Outcome and Six Month Follow Up of Patients After Ultra Rapid Opiate Detoxification (URODSM)

Abstract

Objectives -(1) Evaluate the safety and efficacy of Ultra Rapid Opiate Detoxification (UROD); and (2) evaluate six month outcome data of patients choosing this method.

Design -Two center parallel group clinical trial. No grant funding.

Setting -Two academic medical centers.

Participants -Ninety-three men and 27 women, aged 18 to 55 years, with opiate dependency self selected to undergo detoxification.

Interventions -UROD followed by naltrexone maintenance and an aftercare program. UROD and aftercare costs were the responsibility of the patients and/or their significant others.

Main Outcomes Measure -(1) Completion of UROD as determined by a non reactive response to a naloxone challenge test under anesthesia and non reactive response to naltrexone administration before discharge. (2) Patient outcome as determined at six month follow up of UROD patients' self reported relapse free status confirmed by urine drug screen, significant other reports, and/or therapist reports.

Results -One hundred percent successful detoxification with UROD with low morbidity and no mortality. Relapse data were available for 111/123 procedures performed (90%), with 61/111 patients (55%) with reported relapse free status at the six month follow up interval.

Conclusions -For individuals who are addicted to opioids, the Ultra Rapid Opiate Detoxification method appears to be a viable treatment option.     

Longitudinal Treatment Effects Among Cocaine Users: A Growth Curve Modeling Approach

This study examined longitudinal treatment effects among cocaine users. The study examined a sample of 371 cocaine users screened from arrestees in jails and from patients in sexually transmitted disease clinics and emergency rooms—all in Los Angeles County during 1992–1994. Of the 371 subjects, 121 had never been in treatment and 250 reported a history of participation in drug user treatment (145 subjects' first treatment was for cocaine use and 105 were in treatment for a drug other than cocaine). Data were collected during face-to-face interviews using a natural history interview instrument. We applied a series of growth curve models to investigate treatment effects on cocaine use. For those who had been in treatment for cocaine use, use of cocaine decreased from approximately 70% before treatment to 12% after treatment entry, while no such changes were observed among those who had never been in treatment or those in treatment for other drugs. Relative to nontreated users, cocaine-treated participants showed a greater likelihood of pretreatment use for both initial status (OR = 3.58) and growth rate (OR = 1.05). After treatment entry, cocaine-treated participants as compared to nontreated participants had a lower likelihood of use (OR = 0.27), although their cocaine use after the initial status increased at a greater rate (OR = 1.03). Treated users were five times less likely to use when they were in treatment than when they were out of treatment. Longer treatment retention was related to initially reduced use but not to later rates of change in cocaine use. The study findings support that treatment for cocaine use is effective in reducing cocaine use. Longitudinal models provide opportunities to demonstrate the dynamic relationships between treatment and outcome.     

Effects of Acute Oral Naltrexone on the Subjective and Physiological Effects of Oral D-Amphetamine and Smoked Cocaine in Cocaine Abusers

Despite the prevalent worldwide abuse of stimulants, such as amphetamines and cocaine, no medications are currently approved for treating this serious public health problem. Both preclinical and clinical studies suggest that the opioid antagonist naltrexone (NTX) is effective in reducing the abuse liability of amphetamine, raising the question of whether similar positive findings would be obtained for cocaine. The purpose of this study was to evaluate the ability of oral NTX to alter the cardiovascular and subjective effects of D-amphetamine (D-AMPH) and cocaine (COC). Non-treatment-seeking COC users (N=12) completed this 3-week inpatient, randomized, crossover study. Participants received 0, 12.5, or 50 mg oral NTX 60 min before active or placebo stimulant administration during 10 separate laboratory sessions. Oral AMPH (0, 10, and 20 mg; or all placebo) was administered in ascending order within a laboratory session using a 60-min interdose interval. Smoked COC (0, 12.5, 25, and 50 mg; or all placebo) was administered in ascending order within a laboratory session using a 14-min interdose interval. Active COC and AMPH produced dose-related increases in cardiovascular function that were of comparable magnitude. In contrast, COC, but not AMPH, produced dose-related increases in several subjective measures of positive drug effect (eg, high, liking, and willingness to pay for the drug). NTX did not alter the cardiovascular effects of AMPH or COC. NTX also did not alter positive subjective ratings after COC administration, but it did significantly reduce ratings of craving for COC and tobacco during COC sessions. These results show that (1) oral AMPH produces minimal abuse-related subjective responses in COC smokers, and (2) NTX reduces craving for COC and tobacco during COC sessions. Future studies should continue to evaluate NTX as a potential anti-craving medication for COC dependence.     

