Patients' perspectives on buprenorphine subcutaneous implant: a case series.

BACKGROUND: Considering the enormous burden represented by the opioid use disorder (OUD), it is important to always consider, when implementing opioid agonist therapy (OAT), the potential impact on patient's adherence, quality of life, and detoxification. Thus, the purpose of the study is to evaluate how the introduction of a novel OAT approach influences these key factors in the management of OUD. CASE PRESENTATION: This article marks the pioneering use of OAT through buprenorphine implant in Europe and delves into the experience of six patients diagnosed with OUD at a relatively young age. The patients, comprising both males and a female, are of Caucasian Italian and African Italian ancestry (case 4) and exhibit an age range from 23 to 63, with an average drug abuse history of 19 ± 12 years. All patients were on stable traditional OAT before transitioning to buprenorphine implants. Despite the heterogeneity in social and educational backgrounds, health status, and drug abuse initiation histories, the case series reveals consistent positive treatment outcomes such as detoxification, absence of withdrawal symptoms and of side effects. Notably, all patients reported experiencing a newfound sense of freedom and improved quality of life. CONCLUSIONS: These results emphasise the promising impact of OAT via buprenorphine implants in enhancing the well-being and quality of life in the context of OUD.

The experience of buprenorphine implant in patients with opioid use disorder: a series of narrative interviews.

Background: This study used narrative medicine (NM) to assess the point of view of patients with opioid use disorder (OUD) and the impact that addiction and a new treatment approach via buprenorphine implant had on their daily lives as compared with previous oral Opioid Agonist Therapy (OAT). Methods: Five patients with OUD undergoing treatment with a buprenorphine subcutaneous implant participated voluntarily and provided their anonymity by self-describing, in response to questions prompted by the clinician, their experience with this innovative therapy. The narratives were analyzed according to standard NM methodology. Citations of patients' positive or negative experiences with traditional OAT and buprenorphine implant were classified according to five categories-patient's determination toward complete opioid abstinence, emotional impact, impact on life, smoothness of therapy, and therapy dependency-and quantified to obtain a picture of the overall therapy experience. Results: The analysis revealed the extent of the burden not only of addiction but also of the traditional OAT on patients' life, including relationships with family, job management, and free time. Conversely, the therapy with buprenorphine implant revealed a significant improvement in the quality of life of the patients, who also largely reported a positive emotional outcome during this therapy, as well as a solid determination to achieve complete recovery. Conclusions: This study illustrates the complex problems of living with OUD and provides insights into the added value of an innovative buprenorphine implant therapy that, due to its administration route and prolonged duration, allows patients to take an additional step toward total opioid abstinence and complete recovery of daily life.

A Direct Catalytic Ethanol Fuel Cell (DCEFC) Modified by LDHs, or by Catalase-LDHs, and Improvement in Its Kinetic Performance: Applications for Human Saliva and Disinfectant Products for COVID-19.

In this work, it has been experimentally proven that the kinetic performance of a common Direct Catalytic Ethanol Fuel Cell (DCEFC) can be increased by introducing nanostructured (ZnII,AlIII(OH)2)+NO3-·H2O Layered Double Hydroxides (LDHs) into the anode compartment. Carrying out the measurements with the open-circuit voltage method and using a kinetic format, it has been shown that the introduction of LDHs in the anodic compartment implies a 1.3-fold increase in the calibration sensitivity of the method. This improvement becomes even greater in the presence of hydrogen peroxide in a solution. Furthermore, we show that the calibration sensitivity increased by 8-times, when the fuel cell is modified by the enzyme catalase, crosslinked on LDHs and in the presence of hydrogen peroxide. The fuel cell, thus modified (with or without enzyme), has been used for analytical applications on real samples, such as biological (human saliva) and hand disinfectant samples, commonly used for the prevention of COVID-19, obtaining very positive results from both analytical and kinetic points of view on ethanol detection. Moreover, if the increase in the calibration sensitivity is of great importance from the point of view of analytical applications, it must be remarked that the increase in the speed of the ethanol oxidation process in the fuel cell can also be extremely useful for the purposes of improving the energy performance of a DCEFC.

