Serving Substance Abuse Professionals Since 1993

Last Update: 26.09.07

C O R K O N L I N E

powerpoint presentations
CORK database search
resource materials
bibliographies
clinical tools
user services
newsletters
about cork
home

CORK Bibliography: Detoxification (Alcohol)

76 citations. January 2003 to present

Prepared: September 2007

Addolorato G; Leggio L; Abenavoli L; Agabio R; Caputo F; Capristo E et al. Baclofen in the treatment of alcohol withdrawal syndrome: A comparative study vs diazepam. American Journal of Medicine 119(3), 2006. (25 refs.)

PURPOSE: Benzodiazepines are the drugs of choice in the treatment of alcohol withdrawal syndrome (AWS). Recent data have shown that baclofen may reduce AWS symptoms. At present, no comparative studies between baclofen and any benzodiazepine used in AWS treatment are available. Accordingly, the present study was designed to compare efficacy, tolerability and safety of baclofen versus diazepam in the treatment of AWS. SUBJECTS AND METHODS: Thirty-seven patients with AWS were enrolled in the study and randomly divided into 2 groups. Baclofen (30 mg/day for 10 consecutive days) was orally administered to 18 patients (15 males, 3 females; median age: 46.5 years). Diazepam (0.5- 0.75 mg/kg/day for 6 consecutive days, tapering the dose by 25% daily from day 7 to day 10) was orally administered to 19 patients (17 men, 2 women; median age: 42.0 years). The Clinical Institute Withdrawal Assessment (CIWA-Ar) was used to evaluate physical symptoms of AWS. RESULTS: Both baclofen and diazepam significantly decreased CIWA-Ar score, without significant differences between the 2 treatments. When CIWA-Ar subscales for sweating, tremors, anxiety and agitation were evaluated singly, treatment with baclofen and diazepam resulted in a significant decrease in sweating, tremors and anxiety score, without significant differences between the 2 drug treatments. Both treatments decreased the agitation score, although diazepam was slightly more rapid than baclofen. CONCLUSION: The efficacy of baclofen in treatment of uncomplicated AWS is comparable to that of the "gold standard" diazepam. These results suggest that baclofen may be considered as a new drug for treatment of uncomplicated AWS.

Addolorato G; Leggio L; Abenavoli L; DeLorenzi G; Parente A; Caputo F et al. Suppression of alcohol delirium tremens by baclofen administration: A case report. (review). Clinical Neuropharmacology 26(5): 258-262, 2003. (22 refs.)

Delirium tremens (DT) is a clinical condition that appears in some patients affected by severe alcohol withdrawal syndrome (AWS). DT represents a serious complication, being characterized by elevated morbidity and mortality. Benzodiazepines are presently the drug of choice; however their use is related to several side effects. Baclofen is a stereoselective gamma-aminobutyric acid (GABA(B)) receptor agonist. Recent studies show that baclofen is able to suppress alcohol withdrawal symptoms. At present there are no data on the effects of baclofen administration in AWS complicated by DT. Here, we report a case of DT successfully treated with baclofen. This result indicates that the efficacy of baclofen in the treatment of DT should be examined in future clinical trials.

Alho H; Methuen T; Paloheimo M; Seppae K; Strid N; Apter-Kaseva N et al. Nitrous oxide has no effect in the treatment of alcohol withdrawal syndrome: A double-blind placebo-controlled randomized trial. Journal of Clinical Psychopharmacology 23(2): 211-214, 2003. (20 refs.)

The aim of the present study was to investigate, using a randomized, double-blind, controlled study, the efficacy of nitrous oxide gas (N-sub-2O) in the treatment of alcohol withdrawal syndrome (AWS) in comparison with the administration of oxygen and medical (normal) air. 105 Ss (males and females from Finland, aged 18-60 yrs) who were starting inpatient treatment for AWS gave informed consent for participation. The gases were administered through a nose anesthetic mask. In both genders, no significant differences between treatments were observed in withdrawal severity. No significant differences in the total use of either diazepam or temazepam were observed. The effect of N-sub-2O in the treatment of AWS is not better than that of placebo. Withdrawal did not differ between treatment groups. The study does not, however, rule out the possibility that heavily sedating doses might have an effect, but a double-blind design cannot be used when an obvious sedative effect is apparent.

Allen J; Copello A; Orford J. Fear during alcohol detoxification: Views from the clients ' perspective. Journal of Health Psychology 10(4): 503-510, 2005. (17 refs.)

Little is known about fears experienced during alcohol detoxification. Using qualitative research this preliminary study analysed descriptions of fears during one-to-one interviews about the experience of undertaking alcohol detoxification. Fears about detoxification centred around four main areas: the setting in which the process takes place, the physical consequences of withdrawal, the medication given to manage detoxification and the experience of future daily living without alcohol. The findings suggest that particular attention needs to be paid to the environmental setting of detoxification and the personal meaning of receiving medical care for withdrawal. In addition, more integration of relapse prevention work into the earliest stages of alcohol-related treatment and the provision of accurate information about detoxification may prove effective in reducing fears about the process.

Alwyn T; John B; Hodgson RJ; Phillips C. The addition of a psychological intervention to a home detoxification programme. Alcohol and Alcoholism 39(6): 536-541, 2004. (18 refs.)

Aims: Home detoxification is a recognized method of treating problem drinkers within their own home environment. The aim of this research is to determine whether a relatively brief psychological intervention adds to its effectiveness. Methods: A pragmatic trial with 91 participants randomly assigned to either the psychological intervention or treatment as usual. Community Psychiatric Nurses were trained to administer the brief psychological intervention involving motivational interviewing, coping skills training and social support. A manual was developed in order to standardize the training and implementation. Results: At the 3 month and 12 month follow-up the psychological intervention resulted in significant positive changes in alcohol consumption, abstinent days, social satisfaction, self-esteem and alcohol-related problems. Further, a cost analysis confirmed that the psychological intervention was a ninth of the cost of inpatient treatment. Conclusions: Adding a psychological intervention to a home detoxification programme was successful and cost-effective.

Bayard M; McIntyre J; Hill KR; Woodside J. Alcohol withdrawal syndrome. American Family Physician 69(6): 1443-1450, 2004. (29 refs.)

The spectrum of alcohol withdrawal symptoms ranges from such minor symptoms as insomnia and tremulousness: to severe complications such as withdrawal seizures and delirium tremens. Although the history and physical examination usually are sufficient to diagnose alcohol withdrawal syndrome, other conditions may present with similar symptoms. Most patients undergoing alcohol withdrawal can be treated safely and effectively as outpatients. Pharmacologic treatment involves the use of medications that are cross-tolerant with alcohol. Benzodiazepines, the agents of choice, may be administered on a fixed or symptom-triggered schedule. Carbamazepine is an appropriate alternative to a benzodiazepine in the outpatient treatment of patients with mild to moderate alcohol withdrawal symptoms. Medications such as haloperidol, beta blockers, clonidine, and phenytoin may be used as adjuncts to a benzodiazepine in the treatment of complications of withdrawal. Treatment of alcohol withdrawal should be followed by treatment for alcohol dependence.

Berglund M; Thelander S; Johnsson E. Treating Alcohol and Drug Abuse: An Evidence Based Review. New York: Jossey-Bass, 2005. (Chapter refs.)

This book provides a review of evidence-based treatments for alcohol and drug problems. It suumarrizes the major treatment approaches and then presents the the findings for over 1,600 studies on treatment outcome and treatment effectiveness. In addition to dealing alchol abuse/dependence interventions for harmful use anre also included. The work is organized into 10 chapters followed by four appendices. The initial chapter provides an overview of approaches to the range of alcohol problems, including hazardous use. The next three chapters consider the psychsocial treatment of alcohol dependence; pharmacotherapy for alcohol withdrawal; pharmacotherapy for alcohol dependence. Chapter 5 considers the longer-term treatment outcomes in alcohol and drug dependence along with the natural history in the absence of treatment. Chapters 6-9 focus upon drug dependence: drug therapy for opiate withdrawal; drug therapy for opiate dependence; and drug therapy for cocaine dependence. The final chapter turns to the impact of substance abuse during pregnancy and the neonatal period.

Bertholet N; Daeppen JB. A possible way to motivate ambivalent patients to undergo detoxification. (letter). Alcohol and Alcoholism 41(2): 205-205, 2006. (4 refs.)

Bischof GH; Richmond CJ; Case AR. Detoxification at home: A brief solution-oriented family systems approach. Contemporary Family Therapy 25(1): 17-39, 2003. (43 refs.)

The authors propose an outpatient, solution-oriented, family systems approach to detoxification from alcohol and/or drugs. Research indicates that outpatient detoxification is a viable option, one that will likely be utilized even more frequently as health care costs continue to rise. Nontraditional assumptions about the process of detoxification are suggested that challenge traditional notions about detoxification being only a biomedical, pretreatment event. Criteria are provided for determining the appropriateness of clients for outpatient detoxification and offer information about typical withdrawal symptoms and guidelines for the detoxification environment at home. A case example illustrates the application of this approach in a community mental health program. Suggestions for adapting this approach to various settings are also offered.

Blondell RD. Ambulatory detoxification of patients with alcohol dependence. American Family Physician 71(3): 495-502, 2005. (30 refs.)

Detoxification from alcohol can be undertaken in ambulatory settings with patients who are alcohol-dependent and show signs of mild to moderate withdrawal when they are not drinking. An appropriate candidate for outpatient detoxification should have arrangements to start an alcohol treatment program and a responsible support person who can monitor progress, and should not have significant, acute, comorbid conditions or risk factors for severe withdrawal. Long-acting benzodiazepines, the preferred medications for alcohol detoxification, can be given on a fixed schedule or through "front-loading" or "symptom-triggered" regimens. Adjuvant sympatholytics can be used to treat hyperadrenergic symptoms that persist despite adequate sedation. Progress can be monitored with the use of a standard withdrawal-assessment scale and daily physician contact. Detoxification is not a stand-alone treatment but should serve as a bridge to a formal treatment program for alcohol dependence.

Boeijinga PH; Parot P; Soufflet L; Landron F; Danel T; Gendre I et al. Pharmacodynamic effects of acamprosate on markers of cerebral function in alcohol-dependent subjects administered as pretreatment and during alcohol abstinence. Neuropsychobiology 50(1): 71-77, 2004. (39 refs.)

