withdrawal syndrome were the results of an early use of naltrexone.     

Clonidine Versus Long- and Short-Term Methadone-Aided Withdrawal from Opiates. An Uncontrolled Comparison

Twelve heroin addicts and one methadone addict began withdrawal from street opiates, under clonidine cover, in a general psychiatric ward. Ten (80%) of them completed it within 6 days. Clonidine doses used were lower than in similar studies and all patients were alert and mobile throughout withdrawal. Two other groups of opiate addicts, of similar age and sex, were withdrawn on standard methadone regimens. Clonidine and methadone withdrawal had similar acceptability and attrition rates. Self-reports of subjective discomfort were higher in the clonidine group without affecting compliance with treatment. Withdrawal under clonidine cover deserves further study, in view of the need for postwithdrawal treatment to prevent relapse to opiate use.     

Effects of methadone on cognition, mood and craving in detoxifying opiate addicts: a dose-response study

RATIONALE: Methadone is the most widespread pharmacological treatment for opiate dependency but relatively little is known of its effects on cognitive and psychomotor functioning, drug craving and mood. Objective: The present study aimed to assess the acute effects of methadone in patients admitted to an opiate detoxification programme. METHODS: Patients were randomly allocated to one of two groups who received either 50% or 100% of their daily stabilisation dose, and a placebo, in a double-blind, cross-over design. Twenty patients completed the study, all were assessed pre- and post-drug on 2 separate testing days. RESULTS: Performance on a task tapping episodic memory (delayed recall of a prose passage) was significantly impaired following the 100% daily dose of methadone. Methadone treatment had no effect on craving or mood. Patients were unable to distinguish between methadone and placebo treatments. CONCLUSIONS: A single dose of methadone can induce episodic memory impairment in patients who have a history of heroin use averaging more than 10 years. Such impairment can be avoided by giving methadone in divided doses.     

Use of drug combinations in treatment of opioid withdrawal.

During the last 10 years new approaches for rapid opioid detoxification have included drug combinations such as clonidine and naltrexone to speed and ease the transition from opioid agonist to antagonist maintenance. Other drug combinations include naloxone with midazolam or methohexitone for inpatients, but rapid outpatient methods are more desirable. Clonidine combined with naltrexone enables abrupt opioid withdrawal in 3-5 days in an outpatient/day setting. This approach can be further improved by transition to the partial agonist buprenorphine from either heroin or methadone followed by a 1 day detoxification using naltrexone precipitated withdrawal, ameliorated by clonidine.     

美沙酮、丁丙诺啡、可乐定、纳曲酮“阶梯式”疗法治疗海洛因依赖脱毒后复吸患者33例

采用美沙酮、丁丙诺啡、可乐定、纳曲酮为主药的“阶梯式戒毒疗法”，治疗３３例戒毒后屡次复吸的海洛因依赖者。成功戒断８例，已操守０．５ａ以上，停服纳曲酮２个月以上；仍在服纳曲酮１６例，已分别服用１－４个月，操守率７２．７％；失败９例，其中服纳曲酮１－２个月后又复吸海洛因４例，治疗中失去联系而脱试３例，服纳曲酮１次后，戒断症状重而中止，改为自然康复２例，失败率２７．３％；配合心理疏导，有显著抗复吸作用，心理依赖降低，戒毒效果良好。     

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.     

Long-term methadone maintenance reduces protracted symptoms of heroin abstinence and cue-induced craving in Chinese heroin abusers

BACKGROUND: Cession of heroin use may be followed by a protracted-abstinence (PA) syndrome consisting of craving, negative mood, and physiological changes. PA symptoms have rarely been compared between drug-free and methadone-maintained former heroin users after similar lengths of heroin abstinence. METHODS: Seventy former heroin users were included in one of four groups: in day 15-45 of methadone maintenance therapy (short-term MMT), in month 5-6 of MMT (long-term MMT), opiate-free for 15-45 days after methadone-assisted heroin detoxification (short-term post-methadone), and opiate-free for 5-6 months after methadone-assisted heroin detoxification (long-term post-methadone). PA symptoms (negative mood, dyssomnia, somatization, and craving), and blood pressure and pulse were assessed pre- and post-neutral videotape and pre- and post-heroin videotape. RESULTS: Dyssomnia and the total PA score were worst in short-term post-methadone participants, mood was best in long-term MMT participants, and cue-induced craving was least severe in long-term MMT participants. Blood pressure and pulse did not differ across groups. CONCLUSIONS: Even after acute withdrawal, the first months of heroin abstinence after methadone-assisted detoxification may be more difficult in terms of cue-induced craving and other PA symptoms than the first months of heroin abstinence during MMT. Our findings add to the literature supporting MMT for prevention of cue-induced heroin craving.     

