Perceptions Related to Pharmacological Treatment of Opioid Dependence Among Individuals Seeking Treatment at a Tertiary Care Center in Northern India: A Descriptive Study

Background: Perceptions of individuals with opioid dependence regarding medications used for long-term management of the condition have been explored only by a handful of studies. Interestingly, no study had compared the perceptions regarding buprenorphine, buprenorphine-naloxone, and oral naltrexone in the opioid-dependent subjects from the same setting. Objectives: The present study aimed to examine the perceptions related to treatment of opioid dependence with buprenorphine, buprenorphine-naloxone, and oral naltrexone among individuals seeking help at a tertiary care center. Methods: This was a cross-sectional, observational study with consecutive sampling. Sociodemographic data, Drug Abuse Monitoring System questionnaire, perceptions questionnaire, clinical interview to elicit drug use history, treatment history and details of prior abstinence attempts were completed. Results: Eighty-five subjects were recruited in the study. Fear of becoming dependent (35.3%) was the most common harm reported while withdrawal control (82.4%) was the most common benefit reported with buprenorphine preparations. Precipitated withdrawals (21.2%) were the most common harm reported and prevention of relapse (53%) was the most common benefit reported with oral naltrexone. While patients who believed that buprenorphine or naltrexone were harmful reported durations of treatment that were much shorter than those who did not so believe, there was no statistically significant difference in the actual duration and period of abstinence (p = .34; p = .62). Sociodemographic profile, perceptions related to dosing, nature of medication, expectations from treatment, and duration of illness were also described.     

Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings

Objective A preliminary study examined whether lofexidine decreases stress-induced and cue-induced opioid craving and improves opioid abstinence in naltrexone-treated opioid-dependent individuals. Materials and methods Eighteen opioid-dependent patients were stabilized for 4 weeks with naltrexone (50 mg daily) and lofexidine (2.4 mg bid) before entering a 4-week randomized, double-blind placebo-controlled discontinuation study where one group continued on lofexidine for an additional 4 weeks, while the second was tapered to placebo (Lofexidine–naltrexone vs Placebo–naltrexone). Ten patients also participated in guided imagery exposure to stress, drug cue, and neutral scenarios in a single laboratory session. Results Lofexidine–naltrexone patients had higher opioid abstinence rates and improved relapse outcomes as compared to the Placebo–naltrexone group. Furthermore, Lofexidine–naltrexone patients had significantly lower heart rates and an attenuated stress and drug cue-induced opioid craving response in the laboratory as compared to the Placebo–naltrexone group. Conclusions Although preliminary, these findings are the first to document lofexidine’s potential in addressing stress-related opioid craving and relapse outcomes in humans. The results also suggest that combination therapies that target both drug-related reinforcement (naltrexone) and stress- and cue-related aspects of drug seeking could be beneficial in addiction relapse prevention. Further development of lofexidine to address stress-related opioid craving and relapse is warranted.     

Can Tramadol be Used for Maintenance Treatment of Opioid Dependence?

Background: Certain limitations of the existing opioid substitution therapies necessitate exploration of other options for maintenance of patients with opioid dependence. This study aimed to present the experience of use of tramadol for long-term treatment of patients with opioid dependence. Methods: This was a cross-sectional interview-based observational study conducted in Uttar Pradesh state in India. Patients with opioid dependence who received oral tramadol treatment for a period of more than 6 months were recruited. Outcome was assessed in terms of self-reported abstinence on tramadol. Results: A total of 102 participants were recruited in the study, with a mean age of 41.3 years. All the participants were males. Abstinence to extraneous opioids was reported by 58.8% of the sample, and the median dose of tramadol at which abstinence was achieved was 350?mg/d. Those who reported to be taking natural opioids (raw opium or poppy husk) at the time of seeking treatment had higher rates of achieving abstinence. Conclusions: Tramadol may be a possible option for the maintenance treatment among some opioid-dependent individuals. Further studies are required to establish its efficacy vis-à-vis other medications used in opioid substitution treatment.     

