The Association between Opioid Discontinuation and Heroin Use: A Nested Case-Control Study.

BACKGROUND: Opioid prescribing guidelines recommend reducing or discontinuing opioids for chronic pain if harms of opioid treatment outweigh benefits. As opioid discontinuation becomes more prevalent, it is important to understand whether opioid discontinuation is associated with heroin use. In this study, we sought to assess the association between opioid discontinuation and heroin use documented in the medical record. METHODS: A matched nested case-control study was conducted in an integrated health plan and delivery system in Colorado. Patients receiving opioid therapy in the study period (January 2006-June 2018) were included. Opioid discontinuation was defined as ≥45 days with no opioids dispensed after initiating opioid therapy. The heroin use onset date represented the index date. Case patients were matched to up to 20 randomly selected patients without heroin use (control patients) by age, sex, calendar time, and time between initiating opioid therapy and the index date. Conditional logistic regression models estimated matched odds ratios (mOR) for the association between an opioid discontinuation prior to the index date and heroin use. RESULTS: Among 22,962 patients prescribed opioid therapy, 125 patients (0.54%) used heroin after initiating opioid therapy, of which 74 met criteria for inclusion in the analysis. The odds of opioid discontinuation were approximately two times higher in case patients (n = 74) than control patients (n = 1045; mOR = 2.19; 95% CI 1.27-3.78). CONCLUSIONS: Among patients prescribed chronic opioid therapy, the observed increased risk for heroin use associated with opioid discontinuation should be balanced with potential benefits.

Confirmation of recent heroin abuse: Accepting the challenge.

Confirmation or exclusion of recent heroin consumption is still one of the major challenges for forensic and clinical toxicologists. A great variety of biomarkers is available for heroin abuse confirmation, including various opium alkaloids (eg, morphine, codeine), street heroin impurities (eg, 6-acetylcodeine [6-AC], noscapine, papaverine) as well as associated metabolites (eg, 6-monoacetylmorphine [6-MAM], morphine glucuronides). However, the presence of most of these biomarkers cannot solely be attributed to a previous heroin administration but can, among other things, also be due to consumption of poppy seed products ('poppy seed defense'), opium preparations or specific medications, respectively. A reliable allocation is of great importance in different contexts, for instance in the case of DUID (driving under the influence of drugs) investigations, in driving licence re-granting processes, in workplace drug testing (WDT), as well as in post-mortem identification of illicit opiate use. Additionally, differentiation between illicit street heroin abuse and pharmaceutical heroin administration is also important, especially within the frame of heroin-assisted treatments. Therefore, analysis of multiple biomarkers is recommended when illicit opiate consumption is assumed to obtain the most reliable results possible. Beyond that, interpretation of positive opiate test results requires a profound insight into the great variety of biomarkers available and their validity regarding the alleged consumption. This paper aims to provide an overview of the wide variety of heroin abuse biomarkers described in the literature and to review them regarding their utility and reliability in daily routine analysis.

Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling. The percentage of participants with a plasma l-methadone concentration between 100 and 250 ng/ml was 54.2% among those with a methadone dosage ≥60 mg/day. Plasma l-methadone concentrations were significantly higher in patients with negative urine analyses compared with those with positive urine analyses (median 93 vs. 77 ng/ml, Mann-Whitney test, P<0.05). Above plasma l-methadone concentrations of 200 ng/ml no heroin use was reported and urine analyses were negative. Moreover, above concentrations of 250 ng/ml craving was absent. Examination of demographic correlates of treatment outcome indicated that older age, a stable job and being married were protective against the use of heroin. Mean plasma l-methadone concentration was significantly lower in patients who used cannabis compared with those who did not use cannabis, after adjusting for methadone dosage. In conclusion our results identify specific cut-offs for plasma l-methadone concentrations about which therapeutic response is observed and provide new evidence that therapeutic response is associated with patient׳s demographic characteristics. This underscores the need to monitor plasma methadone concentrations as part of Drug Addiction Services routine practice, in order to provide an objective framework for changing the methadone dosage.

Methadone treatment improves tuberculosis treatment among hospitalized opioid dependent patients in Ukraine.

