Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU). Objective: To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation. Design, Settings, and Participants: This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019. Interventions: Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days. Main Outcomes and Measures: The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality. Results: Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group. Conclusions and Relevance: Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT02723383.

The Safety and Utility of Phenobarbital Use for the Treatment of Severe Alcohol Withdrawal Syndrome in the Medical Intensive Care Unit.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a common reason for admission to a medical intensive care unit (MICU) and requires significant hospital resource utilization. Benzodiazepines are first-line therapy for AWS in many intensive care units. We propose the use of symptom-triggered phenobarbital for the treatment of AWS as a safe alternative to benzodiazepines. METHODS: This was a retrospective observational study of a 4-year period, 2011 to 2015, of all patients with AWS admitted to the MICU of 1 tertiary care hospital and treated with phenobarbital. A symptom-triggered protocol was used. Resolution of AWS was assessed with the Richmond Agitation Sedation Scale to goal score of 0 to -1. The Charlson Comorbidity Index was used as an index of patient illness severity. Complications associated with phenobarbital use and/or the AWS admission were analyzed. RESULTS: Data of 86 AWS patient encounters were analyzed. The mean Clinical Institute Withdrawal Assessment for Alcohol-Revised score of patients admitted to the MICU with AWS was 19 ± 9. The mean phenobarbital dose administered during the MICU stay was 1977.5 ± 1531.5 mg. There were a total of 17 (20%) intubations. The most frequent cause of mechanical ventilation in patients with AWS was loss of airway clearance, followed by hemodynamic instability secondary to upper gastrointestinal bleeding and the corresponding need for endoscopy. CONCLUSIONS: Sole use of phenobarbital use for control of AWS may be a safe alternative to benzodiazepines. Further study is needed to correlate phenobarbital serum levels with clinical control of AWS.

Evaluation of a Symptom-triggered Protocol for Alcohol Withdrawal for Use in the Emergency Department, General Medical Wards, and Intensive Care Unit.

BACKGROUND: Alcohol withdrawal is common in hospitalized patients and symptom-triggered guidelines have been shown to reduce treatment duration, length of stay, and need for mechanical ventilation. OBJECTIVES: To assess the feasibility of incorporating symptom-triggered alcohol withdrawal guidelines early in the hospital course and to evaluate outcomes of patients before and after implementation of the guidelines. METHODS: This was a retrospective pre-post study of adult patients admitted from the emergency department to an urban, academic, tertiary care center. Subjects in the preguideline (PRE) group were given benzodiazepines in a nonprotocolized manner at the discretion of the treating physician, whereas subjects in the postguideline (POST) group were treated according to the alcohol withdrawal guidelines with treatment beginning in the emergency department. RESULTS: The PRE group involved 113 admissions for severe alcohol withdrawal and the POST group involved 103 admissions for severe alcohol withdrawal. The median benzodiazepine dose per day, in milligrams of chlordiazepoxide, was higher in the POST group (100 mg in the PRE group vs. 141 mg in the POST group; P<0.02). A higher percentage of patients in the POST group were admitted to the intensive care unit (4.4% in the PRE group vs. 12.6% in the POST group; P=0.05); however, more patients in the PRE group than in the POST group received continuous intravenous sedation and mechanical ventilation, although the difference was not statistically significant (P=0.37 for both variables). There was no difference between the 2 groups in length of stay in the intensive care unit or hospital or discharge disposition. CONCLUSIONS: Incorporating symptom-triggered guidelines for alcohol withdrawal early in the hospital course at a large medical center is feasible. This approach may result in increased benzodiazepine use, but it seems that it is safe and does not result in adverse outcomes.

Effects of Clavulanic Acid Treatment on Reinstatement to Methamphetamine, Glial Glutamate Transporters, and mGluR 2/3 Expression in P Rats Exposed to Ethanol.

