naltrexone

Pharmacotherapy for Adults With Alcohol Use Disorder in Outpatient Settings: Systematic Review
Background. Unhealthy alcohol use is the third leading preventable cause of death in the United States, accounting for more than 140,000 deaths annually. Only 0.9 percent of Americans who reported having alcohol use disorder (AUD) in the past year indicated they received medication-assisted AUD treatment.

Methods. We updated a 2014 Agency for Healthcare Research and Quality (AHRQ) report on pharmacotherapy for AUD treatment, following AHRQ Evidence-based Practice Center Guidance. We assessed efficacy and comparative effectiveness of specific medications for improving consumption outcomes (Key Question [KQ] 1) and health outcomes (KQ 2). We assessed harms (KQ 3) and sought to identify evidence for the use of pharmacotherapy to treat AUD in primary care (KQ 4) and among subgroups (KQ 5). When possible, we conducted quantitative analyses using random-effects models to estimate pooled effects. When quantitative analyses could not be conducted, we used qualitative approaches.

Results. We included 118 studies (156 articles) in our review, which included 81 studies (106 articles) from the 2014 review and 37 studies (50 articles) published since then. Studies generally included counseling co-interventions in all study groups, and the benefits observed reflect the added benefit of medications beyond those of counseling and placebo. Oral naltrexone at the 50 mg dosage had moderate strength of evidence (SOE) for reducing return to any drinking, return to heavy drinking, percent drinking days, and percent heavy drinking days. The addition of a new randomized controlled trial of injectable naltrexone conducted in a population experiencing homelessness resulted in positive outcomes for a reduction in drinking days and heavy drinking days with low SOE. Acamprosate had moderate SOE for a significant reduction in return to any drinking and reduction in drinking days. Topiramate had moderate SOE for several outcomes as well, but with greater side effects. Two other medications demonstrated low SOE for benefit in at least one consumption outcome—baclofen (reduced return to any drinking) and gabapentin (reduced return to drinking and to heavy drinking). With no new studies on disulfiram, there remains inadequate evidence for efficacy compared to placebo for preventing return to any drinking or for other alcohol consumption outcomes. No new eligible studies provided head-to-head comparisons.

Conclusions. Oral naltrexone at the 50 mg dose had moderate strength of evidence across multiple outcomes and relative ease of use as a once-daily oral medication. Acamprosate and topiramate also have moderate evidence of benefit with a less desirable side effect profile (topiramate) and a higher pill burden (acamprosate). Clinicians and patients may want to consider which treatment outcomes are most important when choosing among the medications. Current data are largely insufficient for understanding health outcomes. Finally, there is relatively little research to assess the use of medications for AUD among subgroups (9 studies) or in primary care settings (1 study).

Author/s:

Melissa McPheeters, Elizabeth A. O’Connor, Sean Riley, Sara M. Kennedy, Christiane Voisin, Kaitlin Kuznacic, Cory P. Coffey, Mark Edlund, Georgiy Bobashev, Daniel E. Jonas

Looking Back, Looking Forward: Current Medications and Innovative Potential Medications to Treat Alcohol Use Disorder

Aubrey Delammermore — Sun, 06 Nov 2022 05:00:00 +0000

Date Added:

November 6, 2022

Journal/Publication:

Alcohol Research Current Reviews

Publisher:

National Institutes of Health

Publication Date:

October 20, 2022

Issue:

Volume:

URL:

Looking Back, Looking Forward: Current Medications and Innovative Potential Medications to Treat Alcohol Use Disorder

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.35946/arcr.v42.1.11

Keywords

alcohol

alcoholism

National Institute on Alcohol Abuse and Alcoholism (U.S.)

National Institutes of Health (U.S.)

naltrexone

PMID (1):

36320345

MeSH

Alcohol Deterrents* / therapeutic use

Alcoholism* / diagnosis

Naltrexone / therapeutic use

alcohol drinking

Alcohol-Related Disorders*

A review of current and potential new medications for treatment of patients with alcohol use disorders. James W. Mold, MD, MPH

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This article is part of a Festschrift commemorating the 50th anniversary of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Established in 1970, first as part of the National Institute of Mental Health and later as an independent institute of the National Institutes of Health, NIAAA today is the world's largest funding agency for alcohol research. In addition to its own intramural research program, NIAAA supports the entire spectrum of innovative basic, translational, and clinical research to advance the diagnosis, prevention, and treatment of alcohol use disorder and alcohol-related problems. To celebrate the anniversary, NIAAA hosted a 2-day symposium, "Alcohol Across the Lifespan: 50 Years of Evidence-Based Diagnosis, Prevention, and Treatment Research," devoted to key topics within the field of alcohol research. This article is based on Dr. Mason's presentation at the event. NIAAA Director George F. Koob, Ph.D., serves as editor of the Festschrift.

Author/s:

Mason, B. J.

Bupropion and Naltrexone in Methamphetamine Use Disorder

Devin Evans — Thu, 21 Jan 2021 06:00:00 +0000

Date Added:

January 21, 2021

Journal/Publication:

The New England Journal of Medicine

Publication Date:

January 14, 2021

Volume:

384

Pages:

140-153

URL:

Bupropion and Naltrexone in Methamphetamine Use Disorder

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2020214

Keywords

Methamphetamine Use Disorder

MeSH

The combination of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) was more effective than placebo for helping adults abstain from methamphetamine. James W. Mold, MD, MPH

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BACKGROUND

The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.

METHODS

We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone–bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone–bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.

RESULTS

A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone–bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone–bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone–bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone–bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone–bupropion during the trial.

CONCLUSIONS

Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo.

