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CORK Bibliography: Detoxification (Alcohol)

31 citations. January 2009 to present

Prepared: September 2012

Amato L; Minozzi S; Davoli M. Efficacy and safety of pharmacological interventions for the treatment of the alcohol withdrawal syndrome. (review). Cochrane Database of Systematic Reviews 6(e-article CD008537), 2011. (43 refs.)

Background: Alcohol abuse and dependence represents a very serious health problem worldwide with major social, interpersonal and legal interpolations. Pharmacological treatments presently used are of uncertain effectiveness and there is even more doubt on the comparative effects and value for money. Objectives: To summarize Cochrane reviews that assess the effectiveness and safety of pharmacological interventions in the treatment of alcohol withdrawal. Methods: We searched the Cochrane Database of Systematic Reviews (30 November 2010). Two authors independently screened, extracted data, summarised key characteristics of the included reviews and assessed their quality using AMSTAR; the quality of the evidence was summarised according to the GRADE methodology. Main results: Five reviews, 114 studies, 7333 participants, satisfied criteria for inclusions. The outcomes considered were alcohol withdrawal seizures, adverse events and dropouts. Comparing the five treatments with placebo, benzodiazepines performed better for seizures, three studies, 324 participants, RR 0.16 (95% CI 0.04 to 0.69), moderate quality of evidence. Comparing each of the five treatments versus specific class of drugs, benzodiazepines performed better than antipsychotics for seizures, 4 studies, 633 participants, RR 0.24 (95% CI 0.07 to 0.88) high quality of the evidence. Comparing different benzodiazepines and anticonvulsants among themselves, 28 comparisons, results never reached statistical significance but chlordiazepoxide performed better. The quality of evidence was high for 3% of the results, moderate for 28%, low for 48% and very low for 20%. Authors' conclusions: Among the treatments considered, benzodiazepines showed a protective benefit against seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with antipsychotics. Nevertheless, no definite conclusions about the effectiveness and safety of benzodiazepines were possible, because of the heterogeneity of the trials both in interventions and in the assessment of outcomes. Data on potential harms are sparse and fragmented. Results do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS, but anticonvulsants seem to have limited side effects. There is also not enough evidence of effectiveness and safety of baclofen, because only one study consider this treatment and of GHB for which no strong differences were observed in the comparisons with placebo, benzodiazepines and anticonvulsants.

Barrons R; Roberts N. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. Journal of Clinical Pharmacy and Therapeutics 35(2): 153-167, 2010. (27 refs.)

Objective: The goal of this review is to evaluate the efficacy and safety of carbamazepine and oxcarbazepine in treatment of alcohol withdrawal syndrome (AWS) and determine the role in therapy of both agents. Methods: Relevant literature was identified through a search of MEDLINE (1966-June 2008), PubMed (1966-June 2008); Cochrane database was performed to identify English-language publications. Search terms included carbamazepine, oxcarbazepine, AWS, alcoholism, substance syndrome withdrawal. Results: In seven studies, including 612 patients, carbamazepine demonstrated significant reduction in alcohol withdrawal scores. However, in comparative trials with a benzodiazepine agent, carbamazepine's ability to prevent alcohol withdrawal seizures (OR = 0 center dot 93; 95% CI = 0 center dot 06-14 center dot 97, P = NS) and delirium tremens (DTs; OR = 1 center dot 25; 95% CI = 0 center dot 28-5 center dot 64, P = NS) was uncertain as a result of insufficient patient enrolment. In three trials, carbamazepine failed to reduce alcohol withdrawal symptoms possibly as a result of delayed administration, inadequate dosage or inadequate sample size. At daily doses of 800 mg either fixed or tapered over 5-9 days, carbamazepine was well tolerated, and safely administered when blood alcohol concentration dropped below 0 center dot 15%. The role of oxcarbazepine in AWS is undefined because of inconsistent findings in two trials. Conclusion: Carbamazepine has demonstrated safety, tolerability and efficacy in treatment of moderate to severe symptoms of alcohol withdrawal in the inpatient setting. However, trials of carbamazepine provide inconclusive evidence for prevention of alcohol withdrawal seizures and DTs in comparison with benzodiazepines. Benzodiazepines remain the primary treatment of moderate to severe AWS.