Evidence demonstrated that the glutamatergic system is implicated in mediating relapse to several drugs of abuse, including methamphetamine (METH). Glutamate homeostasis is maintained by a number of glutamate transporters, such as glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). In addition, group II metabotropic glutamate receptors (mGluR2/3) were found to be implicated in relapse-seeking behavior. Ample evidence showed that ß-lactam antibiotics are effective in upregulating GLT-1 and xCT expression, thus improving glutamate homeostasis and attenuating relapse to drugs of abuse. In this study, we investigated the reinstatement of METH using conditioned place preference (CPP) in male alcohol-preferring (P) rats exposed to home-cage free choice ethanol drinking. Here, we tested the effect of clavulanic acid (CA), a ß-lactam, on the reinstatement of METH-seeking and ethanol drinking. In addition, we examined the expression of GLT-1, xCT, and GLAST as well as metabotropic glutamate receptor (mGluR2/3) in the nucleus accumbens (NAc) shell, NAc core, and dorsomedial prefrontal cortex (dmPFC). A priming i.p. injection of METH reinstated preference in METH-paired chamber following extinction. Chronic exposure to ethanol decreased the expression of GLT-1 and xCT in the NAc shell, but not in the NAc core or dmPFC. CA treatment blocked the reinstatement of METH-seeking, decreased ethanol intake, and restored the expression of GLT-1 and xCT in the NAc shell. In addition, the expression of mGluR2/3 was increased by CA treatment in the NAc shell and dmPFC. These findings suggest that these glutamate transporters and mGluR2/3 might be potential therapeutic targets for the attenuation of reinstatement to METH-seeking.

Baclofen for alcohol withdrawal.

BACKGROUND: Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. OBJECTIVES: To assess the efficacy and safety of baclofen for people with AWS. SEARCH METHODS: We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. SELECTION CRITERIA: We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no significant difference in CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low quality evidence), adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence). AUTHORS' CONCLUSIONS: No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low quality evidence.

IL-23 restoration of Th17 effector function is independent of IL-6 and TGF-ß in a mouse model of alcohol and burn injury.

T cells play a critical role in host defense against intestinal bacteria. We have shown that ethanol combined with burn injury suppresses Peyer's patch (PP) Th17 cytokines 1 d after injury. We assessed the mechanism of suppressed Th17 effector functions. Mice were gavaged with ethanol 4 h before burn injury and euthanized 1, 3, and 7 d after injury. Mesenteric lymph nodes (MLNs), PPs, and spleen Th1 and Th17 cytokines were assessed. A significant decrease in IL-17, IL-22, IL-2, and IFN-γ were observed in all 3 lymphoid organs 1 and 3 d after injury. We used splenic cells to study the role of IL-6, IL-23, TGF-ß, and aryl hydrocarbon receptor (AHR) in suppressing Th17 cytokines. We also assessed whether the AHR agonist 6-formylindolo (3, 2-b) carbazole (FICZ) modulates Th17 cytokines. We found a significant decrease in IL-6 and TGF-ß after ethanol and burn; IL-23 was undetectable. The reconstitution of IL-23 in culture medium increased IL-17 by 2-fold and IL-22 by 20-fold in cells from burn ethanol mice. The restoration of IL-6 and TGF-ß combined did not influence the release of Th17 cytokines. We observed that AHR was necessary for IL-23 restoration of IL-22 after ethanol and burn injury. The AHR agonist FICZ enhanced IL-22, but not IL-17. None of these treatments influenced the release of Th1 cytokines. Together, these results suggest that IL-23 plays a critical role in regulation of Th17 cytokines. Furthermore, IL-6 and TGF-ß do not appear to influence IL-23-mediated restoration of Th17 cytokines after ethanol and burn injury.

Assessment of Pharmacological Treatment Quality: Comparison of Symptom-triggered vs. Fixed-schedule Alcohol Withdrawal in Clinical Practice.

Introduction: Despite the fact, that symptom-triggered alcohol withdrawal treatment is recommended by German guidelines on alcoholism, many hospitals continue to use fixed-schedule protocols, as they have been successfully applied for many years. Methods: This retrospective study compared all patients' records of alcohol withdrawal treatment from October 2010 to November 2011 at Magdeburg's University Department of Psychiatry (n=120). A symptom-triggered protocol with clomethiazole (AESB, n=46) was used in parallel with the existing fixed-schedule protocol with diazepam (n=74). Results: The symptom-triggered group showed less need of pharmacological treatment duration (p<0.001) and cumulative dosage of medication compared to the fixed-schedule protocol (p<0.006). No difference was observed regarding the need of clonidine or haloperidol (to treat blood pressure derailment or delirium) and the incidence of epileptic seizures. Discussion: Based on the shorter treatment duration and a similar rate of complications our department has switched to the symptom-triggered protocol to improve the quality of patient care.

Baclofen for alcohol withdrawal.