Animal studies suggested that acamprosate modulates neuronal hyperexcitability of acute alcohol withdrawal, acting through the glutamatergic neurotransmission. In the present study, we further investigated whether treatment with acamprosate could attenuate the post-alcohol withdrawal hyperexcitability or hyperarousal in humans using brain magnetoencephalography mapping of spontaneous fields. A double-blind, randomised, placebo-controlled study with a parallel group design comparing 2,000 mg/day of acamprosate versus placebo was conducted in alcohol-dependent subjects meeting DSM-IV criteria for alcohol dependence. Treatments were initiated 8 days before alcohol withdrawal and prolonged during the 15 following (abstinence) days. The study demonstrated that during alcohol withdrawal, acamprosate decreased the arousal level as reflected by alpha slow-wave index (ASI) measurement. This effect was mostly evidenced in left parietotemporal regions and, to a lesser extent, in the contiguous anterior, posterior and right-sided regions. In the placebo group, on the contrary, ASI measures increased between day 2 (acute withdrawal) and day 14 (prolonged withdrawal). The present results suggest a sustained effect of acamprosate on the hyperexcitability state due to alcohol withdrawal in alcohol-dependent patients and that acamprosate may have a protective effect when administered 8 days before alcohol withdrawal.

Book SW; Myrick H. Novel anticonvulsants in the treatment of alcoholism. (review). Expert Opinion on Investigational Drugs 14(4): 371-376, 2005. (42 refs.)

There have been many recent developments in the pharmacological management of alcohol withdrawal and alcohol dependence. Although previous treatments had included benzodiazepines as their mainstay, the use of these agents in the alcoholic population is problematic. Benzodiazepines are themselves addictive and they may increase the risk of alcohol relapse. Non-benzodiazepine anticonvulsants such as carbamazepine, valproic acid, gabapentin, vigabatrin and topiramate have been shown to be excellent treatments of both alcohol withdrawal and the prevention of alcohol relapse. Although none of these agents have yet been approved by the FDA, there is growing evidence in the literature to support their use.

Bourin M; Dailly E; Hascoet M. Preclinical and clinical pharmacology of cyamemazine: Anxiolytic effects and prevention of alcohol and benzodiazepine withdrawal syndrome. (review). CNS Drug Reviews 10(3): 219-229, 2004. (61 refs.)

Several studies have suggested that the antipsychotic compound, cyamemazine, possesses anxiolytic properties in humans. The original pharmacological profile of cyamemazine (D-2, 5-HT2A, 5-HT2C, and 5-HT3 receptor antagonist), which was established by binding, microdialysis and behavioral studies, is consistent with these observations. In the light/dark exploration test, cyamemazine demonstrated anxiolytic-like activity by acute, but not chronic administration. By chronic administration, however, cyamemazine increased the time spent in the open arms of the elevated plus maze (EPM) test demonstrating anxiolytic-like activity. The discrepancy between the results obtained in these tests by acute and chronic administration, could be due to a combination of dopamine D2 receptor antagonism with antagonism of the 5-HT2C and 5-HT3 receptors. The action of cyamemazine on both the dopaminergic system and 5-HT3 receptors could also explain the activity of cyamemazine in the management of alcohol withdrawal demonstrated in preclinical studies. This potential indication for cyamemazine and its activity in benzodiazepine withdrawal syndrome have recently been investigated in clinical trials and the results of these studies are presented in this review.

Brems C; Dewane S. Hearing consumer voices: Planning HIV/sexually transmitted infection prevention in alcohol detoxification. Journal of the Association of Nurses in AIDS Care 18(1): 12-24, 2007. (42 refs.)

The literature has provided ample evidence that individuals abusing or dependent upon alcohol are at high risk for contracting HIV and other sexually transmitted infections (STIs). Despite the documented need of this vulnerable group for targeted HIV/STI prevention efforts, no prior research has explored the efficacy and feasibility of HIV/STI prevention for individuals in alcohol detoxification. The current study sought the voices of consumers of such services to get their guidance about successful and necessary features of HIV/STI prevention programs targeted to their needs. Two focus groups conducted yielded exceptionally helpful information. Consumers clearly want to be educated about HIV/STI, seeing this as crucial to their physical well-being and safety. They voiced preferences for nonjudgmental counselors who meet with them on an individual basis in contexts that protect consumer privacy. A clear set of guidelines emerged for an intervention structure that, if carefully honored, has strong likelihood of success in protecting individuals in alcohol detoxification from HIV/STI.

Callaghan RC; Cull R; Vettese LC; Taylor L. A gendered analysis of Canadian aboriginal individuals admitted to inpatient substance abuse detoxification: A three-year medical chart review. (review). American Journal on Addictions 15(5): 380-386, 2006. (44 refs.)

This study examined gender differences within a sample of Canadian Aboriginal individuals admitted to an inpatient, hospital-based substance abuse detoxification program. Even though alcohol was the most frequent primary drug of detoxification for both genders, women received proportionately higher rates of cocaine or opiate detoxification diagnoses. In addition to a younger age, females reported higher rates of physical and sexual abuse. Women were also administered antidepressants, antibiotic medication protocols, and more medical evaluation tests. It appears that Canadian Aboriginal women have a diverse set of psychological and medical needs. This study demonstrates the need for detoxification programs to address the substantial rates of intravenous drug use and the associated risk of infectious disease (eg, Hepatitis C, HIV) among this treatment-seeking population.

Castro VJ. Management of drug and alcohol withdrawal. (letter). New England Journal of Medicine 349(4): 406-406, 2003. (4 refs.)

Kosten and O'Connor suggest propanolol as an alternative for severe cocaine-withdrawal symptoms. The present author describes the possible hazards of treating withdrawl patients with beta-blockers.

Commission on Adolescent Substance and Alcohol Abuse. Treatment of substance use disorders. IN: Evans, DL; Foa, EB; Gur, RE; Hendin H; O'Brien, CP; eds. Treating and Preventing Adolescent Mental Health Disorders: What we Know and What We Don't Know. New York: Oxford University Press, 2005. pp. 391-410. (book refs.)

This chapter adresses the treatment of substance use disorders. Psychosocial treatments, such as: randomized clinical trials, family and multisystem therapies, behavioral therapies, cognitive-behavioral approaches, motivational approaches, and disease model treatments, among others are highlighted. Pharmacological treatments, such as detoxification, and medications for smoking cessation and alcohol abuse in adolescents are also discussed.

Davis JL; Davies S; Wright DC; Falsetti S; Roitzsch JC. Simultaneous treatment of substance abuse and post-traumatic stress disorder: A case study. Clinical Case Studies 4(4): 347-362, 2005. (41 refs.)

The type and timing of treatment for comorbid substance abuse and victimization has been debated in the past decade. Arguments have been made for simultaneous treatment and consecutive treatment of each difficulty. Current issues and a case study in which both problems are treated simultaneously are presented. The patient received inpatient detoxification, inpatient and outpatient group counseling following the 12-step program, and a cognitive-behavioral-oriented outpatient group in the substance treatment component. Multiple Channel Exposure Therapy (MCET), a 12-week manualized treatment developed to treat individuals suffering from both post-traumatic stress disorder and panic disorder, was implemented in the victimization component. At postassessment and at follow-up, the patient no longer met criteria for any pretreatment diagnoses, and her alcohol dependence was in remission. Clinical implications and recommendations for the treatment of substance abuse and victimization are discussed.

Devi G. Management of drug and alcohol withdrawal. (letter). New England Journal of Medicine 349(4): 405-405, 2003. (6 refs.)

In their review of the management of drug and alcohol withdrawal, Kosten and O'Connor advocate the use of diazepam at a dose of 5 to 10 mg every two to four hours for the management of delirium tremens and withdrawal seizures. The present author suggests that, compared to diazepam, intravenous lorazepam treatment is associated with fewer recurrences of seizure and with less need for repeated doses, since its efficacy is higher (82 to 100 percent) than that of diazepam (54 to 100 percent).

Dobrydnjov I; Axelsson K; Berggren L; Samarutel J; Holmstrom B. Intrathecal and oral clonidine as prophylaxis for postoperative alcohol withdrawal syndrome: A randomized double-blinded study. Anesthesia and Analgesia 98(3): 738-744, 2004. (25 refs.)

In this study, we evaluated the effect of intrathecal and oral clonidine as supplements to spinal anesthesia with lidocaine in patients at risk of postoperative alcohol withdrawal syndrome (AWS). We hypothesized that clonidine would have a prophylactic effect on postoperative AWS. Forty-five alcohol-dependent patients (daily ethanol intake >60 g) scheduled for transurethral resection of the prostate were double-blindly randomized into three groups. All patients received hyperbaric lidocaine 100 mg intrathecally. The diazepam group. (DiazG) was premedicated with diazepam 10 mg orally; the intrathecal clonidine group (Clon(i/t)G) received a placebo (saline) tablet and clonidine 150 mug intrathecally; and the oral clonidine group (Clon(p/o)G) received clonidine 150 mug orally. For patients diagnosed with AWS, the Clinical Institute Withdrawal Assessment for Alcohol, revised scale, was used. Twelve patients in the DiazG had symptoms of AWS, compared with two in the Clon(i/t)G and one in the Clon(p/o)G. The median Clinical Institute Withdrawal Assessment for Alcohol, revised scale, score was 12 in the DiazG versus 1 in the clonidine-treated groups. Two patients in the DiazG had severe delirium. Patients receiving oral clonidine had a slightly decreased mean arterial blood pressure 6-12 h after spinal anesthesia (P < 0.05); patients in the DiazG had a hyperdynamic circulatory reaction 24-72 h after surgery. In conclusion, preoperative clonidine 150 mug, intrathecally or orally, prevented significant postoperative AWS in ethanol-dependent patients.

Feige B; Scaal S; Hornyak M; Gann H; Riemann D. Sleep electroencephalographic spectral power after withdrawal from alcohol in alcohol-dependent patients. Alcoholism: Clinical and Experimental Research 31(1): 19-27, 2007. (59 refs.)

Background: Dysfunctional hyperarousal is suspected to be a neurophysiological determinant of relapse in abstinent alcohol-dependent patients. In the present study, we used spectral power analysis of the sleep electroencephalographic (EEG) to quantify brain activity during sleep in patients during subacute withdrawal as well as in control subjects. Our hypothesis was that the subgroup of patients who relapsed within the 3 months to follow-up would exhibit-increased dysfunctional arousal manifested by higher-frequency (b) EEG power during sleep. Methods: Twenty-six alcohol-dependent in-patients were examined with polysomnography over 2 nights 2 to 3 weeks after withdrawal. At the 3-month clinical follow-up assessment, 12 of them had relapsed and 14 abstained. The control group consisted of 23 healthy subjects similar to the patients with alcohol dependence in age and gender distribution. Spectral sleep EEG analysis was performed on both nights (adaptation and baseline) of all subjects. Logarithmic artifact-controlled spectral band power of sleep stage 2 and rapid eye movement (REM) sleep was analyzed for Group, Gender, and Age effects using multiple analyses of covariance. Three groups were compared with the Group factor: relapsers, abstainers, and controls. Results: Generally, both Group and Age effects were significant for the second, baseline night for the visually scored sleep parameters, while spectral EEG parameters showed significant differences in the adaptation night. In the adaptation night, a significant enhancement in the beta 2 band (24-32 Hz) was seen in REM sleep in relapsers relative to both abstainers and controls. Conclusions: The beta 2 increase could be interpreted as a sign of dysfunctional arousal during REM sleep "unmasked" by the additional stressor of sleep environment adaptation. Its determinants are likely to be both premorbid and drinking history related.