Bonnet U; Hamzavi-Abedi R; Specka M; Wiltfang J; Lieb B; Scherbaum N. An open trial of gabapentin in acute alcohol withdrawal using an oral loading protocol. Alcohol and Alcoholism 45(2): 143-145, 2010. (16 refs.)

Aims: Anticonvulsants are increasingly being advocated for the treatment of acute alcohol withdrawal syndrome (AWS) to avoid the addictive properties of established medications. Because earlier works showed that moderate gabapentin doses were too low to clearly ameliorate severe AWS, we tested a higher gabapentin entry dose. Methods: Inpatients (n = 37) with severe alcohol withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-AR) score >= 15 points) were given gabapentin 800 mg, and if their symptom score reduced within 2 h, they were termed 'early responders' and were then treated for 2 days with 600 mg gabapentin q.i.d. (i.e. a total of 3200 mg in the first 24 h) before beginning a taper. Results: Twenty-seven (73%) were early responders (baseline CIWA-AR improved from 17.3 +/- 2.6 to 8.0 +/- 3.6 points). In the remaining 10 patients, baseline CIWA-AR deteriorated within 2 h (from 20.1 +/- 4.6 to 21.5 +/- 4.65 points). These patients were switched to clomethiazole (n = 4) or clonazepam (n = 6), which is the usual treatment. Three of the 'early responders' worsened in the next 36 h and were then reclassified and treated as 'non-responders'. Among them, two developed an epileptic seizure. Conclusion: Oral 800 mg gabapentin (loaded up to 3200 mg in the first 24 h) is helpful only in reducing less severe and less complicated acute AWS.

Corfee FA. Alcohol withdrawal in the critical care unit. (review). Australian Critical Care 24(2): 110-116, 2011. (48 refs.)

Managing acute alcohol withdrawal in critical care presents a unique challenge to the critical care nurse. The prominence of alcohol use within the Australian community means that many critical care admissions involve acute alcohol withdrawal, an alcohol induced illness, or indeed an unrelated admission with underlying heavy alcohol intake. Current statistics suggest 1 in 5 Australians drink to 'risky' levels each month. This suggests that most critical care nurses will encounter a patient who is experiencing active withdrawal from alcohol, often without clear physiological symptomatology. Acute alcohol withdrawal delirium can be difficult to distinguish from other forms of delirium and in the absence of a comprehensive history, alcohol withdrawal and its sequelae may go untreated. Contemporary management guidelines for alcohol withdrawal suggest a common framework of first line benzodiazepine usage, with emerging research focusing on adjunctive therapy aimed at reducing benzodiazepine doses, and therefore reducing length of stay in the critical care unit. The controversial therapy of ethanol infusion and common assessment and withdrawal scales are examined in relation to their usefulness in critical care. Alcohol withdrawal management in critical care necessitates careful nursing assessment, including alcohol usage history, delirium management, withdrawal assessment and symptomatic relief using an evidence-based protocol.

de Millas W; Ganzer F; Kuhn S; Haasen C. Oxazepam versus clomethiazol in alcohol withdrawal treatment. European Addiction Research 16(4): 179-184, 2010. (22 refs.)

The pharmacological management of the alcohol withdrawal syndrome associated with alcohol dependence is heterogeneous; however, according to the guidelines, clomethiazol is the standard medication in Germany. Benzodiazepines offer another safe possibility of treating alcohol withdrawal. In a retrospective study, alcohol-dependent patients treated either with oxazepam (n = 141) or clomethiazol (n = 357) were assessed with respect to the course of treatment and withdrawal symptoms. The results showed that under oxazepam treatment, there were fewer days with severe alcohol withdrawal symptoms and less severe adverse events, but patients receiving clomethiazol treatment had a more severe course of alcohol dependence. Oxazepam is a safe, efficient and cheap drug for the treatment of alcohol withdrawal symptoms, but controlled studies are needed to compare its effectiveness with that of clomethiazol.