BACKGROUND: The treatment baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane review published in Issue 2, 2013. OBJECTIVES: To assess the efficacy and safety of baclofen for people with AWS. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialised Register (searched 13 January 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1), MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), and CINAHL (1982 to January 2015). We also searched registers of ongoing trials, including ClinicalTrials.gov, the ISRCTN registry, and the European Clinical Trials Database. At the same time, we handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. SELECTION CRITERIA: We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed references retrieved for possible inclusion. Any disagreements were resolved by an independent party. We contacted study authors for additional information where needed. We collected adverse effects information from the trials. MAIN RESULTS: Two RCTs with a total of 81 participants were eligible according to the inclusion criteria. One study suggested that both baclofen and diazepam significantly decreased the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) score, without any significant difference between the two interventions. The other study showed no significant difference in CIWA-Ar score between baclofen and placebo, but a significantly decreased dependence on high-dose benzodiazepines with baclofen compared to placebo. Only one study reported on the safety of baclofen, without any side effects. AUTHORS' CONCLUSIONS: The evidence for recommending baclofen for AWS is insufficient. We therefore need more well-designed RCTs to prove its efficacy and safety.

Nuevas perspectivas para el tratamiento del alcoholismo / New perspectives for the treatment of alcoholism

No disponible

[Efficacy of alcohol withdrawal syndrome therapy in patients from Independent Public Hospital for Mental Diseases in Miedzyrzecz]. / Skutecznosc leczenia alkoholowego zespofu abstynencyjnego u pacjentów Samodzielnego Publicznego Szpitala dla Nerwowo i Psychicznie Chorych w Miedzyrzeczu.

Consumption of alcohol is a serious social problem. Research on alcohol addicts prove that its consumption affects the physical and mental health of drinking person, his/her family and the social dimension (eg. crime, unemployment, poverty). The aim of this study was to evaluate the effectiveness of the treatment of alcohol withdrawal syndrome (AW) in patients of 2417 Unit of Treatment of Alcohol Withdrawal Syndromes of Independent Public Hospital for Mental Diseases (SPSNPCH) in Miedzyrzecz. The study was conducted in 122 of 24/7 Unit of Treatment of Alcohol Withdrawal Syndromes (SPSNPCH) treated from January to March 2015. Patients during hospitalization were subjected to intensive pharmacotherapy of AW (Stage I) and cognitive-behavioral therapy (Stage II). Of the group of 122 people starting treatment Stage I was completed by 112 patients (90%); 10 patients (8%) have been discharged at their own request. The participation in Stage II was consented only by 54 patients, of which 6 (4%) withdrew from this form of therapy. Full two-stage treatment consisting of pharmacotherapy of AWS and then psychotherapy was completed only by 48 (39%) patients.

[What can be expected today of pharmacotherapy in the Alcohol Use Disorders?]. / Quelles attentes peut-on avoir aujourd'hui de la pharmacothérapie des troubles liés à l'usage d'alcool?

During the last past years, numerous drug have been proposed to treat Alcohol Use Disorders. Besides classical drugs as acomprosate or naltrexone, new compounds are developed in this new indication. They are used in substitution therapies (baclofen), either when the aim of the treatment is total abstinence from alcohol or as an aid for craving reduction facilitating a "controlled drinking", or also for the maintaining of abstinence (nalmefene). Those drugs, availaible in diferent countries, are now marketed in France (nalmefene). As yet, baclofen may be prescribed in France by the mean of a Temporary Utilisation Recommandation, according to the settlement of the National Medicament Agency. Despite the emphasis of some spectacular effects of baclofen, highly publicised by the media and some enthousiastic practitioners, the drug dosage/frequency has to be assessed by two ongoing controlled studies. The pharmacotherapy remains, however, only one element in the treatment of alcoholism, a complex biopsychosocial disorder. Various forms of psychotherapy remain necessary, the pharmacotherapy being only one, sometimes useful, additionnal treatment.

Genetic polymorphisms and response to medications for alcohol use disorders: a systematic review and meta-analysis.

