Naltrexone, a harm-reduction agent, has seen a surge in popularity, with its use in alcohol use disorder (AUD) treatment in the US tripling from 2015 to 2018. While primarily known for addiction treatment, some have linked naltrexone to weight loss. This raises important questions: Should patients avoid naltrexone due to potential weight-related side effects, or should it be considered as a weight-loss aid? This article delves into the off-label use of naltrexone for weight loss and its associated side effects to provide a comprehensive understanding.
Naltrexone's Role in Addiction Treatment: An Overview
Before exploring the weight reduction aspect, it's crucial to understand naltrexone's primary use in treating substance use disorders (SUDs). Naltrexone was synthesized in 1963, shortly after naloxone was developed. Both drugs are Mu opioid receptor (MOR) antagonists. However, naloxone has a shorter half-life of 3 hours, while oral naltrexone's half-life is approximately 13 hours.
Initially, long-acting methadone was the preferred treatment for opioid addiction. However, as an agonist, methadone had euphoric side effects and a high abuse potential. Naltrexone, a long-acting MOR blocker, quickly gained appeal in the SUD treatment field.
Today, naltrexone is a leading drug for alcohol dependence and opioid addiction in medically assisted treatment (MAT) programs. It is FDA-approved and available as pills or injections under brand names like Revia and Vivitrol. Over time, a potential off-label use emerged based on observed side effects.
Exploring Naltrexone and Weight Loss Side Effects
Loss of appetite is a listed side effect of Revia and Vivitrol. Clinical studies revealed that 14% of individuals using Vivitrol 380 mg intramuscular injections experienced appetite reduction, compared to only 3% in the placebo group.
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This side effect raises two key considerations:
- MAT patients needing naltrexone who want to avoid weight loss.
- Individuals without SUDs seeking weight loss.
For the first group, consulting the care team is crucial to develop a diet and lifestyle that maintains a healthy weight during addiction recovery.
The second group raises the question: Is naltrexone a suitable weight-loss solution for obese patients? To answer this, we must examine how naltrexone (a MOR antagonist) affects appetite and the potential adverse effects of this off-label use.
Possible Mechanisms of Action
Proponents of naltrexone for weight loss often cite its ability to block anticipatory reward. Naltrexone can curb alcohol cravings by reducing the "incentive" to drink. Similarly, it's hypothesized that the drug can help patients avoid no-hunger eating habits like emotional eating.
Additionally, naltrexone blocks the feedback autoinhibition of the hypothalamic pro-opiomelanocortin (POMC). This increases the activity of POMC cells, which can suppress appetite.
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Limitations of Naltrexone for Long-Term Weight Loss
Despite these potential mechanisms, using naltrexone alone for weight loss has significant drawbacks.
Not FDA-Approved: Naltrexone is not FDA-approved for weight reduction. Drug manufacturers must provide clinical data proving a drug's safety and effectiveness for its intended use. Without this, weight loss is an unapproved, off-label application.
Inconclusive Findings: Research on naltrexone's weight-loss effects is mixed. One study suggests it reduces reward-driven eating but doesn't significantly reduce craving intensity. A controlled clinical trial showed that the naltrexone group lost an average of 3.96 lbs, while the placebo group lost 3.3 lbs-an insignificant difference. Another clinical trial found the weight-related effects of naltrexone to be particularly insignificant among male patients.
Variable Side Effects: Even among SUD patients, the evidence isn't conclusive. Weight gain is also a possible side effect of drugs like Revia and Vivitrol. Individuals could lose or gain weight while taking the drug, with no guarantee of either outcome.
Overall, long-term use of naltrexone alone doesn't appear to be effective for meaningful weight loss.
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Combining Naltrexone and Bupropion for Weight Loss: A Promising Alternative
While naltrexone monotherapy is not effective or FDA-approved for weight loss, combining it with bupropion (an antidepressant) shows promise. This combination is available in the US as extended-release tablets under the brand name Contrave, containing 8 mg of naltrexone hydrochloride and 90 mg of bupropion hydrochloride.
How It Works
The exact mechanism of Contrave isn't fully understood, but it's believed to target the hypothalamus and the mesolimbic dopamine reward circuit to suppress hunger and control cravings. Bupropion, a dopamine/norepinephrine reuptake inhibitor, is chemically related to amphetamines, known for their appetite-suppressing effects.
Effectiveness: Studies and Statistics
Studies indicate that the naltrexone/bupropion combination is more effective than either drug alone. Some experts argue that naltrexone without bupropion has no weight loss benefits.
A systematic review of 14 articles reported the combination as promising and well-tolerated. In a 56-week randomized controlled trial, subjects taking a placebo with intensive behavior modification lost an average of 5.1% of their initial weight. In contrast, those using 32 mg of naltrexone with 360 mg of bupropion per day (NB32) alongside behavioral modification lost an average of 9.3%. Overall, 66.4% of the NB32-treated subjects lost at least 5% of their initial weight, and 29.1% lost 15% or more.