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.

Finn KM; Greenwald J. Hospitalists and alcohol withdrawal: Yes, give benzodiazepines but is that the whole story? (editorial). Journal of Hospital Medicine 6(8): 435-437, 2011. (32 refs.)

Ford LK; Zarate P. Closing the gaps: The impact of inpatient detoxification and continuity of care on client outcomes. Journal of Psychoactive Drugs Supplement 6: 303-314, 2010. (13 refs.)

Inpatient detoxification is a critical element of the continuum of care for chemically dependent individuals, especially for those unable to establish sobriety on an outpatient basis. This study evaluated the impact of one such detoxification program on client outcomes during the year after detoxification. The program was a public/private partnership between Ventura County, California, and Tarzana Treatment Center in Los Angeles. Before admission, applicants agreed to enroll in treatment after detoxification. Clients were contacted at one month post-admission and quarterly thereafter for one year to collect data, corroborated by county records, on treatment and outcome variables. The sample included 117 consecutive admissions between July 2007 and June 2009. Detoxification completion rates and follow-up treatment enrollment rates were substantial: 85% of the sample completed detoxification; 71% enrolled in treatment afterward. Client outcomes were positive, particularly for those enrolled in follow-up treatment: compared to clients not completing detoxification, and to client functioning in the year before admission, sobriety and employment rates increased, and rates of homelessness, arrests and days incarcerated decreased. The study concludes that public investment in inpatient detoxification services and aftercare is an effective means to decrease both individual and societal costs of addiction.

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.

Gilbertson R; Boissoneault J; Prather R; Nixon SJ. Nicotine effects on immediate and delayed verbal memory after substance use detoxification. Journal of Clinical and Experimental Neuropsychology 33(6): 609-618, 2011. (54 refs.)

Decrements in verbal memory are commonly reported by detoxified treatment-seeking individuals. Although acute nicotine has been shown to improve attentional performance, its effects on verbal memory in substance abusers have not been addressed. Treatment-seeking alcohol-dependent (ALCs, n = 29; 14 male), illicit-stimulant-dependent (predominantly cocaine; STIMs, n = 25; 15 male), and alcohol-and illicit-stimulant-dependent (ALC/STIMs, n = 50; 35 male) participants with comorbid nicotine dependence were studied. Subjects had been abstinent from their drugs of choice for 41 (+/- 18) days and were in short-term abstinence from tobacco (similar to 8-10 hours). Subjects received double-blind administration of either transdermal nicotine (high dose: 21/14 mg for men and women, respectively, or low dose: 7 mg) or placebo. The Logical Memory (LM) subtest from the Wechsler Memory Scale-Revised (WMS-R) was used to assess immediate and delayed verbal memory recall. Results indicated that STIMs receiving the high dose of nicotine recalled more words at immediate recall than STIMs who received placebo. Trend level differences were also noted at delayed recall between STIM nicotine and placebo doses. Nicotine failed to impact either recall in alcoholic subgroups. Although not the primary focus, results also revealed differences in the forgetting rates between the groups with the ALC/STIMs demonstrating the steepest forgetting slope. In summary, this study suggests that nicotine effects may be differentially experienced by substance-using subgroups; that nicotine may have a direct effect on memory; and that in considering neurocognitive processes (e. g., encoding vs. retrieval), underlying endpoint indicators (e. g., correct recall) may be critical in predicting outcomes.

Gilchrist G; Langohr K; Fonseca F; Muga R; Torrens M. Factors associated with discharge against medical advice from an alcohol and drug inpatient detoxification unit in Barcelona between 1993 and 2006. Heroin Addiction and Related Clinical Problems 14(1): 35-43, 2012. (31 refs.)

