Naltrexone, sold under the brand names Revia and Vivitrol among others, is a medication primarily used to manage alcohol use or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found effective in the treatment of other addictions and may be used for them off-label. An opioid-dependent person should not receive naltrexone before detoxification. It is taken by mouth or by injection into a muscle. Effects begin within 30 minutes, though a decreased desire for opioids may take a few weeks to occur.
Side effects may include trouble sleeping, anxiety, nausea, and headaches. In those still on opioids, opioid withdrawal may occur. Use is not recommended in people with liver failure. It is unclear if use is safe during pregnancy. Naltrexone is an opioid antagonist and works by blocking the effects of opioids, including both opioid drugs as well as opioids naturally produced in the brain.
Naltrexone was first made in 1965 and was approved for medical use in the United States in 1984. Naltrexone, as naltrexone/bupropion (brand name Contrave), is also used to treat obesity. It is on the World Health Organization's List of Essential Medicines.
Medical uses
Alcohol use disorder
Naltrexone has been best studied as a treatment for alcoholism. Naltrexone has been shown to decrease the quantity and frequency of ethanol consumption by reducing the dopamine release from the brain after consuming alcohol. It does not appear to change the percentage of people drinking. Its overall benefit has been described as "modest".
Acamprosate may work better than naltrexone for eliminating alcohol abuse, while naltrexone may decrease the desire for alcohol to a greater extent.
A method pioneered by scientist John David Sinclair (dubbed commercially the “Sinclair Method”) advocates for “psychological extinction” of problem drinking behavior by administering naltrexone alongside controlled alcohol consumption. In effect, he argues naltrexone induced opiate antagonism sufficiently disrupts reflexive reward mechanisms inherent in the consumption alcohol and, given enough repetition, will disassociate positive associations formerly made with the consumption of alcohol.
Opioid use
Long-acting injectable naltrexone, under the brand name Vivitrol, is an opioid receptor antagonist, blocking the effects of heroin and other opioids, and decreases heroin use compared to a placebo. Unlike methadone and buprenorphine, it is not a controlled medication. It may decrease cravings for opioids after a number of weeks, and decreases the risk of overdose, at least during the time period that naltrexone is still active, though concern about risk of overdose for those stopping treatment remains. It is given once per month and has better compliance and effect for opioid use than the oral formulation.
A drawback of injectable naltrexone is that it requires patients with opioid use disorder and current physiological dependence to be fully withdrawn before it is initiated to avoid a precipitated opioid withdrawal that may be quite severe. In contrast, initiation of buprenorphine only requires delay of the first dose until the patient begins to manifest at least mild opioid withdrawal symptoms. Among patients able to successfully initiate injectable naltrexone, long-term remission rates were similar to those seen in clinical naltrexone/buprenorphine administration.
Consequence of relapse when weighting best course of treatment for opiate use disorder remains a concern. Methadone and buprenorphine administration maintains greater drug tolerance while naltrexone allows tolerance to fade, leading to higher instances of overdose in people who relapse and thus higher mortality. Guidelines from the World Health Organization cite evidence of superiority in reducing mortality and retaining patients in care with opioid agonists (methadone or buprenorphine), concluding that most patients should be advised to use agonists rather than antagonists like naltrexone.
A 2011 review found insufficient evidence to determine the effect of naltrexone taken by mouth in opioid dependence. While some do well with this formulation, it must be taken daily, and a person whose cravings become overwhelming can obtain opioid intoxication simply by skipping a dose. Due to this issue, the usefulness of oral naltrexone in opioid use disorders is limited by the low retention in treatment. Naltrexone by mouth remains an ideal treatment for a small number of people with opioid use, usually those with a stable social situation and motivation. With additional contingency management support, naltrexone may be effective in a broader population.