Medications For Alcohol Dependence Research Articles

Pharmacological treatments for alcohol dependence: Evidence on uptake, inequalities and comparative effectiveness from a UK population-based cohort.

We assessed the prevalence of prescribing of certain medications for alcohol dependence and the extent of any inequalities in receiving prescriptions for individuals with such a diagnosis. Further, we compared the effectiveness of two of the most prescribed medications (acamprosate and disulfiram) for alcohol dependence and assessed whether there is inequality in prescribing either of them. We used a nationwide dataset on prescriptions and hospitalisations in Scotland, UK (N = 19,748). We calculated the percentage of patients receiving alcohol dependence prescriptions after discharge, both overall and by socio-economic groups. Binary logistic regressions were used to assess the odds of receiving any alcohol-dependence prescription and the comparative odds of receiving acamprosate or disulfiram. Comparative effectiveness in avoiding future alcohol-related hospitalisations (N = 11,239) was assessed using Cox modelling with statistical adjustment for potential confounding. Upto 7% of hospitalised individuals for alcohol use disorder received prescriptions for alcohol dependence after being discharged. Least deprived socio-economic groups had relatively more individuals receiving prescriptions. Inequalities in prescribing for alcohol dependence existed, especially across sex and comorbidities: males had 12% (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.81-0.96) and those with a history of mental health hospitalisations had 10% (OR 0.90, 95% CI 0.82-0.98) lower odds of receiving prescriptions after an alcohol-related hospitalisation. Prescribing disulfiram was superior to prescribing acamprosate in preventing alcohol-related hospitalisations (hazard ratio ranged between 0.60 and 0.81 across analyses). Disulfiram was relatively less likely prescribed to those from more deprived areas. Inequalities in prescribing for alcohol dependence exists in Scotland with lower prescribing to men and disulfiram prescribed more to those from least deprived areas.

Use of Medications for the Treatment of Alcohol Dependence: A Retrospective Study Conducted in 2011-2012.

Pharmacotherapy for Alcohol Dependence (AD) is underutilized. Barriers preventing the use of AD medications include high prices, lack of access to prescribing physicians, and a limited number of available medications. The study evaluated the use of AD medications in a sample of Italian outpatients who received these medications free of charge, had access to physicians during office hours, and for whom substitution therapy [gamma-hydroxybutyrate (GHB)] was available. We also evaluated the rate of patients who received a combination of non-pharmacological and pharmacological treatments among participants who were still drinking. SCID for AD and questionnaire were filled by to AD outpatients during a face-to-face interview. 345 AD outpatients were interviewed: 58.8% were currently receiving at least one AD medication (GHB: 34.3%, disulfiram: 29.6%, acamprosate: 5.9%; naltrexone: 2.5%; more than one medication: 16.7%). Less than 30% of participants who were still drinking, received a combination of non-pharmacological and pharmacological treatments. Nonetheless, we found higher use of AD medications compared to previous studies conducted in other countries. This higher use of AD medications may be due to access to free medications, prescribing physicians' style, and a larger number of available medications. Our results confirm the underutilization of AD medications, as less than 60% of AD outpatients received medications, and less than 30% of those who were still drinking, received a combination of non-pharmacological and pharmacological treatments. These findings may be useful in improving our knowledge of the barriers that prevent the use of AD medications in clinical practice.

Dual diagnosis: depression and alcohol use disorder

A combination of depression and alcohol use disorder (AUD) is a typical and most common example of a dual diagnosis at the intersection of general psychiatry and addiction psychiatry. A comorbidity of depression and AUD is more common than it can be brought about by mere coincidence, which might be explained to some extent by the synergetic effect of both diseases, with each of them complicating the course and worsening the prognosis of the other. Treatment protocols for patients with depression and comorbid AUD include antidepressants, specific medications for alcohol dependence, and psychotherapy. The first-line antidepressants in the treatment of patients with a comorbid combination of depression and alcohol use disorder, as in other clinical situations implying use of antidepressants, are selective serotonin reuptake inhibitors (SSRIs). Fluvoxamine has certain advantages over the other SSRIs in the treatment of patients with a depression and comorbid AUD.

