Naltrexone vs Buprenorphine

Both medications are effective for OUD when combined with behavioral support. The X:BOT trial comparing extended-release naltrexone injection (Vivitrol) to sublingual buprenorphine-naloxone (Suboxone) found similar relapse rates among patients who successfully started treatment.

However, a critical practical difference is the initiation barrier. Naltrexone requires 7-10 days of complete opioid abstinence before starting (to avoid precipitated withdrawal), which is a significant hurdle — many patients relapse during this washout period. Buprenorphine can be started while a patient is in mild-to-moderate withdrawal, making initiation easier and faster.

Buprenorphine generally shows higher treatment retention rates in real-world settings, partly because of its easier induction process and wider availability.

Naltrexone is not an opioid and has no abuse potential or risk of physical dependence. Common side effects include nausea, headache, injection site reactions (for the monthly injection), and insomnia. A major safety concern: if a patient stops naltrexone and relapses, their opioid tolerance will be greatly reduced, increasing the risk of fatal overdose.

Buprenorphine, as a partial opioid agonist, can cause opioid-type side effects including constipation, headache, nausea, and sweating. Physical dependence develops with regular use, meaning abrupt discontinuation causes withdrawal. There is a low but real risk of misuse, which is why most formulations combine buprenorphine with naloxone (Suboxone) to deter injection misuse.

Both medications have strong overall safety profiles compared to continued opioid use.

Extended-release naltrexone injection (Vivitrol) costs approximately $1,500-$1,800 per monthly injection at retail, though many insurance plans and Medicaid cover it. Oral naltrexone is much cheaper at $30-$90 per month but has poor adherence.

Buprenorphine-naloxone (Suboxone) costs $100-$500 per month depending on formulation (sublingual film vs generic tablets). Generic buprenorphine-naloxone tablets are the most affordable option. Insurance and Medicaid coverage is generally good for both medications.

Extended-release naltrexone (Vivitrol) is a once-monthly injection given at a healthcare provider's office — this removes the daily compliance burden but requires monthly visits. Oral naltrexone is taken daily but has poor real-world adherence.

Buprenorphine is typically taken daily as a sublingual film or tablet. It can be prescribed by certified providers for take-home use, offering flexibility. Monthly injectable buprenorphine (Sublocade) is also available for patients who prefer less frequent dosing.

Access differs: buprenorphine prescribing has been expanded and the previous X-waiver requirement was eliminated in 2023, increasing availability.

The choice between naltrexone and buprenorphine depends on individual circumstances. Buprenorphine may be preferred for patients who cannot achieve the 7-10 day opioid-free period required before starting naltrexone, or who are currently in withdrawal and need immediate symptom relief.

Naltrexone may be preferred for patients who have completed detoxification, who prefer a non-opioid medication, or who benefit from the accountability of monthly injections. It is also an option for patients in settings where opioid agonist treatment is not available.

The most important message is that both medications save lives. The best medication is the one that a patient will start and continue taking. Stigma around medication-assisted treatment is not supported by evidence — these medications are evidence-based, life-saving treatments.