Medication-enhanced behavior therapy for alcohol use disorder: Naltrexone, Alcoholics Anonymous Facilitation, and OPRM1 genetic variation.

Medication-assisted behavior treatment for alcohol use disorder (AUD) holds promise to enhance the efficacy of medication and of behavior therapy when administered individually. The present study examines the treatment benefit of combined outpatient naltrexone (NTX) treatment with Alcoholics Anonymous Facilitation (AAF) behavior therapy, in the context of OPRM1 genotype. The minor OPRM1 Asp40 G-allele has been associated with greater positive reinforcing effects of alcohol consumption and greater alcohol craving, suggesting that individuals carrying the OPRM1 G allele may have an improved naltrexone response. Twenty patients, including 7 G-allele carriers, received 90 days of naltrexone with medication support and dispensing sessions, and ten AAF behavior therapy sessions. During treatment and the eight-week posttreatment follow-up, an overall increase in percent days abstinent was observed for the sample as a whole, but G-allele carriers reported relatively heavier drinking relative to other subjects. These findings suggest that this enhanced medication-assisted behavior treatment is a promising therapeutic combination, and mirror other recent findings that G-allele carriers may require more intensive treatment.

Predictors of Alcohol Withdrawal Readmissions.

AIMS: Hospital readmissions serve as a major benchmark for the quality of care and alcohol withdrawal (AW) may lead to multiple hospitalizations and readmissions. We sought to evaluate readmission rates and predictors of having AW-related readmissions in a nationally representative sample. SHORT SUMMARY: In a nationally representative sample, AW readmission within 30 days and multiple readmissions during the year were high and were particularly predicted by discharge against medical advice (AMA), comorbid psychosis, comorbid depression, poor socioeconomic status, comorbid drug abuse and alcohol-related medical disease. METHODS: Subjects from the 2013 Nationwide Readmissions Database (NRD) with AW as a primary or secondary diagnosis. Cross-sectional and retrospective analyses were performed using regression methods appropriate for the NRD complex sampling design. The outcome measures were AW-related readmission, 30-day readmission and multiple readmissions. RESULTS: In 2013, 393,118 discharges involved ICD-9 coding for AW and 41.5% of these included AW as the primary discharge diagnosis. The rate of AW-related readmission in 2013, as estimated from first-quarter index events, was 58.8% (95% confidence interval (CI) 57.5-60.1), with an average of 1.8 readmissions (95% CI 1.7-1.9). The 30-day readmission rate, estimated from January-November index events, was 19.7% (95% CI 19.0-20.4). The strongest independent predictors of yearly, 30-day and multiple readmission were discharged AMA and comorbid psychotic disorder. CONCLUSION: AW readmission within 30 days and multiple readmissions during the year were common and were particularly predicted by AMA discharge and comorbid psychotic disorder. While these and other factors can help identify high-risk patients, further study to determine causal mechanisms may aid efforts to improve both the outcomes and costs associated with acute AW treatment.

Relationship of Abnormal Chromatographic Pattern for Carbohydrate-Deficient Transferrin with Severe Liver Disease.

AIMS: Serum carbohydrate-deficient transferrin (CDT) is a validated test for chronic heavy alcohol drinking, but CDT abnormalities have been associated with liver disease, limiting its use in these patients. We report here on the association between poor chromatographic resolution of disialotransferrin from trisialotransferrin (the so-called 'di-tri bridging') and liver disease severity and etiology. METHODS: Subjects were patients in whom detailed clinical data, including histology results, were available on their existing liver diseases (n=139). Percent disialo-CDT (%dCDT) was measured by high-performance liquid chromatography, and the risks for di-tri bridging associated with cirrhosis, with and without adjustment for alcohol use and alcohol-related liver disease, were estimated. RESULTS: Di-tri bridging was present in 22/73 (30%) cirrhotic subjects and 7/66 (11%) non-cirrhotic subjects. The unadjusted risk for di-tri bridging in cirrhotics relative to non-cirrhotics was 3.6 (95% confidence interval 1.4-9.2). Adjustment for alcohol-related liver disease and current drinking had little effect on this estimate (adjusted odds ratio 3.4), and neither alcohol-related liver disease nor current drinking were independently associated with di-tri bridging after accounting for the effect of cirrhosis. CONCLUSIONS: The presence of di-tri bridging was associated with cirrhosis in individuals with both alcohol-related and non-alcoholic liver disease, although most cirrhotic subjects did not exhibit di-tri bridging. When di-tri bridging is seen in individuals being tested for chronic heavy drinking, investigation for cirrhosis should be considered. SHORT SUMMARY: There are known liver-disease-associated abnormalities in CDT. In this study, we found that such abnormalities were strongly associated with cirrhosis rather than less-advanced disease, but were only clinically evident in 30% of cirrhotics. Abnormalities also occurred in severe hepatitis without cirrhosis and were not specific for liver disease etiology.