From genetic studies to precision medicine in alcohol dependence

Genetic factors contribute to more than 50% of the variation in the vulnerability to alcohol dependence (AD). Although significant advances have been made in medications for AD, these medications do not work for all people. Precise tailoring of medicinal strategies for individual alcoholic patients is needed to achieve optimal outcomes. This review updates the most promising information on genetic variants in AD, which may be useful for improving diagnostic, therapeutic, and monitoring strategies. We describe genetic candidates of various neurotransmitter and enzyme systems. In addition to biological and allelic associations with AD, genetic effects on AD-related phenotypes and treatment responses have also been described. Gene-gene and gene-environment interactions have been considered. Potential applications of genomewide and epigenetic approaches for identifying genetic biomarkers of AD have been discussed. Overall, the application of genetic findings in precision medicine for AD will likely involve an integrated approach that distinguishes effect sizes of specific genetic predictors with regard to sex, pharmacotherapy, ethnicity, and AD-related aspects and considers gene-gene and gene-environment interactions. Our work may pave the way toward more precise treatment for AD that could ultimately improve clinical management and interventions.

The effects of the monoamine stabilizer (-)-OSU6162 on craving in alcohol dependent individuals: A human laboratory study

Alcohol dependence is associated with a dysregulated dopamine system modulating reward, craving and cognition. The monoamine stabilizer (-)-OSU6162 (OSU6162) can counteract both hyper- and hypo-dopaminergic states and we recently demonstrated that it attenuates alcohol-mediated behaviors in long-term drinking rats. The present Phase II exploratory human laboratory study investigated to our knowledge for the first time the effects of OSU6162 on cue- and priming-induced craving in alcohol dependent individuals. Fifty-six alcohol dependent individuals were randomized to a 14-day-treatment period of OSU6162 or placebo after their baseline impulsivity levels had been determined using the Stop Signal Task. On Day 15, participants were subjected to a laboratory alcohol craving test comprised of craving sessions induced by: i) active – alcohol specific cues, ii) neutral stimuli and iii) priming – intake of an alcoholic beverage (0.20g ethanol/kg bodyweight). Subjective ratings of alcohol craving were assessed using the shortened version of the Desire for Alcohol Questionnaire and visual analog scales (VAS). OSU6162 treatment had no significant effect on cue-induced alcohol craving, but significantly attenuated priming-induced craving. Exploratory analysis revealed that this effect was driven by the individuals with high baseline impulsivity. In addition, OSU6162 significantly blunted the subjective liking of the consumed alcohol (VAS). Although the present 14-day-treatment period, showed that OSU6162 was safe and well tolerated, this exploratory human laboratory study was not designed to evaluate the efficacy of OSU6162 to affect alcohol consumption. Thus a larger placebo-controlled efficacyclinical trial is needed to further investigate the potential of OSU6162 as a novel medication for alcohol dependence.

Effects of idazoxan on alcohol pharmacokinetics and intoxication: a preliminary human laboratory study.

Preliminary basic and human studies suggest that the α2 -adrenergic antagonist idazoxan may represent a novel medication for alcohol dependence. The goal of this study was to evaluate the safety and tolerability of the co-administration of idazoxan with alcohol and explore whether pharmacokinetics (PK) and biobehavioral mechanisms of idazoxan may alter alcohol's effects. This was a preliminary double-blind, single-dose, placebo-controlled, crossover, randomized human laboratory study. Ten social drinkers were dosed, in 2 different alcohol challenge studies (ACS), with a single oral dose of idazoxan (40mg) or placebo, followed by a fixed alcohol dose 60minutes later. Participants returned after a 1-week washout, and they were crossed over to the opposite medication condition. There were no significant differences in adverse events between idazoxan and placebo. Moreover, during the ACS paradigm, 40mg idazoxan was well tolerated with no significant autonomic effects compared to placebo; idazoxan reduced the peak blood alcohol level (p<0.01) and time to peak (p<0.05) compared to placebo. A PK/pharmacodynamic model aligned the biobehavioral effects, demonstrating that the co-administration of 40mg idazoxan with alcohol decreased alcohol-related stimulation (p<0.05) and increased alcohol-related sedation (p<0.05). This study supports the safety and tolerability of 40mg idazoxan when co-administered with alcohol. Additionally, this study suggests that idazoxan may alter the biphasic effects of alcohol by decreasing stimulation and increasing sedation. These findings have implications for further investigation of using idazoxan as a probe to develop potential novel medications to treat alcoholic patients.

