Mismatch negativity: no difference between controls and abstinent alcoholics

BACKGROUND: A number of studies have examined the amplitude of the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. The current study examined MMN in alcoholics abstinent an average of 6.7 years (with a minimum of six months abstinence) compared to controls. This study examined the association of MMN with alcoholism family history density, with indices of the presence and severity of externalizing disorders (a risk-factor for alcoholism), and with alcohol use variables. METHODS: Electroencephalograms were gathered on 76 subjects (38 controls, 38 abstinent alcoholics) during a nonattending mismatch negativity experiment. Measures of alcoholism family history density, disinhibited personality traits, and antisocial symptoms served as measures of risk-factors known to be associated with a genetic liability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. RESULTS: There were no differences in MMN amplitude or latency between controls and abstinent alcoholics. There also were no significant associations between MMN measures and the measures of risk for alcoholism or with the severity of alcohol use or duration of abstinence. CONCLUSIONS: The results suggest that MMN is neither affected in chronic alcoholics nor associated with alcoholism vulnerability, and thus does not reflect a trait marker of alcoholism or alcoholism risk. The current results do not address effects on MMN of acute alcohol ingestion or withdrawal from alcohol.     

Visual P300s in long-term abstinent chronic alcoholics

BACKGROUND: Evidence of reduced P3b amplitudes in chronic alcoholics and individuals at risk for developing alcoholism suggest that the P3b may be an endophenotypic marker for alcoholism. If this is the case, then long-term abstinent alcoholics (LTAAs) should exhibit reduced P3b amplitudes. Thus far, P3b studies on chronic alcoholics have focused primarily on samples with relatively short-term abstinence (less than 15 months). This study examines the amplitude and latency of the P3b and P3a event-related brain electrical components in LTAAs compared with normal controls (NCs) and whether these measures are related to alcohol use and other subject variables. METHODS: Electroencephalographs (EEGs) were recorded on 48 LTAAs (mean abstinence=6.7 years) compared with 48 age-matched and gender-matched NCs during a visual P300 experiment consisting of standard, target, and rare nontarget conditions. This paradigm elicited the P3b (target condition) and the P3a (rare nontarget condition) components. RESULTS: Long-term abstinent alcoholics had reduced P3b amplitudes and increased P3b latencies in comparison with NCs. Long-term abstinent alcoholics also exhibited delayed P3a components, but no P3a amplitude reductions. Alcohol use variables, a family history of alcohol problems, and the duration of alcohol abstinence were not associated with any amplitude or latency variables. CONCLUSIONS: Even after very prolonged abstinence, reduced P3b amplitudes are present in chronic alcoholics and are not associated with any family history or alcohol use variables. These results provide equivocal support for reduced P3b amplitude being an endophenotypic marker for alcoholism, but are also consistent with P3b being affected by a threshold of alcohol abuse, with the effect not resolving over long periods of abstinence.     

A randomized trial of integrated outpatient treatment for medically ill alcoholic men.

BACKGROUND: Medically ill alcoholics often do not respond to conventional alcoholism treatment or decline physician referrals. Integrated outpatient treatment (IOT), a new treatment specifically designed for this population, combines comprehensive medical care with alcoholism interventions. OBJECTIVE: To compare the efficacy of IOT with that of standard treatment approaches. METHODS: One hundred five male veterans with severe medical complications caused by alcoholism and recent drinking were randomly assigned to receive IOT or referral to standard alcoholism and medical treatment and were evaluated over 2 years. Integrated outpatient treatment patients received medical care and alcoholism interventions once or twice monthly. Patients in the control group were referred for alcoholism treatment, but few accepted. However, patients in the control group did engage in outpatient medical care. RESULTS: At baseline, the mean +/- SD age of the control group was 57.2 + 10.0 years, compared with 52.8 +/- 11.5 years in the IOT group (P= .04). The groups were well matched in other respects. The mean +/- SD number of visits over 2 years for the IOT patients was 42.2 +/- 29.1, compared with 17.4 +/- 15.6 for the control patients (P<.001); the frequency of hospital use was similar in both groups. After 2 years, 28 (74%) of 38 surviving IOT patients and 17 (47%) of 36 control patients were abstinent (P=.02). Nearly twice as many control patients (30% [n = 16]) as IOT patients (18% [n= 9]) died, but the results of Cox survival analysis were not significant. There were no differences in symptoms of alcohol dependence, quality of life, or life problems. The incremental cost of IOT was approximately $1100 per patient per year. CONCLUSIONS: Standard medical care alone was surprisingly effective in inducing abstinence in surviving medically ill alcoholics. Integrated outpatient treatment significantly increased both engagement and abstinence for a modest annual cost. Further refinement and testing of IOT is indicated.     

