“What Is Vivitrol?” I get asked that more and more often. Vivitrol is the injection (shot) form of a medication known as Naltrexone. And it’s use has grown significantly over the past several years – and for good reason. This article is intended to give you a little info and hopefully provide some clarity too.
- Most commonly used for Opioid and Alcohol Withdrawal and to inhibit cravings
- Comes in oral (Naltrexone) and IM (Vivitrol) forms
- Must be prescribed by an approved physician
- Is not meant to be a “magic pill” cure
- Like other Medication-Assisted Treatment (MAT) options – the highest successful outcomes are when it is paired with therapy/treatment and support.
- It is very different than other MAT out there at this time.
*If you or someone you love is struggling with addiction, please cheack out this resource page*
Naltrexone is an opioid antagonist that has the highest affinity for the -opioid receptors. In addition to its ability to block the effects of opioids, this compound has very few, if any, inherent effects. In 1994, the Food and Drug Administration of the United States gave its approval for the use of Naltrexone in the treatment of alcoholism (Kranzler, Wesson, Billot, Clinical, & Research, 2004).
In spite of this permission, the studies that have been conducted to determine whether or not Naltrexone is effective in treating alcoholism have produced mixed results. Patients failure to follow the prescribed treatment regimen while taking oral Naltrexone is one factor that contributes to the treatment’s overall lack of efficacy.
Some studies have also shown that in order for subjects to have greater reductions in alcohol consumption and risk of relapse as compared to subjects who were treated with a placebo, they must be highly compliant with the Naltrexone treatment. Utilizing formulations that provide sustained release or depot treatment is one approach that can be taken to address this issue.
VivitrolTM, a depot injectible dosage form of Naltrexone, was approved by the FDA on April 13, 2006, for the treatment of alcohol dependence in patients who are capable of withdrawing from drinking in an outpatient setting and who are not actively drinking at the beginning of therapy. Patients must also not be drinking at the time treatment begins. The recommended dosage of Vivitrol is 380 milligrams, which should be injected once per month or every 28 days.
Both DepotrexTM and NaltrelTM are examples of alternative depot parenteral formulations of Naltrexone. Naltrel helped to promote abstinence and decreased the incidence of relapse in two samples of alcohol-dependent subjects, while Vivitrol was shown to be effective at reducing heavy drinking among alcohol-dependent males (Chick et al., 2000; Monti et al., 2001).
The use of Naltrexone provides a blockade against the intoxicating and reinforcing effects of opioid-like compounds, which, in theory, can result in the elimination of drug-taking behavior. It does not produce euphoric effects, and as a result, it is not abused. Additionally, it does not result in physiological dependence on the user.
Similar to the situation with alcohol, the primary challenge presented by the oral formulation of Naltrexone for the treatment of opium or heroin dependence is low compliance (adherence). Long-acting sustained release formulations of Naltrexone (injectable or implantable) may help to develop compliance and, as a result, augment the efficacy of abstinence-oriented treatments with Naltrexone for heroin or opium dependence. Following the completion of opioid detoxification, the administration of Vivitrol is done for the purpose of preventing a return to opiate dependence (B. A. J. T. Johnson & management, 2007).
Mechanism of Action
Dopaminergic pathways, (which have their origins in the ventral tegmental area, relay to the nucleus accumbens with neuronal inputs from other limbic regions, and progress to the cortex), are responsible for mediating the reinforcing effects of alcohol, which are associated with the substance’s potential for abuse. An antagonist for the mu-opioid receptor, Naltrexone, reduces the positive effects of alcohol through two distinct mechanisms. First, it prevents alcohol from causing beta-endorphin stimulation of dopamine neurons directly in the nucleus accumbens. Second, it prevents beta-endorphin from disabling the tonic inhibition of dopamine cells caused by gamma-aminobutyric acid neurons in the ventral tegmental area (Koob & Research, 2003; Wise & Bozarth, 1987).
Oral Dosage Form and Its Effects
In alcohol-dependent people who had recently stopped drinking, taking oral Naltrexone was effective at reducing the likelihood of relapsing and going back to drinking heavily. Its general effectiveness has been limited by two consequential factors, one of which is that the pharmacokinetic properties of oral Naltrexone lead to significant fluctuations in plasma levels with oral daily dosing. A medication adherence rate of at least 85 percent is necessary in order for there to be a therapeutic response. First, the low plasma trough level of oral Naltrexone reduces the efficacy of the drug, which may explain why this requirement exists. Second, it is believed that high peak levels are responsible for adverse events, and it is estimated that up to 15% of people who receive oral Naltrexone will discontinue treatment due to adverse events, particularly nausea (B. A. Johnson & Ait-Daoud, 2000).