Alcohol-related diagnoses and increased mortality in acute myocardial infarction patients: An analysis of the nationwide inpatient sample.

BACKGROUND: Moderate alcohol consumption has been associated with lower risk of coronary heart disease death, but heavy alcohol consumption may increase risk. OBJECTIVE: We sought to determine the association of alcohol-related diagnoses with in-hospital mortality in patients with acute myocardial infarction (AMI). DESIGN/SETTING/PATIENTS: Discharge data collected from all admissions recorded in the Nationwide Inpatient Sample (NIS) database from 2011. A cross-sectional analysis was performed using regression methods appropriate for the NIS sample design. MEASURES: The outcome measures were in-hospital mortality, length of stay, and cardiac procedures. RESULTS: AMI accounted for 610,963 (1.9%) of adult in-patient admissions, with an in-hospital mortality rate of 5.3%. Alcohol-related diagnoses were associated with increased mortality in AMI patients after controlling for factors associated with alcoholism including age, sex, liver disease, hypertension, diabetes, renal failure, peripheral vascular disease, arrhythmias, drug abuse, gastrointestinal bleed, and smoking (adjusted odds ratio [OR]: 1.5, 95% confidence interval [CI]: 1.2-1.7, P < 0.001). This association was significant in both ST-elevation myocardial infarction patients (adjusted OR: 1.7, 95% CI: 1.4-2.2, P < 0.001) and non-ST-elevation myocardial infarction patients (adjusted OR: 1.3, 95% CI: 1.0-1.7, P = 0.025). Chronic alcohol-related diagnoses were significantly associated with death, but acute alcohol effects (as estimated by withdrawal and intoxication) were not associated. CONCLUSION: Chronic alcohol-related diagnoses were associated with a modest increase in the risk for death in individuals presenting with AMI. This risk was not accounted for by common alcohol-related comorbidities. As a component of global efforts to limit hospital deaths from AMI, future research should identify the factors underlying this association. Journal of Hospital Medicine 2016;11:563-567. © 2016 Society of Hospital Medicine.

Validation of blood phosphatidylethanol as an alcohol consumption biomarker in patients with chronic liver disease.

BACKGROUND: Blood phosphatidylethanol (PEth) is a promising biomarker of alcohol consumption. This study was conducted to evaluate its performance in patients with liver disease. METHODS: This study included 222 patients with liver disease. Patient-reported alcohol use was obtained as a reference standard, and PEth was measured by tandem mass spectrometry. Receiver operating characteristic (ROC) and contingency table analyses were used to assess the performance of PEth in detecting any drinking and averaging 4 or more drinks daily in the past 30 days. RESULTS: At the limit of quantitation (20 ng/ml), PEth was 73% sensitive (95% confidence interval [CI] 65 to 80) and 96% specific (95% CI 92 to 100) for any drinking in the past month. Subjects who drank but had a negative PEth result were mainly light drinkers. Subjects who reported 30-day abstinence but with quantifiable PEth either reported heavy drinking within the past 6 weeks or had data that suggested underreported drinking. At the optimal cutoff concentration of 80 ng/ml, PEth was 91% sensitive (95% CI 82 to 100) and 77% specific (95% CI 70 to 83) for averaging at least 4 drinks daily. CONCLUSIONS: PEth is a useful test for detecting alcohol use in patients with liver disease, but cutoff concentrations for heavy drinking will result in misclassification of some moderate to heavy drinkers.

Care for hospitalized patients with unhealthy alcohol use: a narrative review.

