ABSTRACT
Title
A phase IV, randomized, controlled, open-label, study on efficacy of Naltrexone combined with psychotherapy for treatment of alcohol dependence (Diatrex 0709 Study).
Authors
F. Mattioli1, C. Fucile1, V. Marini1, ML. Zuccoli1, D. Barciocco1, A. Sumberaz2, G. Testino2, A. Martelli1.
1Dept. of Internal Medicine (Di.M.I.) - Clinical pharmacology and toxicology Unit. University of Genoa, Italy.
2Alcohol Related Pathology Unit, San Martino Hospital, Genoa. Italy.
1Dept. of Internal Medicine (Di.M.I.) - Clinical pharmacology and toxicology Unit. University of Genoa, Italy.
2Alcohol Related Pathology Unit, San Martino Hospital, Genoa. Italy.
Abstract
Alcohol dependence represents a multifactorial disorder that includes genetic, neurobiological, psychological, and environmental components. The opioid antagonists may be effective in inducing and maintaining abstinence in alcohol dependent patients; naltrexone (Nalorex®) was approved by FDA and EMA as an oral formulation for the treatment of alcoholism. The efficacy of naltrexone may be increased when combined with psychosocial therapies (CBT, Cognitive Behavior Therapy) (Killeen et al, 2004).
This randomized, controlled, open study was designed to evaluate the efficacy of a six weeks pharmacological treatment with naltrexone associated with CBT, compared to diazepam in monotherapy, in patients with alcohol dependence. The primary objectives of the study was to evaluate the efficacy of naltrexone on daily alcoholic intake, control on alcohol craving, measured with VAS score, changes on behavioural patterns related to alcohol abuse through proper psychological assessment and withdrawal symptoms assessed by CIWA-Ar-C scale. The secondary objective was the evaluation of safety and tolerability of both treatments. The exploratory objective was the analysis of OPRM1 polymorphism to evaluate the possible correlation with naltrexone efficacy (Oslin et al, 2003; Anton et al, 2008).
The study planned to enrol 30 alcohol abusers; patients were randomly assigned in a 2:1 ratio to receive naltrexone 3 days/week (200 mg/week) and psychological support or diazepam (18 mg/die), as control treatment. All patients were monitored by means of biological indexes (i.e. serum alcohol levels, liver function tests (ALT, AST, gGT and MCV) and malondialdehyde (MDA), as marker of oxidative stress.
The study is ongoing; in this at interim analysis on six patients treated with naltrexone and three treated with diazepam, daily alcoholic intake was: 121.7±31.9 g/die at baseline vs. 22.0±22.8 g/die at the end of treatment in naltrexone group (p<0.05); while gGT values were: 146.1±77.2 vs. 94.7±84.4 and MDA levels 1.63±0.61 vs. 1.54±0.54. VAS score were lower at the end of treatment suggesting a reduction in craving (mean: 3.7±2.1 vs. 1.2 ±1.6). Finally, the psychological assessment demonstrated a reduction of depression symptoms and an improvement of alexithymia.
In the diazepam group the data were: daily alcoholic intake 96.7±55.1 g/die at baseline vs. 20.2±34.5 g/die at the end of treatment; gGT: 83.7±57.6 vs. 133.7±141.6; MDA: 1.45±0.61 vs. 1.49±0.50; VAS score: 2.4±1.6 vs. 0.7 ±0.4.
Although a direct statistical comparison of the data obtained with the two treatments is at the moment impossible, we deemed of interest to confirm the efficacy of naltrexone in an Italian clinical setting where these patients are managed as out-patients and a good therapeutic control is more difficult.
Killeen TK et al. (2004). Alcohol Clin Exp Res. 28, 1710-1717.
Oslin DW et al. (2003). Neuropsychopharmacology 28, 1546-52.
Anton RF et al. (2008). Arch Gen Psychiatry 65, 135-44.
This randomized, controlled, open study was designed to evaluate the efficacy of a six weeks pharmacological treatment with naltrexone associated with CBT, compared to diazepam in monotherapy, in patients with alcohol dependence. The primary objectives of the study was to evaluate the efficacy of naltrexone on daily alcoholic intake, control on alcohol craving, measured with VAS score, changes on behavioural patterns related to alcohol abuse through proper psychological assessment and withdrawal symptoms assessed by CIWA-Ar-C scale. The secondary objective was the evaluation of safety and tolerability of both treatments. The exploratory objective was the analysis of OPRM1 polymorphism to evaluate the possible correlation with naltrexone efficacy (Oslin et al, 2003; Anton et al, 2008).
The study planned to enrol 30 alcohol abusers; patients were randomly assigned in a 2:1 ratio to receive naltrexone 3 days/week (200 mg/week) and psychological support or diazepam (18 mg/die), as control treatment. All patients were monitored by means of biological indexes (i.e. serum alcohol levels, liver function tests (ALT, AST, gGT and MCV) and malondialdehyde (MDA), as marker of oxidative stress.
The study is ongoing; in this at interim analysis on six patients treated with naltrexone and three treated with diazepam, daily alcoholic intake was: 121.7±31.9 g/die at baseline vs. 22.0±22.8 g/die at the end of treatment in naltrexone group (p<0.05); while gGT values were: 146.1±77.2 vs. 94.7±84.4 and MDA levels 1.63±0.61 vs. 1.54±0.54. VAS score were lower at the end of treatment suggesting a reduction in craving (mean: 3.7±2.1 vs. 1.2 ±1.6). Finally, the psychological assessment demonstrated a reduction of depression symptoms and an improvement of alexithymia.
In the diazepam group the data were: daily alcoholic intake 96.7±55.1 g/die at baseline vs. 20.2±34.5 g/die at the end of treatment; gGT: 83.7±57.6 vs. 133.7±141.6; MDA: 1.45±0.61 vs. 1.49±0.50; VAS score: 2.4±1.6 vs. 0.7 ±0.4.
Although a direct statistical comparison of the data obtained with the two treatments is at the moment impossible, we deemed of interest to confirm the efficacy of naltrexone in an Italian clinical setting where these patients are managed as out-patients and a good therapeutic control is more difficult.
Killeen TK et al. (2004). Alcohol Clin Exp Res. 28, 1710-1717.
Oslin DW et al. (2003). Neuropsychopharmacology 28, 1546-52.
Anton RF et al. (2008). Arch Gen Psychiatry 65, 135-44.