Blowing Some Lines: Intracultural Variation Among Miami Cocaine Users

Abstract

The practice of injecting shared drugs, in which drug users prepare, divide and inject portions of a drug solution, is a means of transmitting HIV, HCV, and other blood-borne pathogens. This study examined the process of injecting shared drugs among drug users in San Juan, Puerto Rico, through detailed observations of 25 episodes of the injection of shared drugs, and by informal interviewing of episode participants. The ways in which price and packaging of drugs, access to drug preparation materials, and social and economic relations between drug-sharing “partners” influence the process of injecting shared drugs are explored. Because differential power relations, and in turn, injection drug users' exposure to HIV and HCV, are apparent in some drug-sharing partnerships, a key objective of this study was to extend our understanding of contributions or “investments” made by different drug-sharing partners, the benefits and costs that different partners experience, and the extent to which IDUs assume different partner roles. The findings of this small, in-depth qualitative study provide insight into drug users' motivations for injecting shared drugs, and suggest reasons why certain standardized, countrywide HIV/HCV intervention efforts have not been entirely successful in preventing the devastating illnesses that disproportionately affect injection drug users.     

Naltrexone treatment for opioid dependence: Does its effectiveness depend on testing the blockade?

Background

FDA approval of long-acting injectable naltrexone (Vivitrol) for opioid dependence highlights the relevance of understanding mechanisms of antagonist treatment. Principles of learning suggest an antagonist works through extinguishing drug-seeking behavior, as episodes of drug use (“testing the blockade”) fail to produce reinforcement.We hypothesized that opiate use would moderate the effect of naltrexone, specifically, that opiate-positive urines precede dropout in the placebo group, but not in the active-medication groups.

Methods

An 8-week, double-blind, placebo-controlled trial (N = 57), compared the efficacy of low (192 mg) and high (384 mg) doses of a long-acting injectable naltrexone (Depotrex) with placebo ( Comer et al., 2006). A Cox proportional hazard model was fit, modeling time-to-dropout as a function of treatment assignment and urine toxicology during treatment.

Results

Interaction of opiate urines with treatment group was significant. Opiate-positive urines predicted dropout on placebo and low-dose, but less so on high-dose naltrexone, where positive urines were more likely followed by sustained abstinence. Among patients with no opiate-positive urines, retention was higher in both low- and high-dose naltrexone conditions, compared to placebo.

Conclusions

Findings confirm that injection naltrexone produces extinction of drug-seeking behavior after episodes of opiate use. Adequate dosage appears important, as low-dose naltrexone resembled the placebo group; opiate positive urines were likely to be followed by dropout from treatment. The observation of high treatment retention among naltrexone-treated patients who do not test the blockade, suggests naltrexone may also exert direct effects on opiate-taking behavior that do not depend on extinction, perhaps by attenuating craving or normalizing dysregulated hedonic or neuroendocrine systems.     

Sexual Behavior and HBV Infection Among Noninjecting Cocaine Users (NICUs)

The aim is to estimate HBV prevalence and the associated risks among noninjecting cocaine users (NICUs). In 2002–2003, a total of 824 NICUs from Buenos Aires (Argentina) and Montevideo (Uruguay) were interviewed using a structured questionnaire. Serologic tests were carried out for Human Immunodeficiency Virus (HIV), hepatitis B (HBV), syphilis, and others. The population was divided into two serologic groups: HBV-infected and seronegative group. Univariate and binary logistic model were developed. The results seem to indicate that, among NICUs, HBV is transmitted through sexual contact. Prevention measures, including vaccine, are needed in order to control and minimize risks. The study's limitations are noted.     