There is increasing emphasis on screening, brief intervention, and referral to treatment (SBIRT) for unhealthy alcohol use in the general hospital, as highlighted by new Joint Commission recommendations on SBIRT. However, the evidence supporting this approach is not as robust relative to primary care settings. This review is targeted to hospital-based clinicians and administrators who are responsible for generally ensuring the provision of high quality care to patients presenting with a myriad of conditions, one of which is unhealthy alcohol use. The review summarizes the major issues involved in caring for patients with unhealthy alcohol use in the general hospital setting, including prevalence, detection, assessment of severity, reduction in drinking with brief intervention, common acute management scenarios for heavy drinkers, and discharge planning. The review concludes with consideration of Joint Commission recommendations on SBIRT for unhealthy alcohol use, integration of these recommendations into hospital work flows, and directions for future research.

Sensitivity and specificity of urinary ethyl glucuronide and ethyl sulfate in liver disease patients.

BACKGROUND: It is important to monitor alcohol use in the care of patients with liver disease, but patient self-report can be unreliable. We therefore evaluated the performance of urine ethyl glucuronide (EtG) and ethyl sulfate (EtS) in detecting alcohol use in the days preceding a clinical encounter. METHODS: Subjects (n = 120) were recruited at a university-based hepatology clinic or during hospitalization. Alcohol consumption was ascertained by validated self-report measures. Urine EtG (cutoff 100 ng/ml) and EtS (cutoff 25 ng/ml) concentrations were assayed by a contracted laboratory using tandem mass spectrometry. The sensitivity and specificity of each biomarker in the detection of drinking during the 3 and 7 days preceding the clinic visit were determined, as well as the influence of liver disease severity on these results. RESULTS: Urine EtG (sensitivity 76%, specificity 93%) and urine EtS (sensitivity 82%, specificity 86%) performed well in identifying recent drinking, and liver disease severity does not affect biomarker performance. After elimination of 1 false-negative self-report, urine EtG > 100 ng/ml was 100% specific for drinking within the past week, whereas 9% of the subjects without evidence of alcohol drinking for at least 1 week had EtS > 25 ng/ml. CONCLUSIONS: Urine EtG and EtS can objectively supplement the detection of recent alcohol use in patients with liver disease. Additional research may determine optimal methods for integrating these tests into clinical care.

Hair ethyl glucuronide is highly sensitive and specific for detecting moderate-to-heavy drinking in patients with liver disease.

AIMS: Hair ethyl glucuronide (EtG) is a promising biomarker of moderate-to-heavy alcohol consumption and may have utility in detecting and monitoring alcohol use in clinical populations where alcohol use is of particular importance. This study evaluated the relationship between hair EtG and drinking in patients with liver disease. METHODS: The subjects (n = 200) were patients with liver disease who presented for care at a university medical center. Alcohol use during the 3 months preceding participation in the study was assessed, and a sample of hair was obtained for EtG testing. Classification of drinking status (any drinking or averaging at least 28 g per day) by hair EtG was evaluated, as well as the effects of liver disease severity and demographic and hair care factors. RESULTS: The area under the receiver operating characteristic curve for detecting an average of 28 g or more per day during the prior 90 days was 0.93. The corresponding sensitivity and specificity of hair EtG ≥8 pg/mg for averaging at least 28 g of ethanol per day were 92 and 87%, respectively. Cirrhosis and gender may have a modest influence on the relationship between drinking and hair EtG. CONCLUSION: Hair EtG was highly accurate in differentiating subjects with liver disease averaging at least 28 g of ethanol per day from abstainers and lighter drinkers.

Client attitudes toward alcohol use self-report.

Because psychiatric illnesses and problematic alcohol use frequently co-occur and heavy alcohol use can exacerbate depression and anxiety, mental health clinicians should perform alcohol-use screenings. The aim of this study was to determine if psychiatric patients would be accepting of their mental health clinician screening them for heavy alcohol use. Using a written survey, patients rated their levels of agreement with 9 statements regarding opinions about alcohol screening by their mental-health providers. They also completed the Alcohol Use Disorders Identification Test-C (AUDIT-C), a screening instrument for heavy alcohol use. One hundred fifty-four patients were surveyed in 2 psychiatric outpatient clinics. Nearly 40% screened positively for heavy alcohol use on the AUDIT-C. Nearly 8 out of 10 psychiatric patients were in favor of being screened for alcohol use by either self-report or biomarkers, independent of AUDIT-C status and gender. Thus, mental health clinicians should not be deterred from alcohol screening by perceived negative attitudes from patients.