A randomised, controlled trial of low dose naltrexone for the treatment of opioid dependence

AIM: To investigate the efficacy of low doses of naltrexone in relapse prevention for heroin dependence. DESIGN: Double blind, randomised comparison of three groups-Group 1 taking 50mg per day, Group 2: 0.5mg per day, and Group 3: 0.05 mg per day. PARTICIPANTS: Sixty-six dependent heroin users. INTERVENTIONS: After detoxification followed by 1 week on 50mg per day naltrexone, participants were randomised to trial medication. All were offered counselling and monitored with weekly clinical reviews. Research interviews were conducted at three and 6 months. OUTCOME MEASURES: Retention in treatment and heroin use at 3 and 6 months. Secondary outcome measures were side effects and craving. FINDINGS: Mean days retained in randomised treatment were-Group 1: 58.9 days; Group 2: 46.6 days; and Group 3: 47.8 days. Differences in retention were not significant using survival analysis. However, nine of the first 60 participants, transferred to the 50 mg dose, and one transferred to a lower dose (chi-square = 0.142; P = 0.018). At follow-up, there was no relationship between abstinence from heroin and naltrexone dose, nor between level of heroin use and dose. There were no differences between groups in craving or depression. CONCLUSION: Low doses of naltrexone had no discernible advantage, and participants preferred 50mg per day. Despite preference for blocking doses of naltrexone, outcomes appeared to be independent of naltrexone dose.     

可乐宁快速无成瘾性戒毒治疗的效能评估研究

通过对可乐宁与美沙酮不同戒毒效能的比较及可乐宁对于不同等级戒断症状戒毒效能的研究,可以看出可乐宁对于海洛因成瘾者的戒毒治疗是一种有效的方法。它对于各级别戒断症状都有明显的作用。由于可乐宁本身不具成瘾性,所以它是一种值得推广的戒毒治疗药物。其应用剂量以1 mg·d~(-1)左右为宜,个别戒断症状较严重的病例可将剂量提高到1.5 mg·d~(-1),或于戒毒治疗第1,2 d分别给于阿片片剂100 mg和50 mg,以提高戒断症状缓解速度。当可乐宁服用较大剂量时应加强护理,随时观察血压和脉搏的变化。避免突然直立而引起的直立性虚脱。在用药的前3 d,嗜睡、头晕、乏力等症状比较突出,但随剂量逐渐减少,这些症状也随之缓解。可乐宁戒毒治疗的突出不良反应是低血压,虽加用较小剂量三环类抗抑郁药和中药生脉饮,但尚未能得到满意效果,对此在今后的工作中需进一步进行研究并加以解决,以提高戒毒者耐受能力,使可乐宁戒毒治疗方法更加完善。     

全麻下纳曲酮快速阿片类脱毒的初步临床经验

目的··：观察全身麻醉下纳曲酮加洛非西定快速阿片类脱毒（ＲＯＤ）的治疗效果。方法··：２３例接受ＲＯＤ的海洛因依赖者与２０例１０ｄ美沙酮替代递减治疗的海洛因依赖者进行比较。接受ＲＯＤ治疗的患者进行气管插管,硫喷妥钠和氯胺酮静脉复合麻醉。麻醉诱导后,给予纳洛酮２ｍｇ,纳曲酮５０ｍｇ。麻醉结束后患者转入戒毒病房旁的监护病房。ＲＯＤ组在麻醉前及麻醉后２４ｈ,对照组在入院时及入院后ｄ５,进行戒断症状评定。结果··：ＲＯＤ组麻醉后２４ｈ的渴求、焦虑和睡眠障碍分显著低于对照组（Ｐ＜０．０１）,腹泻分高于对照组（Ｐ＜０．０１）,骨骼肌肉疼痛、恶心呕吐及总分与对照组相当（Ｐ＞０．０５）。ＲＯＤ组麻醉后２４ｈ戒断症状总分与海洛因使用量有相关关系（ｒ＝０．４２１,Ｐ＜０．０１）。ＲＯＤ组有７８．２６％的患者接受纳曲酮维持,而对照组只有１０％的患者接受。结论··：ＲＯＤ是一项可选择的脱毒方法     

The use of clonidine in detoxification from opiates

Use of clonidine hydrochloride in detoxification from opiates has demonstrated that this substance can rapidly suppress the signs and symptoms associated with opiate withdrawal. Clonidine hydrochloride, an alpha-adrenergic agonist, is a non-opiate substance. Studies to date indicate that clonidine is useful for withdrawal from methadone maintenance, where it can help in detoxifying the patient in less than 14 days (instead of the usual three to six months) with a high rate of success in achieving zero dosage. The results of a clinical investigation of clonidine are presented and discussed in this paper. It has been shown to suppress signs and symptoms of opiate withdrawal in patients taking up to 75 mg of methadone daily. Shorter-acting narcotics may be withdrawn in less than a week. To prevent relapse, post-detoxification counselling and the use of the narcotic antagonist, naltrexone, are recommended.     