BACKGROUND: Ukraine's volatile syndemics of tuberculosis (TB) and HIV among people who inject drugs (PWIDs) introduces numerous treatment challenges for each condition, including high mortality and development of multi-drug resistant TB (MDR-TB). METHODS: A prospective, non-randomized 90-day observational study was conducted in six Ukrainian TB treatment sites to assess the effectiveness of integrating methadone maintenance (MMT) with TB treatment using: (1) 90-day TB treatment retention; (2) time to treatment discontinuation; (3) TB medication adherence; and (4) subject disposition, including mortality. Of the 110 participants enrolled, 57 received MMT and 53 did not (non-MMT). RESULTS: All of the primary outcomes were significantly better in MMT versus non-MMT groups, including 90-day TB treatment completion (89.5% versus 73.6%; p=0.031), time to TB treatment discontinuation (p=0.039) and TB medication adherence (97.1% versus 86.2%; p<0.001) after controlling for death. The major reasons for treatment non-completion in the non-MMT group included death (N=3), administrative discharge from the clinic (N=5), loss to follow-up (N=2), and arrest (N=4). Overall, 90-day mortality was high (8.2%). After controlling for covariates differing between the two groups at baseline, the only independent predictor of completing 90 days of TB treatment was receipt of MMT in an integrated treatment setting (AOR=3.05; 95% CI 1.08-8.66). CONCLUSIONS: MMT integrated into inpatient TB treatment significantly improves retention in TB treatment and TB medication adherence among PWIDs. These findings call for policy change to increase the number of MMT sites in TB facilities and make MMT a low-threshold treatment option for opioid dependence in Ukraine.

Nucleus accumbens surgery for addiction.

BACKGROUND: Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery because of psychological dependence. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. METHODS: Based on animal experiments, our institute started the clinical trial for the treatment of drug addicts' psychological dependence by making lesions in the bilateral NAc with stereotactic surgery from July 2000. RESULTS: The short-term outcomes were encouraging and triggered rapid application of this treatment in China from 2003 to 2004. However, lack of long-term outcomes and controversy eventually led to halting the surgery for addiction by the Ministry of Health of China in November 2004 and a nationwide survey about it later. Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow-up study showed that the 5-year nonrelapse rate was 58% and the quality of life was significantly improved. Patients had several kinds of side effects, but the incidence rate was relatively low. The patients gradually recovered more than 5 years after the surgery. The side effects did not severely influence an individual's life or work. Nationwide surgery showed that the nonrelapse rate was 50% in the sample of 150 cases, from 1167 patients overall who underwent stereotactic surgery in China. CONCLUSIONS: Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location has a significant impact on treatment efficacy and requires further study. Because ablation is irreversible, the NAc surgery for addiction should be performed with cautiousness, and deep brain stimulation (DBS) is an ideal alternative.

Neurotransmitter-precursor-supplement intervention for detoxified heroin addicts.

This study examined the effects of combined administration of tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan (5-HTP) on heroin withdrawal syndromes and mental symptoms in detoxified heroin addicts. In the cluster-randomized placebo-controlled trial, 83 detoxified heroin addicts were recruited from a detoxification treatment center in Wuhan, China. Patients in the intervention group (n=41) were given the combined treatment with tyrosine, lecithin, L-glutamine and 5-HTP and those in the control group (n=42) were administered the placebo. The sleep status and the withdrawal symptoms were observed daily throughout the study, and the mood states were monitored pre- and post-intervention. The results showed that the insomnia and withdrawal scores were significantly improved over time in participants in the intervention group as compared with those in the control group. A greater reduction in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, and a greater increase in their vigor-activity symptoms were found at day 6 in the intervention group than in the control group (all P<0.05). It was concluded that the neurotransmitter-precursor-supplement intervention is effective in alleviating the withdrawal and mood symptoms and it may become a supplementary method for patients' recovery from heroin addiction.

Urine drug test interpretation: what do physicians know?