Rapid transition from methadone to buprenorphine using naltrexone-induced withdrawal: A case report

Background: Patients taking methadone for opioid use disorder may desire transition to buprenorphine for a number of reasons. However, the current recommended approach for this transition generally takes weeks to months as an outpatient, causing considerable discomfort to the patient and a heightened risk of relapse during the transition period. Case: We describe the case of a patient on methadone maintenance who was rapidly transitioned to buprenorphine because of her desire to not return to her methadone clinic. In order to rapidly transition the patient from methadone to buprenorphine, naltrexone was administered to precipitate acute opioid withdrawal, which was followed soon after by buprenorphine induction. Discussion: Rapid transition from methadone maintenance to buprenorphine can be accomplished in inpatients by precipitating acute withdrawal with naltrexone, providing an effective alternative for patients who cannot tolerate the typical protracted methadone taper required prior to buprenorphine induction as an outpatient.     

Naltrexone alteration of acute smoking response in nicotine-dependent subjects

There are mixed results on the effects of opioid antagonists on acute nicotine response in humans. The present study examined the effects of a single dose of 50 mg oral naltrexone relative to placebo on smoking response in 22 chronic smokers during short-term nicotine abstinence, after acute smoking and subsequent smoking deprivation, and on smoking behavior in a choice paradigm. The results showed that naltrexone significantly reduced immediate postcigarette ratings of smoking craving and desire to smoke and increased light-headedness, dizziness, and head rush (ps < 0.05). Reductions in craving and smoking desire persisted during a subsequent 1 h nonsmoking interval. Naltrexone also was found to significantly reduce the total number of cigarettes smoked in the choice interval, which was supported by objective measures of both reduced CO and plasma nicotine levels (ps < 0.01). Exploratory analyses on potential individual difference factors revealed that smokers with the highest levels of craving during abstinence showed the most pronounced naltrexone attenuation of smoking response. The results support the continued exploration of naltrexone as an adjunct to smoking cessation, especially in identified smoker subgroups most sensitive to the effects of opioid antagonism.     

Gender differences in treatment and clinical characteristics among patients receiving extended release naltrexone

Further research is needed to investigate real-world acceptability of extended-release naltrexone for alcohol and opioid use disorders, and potential gender differences. This study examines treatment and clinical characteristics among men and women receiving extended-release naltrexone in a large, publicly funded substance use disorder treatment system (N = 465; 52% female). Patient demographics, treatment characteristics, and the number of extended-release naltrexone doses received were collected from administrative data and treatment program staff. Additionally, patients provided information on experiences with extended-release naltrexone in an open-ended format at 1, 2, and 3 weeks following their first injection. For a subsample of patients (N = 220), alcohol/opioid cravings and specific adverse effects were also assessed. Compared to men, women reported experiencing a higher rate and mean number of adverse effects. Overall, craving scores showed substantial reductions over time. However, among patients taking extended-release naltrexone for alcohol use, women showed a significantly greater reduction in craving scores compared to men. No gender differences were observed in the number of extended-release naltrexone doses received. Although women may have a greater need for additional support in managing early adverse effects, extended-release naltrexone as an adjunct to psychosocial treatment may be an acceptable and promising treatment approach for both men and women, and particularly for women prescribed extended-release naltrexone for alcohol use. This study contributes further information on patients’ experiences during the early course of extended-release naltrexone treatment in real-world settings. Understanding these experiences may assist policy makers and treatment providers in addressing challenges of implementing this treatment into wider practice.     

A placebo-controlled trial of memantine as an adjunct to injectable extended-release naltrexone for opioid dependence

There is preclinical support for using NMDA receptor glutamatergic antagonists to aid in naltrexone-based treatment of opioid dependence. We hypothesized that adding memantine will improve efficacy of extended-release (XR) naltrexone to prevent relapse. In this double blind study opioid-dependent participants (N = 82) underwent inpatient detoxification and naltrexone induction. During naltrexone initiation participants were randomized to receive memantine 40 mg or placebo and continued treatment for 12-weeks with XR naltrexone and relapse-prevention therapy. Sixty eight percent of participants completed detoxification and received the first dose of XR naltrexone. Rates of trial completion were significantly greater in participants receiving placebo than memantine (70% vs. 43%, p < 0.05). Severity of opioid withdrawal symptoms during the first 3 weeks of the trial appeared to be lower in the group receiving memantine (p = 0.07). Adding memantine does not appear to increase the effectiveness of injectable XR naltrexone as a relapse prevention strategy in opioid dependence and may lead to an increase in treatment drop-out.     