Policies and Toxicological Screenings for No Drug Addiction: An Example from the Civil Aviation Workforce.

INTRODUCTION: Since 2008, Italian legislators, with the aim of ensuring public safety, have made it mandatory for an occupational doctor (OD) to assess specific categories of workers to exclude those who may have consumed drugs of abuse. Due to the relevance of work activities relating to the civil aviation and airport sector, a policy based on the use of training and information tools, as well as a health surveillance protocol, has been undertaken since 2009. MATERIALS AND METHODS: A total of 61,008 workers at a commercial airline underwent health surveillance between 2009 and 2019. Following ≤24 h notification, their urine was screened for opiates, cocaine, cannabinoids, amphetamines, methamphetamines, and methylenedioxymethamphetamine (MDMA) using an immunochemical test. Positive results were confirmed using Gas Chromatography-Mass Spectrometry (GC/MS) or Liquid Chromatography -Mass Spectrometry (LC/MS). In confirmed cases, the workers were declared unfit and sent to a specialized laboratory for a second level analysis. RESULTS: Positive results, initially >1%, have halved in the last four years (<0.5%). The percentage of positive results was consistently very low among pilots and, moreover, the rare positive cases detected were due to a cross-reactivity phenomena. The highest and most discontinuous percentages seen occurred in the population undergoing a pre-employment examination. Regarding the types of substance used, a prevalence of cannabis (58.52%) and cocaine (35.2%) use was observed. CONCLUSIONS: The data presented indicate that the air transport sector, in all its components (ground workers and air crews), has a very limited number of substance abusers, and this number tends to decrease over time and with work seniority. Another aspect of particular interest, and which is more specific to toxicology, concerns the detection of cross-reactivity in urinary immunochemical screening between the antibodies to drugs of abuse and certain other drugs, such as anti-inflammatories or antibiotics; as well as foods, and other commonly used substances.

Milestones to reach Hepatitis C Virus (HCV) elimination in Italy: From free-of-charge screening to regional roadmaps for an HCV-free nation.

Although Italy has been on track for Hepatitis C Virus (HCV) elimination since 2019, it fell off track due to the decrease in the number of treated patients. HCV elimination in Italy will be possible if immediate action is taken. A health policy was implemented beginning in 2021, consisting of screening among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The active screening requires regional governance that manages the processes' complexity integrating a well-organized network between territory assistance and hospital to achieve an effective HCV care cascade. This document aims to support the regional decision-making process by defining paths for screening and linkage-to-care. Implementing active screening strategies beyond a risk-based approach is required as a General Practitioners' task. Simplified paths must be drawn for the key populations screening. The infrastructure built for COVID-19 vaccination could be used also for HCV screening. According to a multidisciplinary care delivery, screening should be supplemented with rapid linkage-to-care and treatment of newly diagnosed patients. The realization of the proactive screening during the first two years is vital because it will define the tracks for the whole HCV cost-effective screening of 1948-1988 birth cohorts in Italy.

Barriers to effective management of hepatitis C virus in people who inject drugs: Evidence from outpatient clinics.

INTRODUCTION AND AIMS: People who inject drugs (PWID) constitute the largest reservoir of hepatitis C virus (HCV). Although effective medications are available and access to care is universal in Italy, the proportion of PWID receiving appropriate care remains low. DESIGN AND METHODS: To identify the major barriers for PWID to HCV treatment we surveyed a large sample of practitioners working in outpatient addiction centres (SerDs). The survey was conducted in two stages and involved 30.3% of SerDs operating in Italy. In the first, SerD physicians completed a questionnaire designed with a Delphi structure. In the second, SerD practitioners completed a targeted questionnaire to identify barriers to four SerD services in HCV management: screening, referral, treatment and harm reduction. RESULTS: The first-stage questionnaire, in which a Delphi and RAND-UCLA method was used, revealed a lack of agreement among the physicians about barriers to health care. The more detailed second-stage questionnaire indicated the barriers to delivering specific SerD services. As regarded the delivery of all four services, the major reasons for treating <50% of patients were: physician and nurse understaffing, technical, economic and logistic issues. In contrast, the practitioners who responded that they follow protocol recommendations often deliver all four services to >50% of patients. DISCUSSION AND CONCLUSIONS: HCV treatment remains out of reach for many PWID attending a drug treatment centre in Italy. To meet the World Health Organisation (WHO) target, there is a need to increase economic, technical and staff support at treatment centres using the protocols and the universal health care already in place.