OBJECTIVE: To determine the level of urine drug test (UDT) interpretive knowledge of physicians who use these instruments to monitor adherence in their patients on chronic opioid therapy. METHODS: A seven-question instrument consisting of six five-option, single-best-answer multiple choice questions and one yes/no question was completed by 114 physicians (77 who employ UDT and 37 who do not) attending one of three regional opioid education conferences. We calculated frequencies and performed chi2 analyses to examine bivariate associations between UDT utilization and interpretive knowledge. RESULTS: The instrument was completed by 80 percent of eligible respondents. None of the physicians who employ UDT answered all seven questions correctly, and only 30 percent answered more than half correctly. Physicians who employ UDT performed no better on any of the questions than physicians who do not employ UDT. CONCLUSIONS: Physicians who employ UDT to monitor patients receiving chronic opioid therapy are not proficient in test interpretation. This study highlights the need for improved physician education; it is imperative for physicians to work closely with certified laboratory professionals when ordering and interpreting these tests.

[Wavelet-based pulse-abnormality analysis for heroin addicts].

Using wavelet transforms method, time-frequency characteristics of pulse signals from 15 heroin addicts and 15 healthy persons were analyzed. According to 3-D and contour plots used to display discrete dyadic wavelet transforms, the significant difference of time-frequency characteristics between the signals of heroin addicts and healthy persons were revealed. A primary criterion was also obtained,with the criterion, 15 heroin addicts were entirely identified, while two healthy subjects were misidentified. The research result shows that the wavelet-based multiresolution analysis is a very effective method to extract characteristics of pulse signals. It is valuable to the diagnosis and therapy for heroin addicts.

Impact of program services on treatment outcomes of patients with comorbid mental and substance use disorders.

OBJECTIVE: This study examined the outcomes of individuals with co-occurring disorders who received drug treatment in programs that varied in their integration of mental health services. Patients treated in programs that provided more on-site mental health services and had staff with specialized training were expected to report less substance use and better psychological outcomes at follow-up. METHODS: Participants with co-occurring disorders were sampled from 11 residential drug abuse treatment programs for adults in Los Angeles County. In-depth assessments of 351 patients were conducted at treatment entry and at follow-up six months later. Surveys conducted with program administrators provided information on program characteristics. Latent variable structural equation models revealed relationships of patient characteristics and program services with drug use and psychological functioning at follow-up. RESULTS: Individuals treated in programs that provided specific dual diagnosis services subsequently had higher rates of utilizing mental health services over six months and, in turn, showed significantly greater improvements in psychological functioning (as measured by the Brief Symptom Inventory and the RAND Health Survey 36-item short form) at follow-up. More use of psychological services was also associated with less heroin use at follow-up. African Americans reported poorer levels of psychological functioning than others at both time points and were less likely to be treated in programs that provided mental health services. CONCLUSIONS: Study findings support continued efforts to provide specialized services for individuals with co-occurring disorders within substance abuse treatment programs as well as the need to address additional barriers to obtaining these services among African Americans.

[Primary discussion on the classification of the TCM patterns and measurable diagnosis of 760 cases of protracted abstinent syndrome by heroin-addiction].

OBJECTIVE: To discuss the TCM pattern classification and measurable diagnosis criterion of the protracted symptoms of heroin-addiction abstinence (PSHAA). METHODS: Through literature review and clinical study, the concept of TCM patterns and diagnostic standard were established, and a TCM pattern scale for quantitatively analysis of PSHAA was formulated. The scale were used on the clinical investigation on the abuser for 5 times on day 15, 30, 60, 90 and 120 after abstinence. Then the TCM patterns of PSHAA was classified using methods of DME and quantitative diagnosis, to create a corresponding scale of diagnostic indexes referring maximum likelihood method. RESULTS: (1) The TCM patterns of PSHAA commonly seen were Toxin-stasis accumulation (TSA) with Qi-blood insufficiency, TSA with Qi-yin deficiency, TSA with Yin-deficiency and Fire-excess and TSA with Yin-Yang deficiency. (2) The retrospective and prospective verification of the scale of diagnostic indexes showed it has high sensitivity and speciality, with low rates of misdiagnosis and of missed diagnosis. CONCLUSION: It is feasible to develop measurable diagnosis on the TCM patterns of PASAA using DME method and measurable diagnostic methods. The scale of diagnostic indexes formulated with the maximum likelihood method of quantified diagnosis has a certain clinical practicability.

