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CORK Bibliography: Detoxification (Alcohol)

49 citations. January 2006 to present

Prepared: September 2009

Elsing C; Stremmel W; Grenda U; Herrmann T. Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit: An open, single-center randomized study. American Journal of Drug and Alcohol Abuse 35(3): 189-192, 2009. (30 refs.)

Background: Clomethiazole (CLO) has been shown to be effective in treating alcohol withdrawal syndrome (AWS). Gamma-Hydroxybutyric acid (GHB) has also been introduced in the treatment of alcoholic patients and is effective in surgical intensive care unit (ICU) patients in preventing and treating AWS. There are no comparative studies between CLO and GHB in a medical ICU setting. Methods: Twenty-six alcoholic patients with severe AWS and concomitant medical diseases were randomally enrolled in the study. CLO was given orally to 12 patients in a dosage of 250 mg every 4 hours as a liquid; GHB (initially 30 mg/kg body weight (BW) followed by 15 mg/kg BW) was administered intravenously to 14 patients. Four major AWS symptoms (tremor, sweating, nausea, restlessness) were scored, and the administration of additional medication was registered. Results: GHB was more effective in treating AWS symptoms. In the GHB group, AWS score dropped from 6.6 2.6 to 1.8 2.1 (p .01), while in the CLO group, the score dropped from 6 2.5 to 4.1 2.4 (n. s.). Differences between groups were significant (p =.021, two-way ANOVA). The treatment did not alter outcome or the duration of ICU stay. No serious side effects were detected. Conclusion: GHB effectively controls AWS symptoms in medical ICU patients. The rapid initial treatment response of GHB in contrast to CLO has no influence on duration of patient withdrawal.

Kampman KM; Pettinati HM; Lynch KG; Xie H; Dackis C; Oslin DW et al. Initiating acamprosate within-detoxification versus post-detoxification in the treatment of alcohol dependence. Addictive Behaviors 34(6-7): 581-586, 2009. (35 refs.)

Objectives: This trial compared the efficacy of acamprosate, started at the beginning of detoxification, to acamprosate started at the completion of detoxification. in the treatment of alcohol dependence. Methods: This biphasic clinical trial consisted of a randomized, double-blind, placebo-controlled Detoxification Phase (DP), followed by a 10-week open-label Rehabilitation Phase (RP). Forty alcohol dependent patients were randomly assigned to receive either 1998 mg of acamprosate daily, or matching placebo. during the DP (5-14 days). After completing cletoxification, all patients received open label acamprosate (1998 mg daily) in the RP. Outcome measures during the DP included: treatment retention, alcohol withdrawal, alcohol consumption, and oxazepam used. Outcome measures during the RP included: treatment retention and alcohol consumption. Results: There were no significant outcome differences between acamprosate and placebo-treated patients during the DP. Patients given acamprosate, compared to placebo, during the DP drank more alcohol in the RP. Conclusions: Starting acamprosate at the beginning of detoxification did not improve DP outcomes. Starting acamprosate after detoxification was completed was associated with better drinking outcomes during subsequent alcohol rehabilitation treatment.

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): 276+, 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.

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.)

Blondell RD; Simons RL; Smith SJ; Frydrych LM; Servoss TJ. Initiation of outpatient treatment after inpatient detoxification. Journal of Addiction Medicine 1(1): 21-25, 2007. (12 refs.)

Additional treatment after inpatient detoxification is recommended; however, many patients fail to initiate aftercare. The purpose of this observational study was to determine which patients hospitalized for alcohol or drug withdrawal subsequently fail to initiate recommended outpatient aftercare treatment by using existing data from medical records. Of 406 patients, 180 (44.3%) did not initiate outpatient aftercare treatment after hospitalization for detoxification. Compared with those who did initiate aftercare, those who did not were less likely to have education beyond high school (44% vs. 32%; P = 0.018), to be enrolled in a managed care health insurance plan (46% vs. 34%; P = 0.013), and to have a family history of chemical dependency (81% vs. 72%; P = 0.049). These values were similar with multiple regression analysis. Of the 406 patients, 11 of 56 (20%) without any of these risk factors, 145 of 314 (46%) with 1 or 2 risk factors, and 24 of 36 (67%) with all 3 of these risk factors did not keep scheduled outpatient appointment for aftercare. These findings suggest that some patients admitted for inpatient detoxification, identifiable by certain admission characteristics, are at risk for failure to link with appropriate outpatient aftercare treatment.

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.

Chabria SB. Inpatient management of alcohol withdrawal: A practical approach. Signa Vitae 3(1): 24-29, 2008. (34 refs.)

