People seeking treatment for opioid dependence or opioid use disorder (OUD) can utilize one of three medications available for OUD treatment. This includes naltrexone, an opioid antagonist that blocks opioid effects and supports abstinence. It is important to understand the risks and requirements of naltrexone treatment before commencement.
- Naltrexone is a medication used for opioid use disorder, available as a daily tablet or monthly injection.
- Naltrexone can be a very effective medication for abstinence and maintenance within OUD treatment, although noncompliance and discontinuation can significantly impair its effectiveness.
- Naltrexone is not usually the first medication choice for OUD treatment, although in some cases it may be the most appropriate and effective.
Understanding naltrexone and how it works
Naltrexone is a medication classed as an opioid antagonist, used to help people maintain abstinence from opioids following opioid dependence or opioid use disorder (OUD). Naltrexone works primarily by blocking opioid receptors in the brain, preventing the effects of opioids. [1]
Naltrexone is approved by the Food and Drug Administration (FDA) for the treatment of OUD and alcohol use disorder (AUD). It can be used in OUD after a detoxification period is completed. For both AUD and OUD, naltrexone can help reduce cravings, adverse effects, and relapse, helping to maintain abstinence [1][2]
Naltrexone is available as an oral tablet to be taken daily or as an extended-release injection administered once monthly. [1]
How naltrexone helps treat OUD
For OUD, naltrexone primarily works by blocking the euphoric and reinforcing effects of opioids, helping prevent relapse and support long-term recovery. Some people also experience reduced cravings, although this effect is less consistent than with opioid agonist medications like methadone and buprenorphine.
Naltrexone treatment for OUD can be commenced after the individual has been abstinent from opioids for 7-10 days. Because naltrexone works as an opioid antagonist, it blocks opioid effects, which can cause a sudden onset of withdrawal symptoms if opioids have been recently used. [1]
Opioids, such as heroin, morphine, and oxycodone, bind to the mu-opioid receptor in the brain, creating their euphoric effects. Naltrexone acts on mu-opioid receptors, blocking other substances from binding to them. This means that, if opioids are used while on naltrexone treatment, they will be unable to cause a euphoric or intoxicating effect. [3]
Because of this, the individual doesn’t experience the same psychological or physical effects that reinforce opioid use. This helps to reduce cravings and opioid use, thus supporting abstinence and preventing relapse. [3]
How effective is it?
While naltrexone can be effective when taken as prescribed for OUD, a prominent issue found with naltrexone treatment is compliance and continuation of treatment. Many people who commence naltrexone oral treatment discontinue treatment within a short period or have difficulties taking the oral tablet daily. [4][5]
Studies show that naltrexone can: [5]
- Reduce the risk of relapse
- Increase treatment retention
- Reduce reincarceration among people with a criminal history
Extended-release injectable naltrexone improves treatment retention compared with oral naltrexone, although overall retention is generally lower than with methadone or buprenorphine. [5][6]
Who should not take naltrexone?
People who should not take naltrexone include: [1][3]
- People who are pregnant or breastfeeding, as the fetus or baby may be impacted by exposure to naltrexone. In some cases, the risk of discontinuing treatment outweighs the risk to the child, although alternative treatments may be preferable.
- Individuals under the age of 18, as the safety of this has not been established.
- People with liver or kidney impairment may require a reduced dose or alternative treatment options.
- People who have NOT been abstinent from opioids for 7-10 days, or who are still experiencing acute opioid withdrawal symptoms.
Why patients must be opioid-free before starting naltrexone
Naltrexone can cause a rapid onset of severe opioid withdrawal symptoms in people who have not been opioid-free for 7- 10 days, which is also known as precipitated withdrawal. If opioids have been used within the days before naltrexone, the naltrexone effectively kicks the opioid off the mu-opioid receptor, causing sudden withdrawal. [1][7]
If a person stops taking opioids and withdrawal symptoms emerge, they can be intense and unpleasant, but are likely to be far less intense than a naltrexone precipitated withdrawal. Because of this, it is necessary to be opioid-free before commencing naltrexone. [7]
Oral naltrexone vs. Vivitrol
Vivitrol is a branded version of extended-release injectable naltrexone. Unlike oral naltrexone, which requires daily tablet administration, Vivitrol requires a once-per-month injection. Because of this, Vivitrol has a much higher success rate, as noncompliance is prevented and people are more likely to remain in treatment. [5][6]
As with oral naltrexone, a common issue with Vivitrol is the introduction of the medication, as it requires 7-10 days of abstinence before commencement. If an abstinence period cannot be confirmed, it may be necessary to commence a low dose of oral naltrexone before increasing the dose or starting injectable treatment.
