Patients’ Perceptions of Opioid Replacement Therapy: a Comparison of Diamorphine and Methadone/Levomethadone

Diamorphine was first legalized as a novel treatment option for heroin dependence in Germany in 2009. Today, specialized clinics in ten German cities provide diamorphine to heavily addicted patients. As the medical and societal context of diamorphine-assisted therapy is evolving, continued research into patients’ perceptions of opioid replacement therapy remains important. From February 2018 to June 2018, we conducted a survey study of outpatients on maintenance treatment with either diamorphine (n = 85) or methadone/levomethadone (n = 126). Patients were asked to complete a self-report questionnaire querying, besides socio-demographic information, the study participant’s satisfaction with the substitute drug, relapse with illicit drugs, patterns of craving, and alcohol consumption. Duration of opioid dependence did not differ significantly between groups. Patients on diamorphine were approximately 3 years younger than patients on methadone/levomethadone. They also had a higher frequency of daily intake of their substitute drug and had had their dosage adjusted more often during the preceding 6 months. Still, diamorphine patients reported greater satisfaction with their substitute drug in tandem with significant reductions in relapse-related behaviors and cravings. While the most common relapse reported by patients on methadone replacement was heroin relapse (68%), most instances of illicit drug use in the diamorphine group involved cocaine (48%). Although self-reported alcohol consumption did not differ significantly between groups, a higher percentage of diamorphine patients than methadone patients endorsed decreased alcohol consumption since entering therapy. Taken together, these findings point to meaningful differences between diamorphine and methadone/levomethadone in opioid replacement therapy.

     

Differences between men and women in the course of opiate dependence: is there a telescoping effect?

According to the so-called telescoping effect, there is a gender-specific course of alcohol dependence with women starting alcohol use later than men and having a faster development of harmful consequences. There are inconsistent data regarding a telescoping effect in opiate dependence. In each of six European centres, 100 opiate addicts were investigated by a structured interview (mainly the EuropASI and CIDI) at admission to various kinds of treatment (TREAT project). In a secondary analysis of the TREAT data, women and men were compared regarding age at onset of heroin use and the current severity of addiction. In addition, a comparison of female (n = 140) and male (n = 140) addicts matched for age and study centre were carried out. Eventually, multiple logistic and linear regressions were done with the interaction term of gender and time of regular consumption as predictor for the severity of dependence, besides, other sociodemographic variables. There was no difference between genders regarding the age at onset of regular heroin consumption. Up to 4 years of regular consumption, there are gender-specific differences in the course of opiate dependence, e.g. a faster progression of legal problems in men and social problems in women. There were no differences in the severity of dependence other than more economic problems for women. A telescoping effect could only partially be observed in this large sample of opiate addicts. A gender-specific course was limited to the first years of consumption, and included domains with a faster progression for men. It has to be assumed that opiate dependence is a rapidly developing disorder with early chronification. Afterwards, only individual courses with influences of the national treatment system were observed.     

Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.     

Comorbid chronic pain and opioid use disorder: literature review and potential treatment innovations

Abstract

Chronic pain (CP) and opioid use disorder (OUD) remain challenging complex public health concerns. This is an updated review on the relationship between CP and OUD and the use of stepped care models for assessment and management of this vulnerable population. A literature search was conducted from 2008 to the present in PubMed, Embase, and PsycInfo using the terms pain or chronic pain and opioid-related disorders, opiate, methadone, buprenorphine, naltrexone, opioid abuse, opioid misuse, opioid dependen*, heroin addict, heroin abuse, heroin misuse, heroin dependen*, or analgesic opioids, and stepped care, integrated services, multidisciplinary treatment, or reinforcement-based treatment. Evidenced-based data exists on the feasibility, implementation, and efficacy of stepped care models in primary care settings for the management of CP and opioid use. Although these studies did not enroll participants with OUD, they included a sub-set of patients at risk for the development of OUD. There remains a dearth of treatment options for those with comorbid CP and OUD. Future research is needed to explore the aetiology and impact of CP and OUD, and greater emphasis is needed to improve access to comprehensive pain and substance use programmes for high-risk individuals.     