Medical treatment of alcohol dependence: a systematic review.

OBJECTIVE: To summarize published data on pharmacologic treatments for alcohol dependence alone and in combination with brief psychosocial therapies that may be feasible for primary care and specialty medical settings. METHODS: We conducted electronic searches of published original research articles and reviews in MEDLINE, SCOPUS, CINAHL, Embase, and PsychINFO. In addition, hand searches of reference lists of review articles, supplemental searches of internet references and contacts with experts in the field were conducted. Randomized controlled studies published between January 1960 and August 2010 that met our inclusion/exclusion criteria were included. RESULTS: A total of 85 studies, representing 18,937 subjects, met our criteria for inclusion. The evidence base for oral naltrexone (6% more days abstinent than placebo in the largest study) and topiramate (prescribed off-label) (e.g., 26.2% more days abstinent than placebo in a recent study) is positive but modest. Acamprosate shows modest efficacy with recently abstinent patients, with European studies showing better results than U.S. ones. The evidence-base for disulfiram is equivocal. Depot naltrexone shows efficacy (25% greater reduction in rate of heavy drinking vs. placebo, in one of the largest studies) in a limited number of studies. Some studies suggest that patients do better with extensive psychosocial treatments added to medications while others show that brief support can be equally effective. CONCLUSIONS: Although treatment effects are modest, medications for alcohol dependence, in conjunction with either brief support or more extensive psychosocial therapy, can be effective in primary and specialty care medical settings.

Identification and risk-stratification of problem alcohol drinkers with minor trauma in the emergency department.

BACKGROUND: Brief alcohol intervention may improve outcomes for injury patients with hazardous drinking but is less effective with increased severity of alcohol involvement. This study evaluated a brief method for detecting problem drinking in minor trauma patients and differentiating hazardous drinkers from those with more severe alcohol problems. METHODS: Subjects included 60 minor trauma patients in an academic urban emergency department (ED) who had consumed any amount of alcohol in the prior month. Screening and risk stratification involved the use of a heavy-drinking-day screening item and the Rapid Alcohol Problems Screen (RAPS). We compared the heavy-drinking-day item to past-month alcohol use, as obtained by validated self-reporting methods, and measured the percentage of carbohydrate-deficient transferrin (%CDT) to assess the accuracy of self-reporting. The Alcohol Dependence Scale (ADS) was administered to gauge the severity of alcohol involvement and compared to the RAPS. RESULTS: Eighty percent of the subjects endorsed at least one heavy drinking day in the past year, and all patients who exceeded recommended weekly drinking limits endorsed at least one heavy drinking day. Among those with at least one heavy drinking day, 58% had a positive RAPS result. Persons with no heavy drinking days (n=12) had a median ADS of 0.5 (range 0 to 3). RAPS-negative persons with heavy drinking days (n=20) had a median ADS of 2 (range 0 to 8). RAPS-positive persons with heavy drinking days (n=28) had a median ADS of 8 (range 1 to 43). CONCLUSION: A heavy-drinking-day item is useful for detecting hazardous drinking patterns, and the RAPS is useful for differentiating more problematic drinkers who may benefit from referral from those more likely to respond to a brief intervention. This represents a time-sensitive approach for risk-stratifying non-abstinent injury patients prior to ED discharge.

Liver disease and HPLC quantification of disialotransferrin for heavy alcohol use: a case series.