AIM: To assess whether response to medications for alcohol use disorders varies by genotype. METHODS: Systematic review and meta-analysis. RESULTS: We found no studies that assessed the clinical utility of genotype-guided dosing strategies or genotype-guided medication selection, and none randomized by genotype. All included studies assessed the association between genotype and response to medication. Of 15 included studies, eight (n = 1365 participants) assessed variation in naltrexone response and polymorphisms of OPRM1. Our meta-analyses for return to heavy drinking found no significant difference between A allele homozygotes and those with at least one G allele, both without (risk difference: 0.26; 95% CI: -0.01-0.53; n = 174) and with inclusion of studies rated as high or unclear risk of bias (risk difference: 0.14; 95% CI: -0.03-0.3; n = 382). For all other polymorphism-medication pairs, we found just one eligible study. CONCLUSION: Estimates of effect for return to heavy drinking suggest it is possible that patients with at least one G allele of A118G polymorphism of OPRM1 might be more likely to respond to naltrexone, but confidence intervals were wide; additional studies are needed to improve confidence in the estimates.

Baclofen for alcohol withdrawal.

BACKGROUND: The treatment baclofen can rapidly reduce symptoms of severe alcohol withdrawal syndrome (AWS) in alcoholic patients, with a significant reduction in the cost. Baclofen is easy to manage, and rare euphoria, craving and other pleasant effects are reported by patients treated with baclofen. OBJECTIVES: To assess the efficacy and safety of baclofen for patients with AWS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (October 2012), MEDLINE (1966 to October 2012), EMBASE (1980 to October 2012) and CINAHL (1982 to October 2012). We also searched registers of ongoing trials, for example ClinicalTrials.gov, Controlled-trials.com, EUDRACT, etc. At the same time, we handsearched the references quoted in the identified trials, and contacted researchers, pharmaceutical companies and relevant trial authors seeking information about unpublished or uncompleted trials. All searches included the non-English language literature. SELECTION CRITERIA: All randomized controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for patients with AWS. Uncontrolled, non-randomized or quasi-randomized trials were excluded. Both parallel group and cross-over design were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed references retrieved for possible inclusion. All disagreements were resolved by an independent party. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: We identified a total of 113 references from all electronic databases searched excluding duplicates. After screening of titles and abstracts, full papers of 10 studies were obtained and assessed for eligibility. Finally, two RCTs with 81 participants were eligible according to the inclusion criteria. Regarding the efficacy, one study suggested that both baclofen and diazepam significantly decreased the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar) score, without any significant difference between the two interventions. The other study showed no significant difference in CIWA-Ar score between baclofen and placebo but a significantly decreased dependence on high-dose benzodiazepines with baclofen compared to placebo. Meanwhile, only one study reported the safety outcomes and there were no side effects in either the baclofen or diazepam groups. AUTHORS' CONCLUSIONS: The evidence for recommending baclofen for AWS is insufficient. More well designed RCTs are needed to prove its efficacy and safety.

[Severe bilateral keratomalacia]. / Schwere bilaterale Keratomalazie.

In contrast to developing countries, xerophthalmia is rather rare in developed countries. Malnutrition (e.g. in mentally deficient or psychiatric patients), chronic liver diseases (e.g. due to alcoholism), or bowel surgery can be reasons for vitamin A deficiency in developed countries. The prodromal stage of hypovitaminosis A is characterized by nyctalopia, which often manifests subclinically. Longer lasting and severe cases of vitamin A deficiency may be complicated by the occurrence of keratinizing metaplasia in the cornea and conjunctiva, xerosis, keratomalacia or blindness.

Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders.

Alcohol abuse and dependence have a staggering socioeconomic impact, yet current therapeutic strategies are largely inadequate to treat these disorders. Thus, the development of new strategies that can effectively prevent alcohol use disorders (AUDs) is of paramount importance. Currently approved medications attempt to deter alcohol intake by blocking ethanol metabolism or by targeting the neurochemical systems downstream of the cascades leading to craving and dependence. Unfortunately, these medications have provided only limited success as indicated by the continued high rates of alcohol abuse and alcoholism. The lack of currently available effective treatment strategies is highlighted by the urgent call by the NIAAA to find new and paradigm-changing therapeutics to either prevent or treat alcohol-related problems. This mini-review highlights recent findings from 4 laboratories with a focus on compounds that have the potential to be novel therapeutic agents that can be developed for the prevention and/or treatment of AUDs.

The effects of ethanol upon hydric balance and arterial pressure in rats: folic acid as a possible hypotensor.