Dysregulation of the hypothalamic-pituitary-thyroid axis in alcoholism

Thyroid dysfunction is a prominent finding in alcoholism. Subclinical and clinical hypothyroidism have been associated with clinical depression and cognitive impairment and may increase the relapse risk among alcoholics. In spite of these important clinical associations, there is no consensus on thyroid dysfunction in alcoholism in the literature. In this paper, we present a review of the literature and develop a hypothesis that may explain dysfunction of the hypothalamic–pituitary–thyroid axis in alcoholism. Based on a Medline research of the years 1980–2001 we found 33 empirical studies that assessed thyroid function in alcoholism. The most consistent findings were a reduction in total thyroxine and total and free triiodothyronine concentrations during early abstinence. About one-third of all alcoholics also displayed a blunted thyroid stimulation hormone (TSH) response in the thyrotrophin-releasing hormone test (TRH-test). Blunting was observed frequently during detoxification, but was also present in some alcoholics after several weeks of abstinence. We suggest that a reduction in peripheral thyroid hormones may be caused by a direct toxic effect of alcohol on the thyroid gland, which induces a central compensatory activation of the hypothalamic–pituitary axis with an increased TRH release. The TRH release induces a downregulation of pituitary TRH receptors, which manifest as a blunted TSH response to the TRH test. We discuss further additional effects of alcohol on thyroid-hormone metabolizing deiodinases and on monoaminergic systems, which may interact directly with mood states among abstinent alcoholics.     

Variation in Alcoholism Treatment Orientation: Differential Impact upon Specific Subpopulations

Treatment programs across the State of New York were studied to determine the differential impact of treatment orientations upon various types of alcoholism clients. 1340 patients from 17 alcoholism treatment programs were treated and followed up 3 and 8 months after treatment. The majority of the clients were categorized as either Behaviorally Impaired Drinkers (n=205) or Alcoholics (n = 814). Each of the treatment programs were classified according to either Peer Group, Rehabilitation Professional, or Medical Orientations. Three different outcome measures were examined: abstinence, amount of alcohol consumed at follow-up, and improvement (life and drinking) at follow-up. The generalizable conclusions were that females had significantly better outcome (78% abstinent) when treated according to a medical orientation. Male Behaviorally Impaired Drinkers had better outcomes when treated in Rehabilitation Professional Orientation (74% abstinent) and male alcoholics had the best outcome in Peer Group (60% abstinent), although male alcoholics achieved similar abstinence rates in Medical (59.5%) and Rehabilitation (55%) orientations.     

Increased Gastrointestinal Symptoms in Chronic Alcoholics

Although chronic alcoholics frequently present with gastrointestinal (GI) symptoms, the precise prevalence of GI symptoms in this group is unknown. Accordingly, we compared the frequency and severity of GI symptoms in 48 male alcoholics with those of 48 nonalcoholic controls. A standardized questionnaire was administered on two separate occasions to all subjects, and 14 GI symptoms were evaluated for three periods (during active drinking, early withdrawal, and sobriety). Symptom severity was assessed with a visual analog scale (1-1O). Both actively drinking and withdrawing alcoholics had more frequent heartburn, nausea, vomiting, diarrhea, and flatulence, and more severe chest pain, milk intolerance, and postprandial fullness. These symptoms were transient and did not correlate with the quantity of alcohol consumed. Thus, alcoholics have more frequent and more severe GI symptoms which resolve quickly during abstinence and which predominantly occur while actively drinking rather than during withdrawal.     