Records from 1,228 consecutively admitted patients (74.5% male) to an inpatient detoxification unit in Barcelona between 1993 and 2006 were examined to determine factors associated with discharge against medical advice (AMA). 21.5% of admissions were discharged AMA. In multiple logistic regression and compared with patients who were medically discharged, those discharged AMA were younger, more likely to be dependent on heroin, other opiates, cocaine or psychostimulants, or to be experiencing reduction or elimination methadone maintenance therapy [reference category: alcohol]. The provision of assistance to clinicians in identifying the patients who are most at risk of leaving inpatient detoxification AMA will enhance their ability to motivate such patients to stay in treatment.

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.

Haley SJ; Dugosh KL; Lynch KG. Performance contracting to engage detoxification-only patients into continued rehabilitation. Journal of Substance Abuse Treatment 40(2): 123-131, 2011. (48 refs.)

In 2006, only 18.7% of Delaware's detoxification patients were admitted to continuing recovery-oriented treatment within 30 days after discharge. In response, Delaware established financial contingencies to (1) maintain 90% detoxification occupancy, (2) make receipt of 10% of the facility's monthly reimbursement contingent on 25% of patients entering treatment, and (3) provide a $500 bonus for every patient with three or more prior detoxification visits who was retained in treatment. Under the performance contract, the detoxification provider (1) maintained the 90% occupancy requirement, (2) achieved the 25% treatment entry target for 7 of 12 months, and (3) observed only 8% (27/337) of detoxification completions that met the targeted length of stay. Continuation to and retention in treatment was even more constrained for patients with three or more prior detoxifications. Contrary to the policy intent, the number of patients with three or more detoxifications in fiscal year (FY) 2008 is nearly triple that of FY 2006. The modest gain in the transition rate was achieved without changes in patient access; the FY 2008 patient population reported significantly higher rates of homelessness and a younger age of first use than before the performance contract in FY 2006. Performance contracting may offer promise for improving transition to treatment rates. However, the unique needs of detoxification patients, the treatment capacity of each level of care to meet patient needs, and the structure of the performance contract must be carefully considered. Performance contracting efforts may be strengthened when service contracts across the system are tightly synchronized.

Hendey GW; Dery RA; Barnes RL; Snowden B; Mentler P. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. American Journal of Emergency Medicine 29(4): 382- 385, 2011. (9 refs.)

Objective: The aim of this study was to compare phenobarbital (PB) versus lorazepam (LZ) in the treatment of alcohol withdrawal in the emergency department (ED) and at 48 hours. Methods: Prospectively, randomized, consenting patients were assessed using a modified Clinical Institute Withdrawal Assessment (CIWA) score and given intravenous PB (mean, 509 mg) or LZ (mean, 4.2 mg). At discharge, LZ patients received chlordiazepoxide (Librium), and PB patients received placebo. Results: Of 44 patients, 25 received PB, and 19 LZ. Both PB and LZ reduced CIWA scores from baseline to discharge (15.0-5.4 and 16.8-4.2, P < .0001). There were no differences between PB and LZ in baseline CIWA scores (P = .3), discharge scores (P = .4), ED length of stay (267 versus 256 minutes, P = .8), admissions (12% versus 16%, P = .8), or 48-hour follow-up CIWA scores (5.8 versus 7.2, P = .6). Conclusion: Phenobarbital and LZ were similarly effective in the treatment of mild/moderate alcohol withdrawal in the ED and at 48 hours.

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.

Keys VA. Alcohol withdrawal during hospitalization. American Journal of Nursing 111(1): 40-44, 2011. (10 refs.)

For a chronic drinker, sudden alcohol withdrawal because of an unexpected hospitalization can lead to escalating withdrawal symptoms and even death if unrecognized and untreated. Nurses need to be aware of the prevalence of alcohol abuse in the United States and consider the possibility of unplanned alcohol withdrawal in their patients. This article discusses the effects on the body of chronic alcohol intake, the potential symptoms of alcohol withdrawal, and ways to recognize and treat these symptoms through early assessment and consistent intervention.