A case of reversible erectile dysfunction with topiramate for alcohol dependence.

To the Editor: There is preliminary evidence that topiramate may reduce consumption in alcohol dependence.1,2 Topiramate is generally well-tolerated despite risks of suicidal thinking, paresthesias, renal stones, and cognitive dysfunction. There are also several case studies reporting erectile dysfunction (ED) with topiramate.3–6 I present a case of a man with alcoholism who developed reversible ED after a trial of low-dose topiramate. Case report. Mr A, a 52-year-old man with hypertension well-controlled with irbesartan and hydrochlorothiazide, hypothyroidism treated with levothyroxine, and obesity (body mass index = 31), presented to an intake appointment at an outpatient substance program after completion of inpatient rehabilitation for alcohol dependence, per DSM-IV-TR criteria. He did not require a detoxification. Prior to the rehabilitation, he had been drinking 6 to 8 mixed drinks 3 or 4 times a week and denied blackouts, withdrawals, delirium tremens, hallucinoses, or seizures. He had no prior history of depression, anxiety, or bipolar or other psychiatric disorders and had received no prior psychiatric medications or treatment. Physical examination, electrocardiogram, urinalysis, and blood tests, including a comprehensive metabolic panel, complete blood count, and thyroid and lipid panel, done 6 weeks prior by his internist revealed no abnormalities. The patient and psychiatrist discussed pharmacologic options for alcohol dependence. Mr A was offered naltrexone but declined. He agreed to topiramate (aware that it was not approved by the US Food and Drug Administration for the treatment of alcohol dependence), mainly because of its favorable effect on weight. He tolerated 1 week of topiramate 25 mg at bedtime without complaint. On day 8, after topiramate was increased to 50 mg/night, he complained that he could not attain or sustain an erection during intercourse but was able to ejaculate. He denied any past ED, even during alcohol consumption, and said he had achieved morning erections most days including while on treatment with topiramate 25 mg/night. He denied any decrease in libido or other sexual dysfunction. The ED persisted for another day until the patient notified the psychiatrist and was advised to stop topiramate treatment. He reported no changes in mood or other side effects. Forty-eight hours later, he reported having normal sexual function again and no further ED. His urine drug screens remained negative. He declined any further work-up since his symptoms resolved. This is the first known reported case of topiramate-induced ED in a patient taking the medication for alcohol dependence. The other known cases of ED are in patients taking topiramate for epilepsy. In most cases, the erectile problems were dose-dependent (with symptom development at doses ranging from 50 to 300 mg), and in all cases were reversible after discontinuation of the medication.3–6 Topiramate has also been reported to cause anorgasmia in patients taking the medication for migraines.7,8 It has been postulated that topiramate induces its effects on sexual function via a vasogenic mechanism.5 Some authors postulated that topiramate causes ED by reducing free testosterone levels or affecting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamatergic pathways, which affect penile blood flow.9,10 Despite associated risk factors (including hypertension and obesity), multiple findings—the absence of a past history of sexual dysfunction, the rapid onset of ED in the context of low-dose topiramate, and resolution after discontinuation—suggest that topiramate was the causative agent. It is important to advise patients with alcohol dependence who are receiving off-label topiramate that ED is possible even at lower doses.

