Tolerability Of Naltrexone Research Articles

Safety and Effectiveness of Naltrexone in the Management of Alcohol Use Disorder in Patients With Alcohol-associated Cirrhosis: First Clinical Observation From Indian Cohort

Naltrexone is a promising drug to treat alcohol use disorder with limited evidence of safety in liver diseases. An observational study was performed to study the safety, effectiveness, and tolerability of Naltrexone in the management of alcohol use disorder in patients with alcohol-associated cirrhosis. Naltrexone was started in patients with alcohol-related liver disease for the management of alcohol use disorder in 86 patients who were followed up for 4 weeks. Baseline liver parameters were compared with those at 4 weeks to establish safety of the drug. Effectiveness was determined by observing reduction in AUDIT scores, craving, number and days of drinking. Self-report of side effects was noted. After 4 weeks of starting Naltrexone there was a decrease in AST-89.86 vs 57.61, ALT-50.19 vs 27.08, SAP-121.81 vs 98.19, GGT-166.93 vs 109 and MELD 16.32 vs 12.13 (none statistically significant). There was a statistically significant reduction in Serum Bilirubin- (4.31 vs 1.98), INR (1.49 vs 1.32), self-reported craving (3.71 Vs 1.97; P= 0.01), AUDIT scores (24.13 Vs 16.91; P <0.01) and number of drinking days in last one month (10.22 Vs 4.19; P= 0.03). The reduction in all liver parameters and AUDIT scores and craving after treatment with Naltrexone supports its safety and utility in the management of alcohol use disorder in alcohol-related liver cirrhosis.

P.623 Efficacy and tolerability of naltrexone in patients with Internet gaming disorder and comorbid alcohol use disorder

P.623 Efficacy and tolerability of naltrexone in patients with Internet gaming disorder and comorbid alcohol use disorder

Naltrexone: A Pan-Addiction Treatment?

Addiction is a major public health problem with few efficacious and safe treatments. The goal of this review is to provide an evidence-based assessment of the therapeutic role of the opioid antagonist naltrexone across the addiction spectrum-substance-based and behavioral. The PubMed database was searched for randomized, placebo-controlled clinical trials that investigated the oral or intramuscular long-acting formulation of naltrexone in substance use disorders or behavioral addictions such as pathological gambling, kleptomania, and trichotillomania. Thirty-nine efficacy studies were retrieved, covering alcohol use disorder (n=22), opioid use disorder (n=6), nicotine use disorder (n=5), stimulant use disorder (n=2), gambling disorder (n=2), trichotillomania (n=1), and kleptomania (n=1). Despite the very different presentations within and between both addiction categories, the data, as a whole, show consistency in favor of naltrexone's relative efficacy and safety. Given the potential benefit and good tolerability revealed in the studies, the high morbidity associated with addiction, and the dearth of alternate treatments, naltrexone would seem like an underutilized treatment option. Further, naltrexone's seemingly broad anti-addiction efficacy supports a shared role for brain opioid pathways in the pathophysiology of addiction, broadly defined. More studies investigating the efficacy and tolerability of naltrexone and other opioid modulators are warranted. Studies should also further examine the effect of combining psychotherapy with naltrexone, as well as the potential role of naltrexone in treating comorbid addictions.

Naltrexone for impulse control disorders in Parkinson disease: a placebo-controlled study.

Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD. Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1:1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score. Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8% (95% confidence interval [CI] -8.7% to 44.2%). While this difference was not significant (odds ratio=1.6, 95% CI 0.5-5.2, Wald χ2 [df]=0.5 [1], p=0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model=-7.37, F[df]=4.3 [1, 49], p=0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo. Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD. This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates.

Efficacy and Tolerability of Naltrexone in the Management of Alcohol Dependence

Naltrexone, a broad opioid-receptor antagonist, was the first medication since disulfiram to be approved by the United States of America Food and Drug Administration for the treatment of alcohol dependence. In the initial clinical trials in the early 1990s, oral naltrexone, 50 mg, was shown to significantly reduce the risk of relapsing to heavy drinking compared to placebo. These early trials were followed by other trials throughout the world such that by 2010 about 4,000 individuals had been studied. Meta-analyses of these trials revealed that oral naltrexone is effective in reducing relapse to heavy drinking but less effective in enhancing abstinence. The effect size is modest, in the .15 to .2 range, which has impacted the adoption of naltrexone use by clinicians. Intramuscular versions of naltrexone active for one month have also shown efficacy. The tolerability of naltrexone is reasonable with the most common side-effect being nausea. Hepatotoxicity with naltrexone has not emerged as a clinical problem at the standard 50 mg dose though at higher doses hepatoxicity is of concern. The length of treatment with naltrexone has not been well studied though many clinicians recommend one year of treatment. Efforts are underway to identify predictors of naltrexone response but, to date, no predictor has achieved clinical utility. It is anticipated that the role of naltrexone and other opioid antagonists in the treatment of alcohol dependence will continue to be refined and that this class of medications will come to be seen as an important option in the clinical care of the patient with alcohol dependence.