Alcohol intake contributes directly or indirectly to 15 to 20% of medical problems in primary care or an inpatient setting. It is estimated that approximately 500,000 episodes of withdrawal will be severe enough to require pharmacologic intervention. The total cost to the United States economy from alcohol abuse was estimated to be $185 billion for 1998. This review attempts to put forth a practical and evidence based approach towards the inpatient management of alcohol withdrawal. Various agents and their pharmacology are described. Strength of evidence regards to efficacy and shorter inpatient stays is examined.

Chandrasekaran PK. Employing mirtazapine to aid benzodiazepine withdrawal. Singapore Medical Journal 49(6): E166-E167, 2008. (10 refs.)

Insomnia and depression are frequently encountered in patients during withdrawal from substances. While there are no approved medications for treating them, off-label attempts to address these phenomena with mirtazapine have shown some promising results. This case describes the use of mirtazapine as an aid in benzodiazepine withdrawal and its potential benefits in alleviating insomnia and depression in a 32-year-old man. It was found to ameliorate sleep myoclonus that was thought to be associated with his withdrawal syndrome. It is hoped this report will generate interest and stimulate further research in this area of psychopharmacology.

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.

Freyer-Adam J; Coder B; Ottersbach C; Tonigan JS; Rumpf HJ; John U et al. The performance of two motivation measures and outcome after alcohol detoxification. Alcohol and Alcoholism 44(1): 77-83, 2009. (20 refs.)

Aims: The aims of this study were to investigate the performance of the treatment version of the Readiness to Change Questionnaire (RCQ[TV]) among individuals currently receiving alcohol detoxification and to develop a treatment version of the Treatment Readiness Tool (TReaT[TV]). Methods: A total of 549 patients (86% men) recruited from two detoxification units were interviewed close to treatment intake and followed up 12 months later. Confirmatory factor analyses and logistic regression analyses were conducted. Results: A modified nine-item version of the RCQ[TV] showed a good fit of the model (CFI = 0.95) and internal consistencies ranging between 0.49 and 0.91. Twelve months later, RCQ-Actors had an odds ratio of 1.95 (95% CI: 1.12-3.37) for being abstinent compared to Precontemplators/Contemplators. The development of the TReaT[TV] resulted in 15 items and 5 scales with a CFI of 0.97 and Cronbach's alphas ranging between 0.59 and 0.94. TReaT[TV] Precontemplators/Contemplators were less likely to utilize help than Maintainers (OR = 0.17, 95% CI: 0.06-0.45). Conclusions: The psychometric properties were modest for the modified RCQ[TV] and good for the TReaT[TV]. Readiness to change and readiness to seek help should be assessed separately among treatment seekers.

Frydrych LM; Greene BJ; Blondell RD; Purdy CH. Self-help program components and linkage to aftercare following inpatient detoxification. Journal of Addictive Diseases 28(1): 21-27, 2009. (11 refs.)

Many patients fail to initiate aftercare for addictive disease rehabilitation following detoxification. This study of 136 inpatients compared characteristics of those who initiated aftercare (behavior therapy or self-help programs) during the week following discharge with those who did not. Among this group of patients, 77% (91/119) linked to aftercare. Self-help treatment related components were associated with increased aftercare treatment attendance rates and included: having a copy of the 12 Steps (81% vs. 46%, P = .002), having read self-help literature (73% vs. 42%, P = .007), and having telephone numbers of self-help program members (50% vs. 18%, P = .008). Those who initiated aftercare treatment were also more likely to have remained abstinent from drugs and alcohol (81% vs. 39%, P .001). Having self-help treatment related components was associated with increased rates of aftercare attendance following hospital inpatient detoxification.

Furieri FA; Nakamura-Palacios EA. Gabapentin reduces alcohol consumption and craving: A randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychiatry 68(11): 1691-1700, 2007. (37 refs.)

Objective: This study examined the efficacy of a 28-day gabapentin treatment in reducing alcohol consumption and craving. Method: A randomized, double-blind, placebo-controlled trial was performed in a Brazilian public outpatient drug treatment center, with 60 male alcohol-dependent subjects with a mean age of 44 years and an average of 27 years of alcohol use, who consumed 17 drinks per day (165-170 g/day) over the past 90 days before baseline and had no other significant medical or psychiatric condition. Subjects were recruited between July 8, 2004, and February 24, 2005. Following screening, 60 subjects were selected and received diazepam and vitamins as treatment for acute withdrawal for at least 7 days. After the detoxification treatment, 30 subjects were randomly assigned to receive gabapentin (300 mg twice daily) for 4 weeks, and 30 subjects, with similar baseline characteristics, were randomly assigned to receive matching placebo tablets for the same period. Results: After 28 days of treatment, the gabapentin group showed a significant reduction in both number of drinks per day and mean percentage of heavy drinking days (p = .02 for both), and an increase in the percentage of days of abstinence (p = .008), compared to the placebo group. Additionally, some improvernent in obsessive-compulsive symptoms was noted in both groups after the treatment, but it resulted in a more pronounced decrease in automaticity of drinking and aspects of craving in the gabapentin group than in the placebo group. Conclusion: Gabapentin reduces alcohol consumption and craving, which may help patients to maintain abstinence. These results, together with the virtual absence of side effects and a favorable safety profile, support gabapentin as a potential drug for the treatment of alcohol withdrawal and dependence.

