Prevalence and Characteristics of Chronic Pain in Buprenorphine and Methadone-Maintained Patients.

Chronic pain and substance use disorders frequently co-occur. Indeed, chronic pain is highly prevalent, affecting 23-68% of patients receiving opioid agonist treatments (OAT) worldwide. The majority of available estimates come from American studies, but data are still lacking in Europe. We aim to provide European estimates of the prevalence of chronic pain in patients receiving OAT using French data, since France is the first European country in terms of number of patients with OAT. The secondary objectives were to characterize the features and management of chronic pain, as well identify associated risk factors. We conducted a multicenter, cross-sectional study, recruiting patients treated either with buprenorphine or methadone in 19 French addiction centers, from May to July 2016. All participants had to complete a semi-directed questionnaire that collected sociodemographic and medical data, pain characteristics, and licit or illicit drug consumption. In total, 509 patients were included. The prevalence of chronic pain was estimated at 33.2% (95% CI: 29.1-37.3). Compared to non-chronic pain patients, chronic pain patients were older (38.4 vs. 36.1 years, p = 0.006), were more unemployed (66 vs. 52%, p = 0.003), had more psychiatric comorbidities (50 vs. 39%, p = 0.02), and split their OAT for pain management more frequently (24 vs. 7%, p = 0.009). Pain intensity was moderate or severe in 75% of chronic pain patients. Among patients with chronic pain, 15.4% were not prescribed, and did not self-medicate with, any analgesic drugs, 52.1% were prescribed analgesics (non-opioid analgesics, 76.3%; codeine, tramadol, opium, 27.2%; and morphine, fentanyl, oxycodone, 11.8%), and 32.5% exclusively self-medicated with analgesics. Moreover, 20.1% of patients with chronic pain also used illicit drugs for pain relief. On multivariate analysis, variables that remained significantly associated with chronic pain were age [OR = 1.03 (95% CI: 1.00-1.05], p = 0.02], anxiety [OR = 1.52 (1.15-2.02), p = 0.003], and depression [OR = 1.25 (1.00-1.55), p = 0.05]. Chronic pain is a highly prevalent condition in patients receiving OAT, and its appropriate management remains uncertain, since insufficient relief and frequent additional self-medications with analgesics or illicit drugs were reported by these patients. Increased awareness among caregivers is urgently needed regarding a systematic and careful assessment, along with an adequate management of chronic pain in patients receiving OAT.

Link Between Perception of Treatment Need and Craving Reports in Addiction.

BACKGROUND: Perception of treatment need (PTN), a component of clinical insight, is associated to negative addiction treatment outcomes when low. Our hypothesis was that lower PTN was associated with less craving when reported retrospectively, the most common measure of craving in clinical settings. OBJECTIVE: To explore the association between PTN and craving among a dataset of subjects with severe substance use disorders. METHODS: Participants were recruited from outpatient addiction clinic admissions or harm reduction program services. Good and low PTN were based on consistency between severe addiction (at least six DSM-5 criteria) and self-report need for addiction treatment from the Addiction Severity Index. Craving was retrospectively characterized over the past 30 days. Multiple regression analyses were conducted. RESULTS: Participants with low PTN (n = 97) retrospectively reported less frequent and intense episodes of craving, compared with participants with good PTN (n = 566) after controlling for sociodemographic factors, addiction type, and severity (p < 0.0001). CONCLUSION: Low perception of treatment need among subjects with severe addictions is associated to less retrospective report of craving, which may contribute to reduced efficiency of treatment. Further studies are needed to explore the mechanisms of the association.

Paritaprevir, ritonavir, ombitasvir, and dasabuvir with and without ribavirin in people with HCV genotype 1 and recent injecting drug use or receiving opioid substitution therapy.

BACKGROUND: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST. METHODS: D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12). RESULTS: Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1; non-adherence, n = 1; incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%-96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1; death, n = 1; virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly/probably related to therapy; nausea and myoclonus). Two cases of reinfection were observed. CONCLUSION: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST.