Psychiatric Comorbidity in Alcoholism: Importance of Ascertainment Source

Although psychiatric comorbidity is often observed among individuals in treatment facilities for alcoholism, the prevalence and pattern of psychiatric comorbidity among alcoholic cirrhotics has not been well characterized. The present study aimed first to compare the prevalence of psychiatric comorbidity in cirrhotic individuals with alcoholism ascertained from a gastroenterology service with alcoholics ascertained from a treatment facility for alcoholism. Consistent with the findings of other investigators, the data suggest that there is a great degree of variability regarding the severity of alcoholism in alcoholic cirrhotic individuals. Furthermore, cirrhotics with alcoholism exhibited a less severe clinical picture of alcoholism as measured by less alcohol dependence and lower prevalence of psychiatric comorbidity than individuals in treatment for alcoholism. The main conclusion of this study is that ascertainment source is an important determinant of psychiatric comorbidity observed in alcoholic samples.     

Alcohol Use by Alcoholics with and without a History of Parental alcoholism

The association between parental history of alcoholism and the nature of alcoholism was assessed using a more reliable measure of family history (Family Tree Questionnaire) and a more comprehensive inventory of alcoholism (Alcohol Use Inventory) than used in earlier studies. Parental alcoholism was associated with more severe alcoholism on most parameters of alcohol use (age of onset, quantity, frequency, preoccupation, and sustained use) and alcohol-related problems (social, vocational, physical, cognitive, and loss of control). The association between parental history of alcoholism and more severe alcoholism in the probands was independent of age of onset of alcoholism, current age, socioeconomic background, and marital status. Parental history positive (PH+) alcoholics were more reliant on alcohol to manage their moods but did not differ significantly from parental history negative (PH-) alcoholics in the use of alcohol to improve sociability or mental functioning or to cope with marital problems. Surprisingly, the degree of concern, guilt, and worry over the negative consequences of drinking was not significantly different for PH+ alcoholics although the negative consequences were clearly much more severe for this group. While the data are inconclusive about the reasons for more severe alcoholism in PH+ alcoholics, greater reliance on ethanol to manage moods and a relative insensitivity to negative consequences could theoretically account for the vulnerability to more severe alcoholism found in PH+ alcoholics.     

Alcoholism and the D2 Receptor Gene

The allelic association of the human dopamine D2 receptor gene and alcoholism was evaluated in 20 male alcoholics and 20 controls (sex, race, and geographic place of birth matched). This study further examines the issue of alcoholism severity and A1 allele frequency. No difference in A1 allele frequency was observed between these two groups. Similarly, no relationship between alcoholism severity and A1 frequency within the alcoholics was demonstrated.     

Increased White Matter Signal Hyperintensities in Long-Term Abstinent Alcoholics Compared with Nonalcoholic Controls

Background: The harmful effects of alcohol dependence on brain structure and function have been well documented, with many resolving with sufficient abstinence. White matter signal hyperintensities (WMSH) are thought to most likely be consequences secondary to the vascular (i.e., hypertension and atherosclerosis) effects of AD. We hypothesized that such effects would persist into long‐term abstinence, and evaluated them in middle‐aged long‐term abstinent alcoholics (LTAA) compared with age and gender comparable nonalcoholic controls (NAC). Methods: Ninety‐seven participants (51 LTAA and 46 NAC) underwent cognitive, psychiatric, and structural brain magnetic resonance image evaluations. WMSH were identified and labeled as deep or periventricular by an automated algorithm developed in‐house. WMSH volumes were compared between groups, and the associations of WMSH measures with demographic, alcohol use, psychiatric, and cognitive measures were examined within group. Results: Long‐term abstinent alcoholics had more WMSH than NAC. There was a significant group by age interaction, with WMSH increasing with age in LTAA, but not in NAC. Within LTAA, WMSH load was independently positively associated with alcohol burden and with age. No associations were evident between WMSH volumes and abstinence duration, family drinking history, years of education, or psychiatric or cognitive variables. Conclusion: The magnitude of alcohol abuse was related to increased WMSH volume. The presence of an age effect in the LTAA but not the controls indicates a synergistic effect wherein alcohol advances the onset of aging‐related WMSH formation. The increased WMSH load did not appear to have any significant clinical correlates, indicating that the white matter lesions in our sample may not have been severe enough to manifest as cognitive deficits. A limitation of the study is that we did not have data on the presence or severity of lifetime or current indices of vascular risk factors such as hypertension, smoking, or diabetes.     