BACKGROUND: It had previously been suggested that individuals with cirrhosis may have a pattern of transferrin glycosylation that interferes with the interpretation of carbohydrate-deficient transferrin (CDT) testing for heavy alcohol use. The goal of this case series was to evaluate the prevalence of liver disease among individuals with poor resolution of transferrin glycoforms by high performance liquid chromatography. METHODS: We reviewed the electronic medical records of 35 consecutive patients with poor chromatographic resolution of disialotransferrin from trisialotransferrin and recorded information on diagnosed liver disease, liver function testing, and other factors. RESULTS: Thirty of the 35 subjects with poor chromatographic resolution of the transferrin glycoforms had sufficient data in the medical record for some estimation of liver function. Of these 30 subjects, 25 had previously diagnosed liver pathology. Of the remaining 5 subjects, 2 had liver imaging results suggestive of benign tumor; the remaining 3 had mildly elevated bilirubin and aminotransferase activity, and low albumin. CONCLUSIONS: Liver abnormalities, but not necessarily cirrhosis, are common in individuals with poor chromatographic separation of transferrin glycoforms, which might lead to false-positive results on CDT testing. However, the chromatographic-based assay can detect this issue, minimizing the reporting of false positives, but not necessarily assisting in valid detection of heavy drinking.

Phosphatidylethanol and alcohol consumption in reproductive age women.

BACKGROUND: Fetal alcohol disorders are preventable, but self-reported alcohol consumption can be misleading and impede effective treatment. Biomarkers represent an alternative method for assessing alcohol use, and this study evaluated the relationship between blood phosphatidylethanol (PEth) and alcohol use in a sample of reproductive age women. METHODS: Alcohol use was estimated by validated self-report methods in 80 nonpregnant women ages 18 to 35. PEth was measured by a contracted laboratory using a liquid chromatography-tandem mass spectrometry assay. Regression methods appropriate for the distribution of PEth were used to define its relationship to alcohol consumption during the prior 2 weeks and explore the effects of drinking patterns on this association. Receiver operating characteristic analysis was used to estimate the sensitivity of PEth for various drinking levels at 95% specific cutoffs. RESULTS: PEth had a positive linear association with grams of alcohol consumed (p < 0.001), and was detectable in 93% of subjects consuming an average of 2 or more drinks per day. The relationship between total alcohol consumption and PEth may be stronger in women with recent heavy drinking days. The relationship between drinking and PEth varied considerably between individuals, and sensitivity for a certain amount of drinking was low at a highly specific cutoff concentration. CONCLUSIONS: PEth is a highly sensitive indicator of moderate and heavy alcohol consumption in reproductive age women and may complement the use of self-report alcohol screens when additional objective markers of alcohol use are desirable. However, choosing a highly valid cutoff concentration for PEth to differentiate various levels of alcohol consumption may not be feasible.

Prevalence of problem drinking and characteristics of a single-question screen.

Hazardous drinking and alcohol use disorders (i.e, abuse and dependence) are common in Emergency Departments (EDs). This study examined 1) the prevalence of these conditions among ED patients and 2) characteristics of a single screening question (having consumed at least five drinks for males or four for females during a single day). Data from the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed. Logistic regression for clustered data was used to estimate the relative risk for past-year ED use associated with hazardous drinking, abuse, and dependence. Contingency tables were analyzed to estimate the sensitivity and specificity of the single-question screen for detecting these conditions. Hazardous drinking was not associated with ED utilization. Alcohol abuse was associated with a relative risk of 1.3 (95% confidence interval [CI] 1.1-1.5) and alcohol dependence with a relative risk of 1.9 (95% CI 1.6-2.2). For current drinkers, the single question screen was 0.96, 0.85, and 0.90 sensitive for hazardous drinking, alcohol abuse, and alcohol dependence, respectively. Individuals with a positive screen in the past year were considered at least hazardous drinkers, and specificity was 0.80, 0.64, and 0.65 for hazardous drinking, abuse, and dependence, respectively. Specificity was modestly increased in women. Most problem drinkers were hazardous drinkers, but only severe alcohol use disorders were particularly prevalent in the ED. The single heavy-drinking-day item appears sensitive for problem drinking. Positive tests must be followed by additional assessment to differentiate hazardous drinking from alcohol use disorders.

Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms.

Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.

Preliminary evaluation of phosphatidylethanol and alcohol consumption in patients with liver disease and hypertension.