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.

Griswold KS; Greene B; Smith SJ; Behrens T; Blondell RD. Linkage to primary medical care following inpatient detoxification. American Journal on Addictions 16(3): 183-186, 2007. (15 refs.)

It is important to address the medical problems of individuals admitted for detoxification by arranging for follow-up with primary care physicians after discharge. This was a prospective cohort study of 119 patients admitted for detoxification. Follow-up data were collected over the telephone one week following discharge. Among this group of patients, 72% had a primary care provider (PCP). Patients who intended to see their provider were statistically more likely to be abstinent on follow-up ( OR = 4.5, CI = 1.24-16.58, p = 0.024). As compared to those patients without primary care follow-up, having a plan to see one's PCP was associated with lower rates of relapse following detoxification.

Gruber VA; Delucchi KL; Kielstein A; Batki SL. A randomized trial of 6-month methadone maintenance with standard or minimal counseling versus 21-day methadone detoxification. Drug and Alcohol Dependence 94(1/3): 199-206, 2008. (28 refs.)

Background: Important questions remain regarding the necessary duration and intensity for methadone treatment to be effective. Methods: As part of a clinical trial of tuberculosis chemoprophylaxis [Batki, S.L., Gruber, V.A., Bradley, J.M., Bradley, M., Delucchi, K., 2002. A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users. Drug Alcohol Depend. 66 283-293. doi:10.1016/SO376-8716(01)00208-3], patients with opioid dependence were recruited from an outpatient 21-day methadone detoxification program and were randomly assigned to one of three treatment conditions: (1) continuation in 21-day methadone detoxification; (2) transfer to 6-month methadone maintenance with only minimal counseling; or (3) transfer to 6-month methadone maintenance with standard twice monthly counseling and as-needed social work and psychiatric services. Both the 6-month maintenance treatments were followed by 1.5 months of detoxification. Urine drug tests and self-report measures were collected at baseline, months 1-6, and month 8.5. Results: Compared to 21-day methadone detoxification, 6-month methadone maintenance with either minimal or standard counseling resulted in fewer opiate positive urine tests and days of self-reported heroin and alcohol use. There was no change in cocaine use or other outcome measures. The increased counseling available in the standard counseling condition did not appear to reduce heroin use further than the minimal counseling condition, in contrast to the effect found for more structured counseling in long-term methadone maintenance (McLellan et al., 1993). Conclusions: Six months of methadone maintenance, even with minimal counseling, reduces heroin and alcohol use more than 21-day methadone detoxification.

Gupta M. Alcohol withdrawal and prolonged hospital stay in a patient with neuroimaging abnormalities: A case report. Alcohol and Alcoholism 44(2): 183-184, 2009. (3 refs.)

A hospital stay of 30 days was required in a 47-year-old woman with alcohol withdrawal. Magnetic resonance imaging (MRI) findings revealed a focal brain stem lesion and multiple focal supracortical abnormalities. Could asymptomatic neuroimaging abnormalities predict risk of complicated alcohol withdrawal? Future clinical observations and longitudinal studies may wish to address this potential risk factor.

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.

Johnson ME; Brems C; Mills ME; Fisher DG. Psychiatric symptomatology among individuals in alcohol detoxification treatment. Addictive Behaviors 32(8): 1745-1752, 2007. (16 refs.)

The coexistence of psychiatric symptomatology among individuals receiving longer-term treatment for alcohol use disorders has been well-established; however, less is known about comorbidity among individuals receiving alcohol detoxification. Using the Brief Symptom Inventory [BSI; Derogatis, L. R. (1992). BSI: Administration, scoring, and procedures manual-II. Towson, NID: Clinical Psychometric Research], we compared psychiatric symptomatology among 815 individuals receiving short-term detoxification services with normative data from non-patients, psychiatric patients, and out-of-treatment individuals using street drugs. Findings revealed that individuals in the current sample reported a wide range of psychiatric symptoms with over 80% meeting BSI criteria for diagnosable mental illness. These BSI scores were significantly more severe than those reported by out-of-treatment individuals using street drugs and most closely resembled BSI scores reported for adult psychiatric inpatients. Findings suggest that routine screening for severe mental health symptoms appears warranted in detoxification units. Such screening would greatly increase the chance that coexistence of substance use and other psychiatric disorders would be properly addressed in ongoing treatment.

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.

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.

Kumar CN; Andrade C; Murthy P. A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal. Journal of Studies on Alcohol and Drugs 70(3): 467-474, 2009. (22 refs.)

