Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone

BACKGROUND: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. METHODS: This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. RESULTS: In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. CONCLUSIONS: Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.     

A randomized controlled trial of interim methadone maintenance

CONTEXT: Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. OBJECTIVE: To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior. DESIGN: Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control. SETTING: A methadone treatment program in Baltimore. PARTICIPANTS: A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. INTERVENTIONS: Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs. MAIN OUTCOME MEASURES: Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment). RESULTS: Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants. CONCLUSION: Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program.     

Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence

OBJECTIVE: Physicians may prescribe buprenorphine for opioid agonist maintenance treatment outside of narcotic treatment programs, but treatment guidelines for patients with co-occurring cocaine and opioid dependence are not available. This study compares effects of buprenorphine and methadone and evaluates the efficacy of combining contingency management with maintenance treatment for patients with co-occurring cocaine and opioid dependence. METHOD: Subjects with cocaine and opioid dependence (N=162) were provided manual-guided counseling and randomly assigned in a double-blind design to receive daily sublingual buprenorphine (12-16 mg) or methadone (65-85 mg p.o.) and to contingency management or performance feedback. Contingency management subjects received monetary vouchers for opioid- and cocaine-negative urine tests, which were conducted three times a week; voucher value escalated during the first 12 weeks for consecutive drug-free tests and was reduced to a nominal value in weeks 13-24. Performance feedback subjects received slips of paper indicating the urine test results. The primary outcome measures were the maximum number of consecutive weeks abstinent from illicit opioids and cocaine and the proportion of drug-free tests. Analytic models included two-by-two analysis of variance and mixed-model repeated-measures analysis of variance. RESULTS: Methadone-treated subjects remained in treatment significantly longer and achieved significantly longer periods of sustained abstinence and a greater proportion drug-free tests, compared with subjects who received buprenorphine. Subjects receiving contingency management achieved significantly longer periods of abstinence and a greater proportion drug-free tests during the period of escalating voucher value, compared with those who received performance feedback, but there were no significant differences between groups in these variables during the entire 24-week study. CONCLUSIONS: Methadone may be superior to buprenorphine for maintenance treatment of patients with co-occurring cocaine and opioid dependence. Combining methadone or buprenorphine with contingency management may improve treatment outcome.     

Thrice-weekly versus daily buprenorphine maintenance.

BACKGROUND: Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose. METHODS: After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use. RESULTS: There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%). CONCLUSIONS: At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.     

Supervised daily consumption, contingent take-home incentive and non-contingent take-home in methadone maintenance

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours.     

行为列联管理在美沙酮维持治疗者中的疗效:一项随机对照研究(英文)

背景为了应对海洛因依赖的严重后果,我国开展了美沙酮维持治疗(methadone maintenance treatment,MMT)项目,但是MMT依从性差。目的评估在美沙酮维持治疗中行为列联管理(contingency management,CM)对阿片类药物依赖者的作用。假设在上海市常规MMT项目基础上结合以奖励机制为基础的CM干预共12周,可提高MMT治疗依从性和增加操守程度。方法来自于3个自愿戒毒MMT门诊的160名海洛因依赖者被随机分入常规治疗组(MMT,n=80)和干预组(MMT+CM,n=80),在前12周每周评估患者的服药行为并进行尿液的毒品检测,随后在第16、20和24周分别进行上述评估检测。结果干预组和常规治疗组完成12周治疗的比例都很高,分别为87.5%和86.2%。12周中,两组服用美沙酮的平均天数差异无统计学意义[70(2.9)d与71(2.7)d],两组未吸海洛因的最长时间(分别为7.4周与6.5周)以及尿检阴性的次数(分别为7.9次与7.6次)也没有明显差异。同样,根据24周的分析提示两组间差异也无统计学意义。用成瘾严重程度指数评估成瘾程度,24周内两组完成随访者的成瘾严重程度都显著下降,但是两组间比较同样无明显差异。结论在我国上海的MMT门诊,以奖励机制为基础的行为列联管理干预并未起到提高治疗依从性和促进保持操守的作用。这与西方研究结果不同。究其原因,一是基线依从性高(86%),二是CM项目提供的奖励相对少。在CM项目中奖励是与场景相关的,因而需要对场景进行仔细的分析,了解在特定场景采用什么特定的奖励措施,以便鼓励目标人群改变行为。     