AIMS: The goal of this preliminary study was to evaluate the relationship between blood phosphatidylethanol (PEth) and recent drinking in patients with liver disease and hypertension. METHODS: Twenty-one patients with liver disease and 21 patients with essential hypertension were recruited at an academic medical center. Alcohol consumption was estimated using validated self-report methods, and blood PEth was measured by HPLC-MS/MS at a contracted laboratory. Nonparametric comparisons were made between abstainers/light drinkers, moderate drinkers consuming between 1 and 3 drinks per day, and those drinking above this level. Regression methods were used to estimate the effects of liver disease, gender, and age on the relationship between PEth and alcohol use, and to estimate the strength of the linear relationship between PEth and drinking. RESULTS: PEth differed significantly between the three drinking groups (P < 0.001). The relationship between PEth and alcohol did not differ between hypertension and liver disease patients (P = 0.696), nor by gender and age. While there was substantial variability between subjects in the PEth concentration given a similar level of reported drinking, the amount of ethanol consumed was strongly associated with the PEth concentration (P < 0.001). CONCLUSION: Results support PEth measurement by HPLC-MS/MS as a promising marker of past 1- to 2-week moderate to heavy alcohol consumption in patients with and without liver disease. PEth appears useful for differentiating abstinence or light drinking from moderate to heavy consumption, but may have limited utility for differentiating moderate from heavy alcohol use.

COMT genotype influences the effect of alcohol on blood pressure: results from the COMBINE study.

BACKGROUND: Heavy drinking can cause chronic hypertension, possibly due to effects on the autonomic nervous system. Catechol- O-methyltransferase (COMT) inactivates catecholamines, and a G to A substitution in codon 108 in the soluble COMT mRNA (or codon 158 in the membrane-bound form) substitutes methionine for valine and alters enzyme activity. METHODS: We evaluated the association of COMT genotype at this locus with blood pressure (BP) in 839 alcohol-dependent individuals before and during participation in an alcoholism treatment trial. Hierarchical linear models were used to account for within-subject correlation on repeated BP measurements, and findings were adjusted for age, gender, ethnicity, alcohol use, body mass index, current smoking, hypertension history, and study site. RESULTS: Relative to those with the val-val genotype, those with the met-met genotype had higher adjusted systolic (+4.9 mm Hg, P < 0.01) and diastolic (+3.2 mm Hg, P < 0.01) BP at baseline. Those with the val-met genotype did not significantly differ from the val-val genotype. Changes in BP between baseline and 4 weeks of alcohol treatment also differed by genotype. Relative to the val-val genotype, the met-met genotype had a greater reduction in adjusted systolic pressure (-3.9 mm Hg, P < 0.01) and diastolic pressure (-2.8 mm Hg, P < 0.01). Corresponding relative reductions for the val-met genotype were -2.2 mm Hg systolic (P = 0.070) and -1.5 mm Hg diastolic (P < 0.05). CONCLUSION: Findings suggest that alcohol-induced BP elevation may be related to the effects of catecholamines and their genetically determined inactivation.

Blood pressure reduction during treatment for alcohol dependence: results from the Combining Medications and Behavioral Interventions for Alcoholism (COMBINE) study.

AIMS: Heavy drinking is associated with hypertension. This study evaluated blood pressure changes occurring during treatment for alcohol dependence. PARTICIPANTS: Subjects included 1383 people participating in the Combining Medications and Behavioral Interventions for Alcoholism (COMBINE) study, a large multi-center treatment study for alcohol dependence. MEASUREMENTS: Methods appropriate for repeated-measures data were used to assess the relationship of percentage of drinking days (PDD) to systolic and diastolic blood pressure over a 16-week treatment period. Modification of these associations by demographic and other variables was assessed. FINDINGS: Blood pressure reduction was evident only in people who were above the median blood pressure at baseline. In this group, systolic blood pressure decreased by an average of 12 mmHg and diastolic blood pressure decreased by an average of 8 mmHg. Blood pressure reduction occurred during the first month of treatment. This effect was similar regardless of age, sex, body mass index, reported history of hypertension and use of anti-hypertensive medications. An observed association between blood pressure and PDD in Caucasians was not evident in African Americans due largely to their lower pre-treatment blood pressure. CONCLUSIONS: Reduction in alcohol consumption has a potent anti-hypertensive effect in alcoholics with higher blood pressure. For hypertensive, alcohol-dependent people, treatment for alcoholism should be considered a major component of anti-hypertensive therapy.