Objective: For important reasons, lorazepam (Ativan) and chlordiazepoxide (Librium) are both popular treatments for alcohol-withdrawal syndrome. Nevertheless, there is little literature directly comparing the two drugs. A formal comparison is desirable because of pharmacokinetic and other differences that could affect safety and efficacy considerations relevant to practice in developing countries. Method: One hundred consecutive consenting male inpatients in a state of moderately severe, uncomplicated alcohol withdrawal at screening were randomized to receive either lorazepam (8 mg/day) or chlordiazepoxide (80 mg/day) with dosing down-titrated to zero in a fixed-dose schedule across 8 treatment days. Double-blind assessments of withdrawal-symptom severity and impairing adverse events were obtained during treatment and for 4 days afterward. Results: One chlordiazepoxide patient developed withdrawal delirium. Lorazepam and chlordiazepoxide showed similar efficacy in reducing symptoms of alcohol withdrawal as assessed using the revised Clinical Institute Withdrawal Assessment for Alcohol scale. During withdrawal, irritability and dizziness were more common with lorazepam, and palpitations were more common with chlordiazepoxide. No difficulties in drug discontinuation or differences in impairing adverse events were observed with either drug. Conclusions: With the treatment schedule used in this study, lorazepam is as effective as the more traditional drug chlordiazepoxide in attenuating uncomplicated alcohol withdrawal. Lorazepam, therefore, could be used with confidence when liver disease or the inability to determine liver function status renders chlordiazepoxide therapy problematic. The absence of clinically significant withdrawal complications with lorazepam in this large study contrasts with findings from previously published studies and suggests that higher doses of lorazepam than those formerly used may be necessary during alcohol withdrawal.

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.

Leggio L; Kenna GA; Swift RA. New developments for the pharmacological treatment of alcohol withdrawal syndrome. A focus on non-benzodiazepine GABAergic medications. (review). Progress in Neuro-psychopharmacology & Biological Psychiatry 32(5): 1106-1117, 2008. (154 refs.)

Alcohol withdrawal syndrome (AWS) can be a life-threatening condition affecting some alcohol-dependent patients who abruptly discontinue or decrease their alcohol consumption. The main objectives of the clinical management of AWS include: to decrease the severity of symptoms, prevent more severe withdrawal clinical manifestations and facilitate entry of the patient into a treatment program in order to attempt to achieve and maintain long-term abstinence from alcohol. At present, benzodiazepines represent the drugs of choice in the treatment of AWS. However, in line with the possible side effects and addictive properties related to benzodiazepine use, there is growing evidence to suggest that non-benzodiazepine GABAergic compounds represent promising medications in the treatment of alcohol-dependent patients. This review focuses on research into non-benzodiazepine GABAergic medications for the treatment of AWS. Among them, carbamazepine, gabapentin and valproic acid are the most studied. The studies on carbamazepine seem to be the most compelling. Preliminary data have also suggested the possible utility of baclofen and topiramate, although further evidence is needed. The promising results in terms of both safety and efficacy are reported. However, we also note the need of more methodologically controlled studies on a greater number of patients, involving more complicated forms of AWS.

Li X; Sun HY; Puri A; Marsh DC; Anis AH. Factors associated with pretreatment and treatment dropouts among clients admitted to medical withdrawal management. Journal of Addictive Diseases 26(3): 77-85, 2007. (33 refs.)

The aims of this study were to identify factors associated with pretreatment and treatment dropouts among individuals accessing an inpatient medical withdrawal management program (Vancouver Detox). Two thousand five hundred sixty-six unique clients, who were referred to Vancouver Detox over two-year period, were assessed. Demographic and drug related variables were analyzed as possible risk factors, and two multivariate logistic regression analyses were conducted. We found that being males being aboriginal, having no children. no fixed address, alcohol as a preferred substance, and being on methadone maintenance treatment at referral were significantly associated with high pretreatment dropout. Significant risk factors for treatment dropout were: being younger, having HCV infection, having a preferred substance other than alcohol, having opiates as a preferred substance, and being discharged on welfare check issue periods or weekends. These findings may help clinicians and decision-makers to initiate corresponding preventive measures to decrease unnecessary attritions and improve utilization of treatment resources.

Lu L; Liu YL; Zhu WL; Shi J; Liu Y; Ling W et al. Traditional medicine in the treatment of drug addiction. (review). American Journal of Drug and Alcohol Abuse 35(1): 1-11, 2009. (146 refs.)