Author/s:

Trivedi, Madhukar H., Walker, Robrina, Ling, Walter, Dela Cruz, Adriane, Sharma, Gaurav, Carmody, Thomas, Ghitza, Udi E., Wahle, Aimee, Kim, Mora, Shores-Wilson, Kathy, Sparenborg, Steven, Coffin, Philip, Schmitz, Joy, Wiest, Katharina, Bart, Gavin, Sonne, Susan C., Wakhlu, Sidarth, Rush, A.J., Nunes, Edward V., Shoptaw, Steven

Evidenced-Based Pharmacotherapies for Alcohol Use Disorder

John Bayhi — Thu, 21 May 2020 16:22:32 +0000

Date Added:

May 21, 2020

Journal/Publication:

Mayo Clinic Proceedings

Publisher:

Elsevier Inc / Mayo Foundation for Medical Education and Research

Publication Date:

May 20, 2020

Volume:

Article in Press

URL:

Evidenced-Based Pharmacotherapies for Alcohol Use Disorder

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.mayocp.2020.01.030

Keywords

MeSH

Pharmacogenomic Testing

united states food and drug administration

A review of pharmacological approaches to the treatment of alcoholism with some clinical pearls from Mayo physicians. James W. Mold, MD, MPH

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Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.

Author/s:

Fairbanks, J, Umbreit, A, Kolla, BP, Karpyak, VM, Schneekloth, TD, Loukianova, LL, Sinha, S

Medication-Assisted Treatment for Opioid-Use Disorder

John Bayhi — Tue, 24 Sep 2019 22:22:30 +0000

Date Added:

October 3, 2019

Journal/Publication:

Mayo Clinic Proceedings

Publisher:

Mayo Foundation for Medical Education and Research / Elsevier Inc.

Publication Date:

September 9, 2019

Issue:

Volume:

Pages:

2072-2086

URL:

Medication-Assisted Treatment for Opioid-Use Disorder

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.mayocp.2019.03.029

Keywords

PMID (1):

31543255

MeSH

Buprenorphine

naltrexone

methadone

opioid-related disorders

analgesics, opioid

outpatients

A nice review of how and when to use the three available medications for treating patients with opioid dependency. James W. Mold, MD, MPH

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The United States is in the midst of a national opioid epidemic. Physicians are encouraged both to prevent and treat opioid-use disorders (OUDs). Although there are 3 Food and Drug Administration-approved medications to treat OUD (methadone, buprenorphine, and naltrexone) and there is ample evidence of their efficacy, they are not used as often as they should. We provide a brief review of the 3 primary medications used in the treatment of OUD. Using data from available medical literature, we synthesize existing knowledge and provide a framework for how to determine the optimal approach for outpatient management of OUD with medication-assisted treatments.

Author/s:

Oesterle, TS, Thusius, NJ, Rummans, TA, Gold, MS

Naltrexone for the treatment of alcoholism: A meta-analysis of randomized controlled trials

Jeffrey Wilson — Wed, 02 Jan 2019 14:38:22 +0000

Date Added:

January 2, 2019

Journal/Publication:

International Journal of Neuropsychopharmacology

Publisher:

Oxford University Press

Publication Date:

June 1, 2005

Issue:

Volume:

Pages:

267-280

URL:

Naltrexone for the treatment of alcoholism: A meta-analysis of randomized controlled trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1017/S1461145704004997

Keywords

alcohol

alcoholism

naltrexone

PMID (1):

15850502

MeSH

alcohol

alcoholism

naltrexone

This Meta-analysis involving 2861 subjects in 24 RCTs found that, in short-term treatment, naltrexone significantly decreased relapses [relative risk (RR) 0.64, 95% confidence interval (CI) 0.51-0.82], but not return to drinking (RR 0.91, 95% CI 0.81-1.02). Short-term treatment of naltrexone significantly increased nausea, dizziness, and fatigue in comparison to placebo [RRs (95% CIs) 2.14 (1.61-2.83), 2.09 (1.28-3.39), and 1.35 (1.04-1.75)].

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Many trials of naltrexone have been carried out in alcohol-dependent patients. This paper is aimed to systematically review its benefits, adverse effects, and discontinuation of treatment. We assessed and extracted the data of double-blind, randomized controlled trials (RCTs) comparing naltrexone with placebo or other treatment in people with alcoholism. Two primary outcomes were subjects who relapsed (including heavy drinking) and those who returned to drinking. Secondary outcomes were time to first drink, drinking days, number of standard drinks for a defined period, and craving. All outcomes were reported for the short, medium, and long term. Five common adverse effects and dropout rates in short-term treatment were also examined. A total of 2861 subjects in 24 RCTs presented in 32 papers were included. For short-term treatment, naltrexone significantly decreased relapses [relative risk (RR) 0.64, 95% confidence interval (CI) 0.51-0.82], but not return to drinking (RR 0.91, 95% CI 0.81-1.02). Short-term treatment of naltrexone significantly increased nausea, dizziness, and fatigue in comparison to placebo [RRs (95% CIs) 2.14 (1.61-2.83), 2.09 (1.28-3.39), and 1.35 (1.04-1.75)]. Naltrexone administration did not significantly diminish short-term discontinuation of treatment (RR 0.85, 95% CI 0.70-1.01). Naltrexone should be accepted as a short-term treatment for alcoholism. As yet, we do not know the appropriate duration of treatment continuation in an alcohol-dependent patient who responds to short-term naltrexone administration. To ensure that the real-world treatment is as effective as the research findings, a form of psychosocial therapy should be concomitantly given to all alcohol-dependent patients receiving naltrexone administration.

Author/s:

Srisurapanont, Manit, Jarusuraisin, Ngamwong