Fitzpatrick M. The meaning of detox. Lancet 361(9351): 94, 2003. (0 refs.)

In this first issue of the new year, the author notes that with the festive season behind, it must be time for "detox." The author notes that in recent years the meaning of the concept of detoxification has changed significantly. Originally, detoxification referred to the process of extracting poisons from the blood stream. More commonly, detoxification refers to withdrawal from alcohol or other drugs, often with the replacement of the addictive drug with another therapeutic drug. However, it now appears to refer to the process of cleansing both mind and body of the polluting effects of modern life. In the modern world, which is cleaner and safer than the world has ever been, many believe there is a constant danger from external contamination. Further, as the market for enemas and colonic irrigation indicates, many people have also internalized the threat and feel the need to protect themselves against an enemy within their own bowels. For the vulnerable person, the greatest threat comes from other people, with the idea of detox extended to "toxic relationships." The author suggests that it might be easy to dismiss "detox" as a harmless fad but he further suggests it may reflect a fearful and misanthropic outlook to the coming year.

Gartenmaier A; Pelzer E; Soyka M. Treatment of alcohol withdrawal syndrome with combined carbamazepine and tiapride in a patient with probable sleep apnoe syndrome - A case report. (letter). Pharmacopsychiatry 38(2): 96-98, 2005. (13 refs.)

The most frequently used agents for treatment of alcohol withdrawal syndrome are benzodiazepines and clomethiazole. Both have the main disadvantage of potential misuse and respiratory depression. Therefore their use in patients with respiratory diseases is limited. In recent years a treatment strategy with combined carbamazepine and tiapride was reported to be an effective alternative in alcohol withdrawal without the risk of respiratory depression. We report the successful treatment with carbamazepine and tiapride of a patient with probable sleep apnoe syndrome and history of withdrawal-related epileptic seizures.

Gillman MA; Lichtigfeld FJ. Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal. Addictive Behaviors 29(6): 1183-1187, 2004. (7 refs.)

We report a randomised double-blind controlled study with an enlarged cohort of participants (N= 5 1) using psychotropic analgesic nitrous oxide (PAN) versus benzodiazepines (BZs) for treating acute alcoholic withdrawal states. An additional 28 participants having received a BZ the night previous to the study were pooled with the previously analysed 23 (with no additional BZ). These pooled results showed that PAN is superior to a BZ regimen at P=.05 level, despite additional BZs. Our work provides further support for previous findings that show that PAN is a safe, rapid, and effective therapy for acute mild to moderately severe withdrawal states.

Gillman MA; Lichtigfeld FJ; Young TN. Psychotropic analgesic nitrous oxide for alcoholic withdrawal states. (review). Cochrane Database of Systemic Reviews 2: CD005190, 2007. (54 refs.)

Background: Alcoholism is a global problem with 5-10% of the world's population demonstrating alcohol-related diseases. One of the most severe consequences of alcohol dependence is the withdrawal syndrome, for which benzodiazepines are the most popular current treatment. An alternative method to benzodiazepine employs psychotropic analgesic nitrous oxide (PAN). Objectives: To assess the effects of PAN for treating alcohol withdrawal states Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Librarylssue 2, 2005), MEDLINE, EMBASE, CINAHL (all to May 2005). We scanned internet websites, reference lists of relevant articles and abstracts of the international Conferences on Alcoholism. We contacted researchers in the field and industry to identify unpublished trials. No language and publication restrictions. Selection criteria Randomised controlled trials including voluntary participants dependent on alcohol. PAN was compared to oxygen and/or benzodiazepine regimens. Data collection and analysis Two authors independently assessed the methodological quality of the trials and extracted data. Main results Five studies, 212 participants, were included. PAN showed improvement of symptoms (RR 1.35; 95% CI 1.01 to 1.79), of the amount and duration of sedative medication and of psychomotor function (WMD -8-71; 95% CI -13.71 to -3.71). At one hour post intervention, no significant differences were found for depression (WMD -2.40; 95% CI -8.70 to 3.89) and anxiety (WMD -3.70; 95% CI -10.53 to 3.12). None of the included studies reported any significant adverse effects of any treatment. Authors' conclusions: Results indicate that PAN may be an effective treatment of the mild to moderate alcoholic withdrawal state. The rapidity of the therapeutic effect of PAN therapy coupled with the minimal sedative requirements, may enable patients to enter the psychological treatment phase more quickly than those on sedative regimens, accelerating the patients recovery. Our review does not provide strong evidence due to the small sample sizes of the included trials. Neither does the review indicate any causes for concern that PAN is more harmful than the benzodiazepines. Clinicians wishing to use PAN may initially wish to do so within trial settings. Further high quality trials should be done to confirm these findings and to investigate whether the PAN therapy has fewer adverse effects than other treatments for the alcohol withdrawal states. Studies to investigate the possible cost-effectiveness of PAN by reducing costly hospital admissions and decreasing post administration supervision also need to be performed.

Grafenreed KM; Lobo B; Sands C; Yates M. Development of an alcohol withdrawal delirium prophylaxis protocol in a community teaching hospital. American Journal of Health-System Pharmacy 61(11): 1151-1155, 2004. (12 refs.)

Alcohol withdrawal syndrome (AWS) formerly known as delirium tremens is a preventable complication of alcohol withdrawal. In acute care settings, patients at risk for AWD often have other emergency medical conditions that can mask or mimic the signs and symptoms of AWS. To avoid the risk of negative outcomes, promptly identifying patients at risk and providing recommended prophylaxis is important. In 1996 Methodist Healthcare University Hospital, affiliated with the University of Tennessee developed guidelines of management of AWS in response to the perception that it was not being prevented adequately. Unfortunately these guidelines were not routinely followed and the perception persisted that not enough was being done to prevent AWS. Therefore the hospital embarked upon a project to identify and characterize patients with AWD, determine whether the cases were potentially preventable, and development a protocol for the prevention of AWD in high-risk patients. For 2001, 70 cases of AWD were identify, and of these 59 cases reviewed. Of these cases of AWD, 58% occurred after hospitalization. The demographics of these patients are described, the course of AWD outlined, and levels of mortality provided. Of note is that 30% required transfer to the ICU for management of AWD. Patients with AWD lacked ED or admission orders for "AWD precautions." (This is despite the fact that 80% had a documented history of alcoholism. The protocol initiated is based on ASAM (American Society of Addiction Medicine) criteria is described, and provides two prophylactic regimens based on the patient's estimated risk to develop AWD. .

Hillemacher T; Bayerlein K; Wilhelm J; Bonsch D; Poleo D; Sperling W. Recurrent detoxifications are associated with craving in patients classified as type 1 according to Lesch's typology. Alcohol and Alcoholism 41(1): 66-69, 2006. (56 refs.)

Aims: Recurrent detoxifications have been suggested to be associated with elevated alcohol craving. The aim of this investigation was to study the influence of preceding detoxifications on craving in patients with alcoholism classified according to Lesch's typology. Methods: We examined 192 patients (154 men, 38 women) after admission for detoxification treatment. Craving was assessed using the Obsessive Compulsive Drinking Scale, and patients were classified into one of the four subgroups of Lesch's typology. The number of preceding detoxifications was assessed with a structured interview. Results: Lesch's typology type 4 patients showed significantly higher craving scores than type 1-3 patients (Mann-Whitney U-Test; P < 0.05). With respect to the influence of recurrent detoxifications, we found a significant correlation between the number of preceding detoxifications and the extent of craving for the whole population (Spearman's rho r = 0.241, P = 0.001, N = 192), particularly for patients of Lesch's type 1 (Spearman's rho r = 0.534, P = 0.001, N = 37). No significant association was found for patients of the other subgroups (Lesch's type 2-4). Conclusion: The influence of recurrent detoxifications on craving is especially important in patients with Lesch's type 1. Our results underline the importance of the kindling effect particularly in this group of patients, possibly mediated by an increase of glutamatergic neurotransmission. Furthermore, our results emphasize the need to classify patients with alcohol-dependency in addiction research.

Hittner JB; Quello SB. Combating substance abuse with ibogaine: Pre- and posttreatment recommendations and an example of successive model fitting analyses. Journal of Psychoactive Drugs 36(2): 191-199, 2004. (50 refs.)

Ibogaine is an indole alkaloid derived from the root bark of the African shrub Tabernanthe iboga and it has been used for many years as a medicinal and ceremonial agent in West Central Africa. Furthermore, both anecdotal observations and recent studies suggest that ibogaine alleviates withdrawal symptoms and reduces drug cravings. Although ibogaine articles typically include information bearing on the duration of drug abstinence following treatment, little if any attention is given to the psychological and environmental factors that might facilitate a positive treatment outcome. Hence, a major purpose of the present review is to suggest a number of theory-driven, pretreatment and posttreatment recommendations that have good potential for enhancing ibogaine's effectiveness. The second major purpose of this review is to demonstrate, through a reanalysis of previously published results, the utility of conducting successive model fitting analyses on ibogaine treatment data. Such analyses are useful for determining both the strength and form of the association between pre-ibogaine treatment variables and post-ibogaine treatment outcomes. Finally, in order to facilitate future quantitative reviews, the authors recommend that a minimum set of patient- and treatment-related variables be included in all ibogaine publications involving human participants.

Huitink J; Buitelaar D. Management of drug and alcohol withdrawal. (letter). New England Journal of Medicine 349(4): 406-406, 2003. (1 refs.)

Kosten and O'Connor describe the treatment of alcohol-withdrawal symptoms with symptom-triggered therapy, rather than with medication given on a fixed scale. However, our clinical experience with patients who have head and neck cancer, among whom the prevalence of alcohol abuse is greater than 60 percent, is that the prevention of alcohol-withdrawal symptoms is even more important. We advise not waiting to provide treatment until withdrawal symptoms start.

Jonkman JN; McCarty D; Harwood HJ; Normand SL; Caspi Y. Practice variation and length of stay in alcohol and drug detoxification centers. Journal of Substance Abuse Treatment 28(1): 11-18, 2005. (24 refs.)

Admissions to 20 publicly funded alcohol and drug detoxification centers in Massachusetts were examined to identify program and patient variables that influenced length of stay. The last admission during fiscal year 1996 was abstracted for patients 18 years of age and older seeking alcohol, cocaine, or heroin detoxification (n = 21,311; 29% women). A hierarchical generalized linear model examined the effects of patient and program characteristics on variation in length of stay and tested case-mix adjustments. Program size had the most influence on mean adjusted length of stay; stays were more than 40% longer in detoxification centers with 35 or more beds (7.69 days) than in centers with less than 35 beds (5.42 days). The study highlights the contribution of program size to treatment processes and suggests the need for more attention to program attributes in studies of patient outcomes and treatment processes.