Aims: To evaluate clinical trials and neurochemical mechanisms of the action of traditional herbal remedies and acupuncture for treating drug addiction. Methods: We used computerized literature searches in English and Chinese and examined texts written before these computerized databases existed. We used search terms of treatment and neurobiology of herbal medicines, and acupuncture for drug abuse and dependence. Results: Acupuncture showed evidence for clinical efficacy and relevant neurobiological mechanisms in opiate withdrawal, but it showed poor efficacy for alcohol and nicotine withdrawal or relapse prevention, and no large studies supported its efficacy for cocaine in well-designed clinical trials. Clinical trials were rare for herbal remedies. Radix Puerariae showed the most promising efficacy for alcoholism by acting through daidzin, which inhibits mitocochondrial aldehyde dehydrogenase 2 and leads to disulfiram-like alcohol reactions. Peyote also has some evidence for alcoholism treatment among Native Americans. Ginseng and Kava lack efficacy data in addictions, and Kava can be hepatotoxic. Thunbergia laurifolia can protect against alcoholic liver toxicity. Withania somnifera and Salvia miltiorrhiza have no efficacy data, but can reduce morphine tolerance and alcohol intake, respectively, in animal models. Conclusions: Traditional herbal treatments can compliment pharmacotherapies for drug withdrawal and possibly relapse prevention with less expense and perhaps fewer side effects with notable exceptions. Both acupuncture and herbal treatments need testing as adjuncts to reduce doses and durations of standard pharmacotherapies.

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.

Nace EP; Tinsley JA. Patients with Substance Abuse Problems: Effective Identification, Diagnosis, and Treatment. New York: W.W. Norton, 2007. (Chapter refs.)

The diagnosis and treatment of substance-abuse disorders are gaining the attention of physicians, with, in a given year, approximately 9% of the U.S. population is found to be dependent on or to abuse alcohol, and almost 4% are dependent on illicit drugs. Nicotine dependence affects some 20% of the population. The book is intended to provide a relatively brief concise overview of the field of substance abuse for the busy practitioner. It reviews the medical literature concerning the basics of addiction and details specific procedures such as detoxification schedules for alcohol, anxiolytic and hypnotic agents, and opioids. Each chapter uses brief vignettes to illustrate concepts, and tables or figures to clarify material. Two special populations are featured in this book: adolescence and late life. It is organized into 10 chapters: (1) Facing the Challenge: Patients with Substance Abuse Problems; (2) Addiction: A Disease of the Reward Pathway; (3) Does the Patient Know Something is Wrong?; (4) Steps to Identification; (5) Making a Diagnosis; (6) Treatment Options; (7) Adolescence (8) Substance Abuse in Late Life; (9) Smoking; and (10) Pharmacologic Treatment.

National Quality Forum. National Quality Consensus Standards for the Treatment of Substance Use Conditions: Evidence-Based Treatment Practices. Washington DC: National Quality Forum, 2007. (24 refs.)

This report grew out of a consensus conference convened by the National Quality Forum. The Executive Summary notes that over the past 15 years, scientific knowledge has substantially increased in respect to treating substance use conditions and that there is growing recognition of substance abuse/dependence as a chronic medical condition. This report assembles a set of 11 detailed, fully specified, evidence-based practices. For each practice the target outcomes are identified, the procedures involved specified, as well as for whom it is intended, the settings in which it is provided, and the personnel involved in providing the services. The practices outlined are applicable across a range of populations, diverse settings, and providers. They fall into four domains - identification of substance use conditions, initiation and engagement in treatment, therapeutic interventions, and continuing care management . These practices include: (1) screening and case finding; (2) adoption of systematic methods and procedures to accomplish case finding; (3) diagnosis and assessment for those with positive screening; (4) brief interventions by a trained clinician; (5) provision of support and other services to promotion initiation of care; (6) management of withdrawal, a necessary precursor of treatment of the substance abuse condition; (7) psychosocial interventions; (8-10) pharmacotherapy for opiate, alcohol and nicotine dependence as an adjunct to psychosocial service; and (11) continuing care management and monitoring. For each of these elements the practice domain is identified, as well as the target outcome, and specification of what is involved. A series of appendices set forth the Members and Board of Directors (drawn from major medical centers, representatives of all major medical professional societies as well as private foundations, and governmental agencies), the members of the Steering Committee and Technical Advisory Panel, selected references, and a summary of the consensus development process.

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.

Nocon A; Berge D; Astals M; Martin-Santos R; Torrens M. Dual diagnosis in an inpatient drug-abuse detoxification unit. European Addiction Research 13(4): 192-200, 2007. (44 refs.)

In Spain, detoxification in general hospitals plays an important role in the medical care of patients. We aim to provide clinicians with information on the prevalence and correlates of psychiatric co-morbidity in drug abusers in detoxification. A sample of 115 substance-abuse inpatients (mean age 31.9 +/- 6.4 years) in a Detoxification Unit of a general university hospital was studied using the Spanish version of the PRISM. Most of the patients had multiple dependence diagnoses and co-morbid axis I or axis II psychiatric disorders. Patients with dual diagnosis showed lower psychosocial functioning than patients without co-morbidity and more dependence diagnoses due to cannabis and sedatives. A total of 80% of the patients successfully completed the detoxification process. The present results enhance the value of detoxification in a general hospital as a first step of the overall treatment strategy.

