Challenges to antagonist blockade during sustained‐release naltrexone treatment

Aims Naltrexone is a competitive opioid antagonist that effectively blocks the action of heroin and other opioid agonists. Sustained‐release naltrexone formulations are now available that provide long‐acting opioid blockade. This study investigates the use of heroin and other opioids among opioid‐dependent patients receiving treatment with long‐acting naltrexone implants, their subjective experience of drug ‘high’ after opioid use, and factors associated with opioid use. Methods Participants (n = 60) were opioid‐dependent patients receiving treatment with naltrexone implants. Outcome data on substance use, drug ‘high’, depression and criminal activity were collected over a 6‐month period. Blood samples were taken to monitor naltrexone plasma levels, and hair samples to verify self‐reported opioid use. Findings More than half [n = 34 or 56%; 95% confidence interval (CI) 44–68%)] the patients challenged the blockade with illicit opioids during the 6‐month treatment period; 44% (n = 26; 95% CI 32–56%) were abstinent from opioids. Mean opioid use was reduced from 18 [standard deviation (SD)13] days during the month preceding treatment to 6 days (SD 11) after 6 months. Of the respondents questioned on opioid ‘high’ (n = 31), nine patients (30%; 95% CI 16–47%) reported partial drug ‘high’ following illicit opioid use, and three (12%; 95% CI 3–26%) reported full ‘high’. Opioid use was associated with use of non‐opioid drugs and criminal behaviour. Conclusions Challenging naltrexone blockade with heroin on at least one occasion is common among sustained‐release naltrexone patients, but only a minority of patients use opioids regularly. Challenges represent a warning sign for poor outcomes and often occur in the context of polydrug use and social adjustment problems.     

Long-term effects of analgesics in a population of elderly nursing home residents with persistent nonmalignant pain

BACKGROUND: Little is known about the long-term effects of analgesics on functional status and well-being of nursing home residents with chronic pain. METHODS: Using the Minimum Data Set, we performed a longitudinal study of nursing home residents (n = 10,372) with persistent pain. Using propensity score adjustment techniques, we compared the effect of different analgesics on changes in physical, cognitive, emotional, and social functioning, and examined rates of adverse events over a 6-month period. RESULTS: There was no change in the analgesic class for at least 6 months for 35.4% of residents, including 40% who received no analgesics during this time. Use of nonopioids was 37.9%, short-acting opioids was 18.9%, and long-acting opioids was 3.3%. We found improvement in functional status (adjusted hazard ratio = 1.85; 95% confidence interval [CI], 1.05-3.23) and social engagement (adjusted hazard ratio = 1.58; 95%, CI, 0.99-2.50) with long-acting opioids compared with short-acting opioids. There were no changes in cognitive status or mood status, or increased risk of depression with use of any analgesics, including opioids. There was a trend toward a lower risk of falls with use of any analgesics (adjusted odds ratio = 0.87; 95% CI, 0.70-1.06). Rates of other adverse events (i.e., constipation, delirium, dehydration, pneumonia) were not found to be higher among chronic opioid users compared to those taking no analgesics or nonopioids. CONCLUSIONS: The use of long-acting opioids may be a relatively safe option in the management of persistent nonmalignant pain in the nursing home population, yielding benefits in functional status and social engagement.     

Opiate users and the first years after treatment: outcome analysis of the proportion of follow up time spent in abstinence

This second report on a follow-up study of drug users focusses on changes that occurred on a number of variables between intake and follow-up and during the follow-up period. The length of abstinence from opiates was considered as a proportion of the total follow-up period. Overall there was a reduction in opiate use, in injecting and sharing equipment at follow-up. There had been, however, a high level of these risky activities during the follow-up period. Sustained abstinence from opiates was associated with increased employment, enhanced social stability and mental health. Intake drug use was strongly related to follow-up drug status. In particular, those who were injectors of multiple drugs at intake were far less likely to be long term opiate abstainers at fallow-up than those who were not injectors at intake or injectors of opiates only.     