Cardiac autonomic modulation during methadone therapy among heroin users: A pilot study

Background

Methadone therapy benefits heroin users in both the medical and psychosocial dimensions. However, both heroin and methadone have cardiac toxicity. Only limited information is available describing the changes in cardiac autonomic function of heroin users and effects of methadone therapy. We conduct the current study to explore the cardiac vagal function in heroin users as well as the impact of lapse and methadone therapy.

Methods

80 heroin users from a methadone therapy clinic were distributed into 31 compliant and 49 incompliant patients according to whether they lapsed into heroin use within 10 days. 40 healthy control subjects were recruited from the community. Participants underwent electrocardiographic recordings and the heroin users were further investigated before and after methadone therapy. Spectral analysis of heart rate variability (HRV) was computed for cardiac parasympathetic modulation (high-frequency power, HF) and cardiac sympathetic modulation (normalized low-frequency power, LF%).

Results

The baseline HRV parameters found lower HF values for heroin users and lower RR interval values for patients with a recent lapse compared with the healthy control subjects. After 1 h of methadone administration, heroin users who had lapsed showed a significant increase in HF but the heroin users who had not lapsed did not.

Conclusion

Our findings suggest that heroin users show decreased cardiac vagal activity and that methadone therapy immediately facilitates vagal regulation in patients with a recent lapse. The differential patterns of autonomic alteration under methadone between those with and without lapse might offer an objective measure of lapse.     

Contingency management in opioid substitution treatment

The majority of opiate-dependent patients in substitution treatment show additional substance-related disorders. Concomitant use of heroin, alcohol, benzodiazepines or cocaine compromises treatment success. Concomitant drug use may be treated by using contingency management (CM) which is based on learning theory. In CM, abstinence from drugs, as verified by drug screenings, is reinforced directly and contingently. Reinforcers used in CM studies with substituted patients were, amongst others, vouchers and take-home privileges. Studies in the USA show a medium average effect of CM on drug consumption rates and abstinence. The effects decrease markedly after the end of the intervention. We discuss whether CM is applicable within the German substitution treatment system and how it can be combined with other interventions such as selective detoxification treatments or cognitive-behavioural programmes.     

Effectiveness of the methadone programme in the treatment of patients on a mephedrone binge and dependent on heroin: a retrospective study, 2010–19

Abstract

Objectives: The purpose of this research was to investigate the effectiveness of the methadone programme in a group of patients taking mephedrone with heroin.

Methods: The research involved 230 people who took part in the methadone programme between 2010 and 2019: 101 people on a mephedrone binge and taking heroin and 129 people addicted to heroin.

Results: Number of re-hospitalisations was higher in a group of patients on a mephedrone binge taking heroin in comparison to heroin dependent patients (91.9 vs 79.8%, p?<?0.01). The interaction of the hepatitis C virus (HCV) infection with the dose of methadone taken explains 67.6% of the variance in the frequency of hospitalisation of the patients on a mephedrone binge (p?<?0.001), and in the case of the dose of methadone alone – only 12% (p?<?0.001). Regression analysis indicated that statistically significant majority of the subjects (p?<?0.001) who received the optimal dose of methadone, namely 100–110?ml, were hospitalised once.

Conclusions: The interaction of the methadone dose with HCV infection plays a very important role in the frequency of hospitalisation of patients taking mephedrone with heroin on a regular basis.