Discriminative stimulus effects of cyclorphan: selective antagonism with naltrexone

The opioid antagonist, naltrexone, was used to identify some of the receptor mechanisms responsible for the discriminative stimulus effects of cyclorphan in the pigeon. Subjects were trained to discriminate 10 mg/kg IM injections of either morphine or dextrorphan from saline injections in a two key drug discrimination procedure in which responding was maintained by food presentation. The dextrorphan-trained birds generalized tol-cyclorphan at 10 mg/kg; naltrexone did not alter thel-cyclorphan dose-response curve for this effect. In the morphine-trained group,l-cyclorphan produced only partial generalization, and naltrexone greatly increased the dose ofl-cyclorphan necessary to produced only These results are consistent with the conclusion that in morphine-trained pigeons the partial generalization tol-cyclorphan is mediated by opioid receptors. Moreover, limited intrinsic efficacy at mu opioid receptors may be the characteristic ofl-cyclorphan that prevents full generalization in morphine-trained pigeons.d-Cyclorphan produced partial generalization in both groups, but the involvement of opioid receptor mechanisms could not be confirmed, as 1 mg/kg naltrexone did not antagonized-cyclorphan in either group.     

Mother’s little helper? Contrasting accounts of benzodiazepine and methadone use among drug-dependent parents in the UK

Aims: To explore the ways in which opioid-dependent parents accounted for their use of opioids and benzodiazepines during and after pregnancy. Methods: Longitudinal qualitative interviews [n?=?45] with 19 opioid-dependent adults recruited in Scotland, UK, were held during the antenatal and post-natal period. Interviews focused on parenting and parenting support within the context of problem drug use and were analysed using a narrative informed, thematic analysis. Findings: The majority of participants described using benzodiazepines in addition to opioids. Almost all indicated a desire to stop or reduce opioid use, whereas cessation or reduction of benzodiazepines was rarely prioritised. In stark contrast to opioid dependence, benzodiazepine dependence was portrayed as unproblematic, therapeutic and acceptable in the context of family life. Whereas opioid dependence was framed as stigmatising, benzodiazepine use and dependence was normalised. An exception was benzodiazepine use by men which was occasionally associated with aggression and domestic abuse. Conclusions: Drug-dependent parents attach different meanings to opioid and benzodiazepine use and dependence in the context of parenthood. Divergent meanings, and stigma, may impact on stated commitment to stability or recovery from dependent drug-use. Attention should be paid to the way in which policy and practice regarding OST and benzodiazepines reflects this divergence.     

Effectiveness of low-dose naltrexone in the post-detoxification treatment of opioid dependence

BACKGROUND: The clinical use of naltrexone (NTX) in the treatment of opioid dependence has been limited because of poor compliance and inconsistent outcomes. In particular, the therapeutic benefit of extended treatment with NTX after opioid detoxification is unclear. The present study evaluated whether the augmentation with low-dose NTX during the post-detoxification treatment of opioid dependence would improve outcomes. METHODS: In an open-label naturalistic design, 435 opioid-dependent patients who had completed inpatient detoxification were offered the choice of entering 1 of the 2 outpatient treatment arms: clonidine extended treatment (CET) (clonidine + psychosocial treatment), or enhanced extended treatment (EET) (oral NTX [1-10 mg/d] + CET) for 21 days. The primary outcome measure was retention in treatment. Secondary outcomes included abstinence from opioids, dropouts, and adherence to postdischarge care. RESULTS: One hundred sixty-two patients (37.2%) accepted EET. Subjects receiving EET stayed longer in the program (F = 64.4; P = 0.000), were less likely to drop out, used less opioids, and followed through with referral to long-term outpatient treatment in a higher number, compared with patients in the CET arm (P = 0.000 in each case). The NTX + clonidine combination was safe and well tolerated. CONCLUSIONS: This preliminary study indicates the potential benefit of augmentation with low-dose NTX to improve outcomes after opioid detoxification for a preferred group of patients. Randomized controlled trials are necessary to further evaluate the role of low-dose NTX in the outpatient treatment of opioid dependence.     