Brain Atrophy and Cognitive Function in Older Abstinent Alcoholic Men

We used computer-aided magnetic resonance image analysis and an age-normed battery of neuropsychological tests to measure brain atrophy and cognitive function in 14 older abstinent alcoholic men and 11 older controls in the expectation that these subject groups would show the greatest and most persistent cerebral effects consequent to chronic alcoholism. The abstinent alcoholics exhibited cognitive impairments (primarily in memory and visual-spatial-motor skills) compared with the controls. In contrast, we found no difference in global cerebral atrophy between the groups, although two alcoholics had extensive atrophy compared with all other subjects. However, there was a stronger association between age and ventricular dilation in the alcoholic sample compared with controls. We conclude that a substrate other than magnetic resonance imaging-detectable global atrophy must underlie the persistent cognitive impairments evident in the sampled alcoholics. Furthermore, if there are global atrophic changes in the brain associated with chronic alcoholism, these effects are not ubiquitous and/or may be reversible in most patients with sufficient abstinence.     

Persistent but less severe ataxia in long-term versus short-term abstinent alcoholic men and women: a cross-sectional analysis

Background: Disturbed gait and balance are among the most consistent and salient sequelae of chronic alcoholism. Results of small sample longitudinal investigations have provided evidence that partial recovery of gait and balance functions in alcoholics may be achieved with abstinence. However, abstinence durations reported have been limited, and their power and generalizability have suffered from small sample sizes. Methods: In this study, we employed a cross‐sectional approach to assess gait and balance functions in short‐term (6 to 15 weeks) abstinent alcoholics (STAA; n = 70) and long‐term (minimum 18 months, mean = 7.38 years) abstinent alcoholics (LTAA; n = 82). STAA and LTAA did not differ with respect to lifetime alcohol consumption, family drinking density, or years of education. In addition, we examined the effects of gender and alcohol use variables. Results: Our main findings were: (i) persistent disturbed gait and balance in STAA and disturbed standing balance in LTAA; (ii) overall less impaired performance of LTAA compared with STAA on gait and balance measures; and (iii) worse performance of STAA (but not LTAA) women, compared with men, on standing balance without visual control. Conclusions: Our results suggest that alcoholics’ gait and balance can continue to recover with long abstinence from alcohol, but that deficits persist, especially in eyes‐closed standing balance. In addition, our results are consistent with more severe alcohol‐induced ataxia in women than in men but suggest that with extended abstinence, women recover gait and balance function to a level comparable with men.     

Outcome of Alcoholism Treatment Among 5578 Patients in an Urban Comprehensive Hospital-Based Program: Application of a Computerized Data System

The Elmhurst Alcoholism Program data system relate* fraction of time patients are in remission to length of time they are known, and permits a systematic search for groups of variables which predict greater abstinence rates. Our program (inpatient detoxification ward, multidisciplinary outpatient clinic, and halfway house) sets abstinence as a goal. After initial data collection (social and demographic variables, income, education, residence, drinking and drug history, legal problems, and prior treatment), we collect data at 30 days after admission and at 2- or 3-month intervals thereafter from all patients who remain in contact. Forty-five percent of all patients are lost before 30 days. Only 32% of those still under observation at 1 yr and 27% of those still under observation at 2 yr claim continual abstinence. From among many combinations of variables examined for predictive power, a group of five was chosen as best. Patients who at their first follow-up interview reported attending AA meetings and taking Antabuse and who in addition had a job at admission, were older, and were admitted through the clinic rather than through inpatient detoxification had a greater fraction of time abstinent. Nevertheless, the best cluster of predictor variables did not account for more than 25% of the variation in rates of abstinence. Many social variables are not independent, and some may merely be indicators of duration or severity of alcoholism. Contemporary alcoholism treatment is, at best, of limited effectiveness.     

Factors affecting %CDT status at entry into a multisite clinical treatment trial: experience from the COMBINE Study