Recommendations for buprenorphine and methadone therapy in opioid use disorder: a European consensus.

INTRODUCTION: Management of patients with opioid use disorder (OUD) commonly includes opioid agonist therapy (OAT) as a part of an integrated treatment plan. These interventions are associated with proven benefits to the individual and society. Areas covered: The use of methadone and buprenorphine within an integrated treatment plan in the management of patients with OUD: this work provides consensus recommendation on pharmacotherapy in OUD to assist clinicians with practical decision making in this field. Expert opinion: Pharmacotherapy is recommended as part of an integrated OUD treatment approach with psychosocial interventions, with the goal of reducing risks of illicit opioid use, overdose mortality, infection with HIV or HCV, improving health, psychological and social outcomes. Access to OAT should be prioritised in the treatment of OUD. Treatment choices in OUD pharmacotherapy should be based on the needs of the individual and characteristics of medications. Recommendations for choices of OAT are based on clinical efficacy, safety, patient preference, side effects, pharmacological interactions, quality of life, dose titration potential and outcomes (control craving, ongoing opioids consumption or other drugs, and potentially psychiatric comorbidities). Special groups, pregnant women, prisoners, patients with mental health problems have specific needs which must be addressed with expert input.

Addiction severity pattern associated with adult and childhood Attention Deficit Hyperactivity Disorder (ADHD) in patients with addictions.

Attention Deficit Hyperactivity Disorder (ADHD) is highly prevalent among adults with addictive disorders, but little is known about addiction patterns associated with ADHD diagnosis. This study examined addiction severity in patients with co-occurring addictive disorders and ADHD controlling for the potential influence of associated psychiatric comorbidity. Data were collected in French outpatient addiction treatment centers. A total of 217 patients seeking treatment for substance or gambling addiction were included. At treatment entry, participants were interviewed with the Addiction Severity Index, the Conners Adult ADHD Diagnosis Interview for the DSM-IV (CAADID), the Mini International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV Axis II for borderline personality disorder (SCID II). History of ADHD was associated with an earlier onset of addiction, poly-dependence (defined by presence of at least two current substance dependence diagnoses in addition to tobacco dependence if present) and borderline personality disorder. Persistence of ADHD during adulthood was associated with a higher prevalence of poly-dependence. This study highlights the need for early implementation of preventive interventions for substance use or behavioral addiction in children/adolescents with ADHD and the need to consider ADHD in the treatment of addictive disorders.

Usefulness and validity of the modified Addiction Severity Index: A focus on alcohol, drugs, tobacco, and gambling.

BACKGROUND: Individuals who seek treatment for an addictive disorder often exhibit comorbid substance use disorders and/or gambling disorder. The lack of a unique severity assessment instrument might be an obstacle for individuals to access integrated and comprehensive treatment. This paper aimed to examine the usefulness and validity of a modified version of the Addiction Severity Index (mASI) to assess all substance use disorders (including tobacco) and gambling. METHODS: Participants (N = 833) were interviewed with the mASI and completed a validity battery questionnaire. The validity and the reliability of the mASI were examined. RESULTS: The mASI was reliable, and its 9 assessed domains showed a relative independence, supporting its multidimensionality. CONCLUSIONS: The standardized properties of the mASI permit a comprehensive and systematic assessment of all addictive disorders independent of individuals' perceived problems and treatment settings, hence facilitating personalized treatment planning.

Association between morningness/eveningness, addiction severity and psychiatric disorders among individuals with addictions.

Studies have shown that Evening-Type (ET) subjects used more stimulating and sedative substances, and presented more psychiatric disorders than Morning-Type (MT) subject. However, there is a lack of data on the chronotype of patients with addiction. The aim of our study was to describe chronotype and associated factors in a sample of outpatients beginning treatment for addiction. Subjects were assessed with the Morningness-Eveningness questionnaire of Hörne & Ostberg, the Addiction Severity Index and the Mini International Neuropsychiatric Interview. In the 333 subjects with an addiction, 20% were MT and 32% were ET. When comparing ET to MT, multivariate analysis showed that ET was significantly associated with poly-problematic addiction, non-substance addictions, cannabis addiction, and mood disorders, but not with severity of addiction. MT was associated with antisocial personality disorder. Results suggested that chronotype was associated with specific addiction pattern and psychiatric disorders.

Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions.

BACKGROUND: One important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices. METHODS: The ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis. RESULTS: HCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively). CONCLUSIONS: Identifying individuals at risk of HCV transmission during methadone treatment such as stimulant users, alcohol dependent individuals, and those at suicidal risk is necessary to optimize response to treatment. Innovative prevention approaches tailored to couples are also urgently needed and could decrease HCV-risk in this population. The trial is registered with the French Agency of Pharmaceutical Products (ANSM) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials. Number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397 and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

Validity of the self-reported drug use section of the Addiction Severity Index and associated factors used under naturalistic conditions.

The study examined the validity of 1848 self-reported uses of drugs determined within an Addiction Severity Index interview in comparison with urinalysis results among drug-dependent subjects undergoing treatment in outpatient clinics (Aquitaine area, southwest France, 1994-2005). Agreement and kappa statistics were calculated for each substance. Factors associated with agreement were defined using a multivariate analysis. The conditional kappa coefficients were excellent for all substances assessed. The accuracy between self-reports and urinalysis results was influenced by factors that only slightly affected conditional kappa coefficients. Clients did not underreport their substance use in naturalistic clinical assessment conditions.

Change in HIV-HCV risk-taking behavior and seroprevalence among opiate users seeking treatment over an 11-year period and harm reduction policy.

Our purpose was to assess change in HIV and HCV prevalence and risk-taking behaviors among IDUs over a period of time that included changes in French Public Health policy. Risk behavior and biological testing for serostatus were collected from cross-sectional samples of yearly new requests for opiate dependence treatment in Aquitaine, France between 1994 and 2004 (n = 648). Coincident declines in injection equipment sharing and HIV prevalence among injectors were observed, while sexual behavior remained stable. There was a decline in HCV prevalence that was not significant among injectors. After controlling for potential confounding variables, participants enrolled after 1995 were less likely to share injection material and those enrolled after 1999 were less likely to share spoons. Our findings give evidence for behavioral and seroprevalence changes among IDUs over a period of time that included changes in needle access policy.

Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study.

Maintenance treatment with buprenorphine tablets (Subutex) has been associated with reductions in heroin use; however, concerns for intravenous misuse exist. A buprenorphine/naloxone formulation (Suboxone) was designed to reduce this misuse risk while retaining buprenorphine's efficacy and safety. This prospective, open-label, multicenter trial compared preferences for buprenorphine and buprenorphine/naloxone in 53 opioid-dependent patients stabilized on buprenorphine. Buprenorphine was first administered at the patient's current dose (Days 1-2), followed by a direct switch to buprenorphine/naloxone (Days 3-5). Global satisfaction rates were high and similar between buprenorphine and buprenorphine/naloxone; however, patients preferred the tablet taste, size, and sublingual dissolution time of buprenorphine/naloxone. At the end of the study, 54% of patients preferred buprenorphine/naloxone, 31% preferred buprenorphine, and 15% had no preference; most patients (71%) wished to continue treatment with buprenorphine/naloxone. This study did not identify any impediments to a direct buprenorphine-to-buprenorphine/naloxone switch and revealed some characteristics that may facilitate treatment with buprenorphine/naloxone.

Comparison of prescriber evaluations and patient-directed self-reports in office-based practice for buprenorphine treatment of opiate-dependent individuals in France, 2002.