Kampman KM; Pettinati HM; Volpicelli JR; Oslin DM; Lipkin C; Sparkman T et al. Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol. American Journal on Addictions 13(1): 74-82, 2004. (20 refs.)

This study compared the effects of alcohol and cocaine dependence severity on the outcome of outpatient detoxification from alcohol and cocaine. Subjects included 84 subjects with both alcohol and cocaine dependence admitted for outpatient detoxification. Fifty-three of the 84 subjects (63%) completed detoxification. Baseline cocaine use, cocaine craving, and cocaine withdrawal symptoms predicted detoxification outcome, whereas alcohol use, alcohol craving, and alcohol withdrawal symptoms did not. Among cocaine- and alcohol-dependent subjects, cocaine dependence severity appears to be a more important predictor of detoxification success than alcohol dependence severity.

Knapp DJ; Overstreet DH; Breese GR. Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/gamma-aminobutyric acid ligands. Alcoholism: Clinical and Experimental Research 29(4): 553-563, 2005. (64 refs.)

Background: Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal-associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of gamma-aminobutyric acid-modulating drugs on social interaction behavior-an established model of anxiety-in rats exposed to repeated cycles of ethanol treatment and withdrawal. Methods: Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl-6, 7-dymerboxy-4-ethyl-beta-carboline-3-carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Results: Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Conclusions: Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid-receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals.

Koethe D; Juelicher A; Nolden BM; Braunwarth WD; Klosterkotter J; Niklewski GN et al. Oxcarbazepine - Efficacy and tolerability during treatment of alcohol withdrawal: A double-blind, randomized, placebo-controlled multicenter pilot study. Alcoholism: Clinical and Experimental Research 31(7): 1188-1194, 2007. (29 refs.)

Objective: Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol dependence and often requires intensive medical treatment. Antiepileptic drugs (AEDs) have been shown to be as efficacious in the treatment of AWS in several controlled trials as benzodiazepines and superior to placebo in relieving alcohol withdrawal symptoms. Oxcarbazepine (OXC), a newer anticonvulsive drug, has a favorable safety profile over carbamazepine (CBZ) and other older AEDs due to its excellent efficacy and better side-effect profile. Methods: The efficacy and tolerability of OXC versus placebo were investigated in 50 inpatients during a 6-day treatment of alcohol withdrawal in a 4-site, double-blind, randomized, placebo-controlled pilot study. The amount of rescue medication of clomethiazole (CLO) capsules needed was chosen as the primary variable. The data were collected between May 2003 and September 2004. Results: No initial differences were found regarding sociodemographic data and alcohol-related parameters, indicating successful randomization. No differences were found in the need for rescue medication CLO, decrease of withdrawal symptoms, or craving for alcohol between the OXC and the placebo group. Subjectively experienced side effects, normalization of vegetative parameters, craving, or improvement of psychopathological parameters were not different between the groups. Conclusion: Despite the negative finding, which may be attributable to the design of the study, OXC still poses an interesting alternative to CBZ and other drugs because other studies have found it not only as efficient but also as having no addictive potential, while additionally possessing an anti-craving effect. Therefore, well-designed investigations with larger cohorts are required to further elucidate this issue.

Kosten T; O'Connor P. Management of drug and alcohol withdrawal - Reply. New England Journal of Medicine 349(4): 406-407, 2003. (5 refs.)

Kosten TR; O'Connor PG. Management of drug and alcohol withdrawal. (review). New England Journal of Medicine 348(18): 1786-1795, 2003. (67 refs.)

Each year in the United States, approximately 8.2 million persons are dependent on alcohol and 3.5 million are dependent on illicit drugs, including stimulants (1 million) and heroin (750,000).1 In a sample from primary care practice, 15 percent of patients had either an "at-risk" pattern of alcohol use or an alcohol-related health problem, and 5 percent had a history of illicit-drug use.2 With rates of substance use so high, all patients should be carefully screened with validated instrument. This review article covers the management of withdrawal for three major drug classes: sedatives, opiates, and stimulants. The discussion of sedative withdrawal -- alcohol and benzodiazepines -- covers clinical presentation and general management, and pharmacologic treatment. The discussion of opiates reviews the clinical presentation, treatment with opioid and non-opioid medications, as well as "ultra-rapid: detoxification. Discussion of stimulants centers on cocaine and amphetamines and again addresses withdrawal, clinical presentation and treatment. The article concludes with attention to the role of the generalist physician, patient clinical characteristics, and referral as compared with direct treatment.

Krupitsky EM; Rudenko AA; Burakov AM; Slavina TY; Grinenko AA; Pittman B et al. Antiglutamatergic strategies for ethanol detoxification: Comparison with placebo and diazepam. Alcoholism: Clinical and Experimental Research 31(4): 604-611, 2007. (52 refs.)

Background: Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N-methyl-D-aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate. Methods: This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately. Results: All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam. Conclusions: This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal.

Lange-Asschenfeldt C; Muller MJ; Szegedi A; Anghelescu I; Klawe C; Wetzel H. Symptom-triggered versus standard chlormethiazole treatment of inpatient alcohol withdrawal: Clinical implications from a chart analysis. European Addiction Research 9(1): 1-7, 2003. (27 refs.)

To evaluate clinical effectiveness and safety of 2 different detoxification treatment protocols, a chart analysis of hospital inpatients consecutively admitted for alcohol withdrawal during one year was undertaken. Records of 33 patients receiving symptom-triggered treatment (using a modified version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale) were compared with those of patients treated by applying a fixed-dose regimen (n = 32). Patients (45.3 +/- 9.8 years, 21% female) of both groups were comparable regarding illness severity, epidemiologic parameters as well as complications during the observed treatment period. Under symptom-triggered therapy, chlormethiazole (CMZ) treatment duration (4.2 +/- 3.5 vs. 7.5 +/- 3.3 days, Mann- Whitney U test: p = 0.0003) and cumulative CMZ dosage (4,352 +/- 4,589 vs. 9,921 +/- 6,599 mg, Mann-Whitney U test: p 0.0004) were significantly reduced. The daily CMZ dose was significantly lower at days 1-5 in the group receiving symptom- triggered treatment. There was no influence of age on the outcome parameters of either treatment group. In conclusion, an individualized symptom-triggered treatment of alcohol withdrawal with CMZ seems to be equally safe but more efficient than a scheduled regimen

Larson MJ; Saitz R; Horton NJ; Lloyd-Travaglini C; Samet JH. Emergency department and hospital utilization among alcohol and drug-dependent detoxification patients without primary medical care. American Journal of Drug and Alcohol Abuse 32(3): 435-452, 2006. (49 refs.)

Utilization of emergency department (ED) services and hospitalization among a cohort of substance abusers are described based on structured research interviews with 470 adults without primary care admitted to an urban residential detoxification program. Cross-sectional analysis of baseline data of subjects found nearly 19% of subjects went to an ED on 2 or more occasions in the 6 months prior to detoxification and 14% were admitted for an overnight hospitalization. Upon further analysis of past 6-month ED utilization, the following factors were independently associated with increased odds of ED use: White race; at least one month homeless in the past 5 years chronic health condition; injury in past 6 months; and subject perception that their substance abuse interfered with seeking care from a regular doctor. Subjects with cocaine as a primary problem had lower odds of ED utilization than a reference group with alcohol as a primary problem.

Le Bon Ol; Murphy JR; Staner L; Hoffmann G; Kormoss N; Kentos M; Dupont P et al. Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post withdrawal syndrome: Polysomnographic and clinical evaluations. Journal of Clinical Psychopharmacology 23(4): 377-383, 2003. (44 refs.)

Alcohol detoxification is accompanied by sustained difficulties in sleep initiation and maintenance and may be a cause of relapse to alcohol use. The treatment of sleep problems with hypnotic drugs is made difficult by cross-tolerance between benzodiazepines and alcohol. We evaluated the capacity of trazodone (TRZ), a 2nd-generation antidepressant with anxiolytic and sedative properties, to increase sleep efficiency in alcohol-dependent Ss after detoxification. 16 Ss completed the TRZ (n=8) or the placebo (PL; n=8) treatment arms. Polysomnographies were performed at baseline after the 1st drug dose and after 4 wks of treatment. The main outcome was sleep efficiency. Secondary outcomes included changes in other sleep parameters, Hamilton Depression Rating and Clinical Global Impression scales. Sleep efficiency was increased in the TRZ group when it was computed after sleep onset, both immediately after 1st administration of the drug and after 4 wks of treatment. No benefit was observed in the PL group. Sleep improvement under TRZ also included the number of awakenings, intermittent wake sleep time, and non-rapid eye movement sleep. Hamilton and Clinical Global scales were better for the TRZ group. TRZ is thus a potential option in the treatment of alcohol post-withdrawal insomnia.

Lingford-Hughes AR; Welch S; Nutt DJ. Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: Recommendations from the British Association for Psychopharmacology. (review). Journal of Psychopharmacology 18(3): 293-335, 2004. (403 refs.)

The British Association for Psychopharmacology guidelines for the treatment of substance misuse, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, in substance misuse, addiction and comorbidity with psychiatric disorders.

Lucht M; Kuehn KU; Armbruster J; Abraham G; Gaensicke M; Barnow S; Tretzel H et al. Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: A controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam. Alcohol and Alcoholism 38(2): 168-175, 2003. (44 refs.)

Aims and Methods: Alcohol withdrawal treatment efficacy of tiapride/carbamazepine (A) vs clomethiazole (B) vs diazepam (C) in non-intoxicated patients and vs tiapride/carbamazepine in intoxicated patients (D; breath alcohol concentration greater than or equal to 1 g/l) was tested (n = 127) in a controlled randomized open-label study. Results: Efficacy and safety were not different between groups (total group: delirium, 3.9%; seizure, 0.8%), except for a lack of efficacy in 18% of intoxicated tiapride/carbamazepine patients. A change of medication in this group was necessary only when primarily intoxicated patients had reached the non-intoxicated range. Conclusions: Treatment with tiapride/carbamazepine in alcohol-intoxicated patients proved to be safe.

Lukasiewicz M; Benyamina A; Reynaud M; Falissard B. An in vivo study of the relationship between craving and reaction time during alcohol detoxification using the Ecological Momentary Assessment. Alcoholism: Clinical and Experimental Research 29(12): 2135-2143, 2005. (69 refs.)