Khalil RB. Tizanidine for alcohol withdrawal treatment. Medical Hypotheses 77(4): 548-549, 2011. (21 refs.)

The noradrenergic system is an important neurotransmission system implicated in the occurrence of alcohol withdrawal symptoms and anxiety leading to relapse during abstinence from alcohol usage. Tizanidine can play a role in alcohol withdrawal since it interferes with the noradrenergic system neurotransmission. Many noradrenergic system inhibitors in the central nervous system have proven their efficacy in the treatment of alcohol withdrawal syndrome. Imidazoline receptors have been also implicated in the pathophysiology of addiction. Tizanidine is an alpha 2-adrenoreceptor agonist that inhibits noradrenaline release and binds to imidazoline receptors. It is used as an antispastic agent due to its central action on noradrenergic system. Although Tizanidine has been tested as a treatment for opioid withdrawal it has not been tried in alcohol withdrawal yet. A theoretical rationale supports the fact that it can be an efficient treatment for the alcohol withdrawal syndrome as well as for the prevention of relapses.

Kork F; Neumann T; Spies C. Perioperative management of patients with alcohol, tobacco and drug dependency. Current Opinion in Anesthesiology 23(3): 384-390, 2010. (73 refs.)

Purpose of review: One in five patients in the perioperative setting has a alcohol use disorder (AUD), one in three patients has a nicotine use disorder (NUD) and one in 10 patients has a drug use disorder (DUD) with a high risk of dependency. Patients with dependencies challenge physicians with various complications within the perioperative setting. Recent findings: Adequate treatment of alcohol, nicotine and drug dependency during the perioperative and intraoperative course requires established screening tools in order to evaluate patients' susceptibility to developing complications. Particularly in these patients, secondary prevention and early treatment is warranted. Summary: Alcohol, nicotine and drug dependency are very treatable. Numerous effective therapeutic options are available and should be offered to patients. Intensive care treatment can be shortened or even avoided by initiating preventive measures. A multimodal approach includes implementation of screening tools, motivational interviewing, preoperative abstinence, individual anaesthesiological treatment, stress reduction preventing delirium and postoperative infection, prevention and treatment of withdrawal syndrome, replacement therapies and provision of preoperative or postoperative detoxification. The implementation rate is very low and urgently requires strategies for improvement.

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.

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.

Lyon JE; Khan RA; Gessert CE; Larson PM; Renier CM. Treating alcohol withdrawal with oral baclofen: A randomized, double-blind, placebo-controlled trial. Journal of Hospital Medicine 6(8): 469-474, 2011. (29 refs.)

BACKGROUND: Abrupt cessation of alcohol intake causes habituated drinkers to experience symptoms of alcohol withdrawal syndrome (AWS). OBJECTIVE: To determine the effect of the gamma-aminobutyric acid (GABA)-B agonist baclofen on the course of acute symptomatic AWS. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical study. SETTING: Two tertiary-care hospitals in Duluth, Minnesota. PATIENTS: Inpatient adults admitted for any reason (including AWS) judged to be at high risk for AWS. INTERVENTION: Inpatients who developed symptoms of AWS received symptom-triggered benzodiazepine treatment using lorazepam by standard protocol, and were randomized to receive baclofen 10 mg or placebo, 3 times per day, orally. MEASUREMENTS: AWS severity was assessed using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar); lorazepam dose was monitored. RESULTS: Seventy-nine subjects were enrolled. The 44 subjects who developed symptoms of AWS were randomized to baclofen or placebo. Thirty-one subjects (18 baclofen, 13 placebo) completed 72 hours of assessments, either entirely as inpatients or with outpatient follow-up. The need for high doses of benzodiazepines (20 mg or more of lorazepam over 72 hours) to control AWS was less likely in the baclofen treatment group (1 of 18) than in the placebo-treated group (7 of 13) (P = 0.004). CONCLUSIONS: We found that the use of baclofen was associated with a significant reduction in the use of high doses of benzodiazepine (lorazepam) in the management of symptomatic AWS. The use of low-dose baclofen in the management of AWS deserves further study, as reduced dependence on high-dose benzodiazepines in AWS management could improve patient safety.