O'Farrell TJ; Murphy M; Alter J; Fals-Stewart W. Brief family treatment intervention to promote continuing care among alcohol-dependent patients in inpatient detoxification: A randomized pilot study. Journal of Substance Abuse Treatment 34(3): 363-369, 2008. (23 refs.)

Alcohol-dependent patients in inpatient detoxification were randomized to treatment-as-usual (TAU) intervention or brief family treatment (BFT) intervention to promote continuing care postdetoxification. BFT consisted of meeting with the patient and an adult family member (in person or over the phone) with whom the patient lived to review and recommend potential continuing care plans for the patient. Results showed that BFT patients (n = 24) were significantly more likely than TAU patients (n = 21) to enter a continuing care program after detoxification. This was a medium to large effect size. In the 3 months after detoxification, days using alcohol or drugs (a) trended lower for treatment-exposed BFT patients who had an in-person family meeting than for TAU counterparts (medium effect), and (b) were significantly lower for patients who entered continuing care regardless of treatment condition (large effect).

Office of Applied Studies, Substance Abuse and Mental Health Administration. 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.

Prince V; Turpin KR. Treatment of alcohol withdrawal syndrome with carbamazepine, gabapentin, and nitrous oxide. American Journal of Health-System Pharmacy 65(11): 1039-1047, 2008. (40 refs.)

Purpose. To evaluate the potential use of carbamazepine, gabapentin, and nitrous oxide as alternatives to symptom-triggered benzodiazepine administration for the treatment of alcohol withdrawal syndrome (AWS), a literature review was conducted. Summary. English-language reports of clinical trials of these agents in AWS, particularly trials that compared them with benzodiazepines or anticonvulsants or used them as benzodiazepine-sparing therapy, were reviewed. Six randomized, double-blind trials compared carbamazepine with agents used in the United States. The results suggest that carbamazepine may be useful for this indication, particularly in outpatient settings, although adverse effects and drug interactions may limit its usefulness. The role of gabapentin is unclear because of the lack of randomized, double-blind, controlled trials and the conflicting results of existing case series and open-label trials. Two poorly designed trials of nitrous oxide had conflicting results. Conclusion. Because of the limitations in evidence accrued so far, the routine use of carbamazepine and gabapentin for the treatment of AWS cannot be recommended, and nitrous oxide should be avoided for this indication.

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.

Sattar SP; Qadri SF; Warsi MK; Okoye C; Din AU; Padala PR et al. Use of alcoholic beverages in VA medical centers. Substance Abuse Treatment, Prevention, and Policy 1: article 30, 2006. (11 refs.)

Background: Benzodiazepines are the first-line choice for the treatment of alcohol withdrawal syndrome. However, several hospitals continue to provide alcoholic beverages through their formulary for the treatment of alcohol withdrawal. While there are data on the prevalence of this practice in academic medical centers, there are no data on the availability of alcoholic beverages at the formularies of the hospitals operated by the department of Veteran's Affairs. Methods: In this study, we surveyed the Pharmacy managers at 112 Veterans' Affairs Medical Centers (VAMCs) to ascertain the availability of alcohol on the VAMC formularies, and presence or lack of a policy on the use of alcoholic beverages in their VA Medical Center. Results: Of the pharmacy directors contacted, 81 responded. 8 did not allow their use, while 20 allowed their use. There was a lack of a consistent policy across the VA medical centers on availability and use of alcoholic beverages for the treatment of alcohol withdrawal syndrome. Conclusion: There is lack of uniform policy on the availability of alcoholic beverages across the VAMCs, which may create potential problems with difference in the standards of care.

Silins E; Sannibale C; Larney S; Wodak A; Mattick R. Residential detoxification: Essential for marginalised, severely alcohol- and drug-dependent individuals. Drug and Alcohol Review 27(4): 414-419, 2008. (52 refs.)

Introduction and Aims. In an era of health care rationalisation, residential detoxification services catering for drug- and alcohol-dependent homeless people are being closed. The principal findings of a recent evaluation of a non-medicated residential detoxification service are presented. The aims were to describe the characteristics of residents, their experience of admission, rates of withdrawal completion, referral patterns, staff and key informant perceptions of the service and its role within the wider treatment system. Design and Methods. A process evaluation was utilised incorporating interviews with residents (n=80) and key informants (n=13); a survey of all service staff (n=10); and demographic and clinical data for all residents (n=392) admitted over one calendar year. Results. Residents were heavily substance-dependent and marginalised, with many exhibiting substantial mental and physical health impairments. Polydrug use and frequent prior engagement with drug and alcohol services were common. The majority completed withdrawal and were referred to further treatment. Residents who presented for heroin and other opiate withdrawal were more likely than other residents to leave before completing treatment (odds ratio 2.47, 95% confidence interval 1.48-4.15). Information from key informants, service staff and residents converged in underscoring the important role performed by the service. Discussion and Conclusion. Out-patient detoxification for homeless and severely drug- and alcohol-dependent populations is unrealistic. For this group, access to residential detoxification is vital as it provides an environment where potentially serious medical and psychological complications can be managed. There continues to be a clear role for supervised withdrawal in such a setting.