The Relationship Between Crime and Opioid Use⋆

Accepting that opioid use and crime are associated and develop together, amongst opioid-using criminals the need for opioids may cause crime on a day-to-day basis or both may tend to be determined by some other set of factors. Previous studies have either failed to allow for such other factors, or have failed to compare opioid users to adequate control groups. From interviews with 151 Scottish prisoners and non-prisoners, divided into five drug-using groups: (1) alcohol only; (2) cannabis and alcohol; (3) other drugs but not opioids; (4) moderate opioids; (5) heavy opioids, data were obtained on drug use frequency, crime frequency and a variety of other variables. It was found that: (1) there were no differences between incarcerated and non-incarcerated opioid users, in fact incarceration had no substantial effects on other variables; (2) heavy opioid users committed crimes significantly more frequently than did moderate opioid users, non-opioid poly drug users, cannabis users or alcohol users. But, moderate opioid users did not commit crimes significantly more frequently than did the other groups; (3) other drugs were related to crime. Polydrug use (including cannabis use) was more related to theft and delinquency than was opioid use. Alcohol use was related to fraud; (4) there were larger explanations of crime than opioid use—criminal experience and polydrug use—and crime was a better explanation of opioid use variance than opioid use was of crime. It is concluded that need for opioids did not simply cause crime. Rather, crime and opioid use tended to influence each other. However, this relationship was not special to opioids but, depending on historical circumstances, could—and to some extent does—apply to any drug. In consequence, society's treatment of drug-using criminals needs to deal with drug use and crime together.     

Alcohol and Opioid Use,Co‐Use,and Chronic Pain in the Context of the Opioid Epidemic: A Critical Review

The dramatic increase in opioid misuse, opioid use disorder (OUD), and opioid‐related overdose deaths in the United States has led to public outcry, policy statements, and funding initiatives. Meanwhile, alcohol misuse and alcohol use disorder (AUD) are a highly prevalent public health problem associated with considerable individual and societal costs. This study provides a critical review of alcohol and opioid misuse, including issues of prevalence, morbidity, and societal costs. We also review research on interactions between alcohol and opioid use, the influence of opioids and alcohol on AUD and OUD treatment outcomes, respectively, the role of pain in the co‐use of alcohol and opioids, and treatment of comorbid OUD and AUD. Heavy drinking, opioid misuse, and chronic pain individually represent significant public health problems. Few studies have examined co‐use of alcohol and opioids, but available data suggest that co‐use is common and likely contributes to opioid overdose‐related morbidity and mortality. Co‐use of opioids and alcohol is related to worse outcomes in treatment for either substance. Finally, chronic pain frequently co‐occurs with use (and co‐use) of alcohol and opioids. Opioid use and alcohol use are also likely to complicate the treatment of chronic pain. Research on the interactions between alcohol and opioids, as well as treatment of the comorbid disorders is lacking. Currently, most alcohol research excludes patients with OUD and there is lack of measurement in both AUD and OUD research in relation to pain‐related functioning. Research in those with chronic pain often assesses opioid use, but rarely assesses alcohol use or AUD. New research to examine the nexus of alcohol, opioids, and pain, as well as their treatment, is critically needed.     

Comparing injecting and non-injecting illicit opioid users in a multisite Canadian sample (OPICAN Cohort)

Illicit opioid use in Canada and elsewhere increasingly involves a variety of opioids and non-injection routes of administration. Injection and non-injection opioid users tend to differ in various key characteristics. From a public health perspective, non-injection routes of opioid use tend to be less harmful due to lesser morbidity and mortality risks. Our study compared current injectors (80%) and non-injectors (20%) in a multi-site sample of regular illicit opioid users from across Canada ('OPICAN' study). In bivariate analysis, injectors and non-injectors differed by prevalence in social and health characteristics as well as drug use. Logistic regression analysis identified city, drug use, housing status and mental health problems as independent predictors of injection status. Further analysis revealed that the majority of current non-injectors had an injection history. Our results reinforce the need to explore potential interventions aimed at preventing the transition from non-injectors to injecting, or facilitating the transition of injectors to non-injecting, as initiated in several other contexts.     

Dual diagnosis patients in substance abuse treatment: relationship of general coping and substance-specific coping to 1-year outcomes

Aims. This study examined general and substance-specific coping skills and their relationship to treatment climate, continuing care and 1-year post-treatment functioning among dual diagnosis patients (i.e. co-occurrence of substance use and psychiatric disorders). Design. In a prospective multi-site study, dual diagnosis patients participating in substance abuse treatment were assessed at intake, discharge and at a 1-year follow-up. Setting. Patients were recruited from 15 substance abuse treatment programs, which were selected from a larger pool of 174 inpatient treatment programs in the Department of Veterans Affairs Health Care System. Participants. A total of 981 male dual diagnosis patients participated in the study. Measurements. Assessments included general and substance-specific coping skills, treatment climate, continuing outpatient care, abstinence and clinically significant psychiatric symptoms. Findings. Dual diagnosis patients modestly improved on general and substance-specific coping skills over the 1-year follow-up period. Patients who were in programs with a 'dual diagnosis treatment climate' and who participated in more 12-Step self-help groups showed slightly more gains in adaptive coping. Both general and substance-specific coping were associated with abstinence, but only general coping was associated with freedom from significant psychiatric symptoms. Conclusions. Enhancing general and substance-specific coping skills in substance abuse treatment may reduce dual diagnosis patients' post-treatment substance use and improve their psychological functioning.     