AIMS: Chronic alcohol intake is related to hypertension. There are, however, few studies concerning the effect of ethanol upon hydric balance in relation to arterial pressure. Folic acid intake has beneficial effects upon the cardiovascular system decreasing hyperhomocysteinemia, however, more studies imply that it is related with other mechanisms. Therefore, we have studied the effects of chronic alcohol intake (30% v/v) upon hydric-saline balance and hypertension and have found that dietary supplementation with folic acid (8 mg/kg) improves the above parameters. MAIN METHODS: Our study used four experimental groups of rats: control, alcohol, alcohol with folic acid and control with folic acid. In all cases we measured the clearance of Na(+), K(+) and aldosterone; osmolarity in urine, liquid and solid ingestion; homocysteine levels in serum; cardiac frequency and arterial blood pressure. KEY FINDINGS: The alcohol intake increases serum aldosterone and homocysteine, which is reflected in an increase in arterial blood pressure. In addition, we have found that alcohol intake reduces both liquid and solid ingestion (causing a malnourishment status), the clearance of creatinine, aldosterone, Na(+) and K(+), and the ratio ClNa(+)/ClCr; it also increases urine osmolarity. Folic acid supplementation increases the clearance of Na(+) and the ratio ClNa(+)/ClCr. SIGNIFICANCE: Folic acid intake improves the hypertension provoked by alcohol by increasing the aldosterone clearance, drastically reducing the serum levels of this hormone and thus its hypertensor effect.

Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied. OBJECTIVE: To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo-controlled study of recently abstinent adults. METHODS: Adults who had ADHD and alcohol use disorders and were abstinent for 4-30 days were randomized to daily atomoxetine 25-100 mg (mean final dose = 89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale. RESULTS: Of 147 subjects receiving atomoxetine (n = 72) or placebo (n = 75) in the primary study, 80 (54%) completed 12 weeks (n = 32 atomoxetine; n = 48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson's r = 0.28; 95% confidence interval [CI] = 0.11-0.43; p = 0.002), and the correlation was most notable with atomoxetine (r = 0.29; CI [0.04 - 0.51]; p = 0.023) rather than with placebo (r = 0.24; CI [0.00-0.46]; p = 0.055). On-treatment drinking levels correlated with AISRS scores (r = 0.12; CI [0.05 -0.19]; p = 0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p < 0.05 for each). CONCLUSIONS: No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations. TRIAL REGISTRATION (BASE STUDY): ClinicalTrials.gov identifier: NCT00190957.

Intensity of symptoms from alcohol withdrawal in alcohol-dependent patients: comparison between smokers and non-smokers.

BACKGROUND: In patients with a dual dependence on alcohol and tobacco, the spontaneous discourse among doctors is not to encourage them to consider preparing to give up both substances. The argument put forward is that withdrawal would be more difficult. We wanted to compare the intensity of withdrawal symptoms in patients hospitalised for alcohol detoxification between smokers and non-smokers. SUBJECT AND METHODS: We compared patients hospitalised for alcohol detoxification who smoke versus non-smokers who received replacement therapy through benzodiazepines and not nicotine replacement. The blood pressure and the cardiac frequency measure on the first day of hospitalisation, the doses of Diazepam dispensed on the first day, and the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar) score on the second day were compared. RESULTS: A trend emerged whereby smoking patients undergoing alcohol detoxification showed higher blood pressure, higher cardiac frequency and required higher doses of benzodiazepines on the first day of hospitalisation. Patients who smoke also had higher CIWA-Ar scores on the second day of hospitalisation. DISCUSSION: From a physiological point of view, the intensity of the symptoms of alcoholic withdrawal seems to be greater in hospitalised patients who smoke vs. non-smokers in the first two days. Does giving up both substances at the same time result in fewer withdrawal symptoms? And in this case, should a double replacement be recommended: benzodiazepines and nicotine replacement therapy? CONCLUSION: To be able to refine the recommendations on alcohol-tobacco dual withdrawal programmes, other studies are needed to compare giving up both substances with or without nicotine replacement.

Stopping insulin and achieving a good metabolic control in a heavy drinker five months after stopping alcohol.

In this case study, we describe a 25 year-old male who showed the symptoms of diabetes after a period of heavy drinking. (HbA1c=13%). Treatment was started with 120 units of insulin. After stopping alcohol consumption and taking an appropriate diet, insulin was tapered down. Five months after the start of treatment, insulin was stopped (HbA1c=5%). The results showed that he was in a good metabolic control after 18 months (HbA1c=5.9%).