Mannelli P; Peindl K; Patkar AA; Wu LT; Tharwani HM; Gorelick DA. Problem drinking and low-dose naltrexone-assisted opioid detoxification. Journal of Studies on Alcohol and Drugs 72(3): 507- 513, 2011. (42 refs.)

Objective: The influence of alcohol use on opioid dependence is a major problem that warrants a search for more effective treatment strategies. The addition of very-low-dose naltrexone (VLNTX) to methadone taper was recently associated with reduced withdrawal intensity during detoxification. In a secondary analysis of these data, we sought to determine whether problem drinking affects detoxification outcomes and whether symptoms are influenced by VLNTX use. Method: Opioid-dependent patients (N = 174) received naltrexone (0.125 or 0.250 mg/day) or placebo in a double-blind, randomized design during methadone-based, 6-day inpatient detoxification. Alcohol consumption was assessed at admission using the Addiction Severity Index and self-report. Outcome measures were opioid withdrawal intensity, craving, and retention in treatment. Results: Problem drinking opioid dependent patients (n = 79) showed episodic heavy alcohol use and reported increased subjective opioid withdrawal intensity (p = .001), craving (p =.001), and significantly lower rate of retention in treatment (p = .02). Individuals with problem drinking and opioid dependence who were treated with VLNTX (n = 55) showed reduced withdrawal (p = .05) and a lower rate of treatment discontinuation (p = .03), resuming alcohol intake in smaller numbers the day following discharge (p = .03). Treatment effects were more pronounced on anxiety, perspiration, shakiness, nausea, stomach cramps, and craving. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Conclusions: Heavy drinking is associated with worse opioid detoxification outcomes. The addition of VLNTX is safe and is associated with reduced withdrawal symptoms and better completion rate in these patients. Further studies should explore the use of VLNTX in detoxification and long-term treatment of combined alcohol-opioid dependence and alcohol dependence alone.

Maremmani AGI; Pani PP; Rovai L; Pacini M; Dell'Osso L; Maremmani I. Long-term gamma-hydroxybutyric acid (GHB) and Disulfiram combination therapy in GHB treatment-resistant chronic alcoholics. International Journal of Environmental Research and Public Health 8(7): 2816-2827, 2011. (48 refs.)

Leading Italian studies support the use of gamma-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30-40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of 'antagonist' effect by using the 'psychological threat' of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its 'non-blockade' effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

Myrick H; Malcolm R; Randall PK; Boyle E; Anton RF; Becker HC et al. A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcoholism: Clinical and Experimental Research 33(9): 1582-1588, 2009. (40 refs.)

Introduction: Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial. Methods: One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) ratings >= 10 were randomized to double-blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels. Results: CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin-treated participants (p = 0.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam-treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam. Conclusions: Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.

Odenwald M; Semrau P. Reducing dropout among traumatized alcohol patients in detoxification treatment: A pilot intervention study. European Addiction Research 18(2): 54-63, 2012. (45 refs.)

Dropout rates from detoxification treatment are high. We tested whether high trauma event load was related to a higher dropout from alcohol detoxification. Furthermore, we studied the feasibility and effects of a short psychoeducational tool to increase retention among traumatized alcohol in-patients. Retention and treatment length were compared between treatment as usual (TAU) and standard therapy plus a psychoeducational group intervention on alcohol drinking related to stress and trauma (PAST). Patients with high trauma load were identified with the Trauma History Questionnaire. Of the 159 in-patients treated during the study period, 66 were included in the analysis: 33 in TAU and 33 in PAST. Sociodemographic characteristics did not differ between the groups. During TAU, patients with high trauma load tended to drop out more often (p = 0.056). Among patients with high trauma load, retention level increased from 29 to 80% (p = 0.006), and among those with low trauma load from 63 to 83% (p = 0.250). Treatment length only tendentially improved among patients with lower burden (p = 0.056). The pilot study supports the idea that detoxification treatment dropout occurs more often among alcohol patients with high trauma load and that their retention can be increased by a psychoeducational group intervention.