• KEY POINTS

• The number of hospitalisations was higher in a group of patients on a mephedrone binge taking heroin in comparison to heroin dependent patients

• The interaction of the sex of the subjects and HCV infection with the dose of methadone taken explains 80.3 and 67.6% of variance in the frequency of hospitalisations, respectively

• The most optimal dose of methadone in the group of people taking mephedrone with heroin ranges between 100 and 110?ml

     

Differential regional effects of methadone maintenance compared to heroin dependence on mu-opioid receptor desensitization in rat brain

Methadone maintenance therapy has been the mainstay of treatment for heroin addiction since the 1970s. Recent studies indicate that methadone is of greater relative intrinsic efficacy than the active metabolites of heroin at mu-opioid receptors and that the extent of mu-opioid receptor desensitization is dependent upon agonist efficacy. Regional differences have been found for mu-opioid receptor desensitization with chronic heroin self-administration, and a similar paradigm was employed to compare regional differences between the effects of heroin and methadone. Rats were trained to self-administer heroin i.v., and the dose available was increased incrementally to a terminal value of 6 mg/kg for each infusion. Half of these rats were allowed to continue to self-administer heroin, while dependence was maintained in the others by hourly infusions of 3 mg/kg of methadone. A separate group of animals was kept on a low dose of heroin. Activation of G-proteins by the high efficacy agonist DAMGO was decreased to a greater extent in animals treated chronically with methadone compared with those allowed to self-administer heroin in amygdala, periaqueductal gray, and subicular nucleus. Activation of G-proteins by the partial agonist endomorphin was decreased in striatum, thalamus, and amygdala in rats from all drug treatment groups, but to a greater extent in the striatum in methadone treated rats compared with the heroin groups. Elucidating the mechanisms by which methadone induces differential desensitization of mu-opioid receptors across brain regions compared with heroin could provide insights to improve the pharmacotherapy of heroin addiction.     

武汉市美沙酮维持治疗门诊调查

目的了解武汉地区美沙酮维持治疗门诊开展概况及运行现状。方法采用从主管部门收集相关信息和现场抽样检测的方式,2010年11月对20家美沙酮维持治疗门诊及其受治者传染性疾病的感染率,服药剂量,维持率及毒品滥用情况进行调查。结果美沙酮维持治疗受治者人日均服药剂量69ml,保持率73.8%;艾滋病检测累计阳性率为0.4%,丙肝阳性率为75.1%,梅毒粗筛阳性率为2.8%;海洛因尿检阳性率为18.68%,苯丙胺阳性率为10.9%,氯胺酮阳性率为6.6%。结论武汉市美沙酮维持治疗工作已经全面展开,要继续提高海洛因依赖患者服药保持率、降低感染性疾病的感染率和减少非法物质滥用。     

Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues

OBJECTIVE: Environmental drug-related cues have been implicated as a cause of illicit heroin use during methadone maintenance treatment of heroin dependence. The authors sought to identify the functional neuroanatomy of the brain response to visual heroin-related stimuli in methadone maintenance patients. METHOD: Event-related functional magnetic resonance imaging was used to compare brain responses to heroin-related stimuli and matched neutral stimuli in 25 patients in methadone maintenance treatment. Patients were studied before and after administration of their regular daily methadone dose. RESULTS: The heightened responses to heroin-related stimuli in the insula, amygdala, and hippocampal complex, but not the orbitofrontal and ventral anterior cingulate cortices, were acutely reduced after administration of the daily methadone dose. CONCLUSIONS: The medial prefrontal cortex and the extended limbic system in methadone maintenance patients with a history of heroin dependence remains responsive to salient drug cues, which suggests a continued vulnerability to relapse. Vulnerability may be highest at the end of the 24-hour interdose interval.     

Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients.