Potential Side Effects
Despite its effectiveness, Contrave has potential drawbacks. Common side effects include:
- Nausea and vomiting
- Constipation/diarrhea
- Sleeping problems
- Dizziness and headache
- Dry mouth
Nausea is a particularly prevalent issue, leading to medication discontinuation in 7% of participants in one study. In the 56-week trial, 34.1% of NB-treated subjects reported nausea, and 4.6% discontinued the study due to it.
Other side effects include tinnitus, allergic reactions, and abdominal pain. The drug could also cause suicidal thoughts, neuropsychiatric adverse effects, and increased seizure risk, necessitating careful monitoring. It's considered a prescription weight-loss medication.
Ideal Candidates
Contrave may be suitable for obese adults with a body mass index (BMI) of 30 kg/m2 or higher. Overweight adults with a BMI of 27 kg/m2 may also benefit if they have conditions like high cholesterol, high blood pressure, or type 2 diabetes. Currax Pharmaceuticals offers an online assessment tool to determine BMI eligibility. Generally, a BMI under 27 doesn't meet the criteria for using the drug.
Who Should Avoid It
Aside from BMI, certain conditions and risk factors make Contrave unsuitable:
- Uncontrollably high blood pressure
- History of seizures
- History of eating disorders like anorexia or bulimia
- Use of monoamine oxidase inhibitors within the last 14 days
- Opioid dependence or current opiate withdrawal (risk of overdose)
- Abruptly stopping alcohol, benzos, barbiturates, or antiepileptics
- Taking other medications containing bupropion
- Taking sedatives like benzos
It's crucial to share your medical history with a healthcare professional before starting Contrave.
Tips for Using the Naltrexone/Bupropion Combination
Healthcare professionals provide detailed usage guides, but here are some general tips:
Fight Nausea With Ginger: Ginger chews and tea can help reduce nausea. If ineffective, consult your doctor for anti-nausea medication.
Drink Plenty of Water: Stay hydrated to reduce constipation. Take the tablet with 8 oz of water and drink more throughout the day. Regular exercise can also help.
Shift to a Healthy Lifestyle: Combine medication with a healthy diet and exercise routine. Clinical studies often incorporate behavioral modification.
Avoid High-Fat Meals With the Dose: Fat content can affect the drug's absorption rate, increasing the risk of seizures.
Take Your Tablets the Right Way: Dosage typically starts small and increases gradually. Never take more than two tablets at once or four tablets in a single day. If you miss a dose, skip it and resume the schedule. Inform your doctor about any missed doses.
Other Off-Label Uses for Naltrexone
Besides weight loss, naltrexone has other off-label uses. Low-dose naltrexone may be prescribed for chronic pain management. Research on its use as an adjunctive agent in treating compulsive disorders has yielded mixed results.
Vivitrol: A Closer Look at Side Effects
Vivitrol, an extended-release injectable form of naltrexone, is widely used in the United States to support recovery from opioid and alcohol addiction. Administered monthly, it blocks opioid receptors in the brain, reducing cravings and the desire to use substances without causing euphoria or physical dependence. As part of Medication-Assisted Treatment (MAT), it's combined with counseling and behavioral therapies.
Weight changes are a possible side effect, with varying direction and extent. Some individuals report weight loss due to appetite suppression or gastrointestinal issues like nausea and occasional vomiting, especially early in treatment. Weight gain has also been observed, making the overall effect unpredictable.
Understanding Weight Changes with Vivitrol
The mechanism behind these changes involves naltrexone interfering with reward pathways that enhance hunger cues and food-related pleasure. As a result, naltrexone may blunt appetite. However, weight changes aren't always solely due to the medication.
In the early weeks of treatment, some patients may experience nausea or reduced appetite, leading to temporary lower food intake and minor weight loss. These symptoms usually improve as the body adjusts. Maintaining balanced nutrition and hydration is essential during treatment.
Open communication with healthcare providers about significant fluctuations is crucial. Personalized approaches to diet and lifestyle can help manage weight effectively. Regular physical activity can improve appetite and metabolic function.
Additional Side Effects of Vivitrol
Beyond changes in appetite or digestion, patients may notice other common side effects, including headaches, dizziness, fatigue, or discomfort at the injection site, such as temporary pain, swelling, or redness.
Weight changes, whether gain or loss, are possible and vary widely. Understanding that appetite suppression and gastrointestinal side effects are common early during treatment can help patients and caregivers prepare for these changes.
Common and Mild Side Effects of Vivitrol
Like other drugs, Vivitrol can cause side effects, some more common than others. More common side effects in people receiving Vivitrol for alcohol dependence include nausea, mild injection site reaction, headache, dizziness or fainting, and reduced appetite. More common side effects in people receiving Vivitrol for opioid dependence include injection site pain, insomnia, the common cold or flu, and toothache. Vivitrol is a long-acting injection, with effects lasting at least a month. If you have side effects, they may improve after a few days or weeks, but some may continue until the injection wears off.
Mild side effects that have been reported with Vivitrol include headache, dizziness or fainting, reduced appetite, insomnia, the common cold or flu, increased blood pressure, toothache, vomiting, diarrhea, abdominal pain, joint pain or stiffness, muscle cramps, anxiety, weakness or fatigue, sleepiness, mild injection site reaction, nausea, and weight gain.