Stanley KM; Worrall CL; Lunsford SL; Couillard DJ; Norcross ED. Efficacy of a symptom-triggered practice guideline for managing alcohol withdrawal syndrome in an academic medical center. Journal of Addictions Nursing 18(4): 207-216, 2007. (20 refs.)

This paper describes our experience with an evidence-based Adult Alcohol Withdrawal Syndrome Practice Guideline in an academic medical center. Combined data from two pilot studies demonstrate the efficacy of this approach for hospitalized patients. One hundred-six guideline-managed patients (pilot) were compared with 82 non-guideline managed patients (control). Pilot patients received significantly less benzodiazepine and significantly more clonidine. Significantly more pilot (34%) than control patients (11%) required no drug therapy to manage or prevent AWS symptoms. Adverse events were similar between groups. Control patients required significantly more sitters. These data suggest that hospitalized patients at risk for AWS can be effectively managed with a standardized, symptom-triggered approach.

Stepanyan TD; Farook JM; Kowalski A; Kaplan E; Barron S; Littleton JM. Alcohol withdrawal-induced hippocampal neurotoxicity In vitro and seizures In vivo are both reduced by memantine. Alcoholism: Clinical and Experimental Research 32(12): 2128-2135, 2008. (77 refs.)

The ethanol withdrawal (EWD) syndrome is typically treated using benzodiazepines such as diazepam. However there is concern that benzodiazepines may not prevent neurotoxicity associated with EWD. Antagonists of glutamate/N-Methyl-D-Aspartate receptors (NMDARs) such as MK801 have been shown to be effective against both EWD-induced neurotoxicity in vitro and seizures in vivo. However, most of these agents have adverse side effects. An exception is the moderate affinity NMDAR channel blocker memantine, used in Alzheimer's dementia. The present studies examined the ability of memantine to protect against EWD-related toxicity in vitro and seizures in vivo. Organotypic hippocampal slice cultures from neonatal rat pups were treated starting at 15 days in vitro with 100 mM ethanol for 10 days followed by a 24-hour EWD period. During the 24-hour EWD period cultures were treated with memantine (15 or 30 mu M). MK801 (10 mu M) was utilized as a positive control. For the in vivo studies, the ability of memantine (2, 5, 10, and 15 mg/kg) to reduce convulsions was analyzed in Swiss-Webster mice using the handling induced convulsion test paradigm. In vitro studies demonstrated that memantine is effective at blocking EWD-induced neurotoxicity. In vivo experiments showed that memantine also significantly reduced convulsions induced by EWD in mice. Memantine may be of therapeutic value during alcohol detoxification by virtue of its having neuroprotective effects in addition to anti-seizure activity. The potential role of memantine in treatment of alcoholism is deserving of further study.

Thombs DL. Introduction to Addictive Behaviours, 3rd ed. Binghamton NY: Guilford Press, 2006

This new edition provides on overview on addictive behavior and professional care. It begins by outlining the multiple approaches to addictive behavior. Chapter 2 focuses upon the disease model, its basic elements, the phenomenon of tolerance and withdrawal, and effects on the brain. Chapter 3 reviews public health approaches and prevention; chapter 4 addresses the construct of co-morbidity. The next three chapters examine the contributions of psychoanalytic approaches, conditioning models and cognitive models. The three concluding chapters examine the family system, social and cultural influences in the emergency of substance use problems, concluding with a description of those factors that facilitate and inhibit change.

Vandivort R; Teich JL; Cowell AJ; Chen H. Utilization of substance abuse treatment services under Medicare, 2001-2002. Journal of Substance Abuse Treatment 36(4): 414-419, 2009

In 2006, the Medicare program covered 37 million elderly persons and 7 million persons younger than 65 years, but little is known about substance abuse (SA) service utilization. Using the 5% Sample of Medicare claims data, the study examines individuals who used SA detoxification ("detox") and/or rehabilitation ("rehab") services under Medicare in 2001 and 2002. SA claimants less than 65 years of age (disabled) were compared to claimants more than 65 years of age (elderly). The disabled were more likely to have a co-occurring mental disorder than elderly claimants (50% vs. 14%) and more likely to have serious mental illness (21% vs. 2.3%). Disabled claimants were more than three times as likely to receive any detox service as elderly claimants (17% vs. 6%). The rate of claimants receiving rehab services within 30 days of detox is about one third for disabled claimants and one quarter for elderly claimants.