The objective of this cross-sectional evaluation study was to compare data generated through prescriber assessments, and data generated from independent direct contact with opiate-dependent patients in office-based practice to evaluate buprenorphine treatment for modality of buprenorphine absorption, benzodiazepine use, and depressive symptoms. A group of buprenorphine office-based practice prescribers was selected to participate in this study. They were asked to screen for inclusion all their patients coming for a visit from February to August 2002. Once included by their prescribing physician, patients were given a series of self-administered questionnaires to be returned directly to the research staff, independently of their prescriber. Each prescriber was given a questionnaire to complete based on their knowledge and interview of the patient. Items assessed were history of current treatment, current substance use, buprenorphine treatment related behavior (daily frequency of intake, route of administration), benzodiazepine use and existence of a major depressive episode. Prescribers and patients' questionnaires were compared. Concordance of both assessments was assessed by kappa statistics. The sensitivity and specificity as well as the positive and negative predictive values of prescriber collected information were compared to that of their patients'. There was an overall good correlation between both data sources on the procedures for buprenorphine use especially for intravenous use of buprenorphine. There were important variations: obtaining buprenorphine without a prescription or with a prescription made by another doctor, intravenous administration of buprenorphine, use of benzodiazepines, and depression were underestimated by prescribers.

French field experience with buprenorphine.

In most European countries, methadone treatment is provided to only 20-30% of opiate abusers who need treatment due to regulations and concerns about safety. To address this need in France, all registered medical doctors since 1995 have been allowed to prescribe buprenorphine (BUP) without any special education or licensing. This led to treating approximately 65,000 patients per year with BUP, about ten times more than with more restrictive methadone policies. French physician compensation mechanisms, pharmacy services, and medical insurance funding all minimized barriers to BUP treatment. About 20% of all physicians in France are using BUP to treat about half of the estimated 150,000 problem heroin users. Daily supervised dosing by a pharmacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use. Intravenous diversion of BUP may occur in up to 20% of BUP patients and has led to various infections and relatively rare overdoses in combination with sedatives. Opiate overdose deaths have declined substantially (by 79%) since BUP was introduced in 1995. Newborn opiate withdrawal in mothers treated with buprenorphine compared to methadone was reported to be less frequent, less severe, and of shorter duration. Although some of the public health benefits seen during the time of buprenorphine expansion in France might be contingent upon characteristics of the French health and social services system, the French model raises questions about the value of tight regulations on prescribing BUP imposed by many countries throughout the world.

[Substitution therapy in drug addictions]. / Thérapeutiques de substitution dans les addictions.

In France, so called "substitution treatments" for addiction are nicotine substitutes for tobacco dependence and buprenorphine, and methadone for opiate dependence. The word "substitution" participates to the uncertainty as to the objective of such treatments. From an addiction psychiatry perspective, these treatments are of interest as pharmacological treatments for maintenance of abstinence. In such a perspective they are not changing one substance of dependence for another. The goal is to reduce craving by low potential reinforcement medications. Conditions for success are a clarification of treatment goal with the patients, adequate dosing, and time. All medical doctors may prescribe buprenorphine for treatment of opiate dependence. Supervised daily dispensing in pharmacies is useful to increase compliance and collaboration, and avoid misuse and diversion. For tobacco dependence, nicotine patch must be clearly differentiated from other nicotine substitutes like gums and inhalers that have significant reinforcing effects. Because the patch is accessible without medical prescription, many patients are not sufficiently medically supervised and dropout frequently. For patients that cannot initially accept the behavioral changes associated to the goal of abstinence, it is legitimate to truly substitute them with less dangerous reinforcing substances. This possibility exists in France only for tobacco use that can be substituted to inhaled or chewed nicotine. It is possible that some reported misuse of buprenorphine and methadone are inadequate attempts to increase the reinforcing effects of these medications.

[Is buprenorphine a potential alternative to methadone for treating pregnant drug users? Inventory of clinical data in the literature]. / La buprénorphine est-elle une alternative potentielle à la méthadone pour le traitement de la femme enceinte toxicomane? Inventaire des données cliniques de la littérature.

In this review of the literature, we collected 102 case reports of newborns exposed in utero to buprenorphine between 1996 and 2000. Reported data show that infants born to a mother taking buprenorphine are delivered at term and have a birth weight close to infants not exposed to these substances. The published data also showed that observations have varied concerning the frequency, intensity, and duration of the withdrawal syndrome in newborns exposed in utero to buprenorphine.