盐酸纳曲酮防复吸初步研究

用盐酸纳曲酮胶囊对１８２例海洛因依赖者脱毒后防复吸治疗，经１２个月临床观察，结果显示：１年内防复吸治疗巩固率为２７．５％。多数人在坚持服药２个月后，恶劣心境、人格扭曲、烦躁不安等精神症状改善，提示盐酸纳曲酮是一种有效的防复吸药物，它给有戒毒愿望的海洛因依赖者摆脱毒品困扰带来一线曙光     

Quality of Life,Needs, and Interest Among Cocaine Users: Differences by Cocaine Use Intensity and Lifetime Severity of Addiction to Cocaine

We examined the quality of life (QoL) of 149 patients who were recruited in 2005 at outpatient treatment centers for cocaine dependence in Spain. Important life areas and life areas with potential need and interest to change in order to improve the QoL were analyzed in terms of patients’ cocaine use intensity within the previous six months and lifetime severity addiction to cocaine. The Spanish versions of the Drug User Quality of Life Scale and the Lifetime Severity Index for Cocaine were used to measure QoL, needs and interest, and severity addiction to cocaine. The data analysis employed t-tests, linear regression, Mann–Whitney U tests, multivariate regression, and chi-square tests. Tailoring treatment programs to address the life areas that are considered relevant to cocaine users considering their intensity of consumption and lifetime severity addiction to cocaine may improve retention and treatment outcomes. Further research needs to consider patients of different ethnic backgrounds and cultural contexts. The study's limitations are noted.     

Detection of antagonist activity for narcotic analgesics in mouse hot-plate test.

On the assumption that by the use of the hot-plate procedure the antagonist properties of narcotic analgesics could be detected, the effect of morphine, pentazocine, nalorphine and naloxone were investigated. The latency of paw-licking and jumping-off were determined and compared. The agonist, morphine, at doses of 0.025, 0.05 and 0.1 mmole/kg injected IP significantly increased paw-lick and jump-off latency above that seen in saline controls. The mixed agonist-antagonist, pentazocine, at doses of 0.048, 0.096 and 0.192 mmole/kg and nalorphine, an antagonist with some agonist activity, at doses of 0.032, 0.064 and 0.128 mmole/kg significantly increased the latency of paw-licking, but did not significantly change the jump-off latency. At a dose of 0.016 mmole/kg naloxone treated mice jumped from the hot-plate significantly sooner than controls but no effects of naloxone on paw-licking latency were observed. These results suggest that agonist properties are involved in the paw-lick response and that antagonistic properties determine jumping-off behavior.     

Bridges and barriers to recovery: Clinical observations from an opiate recovery project

Clinical issues are described in opiate addicts attempting to taper off methadone maintenance, and techniques are suggested to help this patient population. The observations were generated in an experimental “Tapering Network” project, in which opiate addicts on methadone maintenance had the opportunity to receive individual and group counseling, relapse prevention training, self-help groups, and other services. Vignettes illustrate clinical problems with intimacy and social isolation, identity as a former addict, and a “post methadone syndrome” characterized by vulnerability, dramatic swings in mood, and disordered thinking for a period of up to six months after detoxification. To counteract these barriers to recovery, a program model is suggested that uses curricula available in the emerging literature on treatment of substance abuse. These techniques can provide bridges to recovery.     

Opiate antagonists reverse the hypoactivity associated with systemic anaphylaxis in mice

Systemic anaphylaxis in the mouse is associated with marked hypoactivity. This effect is reversed by treatment with the opiate antagonists, naloxone (5–10 mg/kg) or naltrexone (1 mg/kg). Administration of naltrexone methyl bromide (1 mg/kg), a selective peripherally acting opiate antagonist, is ineffective in reversing the hypoactivity induced by anaphylaxis. These results suggest a role for central nervous system opiate mechanisms in the hypoactivity induced by anaphylaxis. They support the hypothesis that endogenous opiates contribute to the pathophysiologic consequences of anaphylactic shock.     

路脱菲及纳曲酮用于海洛因依赖者家庭戒毒治疗模式的探讨

对３６例海洛因依赖者家庭环境中戒毒治疗的观察和研究显示，在充分取得海洛因依赖者及其家属配合的基础上，合理地指导他们使用路脱菲及辅助药物，多数患者可以在家庭环境中顺利完成脱毒治疗，并能在短期内顺利转入纳曲酮维持和逐步进入系统的行为矫正、心理治疗和家庭治疗等综合性抗复吸康复治疗程序，为降低复吸率创造条件。     

Characteristics of Hidden Status Among Users of Crack, Powder Cocaine, and Heroin in Central Harlem

This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin.     

Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal

This study compares the clinical response to lofexidine and clonidine in the out-patient treatment of opiate withdrawal in 50 opiate addicts, using a randomised double-blind study design. Patients were taking 40 mg or less methadone daily, or equivalent amounts of other opiates. Fifty-eight percent of those starting treatment completed detoxification, and were opiate free at 4 weeks: more patients completed withdrawal in the lofexidine group, but the difference was not significant. Clonidine produced more hypotensive effects: more home visits were also required by medical staff. There was no other significant difference in side effects. Both drugs can be used successfully in out-patient detoxification, but lofexidine is more economical in regard to staff time.     

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.     

Is opiate detoxification unsafe in pregnancy?

Despite the widespread avoidance of detoxification in the second or third trimesters, there is no clear evidence to support the view that methadone withdrawal is harmful in pregnant opiate dependent women. We investigated the safety of methadone detoxification in pregnancy in a retrospective case series of 101 pregnant opiate dependent women who underwent a 21-day in-patient methadone withdrawal. One miscarriage occurred in the first trimester (n = 5; incidence rate ratio of 6.87 compared to population norms (95% CI = 0.16–47.3; p = .15)). No miscarriages were observed in the second trimester (n = 54; incidence rate RATIO = 0 compared to population norms (95% CI = 0–3.69; p = .27). One premature delivery occurred in the third trimester (1 in 158 weeks at risk compared to 1 in 150 weeks in population norms; p = .16). Methadone detoxification treatment was not associated with any increased risk of miscarriage in the second trimester or premature delivery in the third trimester.     

Tolerance and Sensitization to the Effects of Cocaine Use in Humans: A Retrospective Study of Long-Term Cocaine Users in Philadelphia

In the effort to develop medications to combat addiction, researchers have developed models that attempt to describe the neurobiological process of cocaine dependence. It has not, however, yet been determined which of these models, if any, best fits the behaviors and experiences of patients. This project retrospectively evaluated changes in patients' experiences with cocaine over time in order to clarify the model that best fits clinical observations. In 2005 and 2007, 100 treatment-seeking, long-term cocaine users were recruited from an urban university-based treatment center in Philadelphia, PA, United States. Each participant was administered the “Cocaine History Questionnaire” which asked them to describe the initiation and escalation of their cocaine usage, changing reward perceptions, and effects of intoxication at certain points in their drug use careers. This data was then analyzed using repeated measures, examining the within subject differences in reported information over the time points. We found evidence that while the amount of drug used increases, self-reported euphoria decreases while negative symptoms associated with cocaine use also increase. The data provide preliminary evidence for the hedonic dysregulation model of addiction. Limitations and implications of the study are discussed in the conclusion.     

快速脱毒加纳曲酮栓植入治疗海洛因依赖疗效观察

目的:寻找一种安全、有效、可靠、病人能够接受的治疗方法,以降低海洛因依赖病人的复吸率。方法:使用全麻下快速药物拮抗脱毒加纳曲酮栓植入方法,治疗海洛因依赖69例,并通过随访的方式跟踪治疗效果。结果:植入长效纳曲酮缓释栓6个月后,患者对海洛因渴求程度分值从植入前2.21±s0.58降至0.21±s0.14,再尝试海洛因率从81.25%降至5.00%。肝功能与植入前相比无明显变化。结论:全麻快速脱毒加长效纳曲酮缓释栓植入的治疗方法安全、有效、可靠,值得推广使用。     

Personality Profile in Young Current Regular Users of Cocaine

This study examined the relationship between the personality profile of a sample of cocaine users and the presence of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnoses and the severity of substance use. A total of 120 participants (46 women, mean age: 23.8 years) from nonclinical settings in Barcelona, Spain, 2003–2006, were assessed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) and the Temperament and Character Inventory-Revised version (TCI-R). Most of the participants had completed more than primary education, nearly half of them were employed, one third lived with parents, and near a quarter had some criminal record. Snorting was the main route of cocaine administration. They were using a mean of 1.82 substances. Cocaine users with low Self-Directedness, low Cooperativeness, and high Self-Transcendence scores in the TCI-R, with high severity of substance use and psychiatric comorbidity, would be suggestive of a possible specific phenotype. The limitations and implications of the study are discussed.