Late- and Typical-Onset Heroin Use Among Older Adults Seeking Treatment for Opioid Use Disorder

ObjectiveAnalyze 10-year trends in opioid use disorder with heroin (OUD-H) among older persons and to compare those with typical-onset (age <30 years) to those with late (age 30+) onset.DesignNaturalistic observation using the most recent (2008–2017) Treatment Episode Data Set-Admissions (TEDS-A).SettingAdmission records in TEDS-A come from all public and private U.S. programs for substance use disorder treatment receiving public funding.ParticipantsU.S. adults aged 55 years and older entering treatment for the first time between 2008 and 2017 to treat OUD-H.MeasurementsAdmission trends, demographics, substance use history.ResultsThe number of older adults who entered treatment for OUD-H nearly tripled between 2007 and 2017. Compared to those with typical-onset (before age 30), those with late-onset heroin use were more likely to be white, female, more highly educated, and rural. Older adults with late-onset were more likely to be referred to treatment by an employer and less likely to be referred by the criminal justice system. Those with late-onset were more likely to use heroin more frequently but less likely to inject heroin than those with typical-onset. Those with typical onset were more likely to receive medication for addiction treatment than those with late-onset.ConclusionLate-onset heroin use is increasing among older U.S. adults. Research is needed to understand the unique needs of this population better. As this population grows, geriatric psychiatrists may be increasingly called upon to provide specialized care to people with late-onset OUD-H.     

Mortality and employment after in-patient opiate detoxification

AimWe considered that completed opiate detoxification resulted in increased life expectancy and earning capacity as compared to non-completed detoxification.MethodsThe cohort study sample included pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Of 404 patients, 58.7% completed the detoxification program and 41.3% did not. The Austrian Social Security Institution supplied data on survival and employment records for every single day in the individual observation period between discharge and December 2007. Statistical analyses included the calculation of standardized mortality rates for the follow-up period of up to 11 years.ResultsThe standardized mortality ratios (SMRs) were between 13.5 and 17.9 during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts (p = 0.003).ConclusionsThe assumption that completers of detoxification treatment have a better outcome than non-completers has not been confirmed. The decrease in mortality with time elapsed since detoxification is interesting. Pure opioid addicts had better employment prospects than poly-substance addicts.     

Effects of cortisol administration on craving in heroin addicts

Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P=0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P=0.0019; after heroin administration: P=0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction.     

Opioid maintenance therapy restores CD4+ T cell function by normalizing CD4+CD25(high) regulatory T cell frequencies in heroin user

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT.     

Maintenance treatment of opiate addicts

Maintenance treatment is now the most common treatment of opiate addicts in Germany. The principle of maintenance treatment is the administration of an opioid in order to suppress withdrawal symptoms and heroin craving. In this manner, maintenance treatment successfully reduces heroin abuse and directly associated risk behaviour. Only a minority of maintenance patients became opiate abstinent (including the maintenance drug). Racemic methadone is the most extensively evaluated maintenance drug. A differential indication between medical opioids has not been scientifically established. According to the German regulations psychosocial support is an obligatory part of maintenance treatment. Most opiate addicts suffer from comorbid mental and somatic diseases. Therefore psychiatric and somatic treatment is indicated and of proven value.     

Chronic naltrexone suppresses platelet aggregation induced by adrenaline and 5-hydroxytryptamine in former heroin addicts

Summary Naltrexone, an opioid receptor antagonist, is used as an adjunct in the treatment of opiate addiction. In former heroin addicts, long-term treatment with naltrexone (350 mg/week for 5 months) resulted in suppression of adrenaline and 5-hydroxytryptamine (5-HT)-induced platelet aggregation. The results demonstrate that sustained blockade of opioid receptors can impair the functional expression of ₂-adrenoceptors and 5-HT₂ receptors in human platelets. These findings may have negative clinical implications in the treatment of opiate addiction with naltrexone.     