Prenatal methadone exposure,meconium biomarker concentrations and neonatal abstinence syndrome

Aims Methadone is standard pharmacotherapy for opioid‐dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes. Design Prospective clinical study. Setting An urban drug treatment facility treating pregnant and post‐partum women and their children. Participants Forty‐nine opioid‐dependent pregnant women received 30–110 mg methadone daily. Measurements Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice‐weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers. Findings There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid and cocaine were also found in 36.7 and 38.8 of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment. Conclusions Methadone and its metabolite 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as 3 months, rather than the currently accepted 6 months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period.     

Alcohol Use among Drug Abusers: Treatment Outcomes in a Therapeutic Community

Male and female dropouts and graduates (N = 248) from a traditional drug-free therapeutic community were followed 2 years after treatment. A 4-hr face-to-face interview traced the social adjustment one year pre-, through all years posttreatment. Results showed that (a) success (no crime and no opioid and/or no use of nonopioid primary drug) was maintained through 2 years of follow-up by 34% of the dropouts and 68% of the graduates; (b) success rates were highest among opioid abusers and the lowest among primary alcohol abusers; (c) among the latter, however, abstinence rates were significantly increased and daily use of alcohol significantly decreased as did criminal involvement; (d) among the opioid abstinent group, alcohol use increased posttreatment but heavy drinking was not prominent indicating no significant shift in substance dependency. Overall, the therapeutic community appears most effective for opioid abusers but has a clear impact on a considerable number of those primarily involved with alcohol and other substance use.     

Alcohol use among drug abusers: treatment outcome in a therapeutic community

Male and female dropouts and graduates (N = 248) from a traditional drug-free therapeutic community were followed 2 years after treatment. A 4-hr face-to-face interview traced the social adjustment one year pre-, through all years posttreatment. Results showed that (a) success (no crime and no opioid and/or no use of nonopioid primary drug) was maintained through 2 years of follow-up by 34% of the dropouts and 68% of the graduates; (b) success rates were highest among opioid abusers and the lowest among primary alcohol abusers; (c) among the latter, however, abstinence rates were significantly increased and daily use of alcohol significantly decreased as did criminal involvement; (d) among the opioid abstinent group, alcohol use increased posttreatment but heavy drinking was not prominent indicating no significant shift in substance dependency. Overall, the therapeutic community appears most effective for opioid abusers but has a clear impact on a considerable number of those primarily involved with alcohol and other substance use.     

Abstinence-contingent recovery housing and reinforcement-based treatment following opioid detoxification

Aims To conduct a randomized, controlled trial of abstinence‐contingent recovery housing delivered with or without intensive day treatment among individuals exiting residential opioid detoxification. Design Random assignment to one of three conditions: recovery housing alone (RH), abstinence‐contingent recovery housing with reinforcement‐based treatment RBT (RH + RBT) or usual care (UC). RH and RH + RBT participants received 12 weeks of paid recovery housing contingent upon drug abstinence. RH + RBT participants also received 26 weeks of RBT, initiated concurrently with recovery housing. Assessments were conducted at 1, 3 and 6 months after treatment enrollment. Setting Out‐patient drug‐free substance abuse treatment program in Baltimore, Maryland. Participants Patients (n = 243) who completed medication‐assisted opioid detoxification. Measurements Primary outcome was drug abstinence (opioid‐ and cocaine‐negative urine and no self‐reported opioid or cocaine use in the previous 30 days). Secondary outcomes included abstinence at all time‐points (1, 3 and 6 months), days in recovery housing and employment. Findings Overall rates of drug abstinence were 50% for RH + RBT, 37% for RH and 13% for UC (P < 0.001). At 6 months, RH + RBT participants remained more likely to meet abstinence criteria than UC participants (37% versus 20%, P = 0.016). Length of stay in recovery housing mediated abstinence outcomes and was longer in RH + RBT (49.5 days) than in RH (32.2 days; P < 0.002). Conclusions Abstinence‐contingent recovery housing improves abstinence in opioid‐dependent adults following medication‐assisted detoxification. The addition of intensive ‘reinforcement‐based treatment’ behavioural counseling further improves treatment outcomes, in part by promoting longer recovery house stays.     

