Pharmacological treatment of alcoholism

1. Pharmacological treatments are effective as part of a treatment plan that includes substantial education, psychological therapy and social support. This paper reviews recent literature on animal models of and treatment for alcohol abuse under seven categories: agents to block craving or reduce alcohol intake, agents to induce aversion to alcohol, agents to treat acute alcohol withdrawal, agents to treat protracted alcohol withdrawal, agents to diminish drinking by treating associated psychiatric pathology, agents to decrease drinking by treating associated drug abuse, and agents to induce sobriety in intoxicated individuals. 2. The benzodiazepines provide safe and effective treatment for detoxification, although current research focuses on finding drugs with a smaller likelihood of dependence. As yet, there are no drugs that effectively reverse the intoxicating effects of alcohol. 3. Currently, only two major groups of drugs that are relatively safe have shown any effect at reducing alcohol consumption: aversives such as disulfiram, and opioid antagonists such as naltrexone. 4. Finally, it is important to customize therapy for each patient rather than putting everyone through a standard treatment plan, especially in regards to the use of antidepressant or antipsychotic medications. Tailoring the program to the patient's needs dramatically improves the outcome of therapy and reduces the risk of adverse effects.     

Research progress on the glia cell line-derived neurotrophic factor

The therapy of the alcohol withdrawal syndrome is very heterogeneous with more than 100 drug combinations. This results from differently qualified physicians and from insufficient pharmacostudies concerning evaluation and psychopathological methodology of the alcohol withdrawal syndrome. The following advices can be given: Physical withdrawal should take place under the conditions of an appropriate hospital with a qualified team. The application of electrolytes and vitamines (B1) may be necessary in alcohol addicts. Less severe alcohol withdrawal syndromes are treated sufficiently with carbamazepine, sometimes it can be necessary to combine it with neuroleptics or benzodiazepines. A secure prevention from delirium tremens and its treatment is only guaranteed by clomethiazole or benzodiazepines. To reduce the doses of those drugs, combinations with neuroleptics are possible. In general voluntary physical withdrawal proves only to be successful if longtime abstinence is planned and a motivation program is setup the for withdrawal treatment.     

Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial

BACKGROUND: The selective serotonergic medication fluoxetine has demonstrated efficacy in the treatment of major depression and has suggested efficacy in the treatment of alcoholism. However, no completed trials with any selective serotonergic medication have been reported in patients who display both major depression and alcoholism, despite previous observations that both depression and alcoholism are associated with low serotonergic functioning. METHODS: Fifty-one patients diagnosed as having comorbid major depressive disorder and alcohol dependence were randomized to receive fluoxetine (n = 25) or placebo (n = 26) in a 12-week, double-blind, parallel-group trial. Weekly ratings of depression and alcohol consumption were obtained throughout the 12-week course of the study. RESULTS: The improvement in depressive symptoms during the medication trial was significantly greater in the fluoxetine group than in the placebo group. Total alcohol consumption during the trial was significantly lower in the fluoxetine group than in the placebo group. CONCLUSIONS: Fluoxetine is effective in reducing the depressive symptoms and the alcohol consumption of patients with comorbid major depressive disorder and alcohol dependence. It is unknown whether these results generalize to the treatment of less depressed and less suicidal alcoholics.     

Addressing comorbid depressive symptomatology in alcohol treatment.

Clinicians often encounter patients who have comorbid alcoholism and depression. The presence of both disorders makes treatment especially challenging. Among individuals seeking treatment for alcohol dependence, depression and depressive symptoms are associated with poorer treatment outcomes, and depressed mood may play an important role in relapse to drinking. Results of a recent study suggest that adding cognitive-behavioral treatment of depression to alcohol treatment can be an effective means of reducing depressive symptoms and improving drinking outcomes in alcoholics with elevated levels of depressive symptoms. This approach may be particularly useful for clinicians seeking a nonmedical intervention to reduce depression during alcohol treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A study of the relationship between home care services and hospital readmission of patients with congestive heart failure

Treatment of the alcohol withdrawal syndrome is best accomplished using pharmacologic agents that have minimal interaction with alcohol, have limited adverse effects, and are without abuse potential. The partial benzodiazepine receptor agonist beta-carboline compound, abecarnil, has been shown in animal and human studies to possess a number of these characteristics and to be useful in the reduction of alcohol withdrawal convulsions in mice. In this study, 49 alcohol-dependent inpatients who exhibited at least moderate symptoms of uncomplicated alcohol withdrawal were treated over a 5-day detoxification period with abecarnil or diazepam and rated daily for alcohol withdrawal symptoms and adverse events. Both the abecarnil and diazepam treatment groups exhibited a similar marked reduction in withdrawal symptoms over time. In addition, similar rates of successful treatment and improvement were observed after 1 day of treatment and at termination in alcoholics treated with either medication. Overall, rates of adverse events and changes in liver enzymes were similar in both treatment groups and were generally benign. Because of the unique pharmacologic profile of abecarnil in animal and in non-clinical human studies, including anticonvulsant action, low abuse liability, and a favorable side effect profile, further study of compounds of the partial benzodiazepine receptor agonist type in the treatment of alcohol withdrawal syndromes seems warranted.     