BACKGROUND: Carbohydrate-deficient transferrin (CDT) occurs as a higher percentage of normal transferrin (%CDT) in heavy drinkers. %CDT is used as a marker of both alcohol use disorder severity and treatment outcome both clinically and in treatment trials. Nevertheless, little is known about the parameters that predict which patients are %CDT positives at treatment entry. These parameters might include level of drinking, days of abstinence before testing, and severity of alcohol dependence before evaluation. METHODS: %CDT levels were collected before randomization from participants of the COMBINE Study, a large federally sponsored multisite clinical trial evaluating medications and behavioral therapies in alcohol-dependent outpatients. %CDT (assayed in a central laboratory) was available in 1,193 individuals for whom drinking history in the 30 days before testing and measures of alcoholism severity were documented. The effects of drinking history and alcohol severity were evaluated for prediction of a %CDT-positive test status. RESULTS: Less percent days abstinent (PDA) and more drinks per drinking day (DDD) were predictive of higher rates of %CDT-positive patients (maximum 67%). Up to 14 days of continuous abstinence before testing did not appear to significantly affect %CDT status. Rates of %CDT positives remained reasonably steady up to about 40% PDA. Years of drinking at dependence levels had an unexpected negative impact on %CDT-positive rates while previous treatment had a small but positive impact of %CDT-positive rates. ADS and DrInC scores had no predictive value over and above recent drinking amounts on %CDT status. CONCLUSIONS: %CDT is more likely to be positive in those who have more days of drinking and to a lesser degree in those who drink more per drinking day. It can remain positive even in those alcoholic subjects who stop drinking many days before testing. Alcoholic subjects with more treatment experiences appear to have a marginally higher %CDT-positive rate.     

Sleep-disordered breathing in alcoholics

Sleep apnea and related disorders contribute to disturbed sleep in abstinent alcoholics. In an earlier report from our group, sleep-disordered breathing was common and increased with age in a cohort of 75 abstinent alcoholics. We now report an extension of the previous work that includes studies of an additional 103 abstinent alcoholics undergoing treatment for alcoholism (total sample = 188) and a comparison group of 87 normal subjects. The presence and severity of sleep-disordered breathing was assessed with polysomnography. Among the alcoholics, sleep-disordered breathing (defined as 10 or more apneas plus hypopneas per hour of sleep) was present in 3% of 91 subjects under age 40, 17% of 83 subjects age 40 to 59, and 50% of 14 subjects age 60 or over. Subjects with sleep-disordered breathing were more likely to be male and had more severe sleep disruption and nocturnal hypoxemia and more complaints related to daytime sleepiness than subjects without sleep-disordered breathing. In a multiple linear regression analysis, age and body mass index were significant predictors of the presence of sleep-disordered breathing, whereas smoking history and duration of heavy drinking were not predictors after controlling for the effects of age and body mass index. Our findings suggest that sleep-disordered breathing contributes significantly to sleep disturbance in a substantial proportion of older alcoholics and that symptomatic sleep-disordered breathing increases with age in alcoholics. Sleep-disordered breathing, when combined with existing cardiovascular risk factors, may contribute to adverse health consequences in alcoholics.     

Elevated myo-inositol in gray matter of recently detoxified but not long-term abstinent alcoholics: a preliminary MR spectroscopy study

BACKGROUND: Individuals in short-term abstinence from chronic alcohol consumption commonly have neuropsychological impairments with parallel abnormalities in brain structure. Stable, long-term sobriety often results in improvements in both brain structure and function, although the mechanisms underlying these changes are currently not well understood. METHODS: To investigate further the neurobiological underpinnings of alcohol-associated brain abnormalities in short-term and long-term abstinence from alcohol, proton magnetic resonance spectroscopy (echo time, 35 msec; repetition time, 1.5 sec) was used to assay metabolites in the anterior centrum semiovale, anterior cingulate gyrus, and right thalamus of two groups of non-Korsakoff alcoholic men, at different stages of abstinence, compared with a control group of alcohol-nonabusing men. Absolute concentrations of N-acetylaspartate, choline, myo-inositol, and creatine were measured in four recently detoxified alcoholics (mean age, 48.7 years; median abstinence, 41.5 days), five long-term abstinent alcoholics (mean age, 45.1 years; median abstinence, 1.7 years), and five nonalcoholic controls (mean age, 45.0 years). RESULTS: Although there were no between-group differences in concentrations of N-acetylaspartate, choline, or creatine, recently detoxified alcoholics had significantly higher myo-inositol in the thalamus, compared with controls and long-term abstinent alcoholics, and significantly higher myo-inositol in the anterior cingulate gyrus, compared with the controls. CONCLUSIONS: Elevations in myo-inositol in recently detoxified alcoholics are compatible with an acute alcohol cytotoxicity model. myo-Inositol is elevated in hyperosmolar states such as hypernatremia, renal failure, and diabetes; alcohol-induced hyperosmolarity may trigger accumulation of myo-inositol to stabilize the intracellular environment. Increases in myo-inositol may also reflect proliferation or activation of glia. The reduction of myo-inositol to control group levels in long-term abstinent alcoholics may reflect osmolar stability in abstinent alcoholics and/or a reduction in glial cell activation.     