Genetic and Environmental Risk Factors for Cannabis Use: Preliminary Results for the Role of Parental Care Perception.

BACKGROUND: Vulnerability to cannabis use (CU) initiation and problematic use have been shown to be affected by both genetic and environmental factors, with still inconclusive and uncertain evidence. OBJECTIVE: Aim of the present study was to investigate the possible interplay between gene polymorphisms and psychosocial conditions in CU susceptibility. METHODS: Ninety-two cannabis users and ninety-three controls have been included in the study. Exclusion criteria were serious mental health disorders and severe somatic disorders, use of other drugs and alcohol abuse; control subjects were not screened to remove Reward Deficiency Syndrome (RDS) behaviors. A candidate gene association study was performed, including variants related to dopaminergic and endocannabinoids pathways. Adverse childhood experiences and quality of parental care have been retrospectively explored utilizing ACES (Adverse Children Experience Scale), CECA-q (Child Experience of Care and Abuse Questionnaire), PBI (Parental Bonding Instrument). RESULTS: Our findings evidenced a significant association between rs1800497 Taq1A of ANKK1 gene and CU. Parental care was found to be protective factor, with emotional and physical neglect specifically influencing CU. Gender also played a role in CU, with males smoking more than females. However, when tested together genotypes and psychosocial variables, the significance of observed genetic differences disappeared. CONCLUSIONS: Our results confirm a significant role of Taq1A polymorphism in CU vulnerability. A primary role of environmental factors in mediating genetic risk has been highlighted: parental care could be considered the main target to design early prevention programs and strategies.

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.

The challenge of perioperative pain management in opioid-tolerant patients.

The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone.

Cannabis and intractable chronic pain: an explorative retrospective analysis of Italian cohort of 614 patients.

BACKGROUND: Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy. We present the first snapshot of the Italian experience with cannabis use for chronic pain over the initial year of its use. METHODS: This is a retrospective case series analysis of all chronic pain patients treated with oral or vaporized cannabis in six hubs during the initial year following the approval of the new Italian law (December 2015 to November 2016). We evaluated routes of administration, types of cannabis products utilized, dosing, and effectiveness and safety of the treatment. RESULTS: As only one of the six centers has extensively used cannabinoids for intractable chronic pain (614 patients of 659), only the population from Azienda Ospedaliero Universitaria Pisana (Pisa) was considered. Cannabis tea was the primary mode of delivery, and in almost all cases, it was used in association with all the other pain treatments. Initial and follow-up cannabinoid concentrations were found to vary considerably. At initial follow-up, 76.2% of patients continued the treatment, and <15% stopped the treatment due to side effects (none of which were severe). CONCLUSION: We present the first analysis of Italian clinical practice of the use of cannabinoids for a large variety of chronic pain syndromes. From this initial snapshot, we determined that the treatment seems to be effective and safe, although more data and subsequent trials are needed to better investigate its ideal clinical indication.

Sexual Dysfunction in Men Receiving Methadone Maintenance Treatment: Clinical History and Psychobiological Correlates.

