Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 295: 2003-2017

Boston University, Boston, Massachusetts, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 06/2006; 295(17):2003-17. DOI: 10.1001/jama.295.17.2003
Source: PubMed


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. Identifier: NCT00006206.

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    • "Estimated alcohol consumption at the daily level is often aggregated to provide various estimates of drinking outcomes , such as percentage of days abstinent, drinks per drinking day, heavy drinking days (where " heavy " drinking is defined as 4 or more drinks for women and 5 or more drinks for men), or drinks per day (Anton et al., 2006; Project MATCH Research Group, 1997). Investigators should report the standard drink unit size and the method of aggregation. "
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    ABSTRACT: The primary goals in conducting clinical trials of treatments for alcohol use disorders (AUDs) are to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past 2 decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. This paper provides a narrative review of guidance on reporting quality in AUD treatment trials. Despite improvements in the reporting of results of treatment trials for AUD over the past 2 decades, many published reports provide insufficient information on design or methods. The reporting of alcohol treatment trial design, analysis, and results requires improvement in 4 primary areas: (i) trial registration, (ii) procedures for recruitment and retention, (iii) procedures for randomization and intervention design considerations, and (iv) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. Copyright © 2015 by the Research Society on Alcoholism.
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    • "These transporters belong to the type 1 phosphate transporter family. VGLUT1 is expressed in the cortex , hippocampus, and thalamus while VGLUT2 is found in the neocortex, olfactory bulb, dentate gyrus, and subiculum; also, co-expression of VGLUT1 and VGLUT2 has been observed in the hippocampus (Herzog et al., 2006). VGLUT1 is suggested to be expressed at synapses associated with low release rates and long-term potentiation, while VGLUT2 is expressed at synapses "
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    • "Whether patients in treatment would reduce their use in response to an attenuated cannabis effect is an empirical question, but this is the mechanism by which naltrexone reduces alcohol use clinically (e.g., Anton et al., 2006). Naltrexone reduced alcohol self-administration in alcoholdependent , nontreatment-seeking research volunteers (O " Malley et al., 2002), similar to the present study, and also decreased the likelihood that alcohol-dependent patients who lapsed after a period of abstinence would return to heavy drinking (O " Malley et al., 1992; Volpicelli et al., 1992). "
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    ABSTRACT: Given that cannabis use is increasing in the US, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Non-treatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18M; 5F) or placebo (0 mg; n=26M; 2F) capsules for 16 days. Before, during and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1, 51.8) the odds of self-administering active cannabis compared to the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.Neuropsychopharmacology accepted article preview online, 16 April 2015. doi:10.1038/npp.2015.108.
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