Weaver M; Jewell C; Tomlinson J. Phenobarbital for treatment of alcohol withdrawal. (editorial). Journal of Addictions Nursing 20(1): 1-5, 2009. (32 refs.)

Weinberg JA; Magnotti LJ; Fischer PE; Edwards NM; Schroeppel T; Fabian TC et al. Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: Results of a randomized trial. Journal of Trauma, Injury, Infection and Critical Care 64(1): 99-104, 2008. (21 refs.)

Background: Although benzodiazepines are the recommended first-line therapy for the prevention of alcohol withdrawal syndrome (AWS), the administration of intravenous ethanol as an alternative prophylactic agent persists in many surgical ICUs. Advocates of this therapy argue that ethanol provides effective prophylaxis against AWS without the excessive sedation observed with benzodiazepine therapy. No study to date, however, has compared the two therapies with regard to their sedative effects. The purpose of this study was to prospectively evaluate the efficacy of intravenous ethanol compared with benzodiazepines for the prevention of AWS with particular emphasis on the sedative effects of each therapy. Methods: During a 15-month period, trauma patients admitted to the ICU with a history of chronic daily alcohol consumption greater than or equal to five beverage equivalents per day were prospectively randomized to one of two 4-day prophylactic regimens: intravenous ethanol infusion (EtOH) versus scheduled-dose diazepam (BENZO). Patients were evaluated with the Riker sedation-agitation scale, a 7-point instrument for the subjective assessment of both sedation (1 = unarousable) and agitation (7 = dangerous agitation). According to protocol, regimens were titrated to achieve and maintain a Riker score of 4 (calm and cooperative). Deviation from a score of 4 during the course of treatment was compared between groups. Results: Fifty patients met study criteria and were randomized after obtainment of informed consent (EtOH, n = 26; BENZO, n = 24). Overall, the EtOH group had a significantly greater proportion of patients who deviated from a score of 4 during the course of treatment (p = 0.020). In both groups, the majority of deviation from a score of 4 reflected periods of under-sedation rather than over-sedation. One patient in the EtOH group failed treatment, requiring diazepam and haloperidol for control of AWS symptoms as per protocol, whereas no patient in the BENZO group failed treatment (p = NS). Conclusion; Concerning the prophylaxis of AWS, intravenous ethanol offers no advantage over diazepam with respect to efficacy or adverse sedative effects. The purported benefit of intravenous ethanol as a prophylactic agent against AWS was not evident.

Wright TM; Myrick H; Malcolm R; Randall P; Boyle E; Henderson S et al. Impact of lifetime alcohol quit attempts and medicated detoxifications on time to relapse during an index alcohol detoxification. Journal of Addiction Medicine 1(1): 15-20, 2007

Previous work has shown that multiple medication-treated alcohol detoxifications are associated with poorer treatment outcomes during subsequent detoxifications. Little is known about the impact of nonmedicated attempts to stop drinking outside the realm of these medically supervised detoxifications on acute detoxification outcomes. This study included 58 subjects enrolled in an outpatient detoxification study. Subjects were asked why and how often they quit alcohol for 3 days or longer during their drinking lifetime using concepts derived from the Cognitive Lifetime Drinking History. The effect of previous attempts at abstinence (both medicated and nonmedicated) on time to relapse during an index detoxification was examined. After the index detoxification, older individuals relapsed later than younger individuals and the number of previous medicated detoxifications rather than total lifetime quit attempts per se was related to quicker relapse. Contrary to expectation, those who reported fewer previous nonmedicated quit attempts tended to relapse sooner than those who reported more past quit attempts. This study supports and extends previous work that suggests that the number of previous medicated detoxifications, rather than the total number of past attempts at abstinence, predicts higher and sooner risk for early relapse drinking during outpatient alcohol detoxification.

Yaldizli O; Euler S; Willi B; Wiesbeck GA; Wurst FM. Spontaneous spinal subarachnoid haemorrhage: A complication of alcohol withdrawal therapy. Drug and Alcohol Review 27(4): 429-432, 2008. (35 refs.)

Background. Non-traumatic spontaneous idiopathic spinal subarachnoid haemorrhage (SSH) is extremely rare. So far, only 12 cases have been described in the literature and there are no data regarding the association between alcohol dependence and SSH. Case Summary. We report the first case of an alcohol-dependent patient with an idiopathic non-traumatic cervical subarachnoid haemorrhage after alcohol withdrawal therapy. Conclusions. Clinicians should be aware of alcohol dependence as an independent risk factor for not only intracranial, but subarachnoid haemorrhage. We recommend performing spinal imaging in alcoholics with sudden onset of severe neck or back pain, even if neurological deficits are absent or coagulation parameters are normal.