The discriminative stimulus effects of naloxone and naltrexone in morphine-treated rhesus monkeys: comparison of oral and subcutaneous administration

  Rationale: Opioid antagonists are used to reverse the toxic effects of opioids, to diagnose opioid dependence and to treat opioid and other (alcohol) drug abuse. Objectives: This study compared the discriminative stimulus effects of two opioid antagonists (naloxone and naltrexone), after parenteral and oral administration. Methods: The discriminative stimulus effects of naloxone and naltrexone were evaluated every 15 min over a 2-h period in four morphine-treated (3.2 mg/kg per day) rhesus monkeys discriminating between subcutaneous (SC) injections of naltrexone (0.01 or 0.032 mg/kg) and saline, while responding under a fixed-ratio 5 schedule of stimulus shock termination. Results: Within 15 min of SC administration, naloxone and naltrexone produced greater than 90% drug-appropriate responding at doses of 0.032 and 0.01 mg/kg, respectively. The largest dose of naloxone (3.2 mg/kg) administered orally produced 82% drug-appropriate responding within 90 min; the same dose of naltrexone administered orally produced greater than 90% drug-appropriate responding within 30 min. Although both drugs were at least 100-fold more potent when administered SC, as compared to orally, there was little difference (3-fold) between the potency of naloxone and naltrexone by either route. Conclusions: These results fail to support the view that naloxone has reduced bioavailability after oral administration, as compared to naltrexone, or that its pharmacokinetic profile is particularly advantageous for some therapeutic settings (e.g. Talwin Nx). Received: 15 July 1998 / Final version: 21 December 1998     

Addiction Diagnostic Update: DSM-III-R Psychoactive Substance Use Disorders

Abstract

This article reviews the Community Reinforcement Approach (CRA) in the treatment of opioid dependence. It covers the use of CRA with both methadone maintenance patients and patients withdrawing from opioids. The data reviewed in the use of CRA in combination with methadone maintenance shows improvement in a number of areas. These include the reduction of opioid use, as well as other drugs of abuse, improved legal status, less psychiatric symptoms, and improved vocational and social functioning. CRA coupled with vouchers can assist in retaining patients in treatment long enough to improve opioid detoxification rates from buprenorphine and coupled with naltrexone may sustain abstinence. Further, the use of a standardized computerized format may extend the utility of CRA.     

The Cost Effectiveness of Naltrexone Added to Cognitive-Behavioral Therapy in the Treatment of Alcohol Dependence

ABSTRACT

The purpose of this study was to evaluate the comparative cost of treating alcohol dependence with either cognitive behavioral therapy (CBT) alone or CBT combined with naltrexone (CBT+naltrexone). Two hundred ninety-eight outpatients dependent on alcohol who were consecutively treated for alcohol dependence participated in this study. One hundred seven (36%) patients received adjunctive pharmacotherapy (CBT+naltrexone). The Drug Abuse Treatment Cost Analysis Program was used to estimate treatment costs. Adjunctive pharmacotherapy (CBT+naltrexone) introduced an additional treatment cost and was 54% more expensive than CBT alone. When treatment abstinence rates (36.1% CBT; 62.6% CBT+naltrexone) were applied to cost effectiveness ratios, CBT+naltrexone demonstrated an advantage over CBT alone. There were no differences between groups on a preference-based health measure (SF-6D). In this treatment center, to achieve 100 abstainers over a 12-week program, 280 patients require CBT compared with 160 CBT+naltrexone. The dominant choice was CBT+naltrexone based on modest economic advantages and significant efficiencies in the numbers needed to treat.     