Chronic cannabis use does not affect the normalization of hypothalamic-pituitary-adrenal (HPA) axis induced by methadone in heroin addicts

The hypothalamic-pituitary-adrenal (HPA) axis activity is usually altered by heroin use. In the present study we evaluated in one hundred twenty-one heroin addicts the effects of marijuana smoking on the normalization of HPA axis upon methadone treatment. The study showed that in heroin addicts who are chronic cannabis smokers a treatment with methadone lasting 12 months was able to normalize both plasma corticotropin (ACTH) and cortisol levels, as well as to control both heroin withdrawal symptoms and opioid craving. As expected in the same group of patients marijuana smoking and its craving were not reduced by methadone treatment. Our data confirm that methadone treatment outcomes are not modified by cannabis use and they add in the literature the evidence that chronic cannabis use is not able to affect the normalization of HPA axis upon methadone treatment in heroin addicts.     

A prospective observational study of heroin users in Johannesburg,South Africa: Assessing psychiatric comorbidities and treatment outcomes

BackgroundDespite the rise in heroin use in sub Saharan-Africa opioid agonist maintenance treatment (OAMT) is still not state-funded in South Africa and many other African countries. In South Africa there has been little data published on the profile of heroin users and the outcomes of treatment for those who attend public treatment services.Methods300 heroin users from two state-funded rehabilitation centres in Johannesburg were studied at entry into rehabilitation and 3-months after treatment. Treatment consisted of inpatient detoxification and inpatient psychosocial rehabilitation. Structured interviews measured changes in drug use, psychopathology and criminality post rehabilitation.ResultsMost (65.7%) smoked heroin in combination with cannabis while 29.7% were injecting users. Almost half the sample (49.3%) had at least one mental illness. Of the 252 (84%) participants seen at 3-month follow-up, 6.3% were abstinent of all substances (excluding tobacco), 65.5% had continued heroin use (CHU) and the balance used other substances. At follow-up there were significant decreases in heroin use (p < 0.0001) and criminality (p < 0.0001). There were however significant increases in alcohol use (p < 0.0001), crystalmetamphetamine use (p = 0.032) and the prevalence of current episode of major depression (p < 0.0001). Just 11.9% received formal psychosocial treatment after leaving rehabilitation. None were on OAMT and only three participants were on psychotropic medication. None were tested for Hepatitis C during the study period and the majority (53%) did not know their HIV status.ConclusionThere are significant gaps in current treatment services for heroin users in South Africa. Retention in treatment and assessment and management of psychiatric and non-psychiatric comorbidities is low. Services need to be more integrated and should also include the provision of OAMT.     

海洛因依赖与人格障碍共病调查

目的：调查海洛因依赖者的人格障碍共病状况。方法：采用美国精神障碍诊断与统计手册第4版（DSM-Ⅳ）系统轴Ⅱ人格障碍访谈问卷（SCID-II）（第2版）对90例海洛因依赖者进行评定及相关统计分析。结果：79例（87.8%）符合至少一种人格障碍,常见的为偏执型、强迫型、反社会型、未加标明组（被动攻击型及抑郁型）、边缘型、回避型、自恋型等,人均患2.5种人格障碍。以戏剧化-情绪组人格障碍最常见。结论：在海洛因依赖者中人格障碍共病现象相当普遍。     

Innovations in agonist maintenance treatment of opioid-dependent patients

PURPOSE OF REVIEW: To provide an overview of published studies on agonist maintenance treatment options for opioid-dependent patients. RECENT FINDINGS: The recent publication of controlled trials confirms earlier clinical evidence of the efficacy of diamorphine (heroin) in the treatment of opioid dependence. Findings show not only efficacy with respect to improvement of health, reduction of illicit drug use, reduction of criminality and stabilization of social conditions, but also cost effectiveness in the treatment of chronic treatment-resistant heroin addicts. SUMMARY: Agonist maintenance treatment has become the first-line treatment for chronic opioid dependence. High-quality studies demonstrate the effectiveness of a growing number of different agonist maintenance treatments for opioid dependence such as methadone and buprenorphine. In addition, there is new evidence for the effectiveness of other agonists, mainly slow-release morphine, intravenous and inhalable diamorphine and possibly oral diamorphine. Maintenance treatment with intravenous or inhalable diamorphine should be implemented into the healthcare system to treat a group of severely dependent treatment-resistant patients. Furthermore, the opioid-dependent patients not under treatment need to be engaged in maintenance treatments through other harm reduction measures. Agonist maintenance treatment is very effective in stabilizing the health condition and social situation, while also reducing harm, thereby increasing life expectancy and quality of life.     