Therefore, optimizing the pharmacokinetic profile of Naltrexone by developing a deep intramuscular injection that would release Naltrexone over the course of several weeks would make the drug more effective as a whole. Therefore, plasma levels would remain relatively constant, and while they would be low enough to cut down on the number of adverse events, they would still be high enough to produce the desired anti-drinking effects. In other words, even though it is not anticipated that the effect size of the long-acting, intramuscular formulation of Naltrexone will be greater than the effect size of oral Naltrexone, it is likely that the overall outcome will be improved because of the increased compliance and longer exposure to a therapeutic dose (Bartus et al., 2003).
Patients are typically given 380 mg of the long-acting injectable (LAI) form of Naltrexone once every 28 days, and oral Naltrexone is typically titrated up to the target dose of 50 mg per day. Although the use of LAI Naltrexone does not require a trial period of oral Naltrexone, it is standard practise to determine the patient’s level of toleraance with oral doses before moving on to higher concentrations. It is possible that the use of LAI Naltrexone has benefits for adherence when compared to the use of oral Naltrexone. This is due to the fact that non-adherence is common among patients who are taking medication for alcohol use disorder.
3.1% of patients in the study were given any form of Naltrexone, but only 0.24% of patients were given LAI Naltrexone. This information was obtained from a study. Even though about 40% of people have experienced alcohol abuse of some kind at some point in their lives, very few people are actually receiving the help they need. According to the findings of the same study, the patients who were given the intramuscular injection were more likely to make use of both outpatient and inpatient mental health services. Patients battling alcohol use disorders who receive treatment that is both pharmacologic and makes use of mental health resources have better outcomes as a result of their treatment. These resources for mental health include individual drug counselling, care management, monitoring of a patient’s substance use, and intensive outpatient treatment, among other options (Aletraris, Shelton, & Roman, 2015; Marienfeld, Iheanacho, Issa, & Rosenheck, 2014).
More research is needed in order to find out the effects and outcomes of drug with the use of oral dosage form and other dosage forms.
Aletraris, Lydia, Shelton, Jeff S, & Roman, Paul M %J Journal of substance abuse treatment. (2015). Counselor attitudes toward contingency management for substance use disorder: Effectiveness, acceptability, and endorsement of incentives for treatment attendance and abstinence. 57, 41-48.
Bartus, Raymond T, Emerich, Dwaine F, Hotz, Joyce, Blaustein, Marc, Dean, Reginald L, Perdomo, Brigido, & Basile, Anthony S %J Neuropsychopharmacology. (2003). Vivitrex®, an injectable, extended-release formulation of naltrexone, provides pharmacokinetic and pharmacodynamic evidence of efficacy for 1 month in rats.28(11), 1973-1982.
Chick, Jonathan, Anton, Raymond, Checinski, Ken, Croop, Robert, Drummond, D Colin, Farmer, Roger, . . . alcoholism. (2000). A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. 35(6), 587-593.
Johnson, Bankole A %J Therapeutics, & management, clinical risk. (2007). Naltrexone long-acting formulation in the treatment of alcohol dependence. 3(5), 741.
Johnson, Bankole A, & Ait-Daoud, Nassima %J Psychopharmacology. (2000). Neuropharmacological treatments for alcoholism: scientific basis and clinical findings. 149(4), 327-344.
Koob, George F %J Alcoholism: Clinical, & Research, Experimental. (2003). Alcoholism: allostasis and beyond.27(2), 232-243.
Kranzler, Henry R, Wesson, Donald R, Billot, Laurent, Clinical, DrugAbuse Sciences Naltrexone Depot Study Group %J Alcoholism:, & Research, Experimental. (2004). Naltrexone depot for treatment of alcohol dependence: a multicenter, randomized, placebo‐controlled clinical trial.28(7), 1051-1059.
Marienfeld, Carla, Iheanacho, Theddeus, Issa, Mohammed, & Rosenheck, Robert A %J Addictive Behaviors. (2014). Long-acting injectable depot naltrexone use in the Veterans’ Health Administration: a national study. 39(2), 434-438.
Monti, Peter M, Rohsenow, Damaris J, Swift, Robert M, Gulliver, Suzy B, Colby, Suzanne M, Mueller, Timothy I, . . . Research, Experimental. (2001). Naltrexone and cue exposure with coping and communication skills training for alcoholics: treatment process and 1‐year outcomes. 25(11), 1634-1647.
Wise, Roy A, & Bozarth, Michael A %J Psychological review. (1987). A psychomotor stimulant theory of addiction.94(4), 469.