BACKGROUND: To study cognitive interference associated with craving for alcohol, the Ecological Momentary Assessment (EMA) method was used to measure the relationship between craving and reaction time. A secondary aim was the study of the predictive factors for craving during alcohol detoxification. The EMA enables both repeated measures of craving in a natural setting and the recording of reaction time without the patient being aware of this. METHODS: Craving for alcohol, reaction time, sadness and anxiety were recorded 8 to 12 times a day, over three weeks of detoxification in 14 alcoholics (n = 1767 measures), on an electronic diary issuing random prompts. Mixed models were used for statistical analysis (alpha = 5%, 1-beta = 88%). RESULTS: Reaction time was significantly increased in univariate analysis when a craving episode occurred but this difference did not persist after multivariate analysis. Craving episodes were more frequent and intense than previously reported. Predictive factors of craving during detoxification were: age, gender, sadness, anxiety and the number of previous detoxifications. Antidepressants, anticraving medications but not benzodiazepines were negatively associated to craving.

Malcolm R. Pharmacologic treatments manage alcohol withdrawal, relapse prevention. Psychiatric Annals 33(9): 593-601, 2003. (60 refs.)

The article aims to describe treatment methods for alcohol withdrawal and relapse prevention; discusses the importance of treatment setting in management of withdrawal; and evaluates the drug options available for treatment of withdrawal and as well as the more limited options available for relapse prevention, which offer only modest effectiveness. Major topics addressed are the use of benzodiazepines for withdrawal, covering both short-acting and symptom triggered protocols and daily-dosing with longer acting benzodiazepines; other medications, mainly the anticonvulsants. In terms of relapse prevention there is discussion of disulfiram, naltrexone, and acamprosate.

Mariani JJ; Levin FR. Pharmacotherapy for alcohol-related disorders: What clinicians should know. Harvard Review of Psychiatry 12(6): 351-366, 2004. (108 refs.)

Alcohol-related disorders are a major public health problem in the United States. Alcohol interacts with several neurotransmitter systems causing both acute and chronic effects in the brain. While the mainstay of treatment of alcohol-related disorders, with the exception of alcohol withdrawal, has historically been psychosocial, pharmacotherapy is increasingly being investigated and incorporated into standard clinical practice. Patients with alcohol use disorders and comorbid psychiatric conditions, most commonly depressive and anxiety disorders, can benefit from symptom-targeted pharmacotherapy, even if the patient fails to achieve abstinence from alcohol. Although benzodiazepines remain the treatment of choice to treat alcohol withdrawal, a variety of other agents is being investigated, particularly in the outpatient setting. Further randomized clinical trials of alcohol-related disorder pharmacotherapy, particularly of comorbid subpopulations, are needed to better inform clinical decision making. The routine exclusion of alcohol-dependent patients from pharmacotherapy trials of psychiatric disorders presents a barrier to gathering more data. Recommendations for future research are discussed.

Mariani JJ; Rosenthal RN; Tross S; Singh P; Anand OP. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal. American Journal on Addictions 15(1): 76-84, 2006. (33 refs.)

Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted.

Mark TL; Dilonardo JD; Chalk M; Coffey RM. Factors associated with the receipt of treatment following detoxification. Journal of Substance Abuse Treatment 24(4): 299-304, 2003. (21 refs.)

This paper examines the determinants of whether an individual received continuing treatment/rehabilitation services 30 days after receiving inpatient substance abuse detoxification. Data came from 1997-1999 employer health insurance claims. Only 49.4% of detoxification episodes were followed by continuing mental health or substance abuse treatment within 30 days after discharge. Some of the factors positively associated with receiving continuing treatment after receiving detoxification included: female gender, being in a behavioral health carve-out plan, and lower cost-sharing requirements for an outpatient substance abuse visit.

Moak DH. Assessing the efficacy of medical treatments for alcohol use disorders. (review). Expert Opinion on Pharmacotherapy 5(10): 2075 -2089, 2004. (132 refs.)

Alcohol use disorders (AUDs) are common health problems that have a significant impact on society as a whole. There is a need for more effective treatments. In the last two decades, evidence for the efficacy of pharmacological approaches to treatment has increased. Although it has long been clear that medications are needed for the treatment of the alcohol withdrawal syndrome, the important role of medications in the longer-term treatment of AUDs has only recently been appreciated. In particular, naltrexone, acamprosate and topiramate appear to be efficacious treatments, especially when combined with psychosocial interventions that emphasise compliance with medication and encourage treatment retention. The goal of this review is to bring together the existing literature supporting the usefulness of pharmacological treatments for the alcohol withdrawal syndrome, for longer-term treatment of AUDs, and for comorbid AUDs and other psychiatric disorders. In addition, opportunities for future research will be identified.

Myrick H; Taylor B; Larowe S; Nguyen S; Boyle E; Cochran K et al. Retrospective chart review comparing tiagabine and benzodiazepines for the treatment of alcohol withdrawal. Journal of Psychoactive Drugs 37(4): 409-414, 2005. (14 refs.)

Although benzodiazepines are the standard of care in the treatment of alcohol withdrawal, several studies have suggested that anticonvulsants may be equally effective at alleviating alcohol withdrawal symptoms and may pose less of a risk of causing rebound of symptoms which could contribute to relapse. This report compares treatment outcomes for patients (N=13) treated for alcohol withdrawal with either the anticonvulsant tiagabine or the benzodiazepines oxazepam and lorazepam. The Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) was utilized to gauge alcohol withdrawal symptoms over the course of the study. When possible, follow-up data was obtained on alcohol use post-treatment. Both benzodiazepines and tiagabine appeared to reduce CIWA-Ar scores at about the same magnitude. There was a trend for tiagabine patients to have less post-detoxification drinking (Fisher exact test, p=0.12). The reduction in alcohol withdrawal symptoms and decreased tendency to relapse observed in patients treated with the anticonvulsant tiagabine suggests that a double-blind, placebo controlled trial may be warranted.

Nace EP. Alcohol. IN: Frances RJ; Miller SI; Mack AH, eds. Clinical Textbook of Addictive Disorders, 3rd edition. New York: Guilford Press, 2005. pp. 75-104. (91 refs.)

This chapter is one of several that deals with a specific drug class. The chapter begins with a discussion of diagnosis and screening. It then considers psychiatric comorbidity, with discussion of accompanying drug abuse/dependence, mood disorders, anxiety disorders, schizophrenia, personality disorders, and eating disorders. Ethnicity and alcoholism is then considered, with discussion of Native Americans, African Americans, Asian Americans, and Hispanics. In addition to description of the pharmacology of alcohol, there is a description of core clinical features -- intoxication, withdrawal, delirium, Korsakoff's psychosis, dementia, sexual dysfunction, sleep disorder, and alcohol induced anxiety, affective, and psychotic disorders -- and a system-oriented review of common medical complications. It concludes by outlining treatment priorities.

Nava F; Premi S; Manzato E; Campagnola W; Lucchini A; Gessa GL et al. Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: An open study vs. diazepam. American Journal of Drug and Alcohol Abuse 33(3): 379-392, 2007. (72 refs.)

In 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics.

Ntais C; Pakos E; Kyzas P; Ioannidis JPA. Benzodiazepines for alcohol withdrawal. (review). Cochrane Database of Systemic Reviews (3): CD005063.pub2, 2005. (94 refs.)

Background: Alcohol withdrawal syndrome is a cluster of symptoms that occurs in alcohol-dependent people after cessation or reduction in alcohol use. This systematic review focuses on the evidence of benzodiazepines' use in the treatment of alcohol withdrawal symptoms. Objectives: To evaluate the effectiveness and safety of benzodiazepines in the treatment of alcohol withdrawal. Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to October 2004) and EU-PSIPSI-Tri database with no language and publication restrictions. We also screened references of retrieved articles. Selection criteria All randomized controlled trials examining the effectiveness and safety of a benzodiazepine in comparison with a placebo or other pharmacological intervention or other benzodiazepine were considered. Data collection and analysis Two reviewers independently assessed trial quality and extracted data. Main results Fifty-seven trials, with a total of 4,051 people were included. Despite the considerable number of randomized controlled trials, there was a very large variety of outcomes and of different rating scales and relatively limited quantitative synthesis of data was feasible. Benzodiazepines offered a large benefit against alcohol withdrawal seizures compared to placebo (relative risk [RR] 0.16; 95% confidence interval [CI] 0.04 to 0.69; p = 0.01). Benzodiazepines had similar success rates as other drugs (RR 1.02; 95% CI 0.92 to 1.12) or anticonvulsants in particular (RR 1.00; 95% CI 0.87 to 1.16) and offered a significant benefit for seizure control against non-anticonvulsants (RR 0.23; 95% CI 0.07 to 0.75; p = 0.02), but not against anticonvulsants (RR 1.99; 95% CI 0.46 to 8.65). Changes in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores at the end of treatment were generally similar with benzodiazepines versus other drugs. Authors ' conclusions: Benzodiazepines are effective against alcohol withdrawal symptoms, in particular seizures, when compared to placebo. It is not possible to draw definite conclusions about the relative effectiveness and safety of benzodiazepines against other drugs in alcohol withdrawal, because of the large heterogeneity of the trials both in interventions and assessment of outcomes but the available data do not show prominent differences between benzodiazepines and other drugs in success rates.

Office of Applied Studies, Substance Abuse and Mental Health Services Administration. National Survey of Substance Abuse Treatment Services (N-SSATS): 2002. Data on Substance Abuse Treatment Facilities. DASIS Series: S-19. Rockville MD: Office of Applied Studies, SAMHSA, 2003. (0 refs.)

This report present the results from the 2002 National Survey of Substance Abuse Treatment Services. Conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA), it is a one day census of all programs, and is intended to collect information on the location, characteristics, and use of alcoholism and drug abuse treatment facilities and services throughout the states, District of Columbia, and other U.S. jurisdictions. The report is organized into six chapters, which provide a description of the study, the trends in facility characteristics, trends in client characteristics, family characteristics and services, client characteristics, and State data. Among the major findings: (1) 13,720 facilities reported a one-day total census of 1,136,287 clients in substance abuse treatment. Those under age 18 represented 8% of total in treatment. (2) Of all the facilities, 61% are operated by private non-profit organization. Twenty-five percent were operated by for profit groups, and the remainder were government programs. (3) Nearly half of all facilities (49%) offered special programs for the dually diagnosed. More than one-third (37%) had programs for adolescents. (4) Nearly half (48%) of all clients ere in treatment for both alcohol and drug abuse. thirty-one percent were being treated for drug abuse only, and 21% were receiving treatment for alcohol only. (5) Outpatient treatment was the widely available type of care, being offered by 74% of al facilities, and intensive outpatient treatment offered by 44%. Day treatment/partial hospitalization was offered by 15% of all facilities. Residential rehab was available in 26% of facilities. Residential detox offered by 8% and hospital inpatient detox available in 7% of facilities. Data is presented in 68 tables and 7 figures.

Office of Applied Studies, Substance Abuse and Mental Health Services Administration. National Survey of Substance Abuse Treatment Services (N-SSATS): 2004. Data on Substance Abuse Treatment Facilities. DASIS Series S-28. Rockville MD: Office of Applied Studies, SAMHSA, 2005. (0 refs.)