Preliminary study of buprenorphine and bupropion for opioid-dependent smokers

In this double-blind, placebo-controlled trial, bupropion (BUPRO, 300 mg/day) was compared to placebo (PBO) for the concurrent treatment of opioid and tobacco addiction in 40 opioid-dependent smokers stabilized on buprenorphine (BUPRE, 24 mg/day). Participants received contingent, monetary reinforcement for abstinence from smoking, illicit opioids, and cocaine. Significant differences in treatment retention were observed (BUPRE+BUPRO, 58%; BUPRE+PBO, 90%). BUPRO treatment was not more effective than placebo for abstinence from tobacco, opioids, or cocaine in BUPRE-stabilized patients. These preliminary findings do not support the efficacy of BUPRO, in combination with BUPRE, for the concurrent treatment of opioid and tobacco addiction.     

A longitudinal study of male buprenorphine addicts attending an addiction clinic in India

Aim. There is a lack of longitudinal studies of buprenorphine dependence, an important opioid dependence in several countries. We investigated the course and outcome of buprenorphine dependence in an Indian clinic-attending cohort. Design. Retrospective longitudinal study. Setting. An addiction clinic in northern India. Participants. Ninety-four male patients with buprenorphine dependence, registered for treatment between 1987 and 1993. Follow-up analyses were conducted for the 52 patients (55% of the index cohort) who completed more than a year of follow-up. In 48% of these 52 patients data were obtained from their clinical records of follow-up, while 52% were contacted specifically to obtain the required data on follow up. Measurement. Baseline demographic and clinical variables; time spent in various phases of use or abstinence; outcome at the latest follow up; transition to other drugs during follow-up period. Findings. Over an average follow-up duration of 3 years, 56% of the time was spent in dependent use, 12% in non-dependent use and 32% in abstinence. By the end of follow-up, 6% of patients were dead (annual death rate 1.9%), 33% were unchanged and 61% were classified as 'improved'. The proportion of patients with 'improved' outcome increased over the years. Patients with poor outcome had shorter follow-up and hospital stay, and had used pentazocine and/or antihistaminic injections in the buprenorphine 'cocktail' more often than those with better outcome. Thirty-two patients shifted to other drugs over the years, notably heroin or polydrug use. These 'transition' patients had a family history of drug use more often, started their drug career earlier, had marital and legal complications more often, spent more time in dependent phase of drug use, underwent multiple hospital admissions but stayed for a shorter period and faced more deaths, when compared to those who did not shift. Conclusion. In clinic-attending male patients with buprenorphine dependence who were followed-up although dependent pattern of use of the drug continued for a long time in their career, there was a slow but progressive improvement. Transition to other drugs was associated with a worse course and outcome as compared to being stable on buprenorphine.     

Five-year alcohol and drug treatment outcomes of older adults versus middle-aged and younger adults in a managed care program

AIMS: This study compared 5-year treatment outcomes of older adults to those of middle-aged and younger adults in a large managed care chemical dependency program. We examined age group differences in individual, treatment and extra-treatment factors, which may influence long-term outcome. DESIGN: Seventy-seven per cent of original study participants completed a telephone interview 5 years after out-patient chemical dependency treatment at Kaiser Permanente. This sample (N = 925) included 65 patients aged 55-77, 296 patients aged 40-54 and 564 patients aged 18-39 (age at baseline). MEASUREMENTS: Measures at follow-up included alcohol and drug use, Addiction Severity Index (ASI), Alcoholics Anonymous Affiliation Scale, social resource and self-reported health questions. Mortality data were obtained from contact with family members of patients as well as automated health plan records. FINDINGS: Older adults were less likely to be drug-dependent at baseline than younger and middle-aged adults, and had longer retention in treatment than younger adults. At 5 years, older adults were less likely than younger adults to have close family or friends who encouraged alcohol or drug use. Fifty-two per cent of older adults reported total abstinence from alcohol and drugs in the previous 30 days versus 40% of younger adults. Older women had higher 30-day abstinence than older men or younger women. Among participants dependent only on alcohol, there were no significant age differences in 30-day abstinence. In logistic regression analysis, age group was not significant. Variables associated with greater age that independently predicted 30-day abstinence in the logistic regression model included longer retention in treatment and having no close family or friends who encouraged alcohol or drug use at 5 years; female gender was also significant. CONCLUSIONS: Results indicate that older adults have favorable long-term outcome following treatment relative to younger adults, but these differences may be accounted for by variables associated with age such as type of substance dependence, treatment retention, social networks and gender. Age differences in these characteristics inform intervention strategies to support long-term recovery of older adults and provide direction for investigation of how age affects outcome.     