Contingency management to enhance naltrexone treatment of opioid dependence: a randomized clinical trial of reinforcement magnitude

Fifty-five detoxified opioid-dependent individuals were randomly assigned to 1 of 3 treatments delivered over 12 weeks: standard naltrexone maintenance, standard naltrexone plus low-value contingency management (CM), or standard naltrexone plus high-value CM. Results suggest that (a) assignment to either CM condition was associated with significant reductions in opioid use over time compared with standard naltrexone treatment; (b) contrasts of high- versus low-value reinforcement magnitude were not significant, suggesting no relative benefit of higher over lower value incentives in this population; (c) participants assigned to either CM group reported significant reductions in readiness to change compared with participants assigned to standard naltrexone treatment. These findings suggest that targeted behavioral therapies can play a substantial role in broadening the utility of available pharmacotherapies.     

褪黑素对海洛因依赖大鼠的作用

目的 :观察褪黑素 (MT)对海洛因 (Her)依赖大鼠的作用。方法 :将 15 0只大鼠随机分为海洛因依赖模型组、海洛因依赖MT保护组和溶媒对照组。分别用海洛因、海洛因加MT或溶媒处理大鼠。 4 2d后将海洛因模型组大鼠随机分为MT治疗组、美沙酮治疗组、海洛因依赖组、自然戒断组、纳洛酮催促戒断组。然后观察自然戒断或ip纳洛酮催促戒断症状 ;进行淋巴细胞增殖反应和亮氨酸脑啡肽 (L -EK)以及β内啡肽 (β -EP)的测定。结果 :MT保护组及MT治疗组均显示 :MT可缓解大鼠的戒断症状 ;促进海洛因依赖大鼠脾淋巴细胞增殖 ;提高海洛因依赖大鼠脑L -EK和 β-EP水平。 结论 :MT可部分控制海洛因依赖大鼠的戒断症状 ;对海洛因造成的细胞免疫功能低下可能有预防和逆转的作用     

Methadone and buprenorphine for the management of opioid dependence in pregnancy

This article provides an overview and discussion of the collective maternal, fetal and neonatal outcome research on women maintained on methadone or buprenorphine during pregnancy. Its focus is on an assessment of the comparative effectiveness of methadone and buprenorphine pharmacotherapy, with particular attention given to recent findings from the literature. Recommendations for clinical practice are outlined, and directions for future research are presented. Findings from comparative studies of methadone and buprenorphine underscore the efficacy of both medications in preventing relapse to illicit opioid use in the treatment of opioid-dependent pregnant patients, as well as the simplicity of induction onto methadone and patient retention while receiving such therapy. Fetal monitoring suggests that buprenorphine results in less fetal cardiac and movement suppression than does methadone. The clinical implications of these findings need future exploration. For the neonate, evidence from studies using a wide range of designs, including retrospective chart reviews, prospective observational studies, and randomized clinical trials, show consistent results, with prenatal exposure to buprenorphine resulting in less severe neonatal abstinence syndrome relative to methadone. Any medication given to pregnant women should be prescribed only after considering the risk?:?benefit ratio for the maternal-fetal dyad. Medication choices for each opioid-dependent patient during pregnancy need to be made on a patient-by-patient basis, taking into consideration the patient's opioid dependence history, previous and current treatment experiences, medical circumstances and treatment preferences. Moreover, for a full remission of opioid addiction to be sustainable, both post-partum and across the lifespan, treatment providers must not rely solely on medication to treat their patients but should also utilize women-specific comprehensive treatment models that address the underlying multifaceted complexities of their patient's lives.     

Trends in Opioid Use Disorder Diagnoses and Medication Treatment Among Veterans With Posttraumatic Stress Disorder