Effect of Prior Narcotic Addiction on Response to Treatment of Alcoholism

We studied the effect of prior narcotic addiction on response to treatment of alcoholism. Patients in the Elmhurst Alcoholism Treatment Program are offered medical care, counseling, disulfiram, and close affiliation with Alcoholics Anonymous. We compared 85 alcoholics who had a history of narcotic use with a control group of 85 alcoholics matched for age, sex, and race who had never used narcotics. Among controls, 30 (35%) became abstinent from alcohol for at least half the time that they were known to us. Of the former narcotic users, only 8 (9%) became abstinent for at least half the time they were known to us. Former narcotic users did poorly in alcoholism treatment, whether or not they had ever been treated with methadone maintenance. Alcohol use. often heavy, began before heroin use in at least half the narcotic group. We conclude that a history of narcotic use reduces markedly the chance of success in conventional alcoholism treatment, and that alcoholism and narcotic addiction develop independently.     

Impulsive responding in alcoholics

BACKGROUND: Impaired decision-making is one diagnostic characteristic of alcoholism. Quantifying decision-making with rapid and robust laboratory-based measures is thus desirable for the testing of novel treatments for alcoholism. Previous research has demonstrated the utility of delay discounting (DD) tasks for quantifying differences in decision-making in substance abusers and normal controls. In DD paradigms subjects choose between a small, immediate reward and a larger, delayed reward. METHODS: We used a novel computerized DD task to demonstrate that abstinent alcoholics (AA, n=14) choose the larger, delayed option significantly less often than control subjects (n=14; p<0.02). This difference in choice tendency was independent of subject age, gender, years of education, or socio-economic status. RESULTS: All subjects discounted as a function of reward delay and amount, with alcoholics demonstrating steeper discounting curves for both variables. This tendency to discount delayed rewards was positively correlated with subjective reports of both alcohol addiction severity (Drug Use Screening Inventory-Revised, Domain 1, p<0.01), and impulsivity (Barratt Impulsivity Scale-11, p<0.004). Novel aspects of this new paradigm include an element of time pressure, an additional experimental condition that evaluated motor impulsivity by assessing the ability to inhibit a pre-potent response, and another control condition to requiring non-subjective choice. CONCLUSIONS: Non-alcoholic controls and alcoholics did not differ on motor impulsivity or non-subjective choice, suggesting that the differing choice behavior of the two groups was due mainly to differences in cognitive impulsivity.     

Toward a Model for Counseling the Wives of Alcoholics

Earlier literature on the wives of alcoholics confused the causes with the effects of alcoholism. Wives of alcoholics were thought to be highly neurotic contributors to their husbands' illness. Furthermore, sexist biases influenced opinion and research with the result that while wives were blamed for their spouses' illness, husbands of alcoholic wives were considered blameless victims. Despite recent gains in the understanding of alcoholism and its effects on family dynamics, treatment of alcoholic marriages continues to reflect subtle sexist attitudes and values. For example, wives are often viewed as little more than adjuncts to their husbands' treatment. Such approaches undermine reality-centered and effective treatment. A model for counseling wives of alcoholics is proposed which addresses her special and separate concerns.     

Current pharmacotherapies of alcoholism: a U.S. perspective

Advances in the neurobiology of addiction and improved clinical trial methodology have accelerated the evaluation of medication for alcoholism. While psychosocial interventions have been useful to reduce consumption and support abstinence, considerable improvement in treatment is needed. Medication can play a crucial role in the reduction of craving and drinking and the maintenance of abstinence. This article reviews pharmacotherapy for alcoholism with an emphasis on the perspective of the United States. The opiate antagonist naltrexone, the glutamate modulator acamprosate, and serotonergic agents will be highlighted in this review. In general, both naltrexone and acamprosate have been found in a number of studies to be efficacious agents for the treatment of alcohol dependence. Serotonin reuptake inhibitors have not consistently shown to be efficacious but may be useful in certain subgroups of alcoholics. The serotonin type-3 antagonist, ondansetron, has shown promise in early-onset alcoholics but needs more extensive study.