A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitary-gonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that methadone dosages were not significantly correlated with sexual dysfunction scores except for 'erectile dysfunction', for which an inverse association was evidenced. Testosterone values showed a significant inverse correlation with ASEX sexual dysfunction scores, CECA-Q neglect scores and psychiatric symptom at SCL 90 among methadone patients. PRL levels were directly and significantly correlated with sexual dysfunction scores, psychiatric symptoms at SCL 90 and CECA-Q neglect scores. Both testosterone and PRL did not correlate with methadone dosages. The present findings appear to support the view of childhood adversities and comorbid psychiatric symptoms contributing to sexual dysfunction and related hormonal changes among methadone patients, challenging the assumption that attributes sexual problems entirely to the direct pharmacological effects of opioid agonist medications.

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.

METODO, a prospective observational study to assess the efficacy and tolerability of methadone in heroin-addicted patients undergoing a methadone maintenance treatment: preliminary results at baseline evaluation.

METODO (methadone efficacy therapy optimization dosage on-going) is a prospective observational study to assess the efficacy and tolerability of methadone in 500 heroin-addicted patients taking a methadone maintenance treatment, enrolled through 2010 to 2011 in five Italian sites, observed over 2 years. The Opiate Dosage Adequacy Scale has been used for the evaluation of the "adequacy" of the methadone dosage and to stratify patients in adequate and not adequate groups. The treatment efficacy has been evaluated in correlation to the dosage adequacy during the visits. Moreover, patients have been evaluated according to the retention rate and duration of retention in treatment and a series of questionnaires.

Psychobiological responses to unpleasant emotions in cannabis users.

Aim of this paper is to investigate the psychobiological reactions to experimentally induced negative emotional states in active marijuana-dependent smokers and whether changes in emotional reactivity were reversed by prolonged abstinence. Twenty-eight patients were randomly included into group A (fourteen active marijuana-dependent smokers) or group B (fourteen abstinent marijuana-dependent subjects). Emotional response evaluation of group B subjects was assessed after 6 months of abstinence. Fourteen healthy volunteers, matched for age and sex, were used as controls. Psychometric and emotional response evaluations were performed by administering Symptoms Check List-90 and State-Trait Anxiety Inventory Y-1 (STAI). Neutral and unpleasant set of pictures selected from the international affective picture system and the Self-Assesment Manikin procedure (SAM) have been used to determine ratings of pleasure and arousal. Before and after the experimental session, blood samples were collected to determine ACTH and cortisol plasma levels. Active cannabis users displayed significantly higher levels of pleasantness SAM scores and lower levels of arousal SAM scores compared to abstinent cannabis users and controls in response to emotional task. In a close parallel with psychological data, hormonal findings indicate a persistent hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in cannabis users, particularly among active marijuana smokers, and an impaired hormonal reaction to negative emotions, in comparison with healthy subjects. The capacity of the HPA axis to respond to stressful stimuli/negative emotions seems to be only partially recovered after 6 months of abstinence. Ours findings, although obtained in a small number of subjects, suggest an association between active cannabis use, subjective reduced sensitivity to negative emotions and threat and HPA axis dysfunction.

Recommendations for the prevention, diagnosis, and treatment of chronic hepatitis B and C in special population groups (migrants, intravenous drug users and prison inmates).

The global spread of hepatitis B virus (HBV) and hepatitis C virus (HCV), their high chronicity rates and their progression to cirrhosis and hepatocellular carcinoma, are major public health problems. Research and intervention programmes for special population groups are needed in order to assess their infection risk and set up suitable prevention and control strategies. Aim of this paper is to give health care professionals information on HBV and HCV infections amongst migrants, drug users and prison inmates. The manuscript is an official Position Paper on behalf of the following Scientific Societies: Italian Association for the Study of the Liver (A.I.S.F.), Italian Society of Infectious and Tropical Diseases (S.I.M.I.T.), Italian Federation Department's Operators and Addiction Services (FederSerD), Italian Prison Medicine and Healthcare Society (S.I.M.S.Pe.). The considered population groups, having a high prevalence HBV and HCV infections, require specific interventions. In this context, the expression "special population" refers to specific vulnerable groups at risk of social exclusion, such as migrants, prison inmates, and intravenous drug users. When dealing with special population groups, social, environmental and clinical factors should be considered when selecting candidates for therapy as indicated by national and international guidelines.

Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: preliminary results of an open randomized study.

An open randomized study lasting 12 months was performed to evaluate the efficacy of methadone or buprenorphine to suppress alcohol use in two hundred and eighteen heroin addicts with alcohol dependence. Daily maintenance doses of methadone were 80, 120, 160, and 200 mg/day, while doses of buprenorphine were 8, 16, 24, and 32 mg/day. As expected, both treatments were able to reduce both heroin use and addiction severity (measured with ASI interview). However, although both medications were able to suppress alcohol use, the highest dose of buprenorphine was better than the highest dose of methadone, in reducing alcohol craving, ethanol intake (measured as daily number of drinks), and the ASI subscale of alcohol use. The mechanism underlying the effects of the opioid maintenance therapy on the reduction of alcohol intake is still unclear. The results of the present study may represent the first clinical evidence of the potential effective use of the highest doses of buprenorphine for the suppression of ethanol intake in heroin addicts with alcohol dependence.

Adrenocorticotropic hormone and cortisol plasma levels directly correlate with childhood neglect and depression measures in addicted patients.

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been reported to be involved in vulnerability to alcohol and drug dependence in humans, possibly underlying both addictive behaviour and depression susceptibility. The aim of the present study was to investigate the possible interactions between childhood adverse experiences, depressive symptoms and HPA axis function in addicted patients, in comparison with healthy control. Eighty-two abstinent heroin or cocaine dependent patients and 44 normal controls, matched for age and sex, completed the symptoms Check List-90 (SCL-90), measuring depressive symptoms, and the Childhood Experience of Care and Abuse Questionnaire. Blood samples were collected to determine adrenocorticotropic hormone (ACTH) and cortisol basal plasma levels at 8:00 and 8:30 a.m. Addicted individuals showed significantly higher neglect and depression scores and ACTH-cortisol plasma levels respect to control subjects. Depression scores at SCL-90 in addicted patients positively correlated with plasma ACTH and cortisol values. In turn, plasma ACTH levels were directly associated with childhood neglect measures, reaching statistical significance with 'mother-neglect' scores. Plasma cortisol levels were related to 'father antipathy' among cocaine addicts. These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may have a persistent effect on HPA axis function as an adult, partially contributing, together with genetic factors and other environmental conditions, to both depressive traits and substance abuse neurobiological vulnerability.

Simultaneous determination of methadone, buprenorphine and norbuprenorphine in biological fluids for therapeutic drug monitoring purposes.

Methadone and buprenorphine are two of the drugs most frequently used for abstinence from illicit opioids and in the treatment of pain. A sensitive and selective high-performance liquid chromatographic method with diode array detection for the simultaneous determination of methadone, buprenorphine and norbuprenorphine has been developed. Separation of the three analytes was obtained by using a reversed-phase column (C8, 250mmx4.6mm i.d., 5microm) and a mobile phase composed of 40% phosphate buffer containing triethylamine, 50% methanol and 10% acetonitrile (final apparent pH 6.0). Loxapine was used as the internal standard. An accurate pre-treatment procedure of biological samples was developed, using solid-phase extraction with C8 cartridges (100mg, 1mL) and needing small amounts of plasma or urine (300microL). The calibration curves were linear over a working range of 10.0-1500.0ng/mL for methadone and of 5.0-500.0ng/mL for buprenorphine and norbuprenorphine in both matrices. The limit of quantitation (LOQ) and the limit of detection (LOD) were 1.0 and 0.4ng/mL for methadone and 0.5 and 0.2ng/mL for both buprenorphine and norbuprenorphine, respectively. The method was successfully applied to the analysis of plasma and urine samples from patients undergoing treatment with these drugs. Precision and accuracy results were satisfactory and no interference from endogenous or exogenous compounds was found. The method is suitable for the simultaneous determination of methadone and buprenorphine in human plasma and urine for therapeutic drug monitoring purposes.

Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: A retrospective study.

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.