This report present the results from the 2004 National Survey of Substance Abuse Treatment Services. Conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA), the survey is a one day census of all programs, and is intended to collect information on the location, characteristics, and use of alcoholism and drug abuse treatment facilities and services throughout the states, District of Columbia, and other U.S. jurisdictions. The report is organized into six chapters, which provide a description of the study, the trends in facility characteristics, trends in client characteristics, family characteristics and services, client characteristics, and State data. There are 104 figures and tables. Among the major findings: (1) 14,167 facilities reported a one-day total census of 1,072,251 clients in substance abuse treatment. Those under age 18 represented 8% of total in treatment. (2) Of all the facilities, 60% are operated by private non-profit organization. Twenty-eight percent were operated by for profit groups, and the remainder were government programs. (3) A bit under half (46%) of all clients were in treatment for both alcohol and drug abuse. Thirty-four percent were being treated for drug abuse only, and 20% were receiving treatment for alcohol only. (4) Outpatient treatment was the most widely available type of care, being offered by 72% of all facilities, and intensive outpatient treatment offered by 442%. On the day of census, 64% of those in care were in outpatient treatment.

Office of Applied Studies. National Survey of Substance Abuse Treatment Services (N-SSATS): 2004. Data on Substance Abuse Treatment Facilities. DASIS Series S-34. Rockville MD: Substance Abuse and Mental Health Services Administration, 2006. (0 refs.)

This report is one in an annual series on the characteristics of treatment facilities in the US. it is based on data for a single, index day. The report is organized in six chapters. The first chapters describes the Survey. Chapter 2 describes the trends found in facility characteristics, for example, in terms of number and type of care offered. Chapter 3 describes the trends in client characteristics -- the number of clients, type of care received, and the substances involved. Chapter 4 deals with the facility characteristics and services, size, utilization rates, programs offered for specific populations -- adolescents, those with co-occurring disorders, with criminal justice involvement, gays and lesbians, seniors, those HIV/AIDS, women, DWI offenders, and pregnant or postpartum women. Chapter 5 describes the client characteristics. Data is drawn from almost 14,000 facilities. Chapter 6 deals with state data. The highlights present trends in facility and client characteristics. Over 13,400 faculties reported, with over 1 million persons in treatment on the index date. About 55% were in treatment within private, non-profit programs. There was an increase in for-profit facilities, and represented about 27% of those in care. Eighty-nine percent of those in treatment were receiving outpatient care; 10% were in non-hospital residential care; and 1% in hospital inpatient care. Adolescents made up about 8% of all clients, and the majority were in special adolescent treatment programs. Of those providing substance abuse treatment, 62% of the facilities, representing 69% of clients, were primarily involved in substance abuse treatment. Twenty-seven percent of programs, representing 24% of those in care, were treated in combined mental health/substance abuse treatment. Outpatient care was provided by 72% of all programs, and had 53% of those in care. Outpatient/partial hospitalization was offered by 14% of facilities and was provided to 12% of all clients in the index date. Nearly half of clients (47%) were being treated for both alcohol and drug abuse. Nationally the rate for treatment was 431 clients per 100,000 population age 18 or over. The median number of clients was 40 persons. Data is summarized and presented in 88 figures and tables.

Parrott S; Godfrey C; Heather N; Clark J; Ryan T. Cost and outcome analysis of two detoxification services. Alcohol and Alcoholism 41(1): 84-91, 2006. (35 refs.)

Aim: To examine the relationship between service use and outcomes (individual and wider consequences) using an economic analysis of a direct-access alcohol detoxification service in Manchester (the Smithfield Centre) and an NHS partial hospitalization programme in Newcastle upon Tyne (Newcastle and North Tyneside Drug and Alcohol Service, Plummer Court). Methods: A total of 145 direct-access admissions to the Smithfield Centre and 77 admissions to Plummer Court completed a battery of questionnaires shortly after intake and were followed up 6 months after discharge. Full economic data at follow-up were available for 54 Smithfield admissions and 49 Plummer Court admissions. Results: Mean total cost of treatment per patient was �1113 at the Smithfield Centre and �1054 at Plummer Court in 2003-04 prices. Comparing the 6 months before treatment with the 6 months before follow-up, social costs fell by �331 on average for each patient at Plummer Court but rose by �1047 for each patient at the Smithfield Centre. When treatment costs and wider social costs were combined, the total cost to society at Smithfield was on average �2159 per patient whilst at Plummer Court it was �723 per patient. Combining the cost of treatment with drinking outcomes yielded a net cost per unit reduction in alcohol consumption of �1.79 at Smithfield and �1.68 at Plummer Court. Conclusions: Both services delivered a flexible needs-based service to very disadvantaged population at a reasonable cost and were associated with statistically significant reductions in drinking. For some patients, there was evidence of public sector resource savings but for others these detoxification services allowed those not previously in contact with services to meet health and social care needs. These patterns of cost through time are more complex than in previous evaluations of less severely dependent patients and difficult to predict from drinking patterns or patient characteristics. More research is required to judge the suitability of generic health state measures commonly in use for health economic evaluations for assessing the short-term outcomes of alcohol treatment.

Polycarpou A; Papanikolau P; Ioannidis JPA; Contopoulos-Ioannidis DG. Anticonvulsants for alcohol withdrawal. (review). Cochrane Database of Systemic Reviews (3): CD005064.pub2, 2005. (155 refs.)

Background: Alcohol withdrawal syndrome is a cluster of symptoms that occurs in alcohol-dependent people after cessation or reduction in alcohol use. This systematic review focuses on the evidence of anticonvulsants' use in the treatment of alcohol withdrawal symptoms. Objectives: To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004); MEDLINE (1966 to October 2004); EMBASE (1988 to October 2004) and EU-PSI PSI-Tri database with no language and publication restrictions and references of articles. Selection criteria: All randomized controlled trials examining the effectiveness, safety and overall risk-benefit of an anticonvulsant in comparison with a placebo or other pharmacological treatment or another anticonvulsant were considered. Data collection and analysis: The authors independently assessed trial quality extracted data. Main results: Forty-eight studies, involving 3610 people were included. Despite the considerable number of randomized controlled trials, there was a variety of outcomes and of different rating scales that led to a limited quantitative synthesis of data. For the anticonvulsant versus placebo comparison, therapeutic success tended to be more common among the anticonvulsant-treated patients, and anticonvulsant tended to show a protective benefit against seizures, but no effect reached formal statistical significance. For the anticonvulsant versus other drug comparison, CIWA-Ar score showed non-significant differences for the anticonvulsants compared to the other drugs at the end of treatment. There was a non-significant decreased incidence of seizures favouring the patients that were treated with anticonvulsants than other drugs, and side-effects tended to be less common in the anticonvulsant-group (RR 0.56; 95% CI 0.31 to 1.02). Authors' conclusions: It is not possible to draw definite conclusions about the effectiveness and safety of anticonvulsants in alcohol withdrawal, because of the heterogeneity of the trials both in interventions and the assessment of outcomes. The extremely small mortality rate in all these studies is reassuring, but data on other safety outcomes are sparse and fragmented.

Ribeiro IM; Vale PJ; Tenedorio PA; Rodrigues PA; Bilhoto MA; Pereira HC. Ocular manifestations in fetal alcohol syndrome. European Journal of Ophthalmology 17(1): 104-109, 2007. (10 refs.)

PURPOSE. To report the prevalence of ocular abnormalities in a group of Portuguese children with a complete fetal alcohol syndrome (FAS). METHODS. Complete ophthalmologic examination in a sample of consecutive children with FAS. Ocular fundus photography was carried out on the cooperative FAS children and on 25 reference Children. Ocular fundus anomalies were recorded by the observation of ocular fundus photography. The ratio between the distance of the center of the disc to the fovea and optic disc diameter (DM/DD) was determined. Small optic disc was defined as a DM/DD ratio above mean control group +1 SD. RESULTS. The authors studied 32 children with FAS (mean age: 9 5 years; 72% boys). The mean corrected visual acuity (VA) was 0.8 +/- 0.2. Refraction ranged from -23.00 to +6.50 spherical equivalent. Ocular findings included short horizontal palpebral fissure (81% of children), strabismus (28% of children), epicanthus (27% of eyes), blepharoptosis (16% of eyes), telecanthus (13% of children), nystagmus (1 child), and cataract (1 eye). Ocular fundus photography analysis showed retinal vessel tortuosity in 30% of the eyes and optic disc hypoplasia in 25%. The mean DM/DD for the control and FAS groups was 2.72 +/- 0.20 and 2.89 +/- 0.25 (p=0.001). Forty percent of the eyes of FAS children had small optic discs. CONCLUSIONS. The most common ocular findings were anomalies of retinal fundus and minor changes in the outer region of the eyes. The authors noted better VA and less severity of disease than others, which might be due to a different selection of patients, different Pattern of alcohol consumption, or genetic differences.

Rissmiller DJ; Biever M; Mishra D; Steer RA. Screening detoxifying inpatients with substance-related disorders for a major depressive disorder. Journal of Clinical Psychology in Medical Settings 13(3): 315-321, 2006. (34 refs.)

The Beck Depression Inventory-Fast Screen for Medical Settings (BDI-FS; [Beck, Steer, & Brown, 2000]) and the Mood Module (MM) from the Primary Care Evaluation of Mental Disorders [Spitzer, Williams, Kroenke, Linzer, deGruy, III, Hahn, & Brody, 1995] were used to screen 100 inpatients detoxifying from alcohol, illicit substances, or both for a major depressive disorder (MDD). Receiver operating characteristic (ROC) analyses indicated that both tests were highly and comparably effective in differentiating patients who were and not diagnosed with a MDD; the ROC areas-under-curves for the BDI-FS and MM were, respectively, .87 and .84. A BDI-FS cut-off score of 10 and above had 90% sensitivity and 78% specificity rates, and a MM cut-off score of 7 and above had 90% sensitivity and 72% specificity rates for discriminating patients with and without a MDD. The clinical advantages and disadvantages of both instruments for rapidly screening detoxifying inpatients for clinical depression were discussed.

Rothman RB; Blough BE; Baumann MH. Dual dopamine/serotonin releasers as potential medications for stimulante and alcohol addictions. (review). AAPS Journal 9(1): E1-E10, 2007. (84 refs.)

We have advocated the idea of agonist therapy for treating cocaine addiction. This strategy involves administration of stimulant-like medications (eg, monoamine releasers) to alleviate withdrawal symptoms and prevent relapse. A major limitation of this approach is that many candidate medicines possess significant abuse potential because of activation of mesolimbic dopamine (DA) neurons in central nervous system reward circuits. Previous data suggest that serotonin (5-HT) neurons can provide an inhibitory influence over mesolimbic DA neurons. Thus, it might be predicted that the balance between DA and 5-HT transmission is important to consider when developing medications with reduced stimulant side effects. In this article, we discuss several issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, we discuss evidence supporting the existence of a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Then we summarize studies that have tested the hypothesis that 5-HT neurons can dampen the effects mediated by mesolimbic DA. For example, it has been shown that pharmacological manipulations that increase extracellular 5-HT attenuate stimulant effects produced by DA release, such as locomotor stimulation and self-administration behavior. Finally, we discuss our recently published data about PAL-287 (naphthylisopropylamine), a novel non-amphetamine DA-/5-HT-releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers might be useful therapeutic adjuncts for the treatment of cocaine and alcohol addiction, obesity, and even attention deficit disorder and depression.