Efficacy and Tolerability of Naltrexone in the Treatment of Alcohol Dependence: Oral versus Injectable Delivery

Oral naltrexone, an opioid antagonist, reduces relapse and heavy drinking in alcohol-dependent patients. However, oral delivery is associated with poor compliance and adverse events. To enhance treatment outcome and reduce side effects, injectable extended-release naltrexone formulations have been developed. Currently, there are no studies available directly comparing oral and injectable formulations of naltrexone in alcohol-dependent patients. This paper reviews the efficacy and adverse events of oral versus injectable extended-release naltrexone. Therefore, data were extracted from two recently published reviews about oral naltrexone in the treatment of alcohol dependence. Pooled outcomes were compared with reported outcomes of recent studies on injectable extended-release naltrexone. Injectable naltrexone seems to be effective in the management of alcohol dependence. Although inconclusive, the available results indicate that the expected advantages of injectable naltrexone over oral naltrexone still have to be proven. Randomized studies with direct comparisons of oral and injectable naltrexone are urgently needed.

A Double-Blind, Placebo-Controlled Study of Naltrexone in the Treatment of Alcohol-Dependence Disorder: Results from a Multicenter Clinical Trial

Background A 12-week, multicenter, double-blind, randomized, parallel-group clinical trial to compare naltrexone and placebo was carried out to determine the efficacy, safety, and tolerability of naltrexone together with a psychosocial intervention in the treatment of alcoholism. Methods A total of 202 alcohol-dependent patients were assigned to 12 weeks’ treatment with either naltrexone or placebo. The relapse rate was evaluated by means of intention-to-treat analyses. Alcohol consumption, craving, adverse events, and changes in the biochemical markers of heavy drinking and possible toxicity were evaluated in the 192 patients who were considered to be assessable. Results The survival function for patients who were treated with naltrexone was significantly better than that of the patients who were treated with placebo (Kaplan-Meier log rank = 4, df = 1, p < 0.05). In addition, 7.9% of patients who were treated with naltrexone relapsed as compared with 18.8% of those who received placebo [χ2= 5.89, df = 2, p= 0.050]. In comparing naltrexone with placebo-treated patients, the most common adverse events were abdominal pain [8.6% vs. 1%; (χ2= 6.1, df = 1, p < 0.05)] and headache [7.5% vs. 1% (χ2= 5.1, df = 1, p < 0.05)]. Conclusions Naltrexone was well-tolerated, as the rate of adverse events was low, and safe, as it did not interfere with the normalization of biochemical markers of heavy drinking or alter liver function markers. Naltrexone seemed to reduce relapse rate to heavy drinking, but we found no differences in other alcohol consumption variables between naltrexone- and placebo-treated groups. Although the naltrexone group showed a tendency to consume fewer drinks per drinking day and had a longer time to first drink, differences were not statistically significant.

A Double‐Blind, Placebo‐Controlled Study of Naltrexone in the Treatment of Alcohol‐Dependence Disorder: Results from a Multicenter Clinical Trial

Background A 12‐week, multicenter, double‐blind, randomized, parallel‐group clinical trial to compare naltrexone and placebo was carried out to determine the efficacy, safety, and tolerability of naltrexone together with a psychosocial intervention in the treatment of alcoholism.Methods A total of 202 alcohol‐dependent patients were assigned to 12 weeks’ treatment with either naltrexone or placebo. The relapse rate was evaluated by means of intention‐to‐treat analyses. Alcohol consumption, craving, adverse events, and changes in the biochemical markers of heavy drinking and possible toxicity were evaluated in the 192 patients who were considered to be assessable.Results The survival function for patients who were treated with naltrexone was significantly better than that of the patients who were treated with placebo (Kaplan‐Meier log rank = 4, df = 1, p &lt; 0.05). In addition, 7.9% of patients who were treated with naltrexone relapsed as compared with 18.8% of those who received placebo [χ2= 5.89, df = 2, p= 0.050]. In comparing naltrexone with placebo‐treated patients, the most common adverse events were abdominal pain [8.6% vs. 1%; (χ2= 6.1, df = 1, p &lt; 0.05)] and headache [7.5% vs. 1% (χ2= 5.1, df = 1, p &lt; 0.05)].Conclusions Naltrexone was well‐tolerated, as the rate of adverse events was low, and safe, as it did not interfere with the normalization of biochemical markers of heavy drinking or alter liver function markers. Naltrexone seemed to reduce relapse rate to heavy drinking, but we found no differences in other alcohol consumption variables between naltrexone‐ and placebo‐treated groups. Although the naltrexone group showed a tendency to consume fewer drinks per drinking day and had a longer time to first drink, differences were not statistically significant.

Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling

Background: The authors’ goal was to assess the efficacy and tolerability of naltrexone in the treatment of pathologic gambling disorder. Methods: Eighty-three subjects who met criteria for DSM-IV pathologic gambling disorder were enrolled in a 1-week single-blind placebo lead-in followed by an 11-week double-blind naltrexone or placebo trial. Naltrexone was started at 25 mg/day and titrated upward until maximum symptom improvement or 250 mg/day was achieved. Gambling symptom change was assessed with the patient-rated Clinical Global Impression (PG-CGI-PT), clinician-rated CGI (PG-CGI-MD), and the Gambling Symptom Rating Scale (G-SAS). Side effects were monitored weekly and liver function tests biweekly. Results: Data from 45 patients were analyzed. Using random regression analysis, significant improvement was noted in all three gambling symptom measures: patient-rated Clinical Global Impression, p < .001; clinician-rated CGI, p < .001; Gambling Symptom Rating Scale, p < .019. At study end, 75% of subjects taking naltrexone were much or very much improved on both the PE-CEI PT and the PG-CGI-MD, compared with only 24% of those on placebo. Elevated liver enzymes occurred in four subjects who were taking analgesics concurrently. Nausea was common during the first week of treatment. Conclusions: Results suggest that naltrexone is effective in reducing the symptoms of pathologic gambling. Until further studies corroborate the present findings, our report should be interpreted cautiously.