Objective: Despite long-standing interest in posttraumatic stress disorder (PTSD) and opioid use disorder comorbidity, there is a paucity of data on the prevalence of opioid use disorder in patients with PTSD. Therefore, there is limited understanding of the use of medications for opioid use disorder in this population. We determined the prevalence of diagnosed opioid use disorder and use of medications for opioid use disorder in a large cohort of patients with PTSD. Methods: We obtained administrative and pharmacy data for veterans who initiated PTSD treatment in the Department of Veterans Affairs (VA) between 2004 and 2013 (N = 731,520). We identified those with a comorbid opioid use disorder diagnosis (2.7%; n = 19,998) and determined whether they received a medication for opioid use disorder in the year following their initial clinical PTSD diagnosis (29.6%; n = 5,913). Using logistic regression, we determined the predictors of receipt of opioid use disorder medications. Results: Comorbid opioid use disorder diagnoses increased from 2.5% in 2004 to 3.4% in 2013. Patients with comorbid opioid use disorder used more health services and had more comorbidities than other patients with PTSD. Among patients with PTSD and comorbid opioid use disorder, use of medications for opioid use disorder increased from 22.6% to 35.1% during the same time period. Growth in the use of buprenorphine (2.0% to 22.7%) was accompanied by relative decline in use of methadone (19.3% to 12.7%). Patients who received buprenorphine were younger and more likely to be rural, White, and married. Patients who received methadone were older, urban, unmarried, from racial and ethnic minorities, and more likely to see substance abuse specialists. While use of naltrexone increased (2.8% to 8.6%), most (87%) patients who received naltrexone also had an alcohol use disorder. Controlling for patient factors, there was a substantial increase in the use of buprenorphine, a substantial decrease in the use of methadone, and no change in use of naltrexone across years. Conclusions: Opioid use disorder is an uncommon but increasing comorbidity among patients with PTSD. Patients entering VA treatment for PTSD have their opioid use disorder treated with opioid agonist treatments in large and increasing numbers. There is a need for research both on the epidemiology of opioid use disorder among patients with PTSD and on screening for opioid use disorder.     

Behavioral naltrexone therapy: an integrated treatment for opiate dependence

Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.     

Web-based behavioral treatment for substance use disorders as a partial replacement of standard methadone maintenance treatment

This study is the first experimental trial to evaluate the effectiveness of a Web-based behavioral intervention when deployed in a model where it partially substituted for standard counseling in a community-based specialty addiction treatment program. New opioid-dependent intakes in methadone maintenance treatment (n = 160) were randomly assigned for 12 months to either: (1) standard treatment or (2) reduced standard treatment plus a Web-based psychosocial intervention, the Therapeutic Education System (TES). Results demonstrated that replacing a portion of standard treatment with TES resulted in significantly greater rates of objectively measured opioid abstinence (48% vs. 37% abstinence across all study weeks; F(1, 158) = 5.90, p < .05 and 59% vs. 43% abstinence on weeks participants provided urine samples for testing; F(1, 158) = 8.81, p < .01). This result was robust and was evident despite how opioid abstinence was operationally defined and evaluated. The potential implications for service delivery models within substance abuse treatment programs and other healthcare entities are discussed.     

A mu opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients

Rationale  Previous studies have demonstrated an association between genetic polymorphisms of the μ opioid receptor gene (OPRM1) and response to naltrexone treatment. The Asp40 variant genotype previously shown to be associated with naltrexone treatment response is known to be relatively common among Koreans. Objectives  This study was conducted to prospectively investigate the relationship between genotype and response to open-label naltrexone treatment in Korean alcohol-dependent subjects. Materials and methods  Sixty-three alcohol-dependent subjects were prescribed naltrexone for 12 weeks in combination with cognitive behavioral therapy. Thirty-two subjects were adherent, taking the medication at least 80% of the treatment days [16 Asn40 (A/A) patients and 16 Asp40 variant (A/G or G/G) patients]. Results  Subjects adherent to naltrexone treatment with one or two copies of the Asp40 allele took a significantly longer time than the Asn40 group to relapse (p = 0.014). Although not significant, the Asn40 group treated with naltrexone had a 10.6 times greater relapse rate than the Asp40 variant group. There was no significant difference between the Asn40 group and the Asp40 variant group treated with naltrexone in rates of abstinence. Conclusions  These results demonstrating a higher therapeutic effect of naltrexone in Korean alcohol-dependent individuals with the Asp40 variant genotype than the Asn40 genotype are consistent with previous study results in individuals of European descent. This is the first study to examine the pharmacogenetics treatment response to naltrexone in non-European subjects.