Development of an alcohol withdrawal clinical pathway: an interdisciplinary process

Studies show that as many as 40 percent of all patients in general hospitals are admitted because of complications related to alcoholism. However, the literature has little in specific clinical pathways, treatment protocols, or guidelines for the interdisciplinary care of these patients in the acute care setting. Furthermore, the little information that is published shows a lack of consistency in recommended treatment regimes. This article reviews a coordinated, interdisciplinary effort in developing and implementing a clinical pathway for alcohol withdrawal.     

Traumatic neurosis in the etiology of alcoholism: Viet Nam combat and other trauma

Traumatic neurosis from Viet Nam combat or other sources includes many symptoms that can be effectively self-medicated with alcohol, at least initially. These symptoms include chronic anxiety and restlessness, insomnia, and recurrent frightening dreams. Repeated self-medication with alcohol results in tolerance and a need to increase the amount consumed. Attempts to decrease consumption or to abstain can lead to alcohol withdrawal symptoms similar to and exacerbating the initial symptoms of traumatic neurosis. Continuing alcohol use, with the establishment of a vicious circle, can follow. The authors present three case examples. They note that treatment of alcoholism under the conditions described requires specific attention to the underlying traumatic neurosis.     

The glutamatergic basis of human alcoholism

OBJECTIVE: Although alcoholism is one of the most common psychiatric diagnoses, understanding of its pathophysiology remains poor. Accumulating evidence suggests that neurophysiological and pathological effects of ethanol are mediated to a considerable extent through the glutamatergic system. This article reviews the evidence of ethanol's effects on glutamatergic transmission and proposes a glutamatergic basis for alcoholism. METHOD: The information was derived from original research. The authors located more than 100 articles from psychiatry and neuroscience journals that related ethanol to glutamatergic transmission. They critically reviewed the neurobiology of the glutamatergic system in alcoholism and synthesized a unifying glutamatergic theory. RESULTS: Acute effects of ethanol disrupt glutamatergic neurotransmission by inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor. Prolonged inhibition of the NMDA receptor by ethanol results in development of supersensitivity; acute removal of ethanol causes marked augmentation of activity of postsynaptic neurons, such as those in the noradrenergic system, and, in the extreme, glutamate-induced excitotoxicity. Neurobiological effects of alcoholism, such as intoxication, withdrawal seizures, delirium tremens, Wernicke-Korsakoff syndrome, and fetal alcohol syndrome, can be understood as a spectrum of consequences of ethanol's effect on the glutamatergic system. CONCLUSIONS: A host of findings support the hypothesis that the unifying mechanism of action of ethanol in interference with glutamatergic neurotransmission, especially through the NMDA receptor. Alcoholism may be considered another member of the expanding family of glutamate-related neuropsychiatric disorders. These insights should increase understanding of the biologic vulnerabilities leading to ethanol abuse and dependence and aid development of more effective pharmacologic interventions.     

Human mu-opioid receptor variation and alcohol dependence

Mu-Opioid receptor-mediated neurotransmission is involved in the reward, tolerance, and withdrawal effects of alcohol. The present association study tested the hypothesis that the common Asn40Asp substitution polymorphism in the N-terminal domain of the human mu-opioid receptor (OPRM) confers vulnerability to subtypes of alcohol dependence. The genotypes of the Asn40Asp substitution polymorphism were assessed in 327 German alcohol-dependent subjects (according to ICD-10) and in 340 control subjects of German descent, using an assay based on allele-specific polymerase chain reaction. To select alcoholics with a presumed high genetic load, three subgroups were delineated, marked by (1) a family history of parental alcoholism (n = 114); (2) the inability to abstain from alcohol before the age of 26 years (n = 73); and (3) a history of alcohol withdrawal seizure or delirium (n = 107). The frequency of the Asp40 allele did not differ significantly between the controls [f(Asp40) = 0.078] and either the entire group of alcoholics [f(Asp40) = 0.107; p = 0.066], or the alcoholics with parental alcoholism [f(Asp40) = 0.114; p = 0.094], or the early-onset alcoholics [f(Asp40) = 0.096; p = 0.471,[ or the alcoholics with severe withdrawal symptoms [f(Asp40) = 0.098; p = 0.350]. Our results do not provide evidence that the common Asn40Asp substitution polymorphism of the OPRM gene contributes a major effect to the pathogenesis of alcohol dependence.     