Serious Side Effects of Vivitrol
While not common, treatment with Vivitrol can cause serious side effects, including eosinophilic pneumonia, sudden opioid withdrawal (if you’ve used an opioid in the 7 to 14 days before a Vivitrol dose), depression and suicidal thoughts or behaviors, allergic reaction, liver damage, and severe injection site reactions.
It is essential to contact your doctor right away if you develop serious side effects while being treated with Vivitrol.
Managing Vivitrol Side Effects: Practical Tips
- Injection Site Reactions: Vivitrol must be administered by a healthcare professional using the correct needle and injection technique to minimize the risk of injection site reactions. If you have an injection site reaction that’s bothersome, severe, doesn’t get better after a few days, or worsens, talk with your doctor.
- Depression and Suicidal Thoughts: Consider telling your family or close friends that you’re receiving Vivitrol treatment, so they can watch for any changes in your mood or behavior. If you have symptoms of depression, or any other changes in your mood or behavior, talk with your doctor right away.
- Liver Damage: Your doctor will order liver function tests (LFTs) to check the health of your liver during Vivitrol treatment. If you have symptoms of liver damage during Vivitrol treatment, see your doctor right away.
- Nausea: Talk with your doctor if you have nausea that’s bothersome after receiving Vivitrol. They can recommend ways to help reduce this side effect.
- Weight Gain: During your Vivitrol treatment, talk with your doctor about your diet and nutrition. If you’re concerned about gaining or losing weight, talk with your doctor.
- Allergic Reaction: For mild symptoms of an allergic reaction, call your doctor right away. But if your symptoms are serious and you think you’re having a medical emergency, immediately call 911 or your local emergency number.
Important Considerations Before Starting Vivitrol
Be sure to talk with your doctor about your health history before starting Vivitrol treatment, especially if you have a history of allergic reaction, recent use of opioids, bleeding problems, kidney problems, or liver problems.
Naltrexone and Weight Loss: Contradictory Findings
Naltrexone has been linked to weight loss, so much so that it is sometimes used specifically for that purpose. Naltrexone can cause nausea, and it has also been linked to reduced food consumption, directly affecting a person’s appetite even if they don’t experience nausea. A 2020 review of available data on the safety and efficacy of naltrexone for weight loss in adult patients found that the medication can be used as a promising therapy for obese patients.
A 2000 study in the Journal of Clinical Psychopharmacology examined naltrexone-induced nausea in patients taking the medication for treatment of alcohol dependence. The study noted that the medication is well tolerated by most people with AUD but that a subset feel nauseous on it, with 15% of the subjects examined in the study reporting moderate to severe nausea. This study also found risk of nausea was “significantly predicted by age, gender, intensity of drinking, duration of abstinence, and the interaction of abstinence duration and intensity of drinking.” Younger patients and female patients were associated with higher risks of nausea. Nausea and vomiting can lead to weight loss.
A 2011 study examined weight changes that occurred among opioid-dependent patients taking either naltrexone or methadone as part of their treatment. Methadone is an opioid agonist, which this study noted is often associated with weight gain. Contrary to the other studies discussed, this study didn’t seem to link the use of naltrexone in addiction treatment to weight loss. It found weight change didn’t significantly vary between patients on methadone and patients on naltrexone.
The mechanism by which Vivitrol can impact weight isn’t fully understood. The current literature suggests it’s a combination of factors. First, the medication can directly affect appetite. When used to treat addiction, nausea is also relatively common with Vivitrol, which can further affect appetite and a person’s ability to eat even if they’re hungry. With that said, the 2011 study discussed earlier shows that at least some people who take Vivitrol experience weight gain, although the gain doesn’t seem to be especially high.
If you’ve been prescribed Vivitrol to treat addiction or drug dependence, it’s important to understand that weight loss or gain isn’t the goal of your treatment. If you are concerned that you may be losing or gaining weight too quickly, or if weight change is otherwise impacting your quality of life, talk to your doctor. As you participate in a comprehensive addiction treatment program, you’ll work on implementing changes to build a healthier life in recovery.
Risks of Using Revia (Naltrexone) for Weight Loss
People have begun taking low-dose naltrexone (Revia) or a combination naltrexone/bupropion formula in order to lose weight. Naltrexone/bupropion has been FDA-approved for weight loss in some patients, whereas naltrexone on its own has not been approved and is considered off-label. Taking Revia for weight loss can negatively affect your physical and psychological health, especially for those with a history of dieting. This is because dieting is a risk factor for disordered eating and developing an active eating disorder. In fact, research has shown that about one-quarter of individuals who engage in severe dieting develop an eating disorder. You should always consult your doctor, and your medical team, before taking medication for weight loss.
Common and Severe Side Effects of Naltrexone
Common side effects of naltrexone use may include nausea and vomiting, dizziness, sleepiness, sleep disturbances, muscle cramps and joint pain, headache and toothache, flu-like symptoms, anxiety and irritability, and constipation or diarrhea.