Implantes de naltrexona: un avance terapéutico, tanto comportamental como farmacológico / Naltrexone implants: a real therapeutic avance both behavioural as well as pharmacological

A principios de los setenta, los pioneros del tratamiento con naltrexona (NTX) comprendieron que un implante o inyección depot de NTX ayudaría a eliminar el bajo seguimiento del tratamiento. Los primeros estudios en animales sobre formulaciones implantables aparecieron a mediados de los setenta, y los estudios en humanos pronto demostraron que los niveles efectivos de NTX en plasma podían mantenerse varias semanas con formulaciones implantables estándar. Pero sólo en los últimos años han podido emplearse implantes y depots para uso clínico. Un número creciente de artículos describen su efectividad en la prevención de recaídas, incluyendo casos de médicos y embarazadas adictos y adolescentes problemáticos que consumen frecuentemente sobredosis de opiáceos. Los niveles típicos de NTX en plasma derivados de los implantes pueden bloquear completamente los efectos de los opiáceos de hasta 500 mg de heroína farmacológica durante más de seis meses. Incluso los implantes de 'primera generación', de más corto efecto, reducen considerablemente los elevados índices de temprana reincidencia comunes tras una desintoxicación de opiáceos. Los depots de NTX tienen también potencial en los tratamientos del alcoholismo. Pero la naturaleza farmacológica de los implantes de NTX no debe ocultar que también facilitan y refuerzan importantes procesos psicológicos cruciales en el éxito a largo plazo de los tratamientos de adicción. El desarrollo de agentes bloqueadores de larga duración para otras drogas de consumo significa que los nuevos principios de los tratamientos con implantes de NTX podrán aplicarse pronto a problemas relacionados con benzodiacepinas, estimulantes y cannabis. Recomendamos el término 'abstinencia antagonista-asistida' para este enfoque, pero insistimos en que los tratamientos de mantenimiento siguen ocupando un importante lugar (AU)

The pioneers of naltrexone (NTX) treatment the early 1970s realized that an implant or depot injection of NTX would largely eliminate the poor compliance that undermined its potential effectiveness. Animal studies of implantable formulations appeared in the mid-1970s and human studies soon showed that effective plasma NTX levels could be maintained for several weeks using standard implant formulations. Yet only in the past few years have implants and depot injections become available for clinical use. This paper reviews their development, their rationale and the increasing number of papers describing their effectiveness for relapse prevention in a surprisingly wide range of indications, including addicted physicians, pregnant addicts and troubled adolescents taking frequent opiate overdoses. It is clear that typical plasma levels of NTX from implants can completely block opiate effects from as much as 500 mg of pharmaceutical heroin and effective blockade can be maintained for well over six months. Even shorteracting 'first generation' implants appear to reduce considerably the high rates of early relapse that are common after opiate detoxification. Depot NTX also has potential in alcoholism treatment. However, the obviously pharmacological nature of NTX implants should not obscure the fact that they also facilitate and reinforce important psychological processes that may be crucial to the long-term success of addiction treatment. The development of long-acting blocking agents for other drugs of abuse means that the emerging principles of treatment with NTX implants may soon be applied to problems involving benzodiazepines, stimulants and cannabis. We suggest the term 'Antagonist-Assisted Abstinence' for this approach but stress that maintenance treatments continue to have an important place (AU)

Treating substance abuse in schizophrenia. An initial report.

Schizophrenia patients show alarmingly high rates of substance use disorders. These patients experience neurocognitive and social deficits that make it difficult for them to benefit from effective treatment strategies designed for less-impaired populations. Previously, we described Behavioral Treatment for Substance Abuse in Schizophrenia and discussed how the program was adapted for this population. Here we provide an update of BTSAS, discuss our clinical experience running the intervention, and review how it has changed over five years of development. We present attendance, participation, and substance use data on patients who consented to attend (n = 42), completed (n=14), and dropped out (n = 14) of the program. Outcome data are provided for 14 patients, and comparisons are made between good (n = 5; > or = 67% of urine tests clean from a goal drug over 6 months) and poor (n = 9; < or = 66% of urine tests clean) progress patients. Implications for the treatment are discussed.