Combating opiate dependence: a comparison among the available pharmacological options

Pharmacotherapies for heroin addiction may target opiate withdrawal symptoms, facilitate initiation of abstinence and/or reduce relapse to heroin use either by maintenance on an agonist or antagonist agent. Available agents include opioid agonists, partial opioid agonists, opioid antagonists and alpha 2 -agonists for use during managed withdrawal and long-term maintenance. Experimental approaches combine alpha 2 -agonists with naltrexone to reduce the time of opiate withdrawal and to accelerate the transition to abstinence. Recently, buprenorphine has been introduced in the US for office-based maintenance, with the hope of replicating the success of this treatment in Europe and Australia. Naloxone has been added to buprenorphine in order to reduce its potential diversion to intravenous use, whilst facilitating the expansion of treatment. Although comprehensive substance abuse treatment is not limited to pharmacotherapy, this review will focus on the rationale, indications and limitations of the range of existing medications for detoxification and relapse prevention treatments. The two major goals of pharmacotherapy are to relieve the severity of opiate withdrawal symptoms during the managed withdrawal of the opioid and to prevent relapse to heroin use either after abstinence initiation or after being stabilised on a long-acting opiate agonist, such as methadone.     

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.     

Experience with clonidine-naltrexone for rapid opiate detoxification

The use of naltrexone results in an accelerated opiate withdrawal. By combining clonidine with naltrexone, severity of the withdrawal is modified. This paper describes the author's experience with use of this protocol in 55 episodes of opiate detoxification. Commercially available naltrexone (Trexan) and clonidine tablets were used in the setting of a medical detoxification unit. Of 55 detoxifications, 51 were successfully completed. Results confirm the clinical utility of this protocol as evidenced by rapid detoxification, minimal dropout, and induction of naltrexone maintenance.     

Clonidine in Opiate Withdrawal: Review and Appraisal of Clinical Findings

Studies in animals and humans have demonstrated that clonidine hydrochloride, an alpha-2-nor-adrenergic agonist, significantly attenuates the opiate withdrawal syndrome. Inpatient and outpatient clinical studies have shown that clonidine is a reasonably safe, specific, and effective agent for detoxifying opiate addicts. Clonidine seems best suited for use as a transitional treatment between opiate dependence and induction onto the opiate antagonist naltrexone. Dosage regimens of clonidine must be individualized according to symptoms and side effects and closely supervised because of varying sensitivity to clonidine's sedative, hypotensive, and withdrawal-suppressing effects. Clonidine is an important new treatment option for selected opiate addicts and may be the treatment of choice when detoxification using methadone is inappropriate, unsuccessful, or unavailable. Lofexidine, a structural analogue of clonidine, may be safer and more effective as an opiate detoxification treatment. It has similar withdrawal-suppressing actions but causes little hypotension and sedation. Although clonidine and lofexidine may be highly effective in helping opiate addicts achieve initial abstinence, a multi-modality aftercare treatment approach including naltrexone and psychotherapy may be necessary to maintain an abstinent state.     

Current pharmacotherapies for opioid dependence

Pharmacotherapy of intravenous opioid abusers has taken on increased urgency with the acquired immunodeficiency syndrome (AIDS) epidemic, because in major cities intravenous drug abuse now accounts for half of new AIDS cases. The pharmacotherapy of acute dependence and withdrawal has benefited from the use of clonidine, particularly in combination with antagonist-precipitated withdrawal. However, protracted abstinence and its associated risk of relapse to drug abuse has underscored the need for maintenance pharmacotherapies. Maintenance pharmacotherapies such as methadone and naltrexone are frequently needed to sustain outpatient retention and abstinence from heroin. Methadone is more widely used than is naltrexone, an oral, long acting heroin blocker that can maintain drug abstinence after detoxification. Because of limitations in both of these maintenance agents, two investigational maintenance treatments have been tested: levo-alpha-acetylmethadol (LAAM), a long-acting form of methadone, and buprenorphine, a long-acting mixed opioid agonist-antagonist with properties similar to either methadone or naltrexone, depending on dose. Clinical use, limitations, and outcome with each medication are reviewed.