Search tips
Search criteria

Results 1-5 (5)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Neurocognitive performance, alcohol withdrawal and effects of a combination of flumazenil and gabapentin in alcohol dependence 
Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of two medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pre-treatment AW (Anton et al., 2009). This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone.
Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial.
AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking.
Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains.
PMCID: PMC3166540  PMID: 21631542
alcoholism; anticonvulsant; GABA; neurocognitive; withdrawal
2.  Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis 
The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways. Although conflicting results have been obtained, most studies support the hypothesis that iron plays a role in hepatic lipogenesis. Iron is an integral part of some enzymes and transporters involved in lipid metabolism and, as such, may exert a direct effect on hepatic lipid load, intrahepatic metabolic pathways and hepatic lipid secretion. On the other hand, iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation, a hypothesis which is currently the focus of much research in the field of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportin and the iron regulatory molecule hepcidin. The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NASH. More defined studies are required to improve our understanding of these effects.
PMCID: PMC3442203  PMID: 23002334
Lipids; Iron; Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis; Hepcidin; Oxidative stress
3.  Gabapentin Combined with Naltrexone for the Treatment of Alcohol Dependence 
The American journal of psychiatry  2011;168(7):709-717.
Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms (e.g. insomnia, mood instability), most evident during early abstinence, might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and early relapse. This clinical trial evaluated whether gabapentin, in conjunction with naltrexone, was better than naltrexone alone and/or placebo during the early drinking cessation phase (first six weeks) and whether this effect persisted.
A total of 150 alcohol-dependent individuals randomly received sixteen weeks of naltrexone alone (50 mg/day [N= 50]), with gabapentin (up to 1200 mg/day [N=50] for the first six weeks), or double placebo (N= 50) while receiving medical management.
During the first six weeks, the naltrexone/gabapentin group had 1) a longer delay to heavy drinking than the naltrexone-alone group (p =0.04) which was similar to the placebo group, 2) had less heavy drinking days than the naltrexone-alone group (p= 0.0002) which did worse than placebo, and 3) had less drinks/drinking day than the naltrexone-alone group (p=0.02) and the placebo group (p=0.01). These differences faded over the remaining study weeks. Poor sleep was associated with more drinking in the naltrexone-alone group, but not in the combined group, while an alcohol withdrawal history was associated with better response in the combined group.
The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first six weeks after cessation of drinking. This effect did not endure once gabapentin was discontinued. Future studies should evaluate gabapentin alone and over longer durations of treatment.
PMCID: PMC3204582  PMID: 21454917
4.  Revisiting the Cost-Effectiveness of the COMBINE Study for Alcohol Dependent Patients: The Patient Perspective 
Medical care  2010;48(4):306-313.
Most cost and cost-effectiveness studies of substance abuse treatments focus on the costs to the provider/payer. Although this perspective is important, the costs incurred by patients should also be considered when evaluating treatment. This paper presents estimates of patients’ costs associated with the COMBINE alcohol treatments and evaluates the treatments’ cost-effectiveness from the patient perspective.
Study Design
A prospective cost-effectiveness study of patients in COMBINE, a randomized controlled clinical trial of 9 alternative alcohol treatment regimens involving 1,383 patients with diagnoses of primary alcohol dependence across 11 U.S. clinic sites. We followed a micro-costing approach that allowed estimation of patients’ costs for specific COMBINE treatment activities. The primary clinical outcomes from COMBINE are used as indicators of treatment effectiveness.
The average total patient time devoted to treatment ranged from about 30 hours to 46 hours. Time spent traveling to and from treatment sessions and participation in self-help meetings accounted for the largest portion of patient time costs. The cost-effectiveness results indicate that 6 of the 9 treatments were economically dominated and only 3 treatments are potentially cost-effective depending on patient’s willingness to pay for the considered outcomes: medical management + placebo, medical management + naltrexone, and medical management + naltrexone + acamprosate.
Few studies consider the patient’s perspective in estimating costs and cost-effectiveness even though these costs may have a substantial impact on a patient’s treatment choice, ability to access treatment, or treatment adherence. For this study, the choice of the most cost-effective treatment depends on the value placed on the outcomes by the patient, and the conclusions drawn by the patient may differ from that of the provider/payer.
PMCID: PMC3140763  PMID: 20355261
5.  The Effects of Opiate Use and Hepatitis C Virus Infection on Risk of Diabetes Mellitus in the Women’s Interagency HIV Study 
Opiate use is common in HIV- and hepatitis C virus (HCV)-infected individuals, however its contribution to the risk of diabetes mellitus is not well understood.
Prospective study of 1,713 HIV-infected and 652 uninfected participants from the Women’s Interagency HIV Study between October 2000 and March 2006. Diabetes defined as fasting glucose ≥126 mg/dl, or self-report of diabetes medication use or confirmed diabetes diagnosis. Opiate use determined using an interviewer-administered questionnaire. Detectable plasma HCV RNA confirmed HCV infection.
Current opiate users had a higher prevalence of diabetes (15%) than non-users (10%, p=.03), as well as a higher risk of incident diabetes (adjusted relative hazard [RHadj] 1.58, 95% CI 1.01, 2.46), after controlling for HCV infection, HIV/antiretroviral therapy status and diabetes risk factors including age, race/ethnicity, family history of diabetes and body mass index. HCV infection was also an independent risk factor for diabetes (RHadj 1.61, 95% CI 1.02, 2.52). HCV-infected women reporting current opiate use had the highest diabetes incidence (4.83 cases/100 person-years).
Among women with or at-risk for HIV, opiate use is associated with increased diabetes risk independently of HCV infection. Diabetic screening should be part of care for opiate users, and those infected with HCV.
PMCID: PMC3069645  PMID: 20190642
opiate use; diabetes mellitus; fasting glucose; Hepatitis C virus; HIV; women

Results 1-5 (5)