Ryan T; Webb L; Meier PS. A systems approach to care pathways into in-patient alcohol detoxification: Outcomes from a retrospective study. Drug and Alcohol Dependence 85(1): 28-34, 2006. (36 refs.)

This paper describes the effects of the adoption of a systems approach to alcohol service delivery by four previously separate organisations in Manchester, UK that commenced in 1997. The study examined a database of 5542 admissions for in-patient detoxification between 1995 and 2003, which permitted the analysis of changes occurring in the composition of the client group after the adoption of the new model. Findings suggest that working with the systems approach resulted in more effective targeting of people with higher levels of alcohol dependency towards in-patient detoxification. Females and people in stable housing also benefited from increased access in the new system. Increases in planned discharges were observed across all demographic variables, although alcohol-dependent males without stable accommodation found it more difficult to access in-patient detoxification after the new model was introduced. We conclude that in comparison to a loose network of services a co-ordinated and managed service system can improve targeting for in-patient detoxification for most people with severe alcohol dependence but may not do so for all who need access.

Sannibale C; Fucito L; O'Connor D; Curry K. Process evaluation of an out-patient detoxification service. Drug and Alcohol Review 24(6): 475-481, 2005. (69 refs.)

This paper describes the process evaluation of an out-patient detoxification service (ODS) established by Drug Health Services (DHS) to increase the supervised withdrawal options for substance users in a Sydney metropolitan Area Health Service. The ODS aimed to provide a safe and effective supervised withdrawal to substance users who were at low risk of severe withdrawal, engage those with severe dependence in further treatment and increase the involvement of general practitioners (GPs) in the medical care of ODS clients. During its first 10 months of operation, the ODS received 199 inquiries, assessed 82 individuals and admitted 76 clients for detoxification. Withdrawal treatment proceeded without complications and within the expected time frames. Fifty-four clients completed withdrawal, 10 ceased treatment, 10 remained in treatment without completing withdrawal and two were transferred elsewhere. Clients who injected substances (mainly heroin) daily at admission, compared to others, were less likely to complete withdrawal and more likely to use a range of non- prescribed substances during withdrawal. One-fifth of clients went on to further treatment with DHS, attending at least once. Overall, the ODS met its goals, providing a safe and effective supervised withdrawal to local residents, especially women, young people and those withdrawing from benzodiazepines who had significant substance dependence, impairment and previous alcohol and other drug (AOD) treatment. Non- injecting substance users benefited most from the ODS in terms of withdrawal completion and ongoing treatment. The level of GP involvement in the conjoint care of ODS clients remained constant over time. The development and expansion of the ODS are discussed.

Seifert J; Peters E; Jahn K; Metzner C; Ohlmeier M; Wildt BT et al. Treatment of alcohol withdrawal: Chlormethiazole vs. carbamazepine and the effect on memory performance. A pilot study. Addiction Biology 9(1): 43-51, 2004. (36 refs.)

Although relatively little attention has been paid to the question how acute alcohol withdrawal might affect cognitive functions, this factor remains of particular interest because it influences psychotherapeutic treatment during detoxification. The clinical outcome and neuropsychological state of 37 inpatients with alcohol withdrawal was investigated in a randomized single-blind approach. Two different medical strategies [chlormethiazole (CMZ) vs. carbamazepine (CBZ)] in the treatment of inpatients with alcohol withdrawal syndrome were compared. Among comparable groups (related to gender, age, initial alcohol level, severity of abuses, severity of initial withdrawal symptoms such as tremor, perspiration, psychomotor agitation, hallucinations, orientation, intelligence, patient demographics), CBZ is just as potent as CMZ in therapy of withdrawal symptoms (circulatory function, vegetative function, psychomotor activity). Patients in both groups showed initial impairments in some neuropsychological tests (d2, Zahlen-Verbundings test, Beck Depression Inventory, Anxiety Sensitivity Index) with significant improvement during detoxification. Additionally, CBZ-treated patients showed significantly better verbal memory performance during the first days of treatment. Without any addictive potential, CBZ therapy could be very supportive in alcohol detoxification. In addition a higher verbal memory performance state could be favourable for a psychotherapeutic approach.

Soyka M; Horak M. Outpatient alcohol detoxification: Implementation efficacy and outcome effectiveness of a model project. European Addiction Research 10(4): 180-187, 2004. (46 refs.)

Background: The aim of the study was to examine the practicability and implementation efficacy of an alcohol outpatient detoxification model and the concomitant 'motivational' psychotherapeutic approach. Method: This was an open prospective study to examine the implementation efficacy, practicability and medical safety of a novel psychotherapy-based, integrated outpatient detoxification model in alcohol-dependent patients. Patients were carefully screened for relevant neuropsychiatric disorders and other exclusion criteria and then seen on a daily outpatient basis for 5-7 days. Patients received psychotropic or other medication, if necessary (CIWA-A score >16). Beside management of withdrawal symptoms, psychotherapeutic interventions were conducted to motivate the patient for further alcohol therapy. Results: Of 557 patients screened 331 entered the program. For medical reasons 226 patients had to be admitted for inpatient detoxification, 122 patients in a special alcohol unit, 101 patients in a general hospital. 198 (60%) of the outpatients received psychotropic medication during treatment. 312 (94%) of these patients successfully completed treatment. 301 (91% of the initial sample) patients entered a consecutive 3-month motivational phase of a two-phase alcohol treatment program. 139 (46%) patients successfully completed the 1-year consecutive outpatient treatment. Conclusions: Outpatient detoxification, at least in a highly structured frame, can be considered as a safe and efficient therapeutic approach. The data of this study also indicate that psychotherapeutic interventions and motivation for further abstinence and treatment may work in alcohol-dependent patients on an outpatient basis. Further controlled trials are necessary to compare the effects of outpatient versus inpatient withdrawal.

Srisurapanont M; Jarusuraisin N. Opioid antagonists for alcohol dependence. (review). Cochrane Database of Systemic Reviews 1(CD001867.pub2), 2005. (71 refs.)

Background: Opioid antagonists can decrease alcohol consumption in animals. Their harms and benefits have been examined in many clinical trials. Objectives: To determine the effectiveness of opioid antagonists in attenuating or preventing the recommencement of alcohol consumption in patients with alcohol dependence in comparison to placebo, other medications and psychosocial treatments. In addition, discontinuation rate, death, patient satisfaction, functioning, health-related quality of life and economic outcomes were also evaluated. Search strategy The specialised register of the Cochrane Group on Drugs and Alcohol was searched until September 2003. The search was integrated with previous searches of Cochrane Controlled Trials Register (Cochrane Library 2001, issue 4), MEDLINE (1966 - October 2001), EMBASE (1980 - December 2001) and CINHAL (182 - December 2001). Du Pont Pharmaceutical and Ivax Corporation were contacted for information regarding unpublished trials. The reference lists of the obtained papers were also examined. Selection criteria All relevant randomised controlled trials (RCTs) were included. Participants were people with alcohol dependence. Naltrexone (NTX), nalmefene (NMF) and other opioid antagonists with/ without other biological or psychosocial treatments were examined. Two primary outcomes were number of participants with relapses (including those who return to heavy drinking) and number of participants who return to drinking. Other outcomes of interest were time to first drink, percentage or number of drinking days, number of standard drinks, craving, percentage or number of days or episodes of heavy drinking, amount of alcohol consumed, discontinuation rate, patient satisfaction, impaired function, health-related quality of life, economic and death. Data collection and analysis: Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis. The Relative Risk with the 95% confidence interval was used to assess the dichotomous data. A weighted (or standardised) mean difference (WMD or SMD) with 95% confidence interval was used to assess the continuous data. Main results The review included 29 RCTs presented in 36 articles. Except two RCTs of nalmefene, all others investigated NTX. In comparison to placebo, a short-term treatment of NTX significantly decreased the relapse [RR (95% CI) = 0.64 (0.51 to 0.82)] and was likely to decrease the return to drinking [ RR (95% CI) = 0.87 (0.76 to 1.00). In the respect of acceptability, NTX treatment significantly diminished treatment withdrawal [RR (95% CI) = 0.82 (0.70 to 0.97). While a medium-term treatment of NTX gave no benefit in the respect of relapse prevention, it was found to be beneficial on two of four secondary outcomes by increasing time to first drink and diminishing craving. A medium-term treatment of NTX was superior to acamprosate in reducing relapses, standard drinks and craving. NTX plus an intensive psychosocial treatment (PST) was not superior to NTX plus a simple PST on any primary and secondary short-term outcomes. For a medium-term treatment, NTX plus an intensive PST was superior to NTX plus a simple PST in increasing time to first drink and decreasing craving. Authors' conclusions The review findings support that short-term treatment of NTX decreases the chance of alcohol relapses for 36% (number-needed-to-treat or NNT = 7) and likely to reduce the chance of returning to drinking for 13% (NNT = 12). In comparison to placebo group, NTX treatment can lower the risk of treatment withdrawal in alcohol-dependent patients for 28% (NNT = 13). Some major limitations of the available evidence include short study duration in many trials, small sample sizes in most trials and lack of data on psychosocial benefits. In conclusion, NTX should be accepted as a short-term treatment for alcoholism. Strategies to improve adherence to NTX treatment, eg, PSTs and management of adverse effects, should be concomitantly given. We have not yet known so far how long alcohol-dependent patients who respond to NTX treatment should continue their treatment. Due to too little evidence, NMF should have no role for the treatment of alcohol dependence.

Stanley KM; Worrall CL; Lunsford SL; Simpson KN; Miller JG; Spencer AR. Experience with an adult alcohol withdrawal syndrome practice guideline in internal medicine patients. Pharmacotherapy 25(8): 1073-1083, 2005. (12 refs.)