Sleep and rheumatic disease

Patients with rheumatic diseases often exhibit sleep disturbance. Identification of primary sleep disorders; medical, neurologic, and psychologic illnesses; circadian factors; and the use and effect of medications, drugs, and alcohol will provide a strong basis for pursuing both pharmacologic and nonpharmacologic intervention. Recent clinical research confirms the frequent comorbidity of sleep disturbance, pain, fatigue, stress, and mood disturbance in patients with rheumatic disease. It is essential for effective management to recognize these "symptom syndromes" that are often responsive to treatment (suggesting a common biologic action and effect of the drugs used) despite a continuing presence of underlying chronic disease. The pathophysiologic relationships of these comorbid symptoms are mostly unknown, so this is an area for further study.     

Assessment of alcohol use with multidimensional concepts and measures.

Reviews the results of selected studies by the authors (1969, 1970, and 1973) on 5,000 patients undergoing treatment for alcoholism. Findings support a multidimensional perspective of alcoholism. Data on the covariations among self-reported symptoms and other drinking-related variables indicate 15 psychometrically independent 1st-order factors and 5 broad 2nd-order dimensions. These factors provide reliable operational definitions of alcoholism that correspond to different constructs and have different relations to variables reflecting etiology, personality, treatment outcome, and life-span development. These factors provide a basis for the diagnosis of a variety of alcohol-related problems and for the design of effective programs of therapy. It is concluded that future research on alcohol abuse should be based on multivariate measurement. (71 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cultural context of psychological approaches to alcoholism: Can we control the effects of alcohol?

Argues that the unique history of alcohol use in the US has led to the ascendance of disease theory as the dominant conception of alcoholism. Social-scientific research has consistently conflicted with disease theory, but psychological and other nondisease conceptions of alcoholism are not well-represented in the public consciousness, in treatment programs, or in policies for affecting nationwide drinking practices. Conflict in the field has intensified in the last decade, most notably surrounding the issue of controlled drinking in alcoholism treatment. It is suggested that the current cultural attitude toward alcoholism in the US, one strongly influenced by disease notions, has not led to an improvement in society's drinking problems and that there continues to be a need for psychologists to present alternative views of alcoholism. The concepts of dependence and addiction as related to alcohol and to drugs are discussed. (3 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

New drugs in the treatment of alcoholism

Pharmacotherapy of alcoholism is improving rapidly with the introduction of new agents. New knowledge about the neurobiology of alcoholism is necessary for the clinician, who has to establish the diagnosis. Useful pharmacological agents for the treatment of alcohol dependence can be classified into four groups: (1) agents for the treatment of the withdrawal syndrome, (2) aversive agents, (3) therapeutic agents for comorbidity, (4) new agents to reduce craving for alcohol or prevent relapse. These new agents derive from research in four directions, based on neurobiological hypotheses: (a) the glutamatergic hypothesis with acamprosate, (b) the opioid hypothesis with naltrexone, (c) the serotonergic hypothesis with the new antidepressants, and (d) other hypotheses, including dopaminergic, peptidic etc. Of these new agents, acamprosate has undergone most study in controlled clinical trials around Europe. Its efficacy has been demonstrated statistically, it is well tolerated and does not interact with alcohol. Acamprosate can be associated with disulfiram therapy. Future perspectives for treatment and research are discussed, in particular with regard to therapeutic associations.     

Psychotropic drugs and behavior

Behavioural modifications induced by psychotropic drugs results primarily from their pharmacological properties. According to classification of psychotropic drugs, sedative compounds contrast with psychostimulating medications. Behavioural effects of psychotropic drugs depend on dosing, subject's status (patient or healthy volunteer), acute or chronic administration, and environment. Some psychotropic compounds, particularly sedative drugs, decrease the level of mental alertness and cognitive functioning. But those deleterious effects tend to disappear during the course of a repeated administration. Some psychotropic drugs, especially benzodiazepines, induce a tolerance effect, eventually a psychic or a physiological dependence state evidenced by withdrawal reactions. Such similar dependence processes have been reported with other psychotropic drugs. Forensic problems have been attributed to some psychotropic compounds, like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism; Psychotropic drugs usually can confer a positive effect on behaviour owing to their therapeutic action by the way of improving the illness and consequently the life of patients in the cases of depression, anxiety or schizophrenia.     