Sarff M; Gold JA. Alcohol withdrawal syndromes in the intensive care unit. (review). Critical Care Medicine 8(9, supplement): S494-S501, 2010. (100 refs.)

This article reviews the pathophysiology, diagnosis, and treatment of alcohol withdrawal syndromes in the intensive care unit as well as the literature on the optimal pharmacologic strategies for treatment of alcohol withdrawal syndromes in the critically ill. Treatment of alcohol withdrawal in the intensive care unit mirrors that of the general acute care wards and detoxification centers. In addition to adequate supportive care, benzodiazepines administered in a symptom-triggered fashion, guided by the Clinical Institute Withdrawal Assessment of Alcohol scale, revised (CIWA-Ar), still seem to be the optimal strategy in the intensive care unit. In cases of benzodiazepine resistance, numerous options are available, including high individual doses of benzodiazepines, barbiturates, and propofol. Intensivists should be familiar with the diagnosis and treatment strategies for alcohol withdrawal syndromes in the intensive care unit.

Teixeira J; Mota T; Fernandes JC. Nutritional evaluation of alcoholic inpatients admitted for alcohol detoxification. Alcohol and Alcoholism 46(5): 558-560, 2011. (33 refs.)

Aims: To assess nutritional risk of alcoholic patients admitted for alcohol detoxification. Methods: Screening of nutritional risk of alcoholic patients using the Malnutrition Universal Screening Tool. Results: Fifty-three percentage patients at presentation were rated as being at medium or high risk of malnutrition. Conclusion: Malnutrition should be actively considered and screened for in alcoholic patients admitted for alcohol detoxification due to its high prevalence and benefits obtained from treatment.

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.

Vollstadt-Klein S; Loeber S; Kirsch M; Bach P; Richter A; Buhler M et al. Effects of cue-exposure treatment on neural cue reactivity in alcohol dependence: A randomized trial. Biological Psychiatry 69(11): 1060- 1066, 2011. (44 refs.)

Background: In alcohol-dependent patients, alcohol-associated cues elicit brain activation in mesocorticolimbic networks involved in relapse mechanisms. Cue-exposure based extinction training (CET) has been shown to be efficacious in the treatment of alcoholism; however, it has remained unexplored whether CET mediates its therapeutic effects via changes of activity in mesolimbic networks in response to alcohol cues. In this study, we assessed CET treatment effects on cue-induced responses using functional magnetic resonance imaging (fMRI). Methods: In a randomized controlled trial, abstinent alcohol-dependent patients were randomly assigned to a CET group (n = 15) or a control group (n = 15). All patients underwent an extended detoxification treatment comprising medically supervised detoxification, health education, and supportive therapy. The CET patients additionally received nine CET sessions over 3 weeks, exposing the patient to his/her preferred alcoholic beverage. Cue-induced fMRI activation to alcohol cues was measured at pretreatment and posttreatment. Results: Compared with pretreatment, fMRI cue-reactivity reduction was greater in the CET relative to the control group, especially in the anterior cingulate gyrus and the insula, as well as limbic and frontal regions. Before treatment, increased cue-induced fMRI activation was found in limbic and reward-related brain regions and in visual areas. After treatment, the CET group showed less activation than the control group in the left ventral striatum. Conclusions: The study provides first evidence that an exposure-based psychotherapeutic intervention in the treatment of alcoholism impacts on brain areas relevant for addiction memory and attentional focus to alcohol-associated cues and affects mesocorticolimbic reward pathways suggested to be pathophysiologically involved in addiction.

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