Among people who successfully detox and begin treatment, extended-release naltrexone has been shown to be similarly effective to buprenorphine for preventing relapse. However, fewer patients are able to start naltrexone because it requires a prolonged opioid-free period before initiation. [3][8]
Safety, side effects, and contraindications
Naltrexone treatment can cause side effects, particularly at the start of treatment, such as: [1]
- Stomach issues, such as diarrhea and cramps
- Slight increase in blood pressure
- Headaches
- Reduced energy
- Sleep disturbances
When naltrexone is used long-term, side effects tend to be minimal, and it is considered a safe long-term treatment option.
Naltrexone should not be used with: [1]
- Opioids
- Bremelanotide
- Thioridazine
Overdose risk after discontinuation
People taking naltrexone should be aware of the risk of overdose after discontinuation. People with OUD are likely to build a tolerance to opioids, which, during treatment like naltrexone, will be significantly reduced, and sensitivity to opioids will be higher. This means that, if opioid use is resumed at previous doses, there is a high risk that these doses will now be dangerously high and may lead to overdose. [3]
What to expect during treatment
Someone commencing naltrexone treatment will have completed a full assessment and received a clinical recommendation for treatment planning. They can expect a necessary detoxification phase of 7-10 days, followed by commencement of the medication.
A treatment plan might include commencing oral naltrexone. This might start at a low dose, to be gradually increased as safety is established. Administration could transition to a once-monthly injection, although this will depend on individual needs. [1][7]
Cost and insurance coverage
Insurance providers generally will cover some, if not all, of the cost of OUD treatment medications such as Naltrexone. It is advisable to consult with the insurance provider before commencing treatment to confirm this.
Oral naltrexone is cheaper than extended-release injectable naltrexone when comparing 30-day costs, although overall treatment costs may be lower when using injectable naltrexone. [6]
Duration of treatment
Treatment duration varies depending on individual needs and medication effectiveness. Naltrexone can be used long-term as a safe and effective option.
Follow-up care and monitoring
Side effects are generally common at the start of a new treatment, and the individual will engage in regular reviews with a clinician to monitor safety and effectiveness throughout treatment. Initially, reviews will be required on a regular basis, which can become less frequent as treatment continues.
Long-term recovery planning
If naltrexone is used long-term, it might be more likely to be administered as a monthly injection once safety and effectiveness have been established. This should form part of an integrated treatment plan, involving relapse prevention, psychological and behavioral support, and other treatment approaches. [1][3]
Naltrexone vs. Methadone vs. Buprenorphine
Naltrexone, methadone, and buprenorphine are all FDA-approved medications for OUD, and all are deemed to be safe and effective treatments. The most appropriate treatment option will vary depending on the individual and their needs. Key comparisons include: [1][2][9]
| Buprenorphine | Methadone | Naltrexone | |
|---|---|---|---|
| Mechanism | Partial opioid agonist | Opioid agonist | Opioid antagonist |
| Overdose risk | Low risk due to ceiling effect | Potentially high risk | None |
| Misuse risk | Potential risk | Potential risk | None |
| Effectiveness | Highly effective treatment | Highly effective treatment | Extended-release injection found to be very effective |
| Administration | Daily dose, can be taken at home | Daily dose, must be administered in a clinic | Daily tablet or once-monthly injection |
| Timeline | Once withdrawal has commenced, around 24 hours after the last opioid dose | Immediate commencement | 7-10 days opioid free |
| Clinical recommendation | First-line treatment | First-line treatment | Tablets are no longer commonly recommended. Injection (Vivitrol) is more often recommended after detox, depending on career requirements, or to avoid abuse potential |
Choosing and preparing to start naltrexone
A medical professional or substance use disorder treatment specialist can help determine readiness for naltrexone treatment and discuss all available treatment options.
Before starting naltrexone, these are things to consider or discuss with your provider:
- How long ago was the last dose of opioids?
- Have withdrawal symptoms reduced?
- Do physical and mental health allow for safe naltrexone use?
- Have motivation and willingness to engage in treatment been established?
- Have treatment plans and goals been discussed?
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