BACKGROUND: Alteration in noradrenergic regulation as well as alteration in the hypothalamic-pituitary-adrenal (HPA) axis have been associated with opioid dependence and acute abstinence symptoms. METHODS: This double-blind, placebo-controlled study evaluated subjective, physiologic, and biochemical responses to yohimbine (.4 mg/kg, IV) in eight patients receiving methadone and compared results to those from a pool of nine healthy volunteers. All subjects were compared for panic anxiety symptom scale (PASS) scores, systolic and diastolic blood pressure, heart rate, plasma 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol. RESULTS: Yohimbine elicited objective and subjective opioid withdrawal and elevated craving for opioid drugs in methadone patients. Significant yohimbine effects were seen across the combined subject group for PASS, physiologic measures, MHPG, and cortisol. Methadone patients had lower baseline MHPG levels. Methadone group interactions with yohimbine were seen for systolic blood pressure and cortisol levels. CONCLUSIONS: Methadone-maintained patients are sensitive to the postsynaptic effects of noradrenergic-facilitating medications, experiencing greater physiologic and psychological symptoms, including an increase in craving. The effect on cortisol supports the above conclusion and is consistent with HPA axis perturbation in opioid dependence as reported in other studies and extends these observations to stable methadone-maintained patients. Medications that increase synaptic noradrenaline should be used with care in opioid-dependent patients.     

EEG findings in heroin addicts during induction and maintenance on methadone.

This study investigated changes in the EEG of addicts initially on heroin as they progressed through the induction and maintenance phases of a methadone program. Spectral analysis of bipolar recordings revealed significant consistent differences only in the eyes-closed resting state. Patients under the influence of heroin showed large sharp peaks at 9-10 c/sec, particularly in the parieto-occipital recording. Methadone induction led either to marked reduction of this peak and widening of alpha band activity or to an increase in frequency of the alpha peak to 12 c/sec. After several months of methadone the alpha peak was still absent unless heroin abuse was present, a theta peak was present in three of four patients, and the alpha bandwidth remained broad. Changes in the theta band were more difficult to interpret.     

美沙酮合并心理干预对海洛因依赖者的影响

目的:评估心理干预对美沙酮维持治疗患者的应对方式、压力感受和自我效能状况的影响。方法:将美沙酮维持治疗门诊的海洛因依赖者分为研究组(n=71)和对照组(n=55)。研究组给予为期3个月的心理干预。两组在入组时,1个月后以及3个月后评定应对方式问卷(SCSQ)、压力感受量表(PSS)、自我效能量表(SES),并进行评分比较。结果:与入组时相比,研究组干预后1个月、3个月应对方式、压力感受、自我效能评分的差异均有统计学意义(P<0.01)。干预后1个月两组间积极应对方式、压力感受评分差异有统计学意义(P<0.05),消极应对方式、自我效能评分差异无统计学意义(P>0.05);干预后3个月两组间积极应对方式、消极应对方式、压力感受、自我效能评分差异均有统计学意义(P<0.05)。两组维持治疗率差异有统计学意义(P<0.01)。结论:心理干预有利于改善海洛因依赖者的应对方式和自我效能,提高美沙酮维持治疗率。     

A web-based therapeutic workplace for the treatment of drug addiction and chronic unemployment

This article describes a Web-based therapeutic workplace intervention designed to promote heroin and cocaine abstinence and train and employ participants as data entry operators. Patients are paid to participate in training and then to perform data entry jobs in a therapeutic workplace business. Salary is linked to abstinence by requiring patients to provide drug-free urine samples to gain access to the workplace. Prior data show that a prototype of the intervention could promote drug abstinence. Preliminary data on the Web-based intervention suggest that it should be able to teach adults with histories of chronic unemployment and drug addiction to become skilled data entry operators in about 3 to 6 months. Early experience in the business provides preliminary evidence that it might become financially successful. The therapeutic workplace intervention may serve as an effective and practical long-term treatment for chronic unemployment and heroin and cocaine addiction.     

Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: a National Drug Abuse Treatment Clinical Trials Network study

BACKGROUND: Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence have improved treatment outcomes of substance abusers, but have not been widely implemented in community drug abuse treatment settings. OBJECTIVE: To compare outcomes achieved when a lower-cost prize-based contingency management treatment is added to usual care in community methadone hydrochloride maintenance treatment settings. DESIGN: Random assignment to usual care with (n = 198) or without (n = 190) abstinence incentives during a 12-week trial. SETTING: Six community-based methadone maintenance drug abuse treatment clinics in locations across the United States. PARTICIPANTS: Three hundred eighty-eight stimulant-abusing patients enrolled in methadone maintenance programs for at least 1 month and no more than 3 years. INTERVENTION: Participants submitting stimulant- and alcohol-negative samples earned draws for a chance to win prizes; the number of draws earned increased with continuous abstinence time. MAIN OUTCOME MEASURES: Total number of stimulant- and alcohol-negative samples provided, percentage of stimulant- and alcohol-negative samples provided, longest duration of abstinence, retention, and counseling attendance. RESULTS: Submission of stimulant- and alcohol-negative samples was twice as likely for incentive as for usual care group participants (odds ratio, 1.98; 95% confidence interval, 1.42-2.77). Achieving 4 or more, 8 or more, and 12 weeks of continuous abstinence was approximately 3, 9, and 11 times more likely, respectively, for incentive vs usual care participants. Groups did not differ on study retention or counseling attendance. The average cost of prizes was 120 dollars per participant. CONCLUSION: An abstinence incentive approach that paid 120 dollars in prizes per participant effectively increased stimulant abstinence in community-based methadone maintenance treatment clinics.     

参与美沙酮维持治疗的海洛因成瘾者自我报告的抑郁症状严重程度：一项横断面调查

背景：美沙酮维持治疗(methadone maintenance treatment, MMT)是一种公认的有效降低毒瘾的措施。美沙酮维持治疗可以减少海洛因成瘾戒断症状,并因此可以提供心理和社会支持,对吸毒者的康复至关重要。
　　目标：比较目前正在接受MMT的海洛因成瘾者和没有接受MMT的海洛因成瘾者之间的抑郁症状严重程度。
　　方法：本研究运用了Beck-13(13-item version of the Beck Depression Inventory, BDI-13)抑郁自评量表和人口学历史资料调查表,对中国三个城市9个美沙酮治疗中心的929例正在接受MMT的海洛因成瘾患者（平均已接受9个月MMT治疗）和已经在中心注册参加MMT治疗但尚未开始的238例海洛因成瘾患者进行评估。
　　结果：与正在接受MMT的成瘾者中有68%(628/929)报告抑郁症状相比,79%(188/238)的未治疗成瘾者报告有抑郁症状(X2=11.69,p<0.001)。未经治疗组的BDI评分中位数（四分位区间）是10.4(7.9-11.4),而MMT 组BDI评分中位数是8.0(5.7-11.6),两者有显著差异(Z=2.75, p=0.006)。在MMT组内,自我报告的抑郁症状严重程度与参加MMT时间呈负相关(rs=-0.24,Z=2.88, p=0.004)。多元线性回归分析发现,在控制所有人口学变量后,治疗组的抑郁症状严重程度仍然轻于非治疗组。在控制MMT疗效后,自我报告家庭关系较差(β=0.118,t=6.56, p<0.001)以及离异(β=0.120,t=3.73, p<0.001)的海洛因成瘾患者抑郁症状较严重。
　　结论：中度至重度抑郁症状常见于海洛因成瘾患者。MMT治疗与海洛因成瘾患者抑郁症状较轻相关,但需要采用前瞻性随机对照试验来确定MMT是否确实改善了海洛因成瘾患者的抑郁症状。与家庭成员的关系较差也与海洛因成瘾患者的抑郁症状有关,这表明对海洛因成瘾患者的治疗需要纳入一些方法来帮助海洛因成瘾患者修复由于他们成瘾造成的社会关系割裂。     

A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial

OBJECTIVE: Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment. METHOD: This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs. RESULTS: Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms. CONCLUSIONS: A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.