Gabapentin

Gabapentin

Comment on: “Management of Alcohol Dependence in Patients With Liver Disease”

Addolorato et al. [1] recently published a welcome review article in CNS Drugs, entitled ‘‘Management of alcohol dependence in patients with liver disease’’. Alcoholic liver disease (ALD) is too often forgotten within the numerous review articles that are regularly published on alcoholdependence medications, whereas cirrhosis is one of the most dramatic consequences of alcohol dependence and can deeply affect the safe use of numerous medications. Addolorato and colleagues [2] state that the gamma amino-butyric acid type B (GABAB) receptor agonist baclofen should be currently preferred in ALD because baclofen was the sole drug that had a good efficacy/safety profile in ALD patients with alcohol dependence in a study whose results were published in The Lancet. Albeit relevant, this conclusion is relatively ironic in the sense that an off-label treatment for alcohol dependence has exhibited higher evidence in ALD than any of the currently approved medications. This indicates to what extent this field of research has been neglected until now. Although baclofen is definitely one of the most promising drugs for treating alcohol dependence in ALD patients, several important safety concerns remain in using this drug in ALD. The findings of the study in The Lancet were obtained from patients with no psychiatric history and who had undergone permanent monitoring by close relatives throughout the trial period. Moreover, as baclofen was particularly effective in maintaining abstinence, only nine patients within the baclofen group experienced relapse, and the amounts of alcohol drinking were not detailed. Thus, possible interactions between baclofen and alcohol intoxication were difficult to identify. Additionally, no patient presented with hepatic encephalopathy, although this condition has been hypothesized to result from GABArelated mechanisms [3]. For all of these reasons, despite the important advances provided by this study, several safety concerns still persist for baclofen because the patient profiles and monitoring conditions in this study were not comparable to those of real-life patients, in whom significant psychiatric co-morbidities; persisting or recurrent alcohol abuse; or ALD complications, such as encephalopathy, may be found. We believe that the question of dose is even more crucial. In the aforementioned study, baclofen was tested at 30 mg/day. Addolorato’s Roman team has published many articles using this dose, which has thus made the dose the most studied and most supported by evidence in the offlabel use of baclofen for abstinence maintenance. However, a dose–response effect of baclofen has been suspected in alcohol dependence [4], and this drug has recently been used in clinical practice at very high doses, i.e., up to 300 mg/day or more, and notably more with a purpose of temperance than of abstinence [5–8]. Although several of these uses have been limited to last-resort situations by hospital teams that could provide enhanced patient monitoring [9, 10], there also exists certain spreading, albeit less visible, practices of prescribing of high-dose baclofen, notably in France [10]. The possible hepatic toxicity of B. Rolland (&) A. Louvet O. Cottencin R. Bordet University of Lille Nord de France, 59045, Lille, France e-mail: benjrolland@gmail.com; benjamin.rolland@chrulille.fr

Group management of pharmacotherapy for alcohol dependence: Feasibility and impact on adoption

One of the barriers to initiating patients on medications for alcohol dependence is concern about the work involved in providing ongoing medication management. In this brief report, we describe our initial experiences with a medication management group, initially implemented to provide continued access during a staffing shortage. We describe the group structure and functioning, and provide initial analysis of the groups’ impact on access and adoption of pharmacotherapy for alcohol dependence. Results of an interrupted time series analysis in one Veterans Health Administration (VHA) facility provide support for the notion that the group format is not only feasible but can actually increase access to these under-utilized medications (e.g., naltrexone and acamprosate). The number of patients receiving these medications was already increasing in this facility before the switch to group appointments, but this rate of initiation increased almost 3-fold after the onset of the groups.