Longitudinal predictors of depressive symptoms among low income injection drug users

Effects of changes in physical health status and drug use, and prior social support on depressive symptoms were assessed in low income injection drug users. Data are from participants (n = 503) enrolled at baseline (1994-1995) who remained at one-year follow-up (79%), of whom 37% were HIV-positive and 36% female. Physical health was measured by HIV symptoms, AIDS, CD4 count and functional limitation (IADLs). One-third scored high on depressive symptoms (CES-D > or = 16) at one-year follow-up, representing no statistically significant change from baseline (38%). In multiple logistic regression, after controlling for baseline depression scores (OR = 6.11, p < 0.001) and drug use (OR = 1.20, p = 0.192), baseline functional limitation (OR = 3.28, p < 0.001) and declining functioning (OR = 3.60, p < 0.001) were positively, and quitting drug use was negatively, associated with depressive symptoms at follow-up. Low social support at baseline (OR = 0.58, p < 0.10) was marginally predictive of depressive symptoms. Depressive symptoms did not differ by gender. For HIV-positive respondents, functional limitation was predictive of depressive symptoms, but HIV illness and drug use were not. Facilitating drug treatment and preventive medical care may aid in reducing depression in this population. For HIV-positive drug users, drug treatment prior to AIDS may help reduce depressive symptoms, with potential implications for HIV service utilization and medical adherence.     

Factors associated with abstinence,lapse or relapse to heroin use after residential treatment: protective effect of coping responses

Aims   This study investigates factors associated with abstinence, lapse or relapse to heroin use after residential treatment and, specifically, the extent to which changes in cognitive, avoidance and distraction coping responses were related to heroin use and other drug use outcomes.
Design, setting, participants  The sample comprised 242 clients from 23 residential programmes in the NTORS project, who used heroin before treatment and who were followed-up after treatment during the first 12 months of the study.
Measurements   Data on client characteristics and problems, coping responses, drug use and other outcomes, were collected by structured face-to-face interviews.
Findings   Many clients (60%) used heroin after treatment, with the first occasion of heroin use usually occurring very soon after leaving treatment: 40% remained abstinent from heroin. Analyses were conducted for three groups based upon heroin outcome status (abstinent, lapsed, relapsed). Clients who avoided a full relapse to heroin use (abstinent and lapse groups) consistently made more use of cognitive, avoidance and distraction coping strategies at follow-up than at intake. Treatment completion was related to better outcome. The lapse and relapse groups reported higher rates of use of illicit drugs other than heroin after treatment than the abstinent group.
Conclusions  Despite generally satisfactory drug use outcomes, the lapses and relapses to heroin use give rise to concern. Treatment services should develop further and strengthen relapse prevention and relapse coping skills among drug misusers.     

Slow-release oral morphine versus methadone: a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence

AIMS: To evaluate slow-release oral morphine (SROM) as an alternative maintenance pharmacotherapy to methadone for treatment of opioid dependence. DESIGN: Open-label crossover study. SETTING: Out-patient methadone maintenance programme. PARTICIPANTS: Eighteen methadone maintenance patients. Intervention Participants were transferred from methadone to SROM (once-daily Kapanol trade mark ) for approximately 6 weeks before resuming methadone maintenance. MEASUREMENTS: Patient outcomes were assessed (1) during the transition between medications (dose requirements, withdrawal severity) and (2) after at least 4 weeks on a stable dose of each drug (treatment preference, patient ratings of treatment efficacy and acceptability, drug use, health, depression and sleep). FINDINGS: Transfer from methadone to SROM was associated with relatively mild withdrawal for the first 5 days; the final mean SROM : methadone dose ratio was 4.6 : 1. Compared to methadone, SROM was associated with improved social functioning, weight loss, fewer and less troublesome side-effects, greater drug liking, reduced heroin craving, an enhanced sense of feeling 'normal' and similar outcomes for unsanctioned drug use, depression and health. The majority of subjects preferred SROM (78%) over methadone (22%). CONCLUSIONS: These findings provide justification for further evaluation of SROM as a maintenance pharmacotherapy for opioid dependence.