Neuromodulation With Burst and Tonic Stimulation Decreases Opioid Consumption: A Post Hoc Analysis of the Success Using Neuromodulation With BURST (SUNBURST) Randomized Controlled Trial

ObjectivesThe SUNBURST study was a prospective, multicenter, randomized crossover trial of a single device delivering burst and tonic spinal cord stimulation (SCS) for chronic trunk and/or limb pain. We performed a post hoc analysis of opioid consumption at baseline and after device implantation.Materials and MethodsAfter implantation, 100 patients were randomized to one mode (tonic or burst) for 12 weeks, and the other mode for the subsequent 12 weeks. After the crossover period (24 weeks), patients chose their preferred mode and were assessed for one year. We analyzed 69 patients who took opioid medication at baseline. The primary endpoint was opioid consumption in morphine milligram equivalents (MMEs) at baseline and 12 months postimplantation. Subgroup analysis included opioid consumption based on Center for Disease Control markers (<50, 50–90, 90–120, >120 MME/day) and stimulation mode preference.ResultsOpioid consumption at 12 months was lower compared to baseline (53.94 vs. 79.19 MME, MD −25.25, 95% CI −43.77 to 6.73, p = 0.008). By 12 months, 11 of 69 patients (15.9%) discontinued all opioid (p = 0.001). Based on CDC dose markers, the proportion of patients taking >120 MME/day decreased by 61.7% at 12 months postintervention compared to baseline (p = 0.043). Forty-five of 69 patients (65.2%) preferred burst SCS while 15 of 69 patients (21.7%) preferred tonic SCS (p < 0.001).ConclusionA device delivering tonic and burst SCS was associated with decreased opioid consumption after 12 months in patients with chronic trunk and/or limb pain. The proportion of patients reporting the highest opioid intake (>120 MME/day) decreased to a lower CDC dose category by 61.7%, carrying important implications for those at highest risk for opioid-related substance use disorder, overdose, and death.     

Association between gene variants and response to buprenorphine maintenance treatment

A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in “non-responder” than in “responder” individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and behavioral problems, would have influenced the effects of BUP-induced dopamine release, modulated through mu and kappa opioid receptors, and probably the related reinforcing capacity of the drug.     

Heroin craving and its correlations with clinical outcome indicators in people with heroin dependence receiving methadone maintenance treatment

BackgroundCraving for substance use has been added as one of the diagnostic criteria of substance use disorders in DSM-5. However, further research is necessary to examine and expand the clinical potential of craving in the assessment and treatment for heroin users. This study aimed to examine the psychometrics of the Desire for Drug Questionnaire–Chinese Mandarin version (DDQ-CM) and its clinical utility of assessing craving for heroin measured among heroin users with methadone maintenance treatment (MMT).MethodSelf-reported craving for heroin use was measured on the DDQ-CM and visual analog scale among 314 intravenous heroin users receiving MMT. Self-reported heroin dependence, attitude toward heroin use, readiness to change heroin use, and depression were collected.ResultsThe results found that although the original three-factor model was acceptable for applying the DDQ-CM for heroin users with MMT, only the concurrent validity of the subscales of Desire and Intention and Negative Reinforcement was supported but not that of Control. Meanwhile, the levels of craving on the subscales of Desire and Intention and of Negative Reinforcement on the DDQ-CM were positively associated with the levels of heroin dependence, positive and negative attitudes toward heroin use, and depression, but negatively associated with readiness to change heroin use.ConclusionsThis study supported the application of the subscales of Desire and Intention and Negative Reinforcement on the DDQ-CM to measure heroin craving in Taiwanese-Chinese heroin users and supported the clinical implication of craving in heroin users with MMT.     

An open pilot study of zonisamide augmentation in major depressive patients not responding to a low dose trial with duloxetine: preliminary results on tolerability and clinical effects

Background

The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months.

Methods

Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period.

Results

No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology.

Conclusions

Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.