Sertraline treatment of comorbid posttraumatic stress disorder and alcohol dependence

BACKGROUND: Posttraumatic stress disorder (PTSD) often co-occurs with alcohol dependence, yet little is known about treatment of this comorbidity. The serotonin selective reuptake inhibitors have been shown preliminarily to be effective in decreasing symptoms of PTSD but have not been studied in individuals with comorbid alcohol dependence. This is of particular interest as the SSRIs also have a modest effect in decreasing alcohol consumption. METHOD: In this preliminary trial, nine subjects with comorbid PTSD and alcohol dependence were treated in an open-label trial with sertraline for a 12-week period. Symptoms of PTSD and depression were monitored monthly with the Impact of Event Scale and the Hamilton Rating Scale for Depression (HAM-D). Alcohol consumption was monitored by a self-report instrument (Time-Line Follow-Back). RESULTS: There were significant decreases in all three symptom clusters of PTSD measured by overall PTSD symptom scores (p < or = .001) and in HAM-D scores (p < or = .001) during the follow-up period. Days of abstinence increased and average number of drinks decreased during the follow-up period. Four subjects claimed total abstinence during the follow-up period. CONCLUSION: While limited by small sample size and the open-label, nonblinded study design, this study suggests that sertraline may be useful in the treatment of PTSD complicated by alcoholism. The medication was well tolerated and subjects showed improvement in PTSD symptoms as well as decreased alcohol consumption. A controlled trial of sertraline in this population would be of interest.     

Comment on Miller and Hester's "Inpatient alcoholism treatment: Who benefits?"

W. R. Miller and R. K. Hester (see record 1986-28253-001) conclude that inpatient treatment of alcoholism is no more effective than outpatient treatment of alcoholism for most individuals. However, they fail to adequately distinguish between alcohol abuse and alcohol dependence, draw their conclusions from admittedly methodologically weak studies, and appear to prefer outpatient treatment because it is cheaper. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cloning and overexpression in Escherichia coli of the gene encoding citrate synthase from the hyperthermophilic Archaeon Sulfolobus solfataricus

A transurethral resection of the prostate is a good operation to relieve bladder outflow obstruction and has a low incidence of complications. However, recent work suggests that many men with symptoms may not require an operation, and it can probably be delayed in a majority for many years. This may be particularly important in old and frail patients. Many men with outflow obstruction have irritative symptoms such as urgency, frequency and nocturia; these could be treated with anticholinergics, provided they have normal flow rates and small or absent residual urine volumes. Pharmacological treatment to relieve outflow obstruction is disappointing. There may be some benefit from alpha-adrenoreceptor antagonists, but the place for 5 alpha-reductase inhibitors is still unsure. All drugs have side effects which are unacceptable in patients who are not bothered by their urinary symptoms and can wait for active treatment.     

Co-morbidity and familial aggregation of alcoholism and anxiety disorders

BACKGROUND: This study examined the patterns of familial aggregation and co-morbidity of alcoholism and anxiety disorders in the relatives of 165 probands selected for alcoholism and/or anxiety disorders compared to those of 61 unaffected controls. METHODS: Probands were either selected from treatment settings or at random from the community. DSM-III-R diagnoses were obtained for all probands and their 1053 first-degree relatives, based on direct interview or family history information. RESULTS: The findings indicate that: (1) alcoholism was associated with anxiety disorders in the relatives, particularly among females; (2) both alcoholism and anxiety disorders were highly familial; (3) the familial aggregation of alcoholism was attributable to alcohol dependence rather than to alcohol abuse, particularly among male relatives; and (4) the the pattern of co-aggregation of alcohol dependence and anxiety disorders in families differed according to the subtype of anxiety disorder; there was evidence of a partly shared diathesis underlying panic and alcoholism, whereas social phobia and alcoholism tended to aggregate independently. CONCLUSIONS: The finding that the onset of social phobia tended to precede that of alcoholism, when taken together with the independence of familial aggregation of social phobia and alcoholism support a self-medication hypothesis as the explanation for the co-occurrence of social phobia and alcoholism. In contrast, the lack of a systematic pattern in the order of onset of panic and alcoholism among subjects with both disorders as well as evidence for shared underlying familial risk factors suggests that co-morbidity between panic disorder and alcoholism is not a consequence of self-medication of panic symptoms. The results of this study emphasize the importance of examining co-morbid disorders and subtypes thereof in identifying sources of heterogeneity in the pathogenesis of alcoholism.     

Ten questions about alcohol as identifier of addiction problems. Psychometric tests at an emergency psychiatric department

It is important to develop and evaluate methods of identifying alcohol dependent patients and patients at risk of alcohol problems. The World Health Organisation recommends a 10-item questionnaire, AUDIT (Alcohol Use Disorders Identification Test), which assesses hazardous alcohol use, dependence symptoms, and harmful alcohol use. The article describes a Swedish version of AUDIT that has been psychometrically tested on a sample of patients admitted to a psychiatric emergency ward. Both internal consistency, reliability and validity were found to be satisfactory in terms of sensitivity and specificity in predicting DSM alcoholism diagnoses.