Effect of repeated treatment with topiramate on voluntary alcohol intake and beta-endorphin plasma level in Warsaw alcohol high-preferring rats

RationalePharmacological treatment currently used for alcohol dependence is not sufficient for the all patients, and there is a crucial need to find more effective treatments. Recent studies indicate that topiramate is likely the most promising new medication for alcohol dependence. The rationale for topiramate as treatment for alcohol addiction is based on its multifaceted neurochemical activity that targets multiple neural pathways.ObjectivesThis study aims to assess the effect of repeated treatment with topiramate on voluntary alcohol intake and beta-endorphin plasma level in rats selectively bred for high alcohol preference.MethodsInitially, Warsaw high preferring rats (N = 50) were given a 24-h/day free choice between a 10 % (v/v) alcohol solution and water for three consecutive weeks. Subsequently, rats were administered with topiramate (40 or 80 mg/kg b.w.) or vehicle for 14 days and ethanol intake was measured daily. Subsequently, we examined the effects of topiramate on plasma beta-endorphin levels, while alcohol was available and when it was not available for an extended period time.ResultsWe observed significantly increase in the levels of beta-endorphin in rats with free access to alcohol both in a topiramate- or vehicle-treated group. However, in topiramate-treated group, a voluntary consumption of alcohol diminished in comparison with the vehicle-treated rats.ConclusionThe results from this study indicated that topiramate reduces voluntary alcohol intake and support our previous findings that the increase of beta-endorphin level is responsible at least partly for the effectiveness of drugs in treating the alcohol addiction.

Medical treatment of alcohol dependence: a systematic review.

To summarize published data on pharmacologic treatments for alcohol dependence alone and in combination with brief psychosocial therapies that may be feasible for primary care and specialty medical settings. We conducted electronic searches of published original research articles and reviews in MEDLINE, SCOPUS, CINAHL, Embase, and PsychINFO. In addition, hand searches of reference lists of review articles, supplemental searches of internet references and contacts with experts in the field were conducted. Randomized controlled studies published between January 1960 and August 2010 that met our inclusion/exclusion criteria were included. A total of 85 studies, representing 18,937 subjects, met our criteria for inclusion. The evidence base for oral naltrexone (6% more days abstinent than placebo in the largest study) and topiramate (prescribed off-label) (e.g., 26.2% more days abstinent than placebo in a recent study) is positive but modest. Acamprosate shows modest efficacy with recently abstinent patients, with European studies showing better results than U.S. ones. The evidence-base for disulfiram is equivocal. Depot naltrexone shows efficacy (25% greater reduction in rate of heavy drinking vs. placebo, in one of the largest studies) in a limited number of studies. Some studies suggest that patients do better with extensive psychosocial treatments added to medications while others show that brief support can be equally effective. Although treatment effects are modest, medications for alcohol dependence, in conjunction with either brief support or more extensive psychosocial therapy, can be effective in primary and specialty care medical settings.

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

Harmful alcohol use is a risk factor in more than 60 diseases and injuries resulting in approximately 2.5 million deaths per year worldwide. In the United States (US) and Europe, there are only a few medications approved for alcohol dependence (AD) however, these medications have only been moderately effective and there is a crucial need for more effective treatments. This review briefly summarizes research on currently approved medications for AD, as well as promising medications like topiramate, baclofen and ondansetron. Topiramate is likely the most promising new treatment for AD, however, further research is needed to determine the optimal dose and appropriate length of treatment. Baclofen, a GABA(B) agonist, is a promising medication as a treatment for AD, especially for patients with AD and severe liver disease. Ondansetron has shown promising results as a potential medication for AD, but only within a certain subtype of individuals. This review also discusses more recent findings on other potential pharmacotherapies for AD, such as serotonin-specific reuptake inhibitors (SSRIs; i.e. sertraline), aripiprazole and prazosin, as well as on some examples of other potentially interesting new neuropharmacological targets (i.e. cannabinoid receptors, CRF, NPY, ghrelin). Finally, the present review also discusses the attempts to personalize medication for AD treatment by alcohol typology and pharmacogenetics.

Treatments for Alcohol Dependence: Rethinking the Role of Comorbidity and Clinical Subtypes

Treatments for Alcohol Dependence: Rethinking the Role of Comorbidity and Clinical Subtypes