Claudio Leonardi

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.

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.

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.

Dysregulated responses to emotions among abstinent heroin users: Correlation with childhood neglect and addiction severity ☆

The aim of this paper was to investigate the subjective responses of abstinent heroin users to both neutral and negative stimuli and the related hypothalamus-pituitary-adrenal reactions to emotional experience in relationship to their perception of childhood adverse experiences. Thirty male abstinent heroin dependents were included in the study. Emotional responses and childhood neglect perception were measured utilizing the State-Trait Anxiety Inventory Y-1 and the Child Experience of Care and Abuse Questionnaire. Neutral and unpleasant pictures selected from the International Affective Picture System and the Self-Assessment Manikin procedure have been used to determine ratings of pleasure and arousal. These ratings were compared with normative values obtained from healthy volunteers used as control. Blood samples were collected before and after the experimental sessions to determine both adrenocorticotropic hormone and cortisol plasma levels. Basal anxiety scores, cortisol and adrenocorticotropic hormone levels were higher in abstinent heroin users than in controls. Tests showed that anxiety scores did not change in controls after the vision of neutral slides, whilst they did in abstinent heroin addicts, increasing significantly; and increased less significantly after the unpleasant task, in comparison to controls. Abstinent heroin users showed significantly higher levels of parent antipathy and childhood emotional neglect perception than controls for both the father and the mother. Plasma adrenocorticotropic hormone and cortisol levels did not significantly increase after unpleasant slide set viewing among addicted individuals, because of the significantly higher basal levels characterizing the addicted subjects in comparison with controls. Multiple regression correlation showed a significant relationship between childhood neglect perception, arousal reaction, impaired hypothalamus-pituitary-adrenal axis response and addiction severity. Early adverse experiences seem to affect the entire interaction between hyper-arousal, reduced hormonal response to stress and addiction severity. Our findings, although obtained in a small number of subjects, indicate a significant link between the perception of parental style/care/support during childhood and the ability to cope with stressful emotional stimuli in adulthood and addiction severity.

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

ABSTRACT 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.

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.