Study Objective. To standardize treatment of alcohol withdrawal syndrome (AWS) in internal medicine patients using an adult AWS practice guideline with a symptom-triggered management approach. Design. Prospective interventional (pilot group) and retrospective (control group). Setting. University teaching hospital. Patients. Thirty-two internal medicine patients identified as being at risk for AWS and treated according to the AWS practice guideline who were compared with 49 internal medicine patients managed with nonstandardized approaches. Intervention. Patients in the pilot group were assessed using the AWS type indicator. They received lorazepam, clonidine, or haloperidol, based on AWS type indicator assessment and adult AWS practice guideline criteria. Measurements and Main Results. Data collected and analyzed were drugs administered to control AWS symptoms, use of sitters and physical restraints, length of hospital stay, and discharge from hospital receiving tapered drug therapy. Pilot patients received 46.6% less benzodiazepine (p=0.001), 20% more clonidine (p=0.01), and 18.2% more haloperidol (p=0.002) than control patients. No drug therapy was required in 19% of pilot patients compared with 2% of controls (p=0.01). Significantly more control (71.4%) than pilot patients (18.8%) were discharged with tapered benzodiazepine therapy (p <= 0.01). No significant differences were found between groups for sitters, restraints, or hospital length of stay. Conclusion. This pilot project suggests that internal medicine patients at risk for AWS can be managed with a standardized, symptom-triggered approach using decreased amounts of benzodiazepine in combination with adjunctive agents to treat adrenergic hyperactivity and delirium. Further data are necessary to determine the impact of the practice guideline on patient outcome measurements.

Strobbe S; Brower K; Galen L. Patient satisfaction with outpatient detoxification from alcohol. Journal of Addictions Nursing 15(1): 23-29, 2004. (15 refs.)

Outpatient medical detoxification has become an increasingly common form of treatment for mild to moderate alcohol withdrawal, yet few studies have examined this phenomenon from the patient's perspective. Therefore, we reviewed Patient Satisfaction Survey (PSS) results from each of 57 alcohol-dependent patients who successfully completed a course of outpatient detoxification from among 64 who initiated such treatment in conjunction with an intensive day treatment program (89%). Those who completed detoxification were asked to evaluate specific aspects of clinical care. On a 5-point Likert scale, subjects responded to statements related to safety, comfort, information and instructions about medications, availability of the nurse, and participation in the day treatment program. Additional qualitative feedback was sought through two open-ended questions to determine what was viewed as most helpful, and suggestions for program improvement. High rates of completion and patient satisfaction were realized with outpatient detoxification from alcohol when administered in an intensive day treatment program.

Strobbe S; Brower KJ; Galen LW. Gender and outpatient detoxification from alcohol. Journal of Addictions Nursing 14(1): 19-25, 2003. (27 refs.)

Based on gender, we compared demographics, clinical characteristics, and completion rates for outpatient detoxification from alcohol, using oxazepam in conjunction with an intensive day treatment program. Among 64 consecutive patients, nearly half were female. Women were significantly more likely than men to be Medicaid recipients, to have received past mental health treatment, and to have used illicit substances in the four weeks prior to detoxification. Despite these added risk factors, there were no clinical differences noted between men and women in terms of severity of alcohol withdrawal, completion rates for outpatient detoxification, length of detoxification in days, total oxazepam dose in rag/kg, or transition to continued substance abuse treatment. Overall, 89% of patients completed detoxification. These findings suggest that the clinical course of alcohol withdrawal is similar between women and men, and that women can achieve high rates of completion with outpatient detoxification when administered in a day treatment program.

Sweeney LP; Samet JH; Larson MJ; Saitz R. Establishment of a multidisciplinary health evaluation and linkage to primary care (HELP) clinic in a detoxification unit. Journal of Addictive Diseases 23(2): 33-45, 2004. (26 refs.)

We evaluated the feasibility of establishing a multidisciplinary Health Evaluation and Linkage to Primary care (HELP) clinic at an urban residential detoxification unit. Patients received a clinical evaluation and facilitated linkage to primary medical care including personalized referral, reminders, and appointment rescheduling. Of 235 adults reporting alcohol, cocaine or heroin as first or second drug of choice and without a primary care physician, 178 (76%) received a full HELP clinic evaluation, 35 (15%) some clinic components, and 7 (3%) only a primary care appointment. Of those with a full evaluation, 28% received pneumococcal vaccination, and most received health behavior counseling. Over the subsequent 2 years, 131 (60%) of the 220 patients whom had any contact with the HELP clinic had at least one primary care visit. A multidisciplinary health clinic to evaluate patients during detoxification is feasible and can link patients with substance dependence to primary medical care.

Takeshita J. Use of propofol for alcohol withdrawal delirium: A case report. (letter). Journal of Clinical Psychiatry 65(1): 134-135, 2004. (3 refs.)

Trumpler F; Oez S; Stahli P; Brenner HD; Juni P. Acupuncture for alcohol withdrawal: A randomized controlled trial. Alcohol and Alcoholism 38(4): 369-375, 2003. (30 refs.)

Background and Aims: Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Methods: Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Results: Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. Conclusions: The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

University of York, NHS Centre for Reviews and Dissemination, York, UK. The drug treatment of alcohol withdrawal symptoms. (Cochrane Review of Effects). , 2003. (2 refs.)

Reviewed Source: Williams D, McBride A J, The drug treatment of alcohol withdrawal symptoms: a systematic review. Alcohol and Alcoholism, 1998, 33(2), 103-115. The authors' conclusion was that the methodological design was often poor. Futher research using better methods is needed to allow comparison of different drugs in the treatment of alcohol withdrawal symptoms. Given the available data, a long-acting benzodiazepine should be the drug of first choice. COMMENTARY: The literaturesearch, the inclusion and the method for quality assessment wre described. The data form the included sturides ere preented, but thnumber of patients in each group within the studies was unavailable. the authors' conclusions seemed appropriate. The limitations of the evidence were notd. IN: Cochrane Library, Volume 1 Update Software Oxford

Voris J; Smith NL; Rao SM; Thorne DL; Flowers QJ. Gabapentin for the treatment of ethanol withdrawal. Substance Abuse 24(2): 129-132, 2003. (7 refs.)

Benzodiazepines (BZDs) are the drug of choice for the suppression of alcohol withdrawal symptoms. Gabapentin, a drug approved for use as adjunctive therapy in the treatment of partial seizures, has none of the BZD-type difficulties (drug interactions, abuse potential). We retrospectively report on the use of gabapentin for ethanol withdrawal in 49 patients. Thirty-one patients were treated in the outpatient program and 18 in the general inpatient psychiatric unit. Positive outcomes as evidenced by completion of gabapentin therapy were achieved in 25 out of 31 outpatients and 17 out of 18 inpatients. Statistical significance was reached regarding the positive relationship between prior ethanol use and inpatient "as needed" benzodiazepine use. Both sets of data suggest that gabapentin works well for the mild to moderate alcohol withdrawal patient.

Vorma H; Naukkarinen H; Sarna S; Kuoppasalmi K. Symptom severity and quality of life after benzodiazepine withdrawal treatment in participants with complicated dependence. Addictive Behaviors 29(6): 1059-1065, 2004. (12 refs.)

The aims of the present study were to assess changes in psychopathology and quality of life after withdrawal treatment in participants with benzodiazepine dependence that was in most cases complicated by harmful and hazardous alcohol use or high benzodiazepine doses. Seventy-six participants with benzodiazepine dependence (DSM-III-R) who participated in a randomized clinical trial of two different gradual withdrawal treatment approaches were initially assessed by Symptom Checklist-90 (SCL-90), visual analogue scales (VASs), and the Health-Related Quality of Life battery (HRQOL). The assessments were repeated after treatment ended and again after a follow-up averaging 11 months. During the study, all measurements for the participants with clinically significant (over 50%) benzodiazepine-dose decreases improved more than those for the participants with smaller decreases, and differences in the HRQOL energy/vitality, home management, and life satisfaction scores were significant. Our data indicate that in participants with complicated. benzodiazepine dependence, clinically significant dose decreases are associated with improvements in their self-rated quality of life.

Zimberg S. Alcoholism and substance abuse in older adults. IN: Frances RJ; Miller SI; Mack AH, eds. Clinical Textbook of Addictive Disorders, 3rd edition. New York: Guilford Press, 2005. pp. 396-410. (50 refs.)

This chapter discusses the prevalence of alcoholism and prescription drug abuse among the elderly. Diagnostic approaches are noted, including detection in the general hospital, and age specific approaches to treatment.

Zinn S; Bosworth HB; Edwards CL; Logue PE; Swartzwelder HS. Performance of recently detoxified patients with alcoholism on a neuropsychological screening test. Addictive Behaviors 28(5): 837-849, 2003. (55 refs.)

Objective: Early in recovery from alcoholism, cognitive deficits may compromise patients' utilization of rehabilitative information. Cognitive impairment in a sample of newly detoxified inpatients with alcoholism was examined using the Neurobehavioral Cognitive Status Examination (NCSE). Methods: Consecutively admitted psychiatric inpatients (N=233) with an alcohol-related primary diagnosis (63% male, mean age 46.3) were administered the NCSE following medical stabilization. Within-samples differences between age and diagnostic groups were examined and scores were compared to normative samples. Results: Inpatients older than 50 demonstrated significant cognitive deficits for all scales except Attention. In comparison with normative samples, patients with alcoholism produced lower scores, with the most pronounced deficits among middle-aged patients. In alcohol-abusing patients with medical comorbidities, language deficits and more severe memory deficits were observed. Abuse severity or comorbid psychiatric disorder produced no differences in NCSE scores. Conclusions: Neuropsychological screening following detoxification in patients diagnosed with an alcohol disorder reflected the effects of increased age and medical comorbidity. Our finding of frequent deficits in abstraction, comprehension, and memory suggests that cognitive-behavioral treatments for inpatients may be less effective if cognitive impairment is not considered.

Zullino DF; Krenz S; Zimmerman G; Miozzari A; Rajeswaran R; Kolly S et al. Topiramate in opiate withdrawal- comparison with clonidine and with carbamazepine/mianserin. Substance Abuse 25(4): 27-33, 2005

There are some rationales for developing anticonvulsants for the treatment of substance abuse. The blockade of the AMPA/kainate subtype of glutamate receptor by topiramate may be of particular interest, as preclinical studies of withdrawal from opioids suggest that whilst AMPA-receptor antagonists may not be able to prevent tolerance or dependence from developing, they may ameliorate both physical and emotional consequences of withdrawal. Methods. Ten consecutively admitted patients treated with topiramate were compared in a retrospective naturalistic drug utilization observation study with 10 consecutively admitted patients treated with clonidine and with 10 consecutively admitted patients treated with a carbamazepine/ mianserin combination. Results. In 9 cases of the clonidine group and in 7 carbamazepine/mianserin treated patients the dose had been reduced, whereas this occurred in only 2 topiramate treated patients (p < 0.01). Patients in the topiramate group received less p.r.n. myorelaxant medication than the two other groups, and there was a significant difference between the three groups with regard to p.r.n. analgesics (p < 0.05), topiramate and clonidine treated patients receiving fewer analgesics than the carbamazepine/mianserin group. Conclusions. Compared to clonidine and carbamazepine/mianserin, a detoxification scheme using high initial and then decreasing doses of topiramate appeared to be appropriate for most patients and as associated with less analgesic and myorelaxant comedication, indicating a more promising efficacy at the used doses.