Efficacy of extended-release naltrexone in patients with relatively higher severity of alcohol dependence.
ABSTRACT Because some literature reviews have suggested that naltrexone's benefit may be limited to less-severe alcohol dependence, and exclusively to reduction in heavy drinking rather than abstinence, we examined the efficacy of once per month, injectable extended-release naltrexone (XR-NTX 380 mg) in patients with relatively higher severity alcohol dependence.
Post hoc analyses examined data from a multicenter, placebo-controlled, 24-week randomized trial of XR-NTX for alcohol dependence (N = 624). We analyzed treatment effects in alcohol-dependent patients who had higher baseline severity, as measured by: (i) the Alcohol Dependence Scale (ADS) or (ii) having been medically detoxified in the week before randomization. Efficacy was also examined via the relationship between pretreatment severity indices and reporting at least 4 days of lead-in abstinence prior to treatment-a major predictor of good outcome in the original study.
Higher severity alcohol-dependent patients, defined by the ADS, when receiving XR-NTX 380 mg (n = 50) compared with placebo (n = 47), had significantly fewer heavy-drinking days in-trial (hazard ratio=0.583; p = 0.0049) and showed an average reduction of 37.3% in heavy-drinking days compared with 27.4% for placebo-treated patients (p = 0.039). Among those who had a detoxification just prior to randomization, these reductions were 48.9% (XR-NTX 380 mg; n = 11) and 30.9% (placebo; n = 15) (p = 0.004). Subjects with at least 4 days of pretreatment abstinence (n = 82) versus those without (n = 542) had significantly higher pretreatment ADS scores (p = 0.002) and were more likely to require detoxification prior to randomization (p < 0.001). Patients with lead-in abstinence experienced significantly better maintenance of initial and 6-month abstinence.
These secondary analyses support the efficacy of XR-NTX 380 mg in relatively higher severity alcohol dependence for both reduction in heavy drinking and maintenance of abstinence, with implications for the role of adherence pharmacotherapy.
- Drug Metabolism and Disposition 2(6):506-12. · 3.36 Impact Factor
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ABSTRACT: The purpose of this study was to determine the prevalence of recovery from alcohol problems with and without treatment, including whether such recoveries involved abstinence or moderate drinking. Data from two surveys of randomly selected adults in the general population were analyzed. Random-digit dialing was used to conduct telephone interviews with 11,634 and 1034 respondents. Respondents 20 years of age or older were categorized on the basis of drinking status and history. Both surveys found that most individuals (77.5% and 77.7%) who had recovered from an alcohol problem for 1 year or more did so without help or treatment. A sizable percentage (38% and 63%) also reported drinking moderately after resolving their problem. These two surveys are among the first to report prevalence rates for recovery from alcohol problems for treated and untreated individuals and for moderation and abstinence outcomes.American Journal of Public Health 08/1996; 86(7):966-72. · 3.93 Impact Factor
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ABSTRACT: Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. Percent days abstinent from alcohol and time to first heavy drinking day. All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. clinicaltrials.gov Identifier: NCT00006206.JAMA The Journal of the American Medical Association 06/2006; 295(17):2003-17. · 29.98 Impact Factor