Suboxone, methadone, naltrexone: what the medications actually do

Sooner or later a doctor says the word Suboxone, and the family goes quiet. Then somebody says the sentence: isn’t that just trading one addiction for another?

We are not clinicians. We do not prescribe, and nothing here is medical advice; that conversation belongs to the person and their doctor. But families are routinely asked to form an opinion on this without ever being shown the evidence, and the evidence is not close. So here it is, in plain terms.

What the medications are

Three are used for opioid addiction.

Methadone. A long acting opioid, taken once a day, usually at a licensed clinic. It settles onto the same receptors the drug used, but steadily, with no rush and no crash. Withdrawal stops. Craving drops a lot. The person can hold a job and sleep at night.

Buprenorphine (brand names Suboxone, Sublocade). Also an opioid, but a partial one. It has a ceiling: past a certain dose, more does not produce more effect, which is why it is much harder to overdose on. It can be prescribed in a regular doctor’s office, and there is a monthly injection version.

Naltrexone (brand name Vivitrol, also a daily pill). Not an opioid at all. It blocks the receptors, so opioids stop working. It has one catch, and it is a big one: a person has to be completely through withdrawal before starting, or the blocker throws them into it.

Two are used for alcohol: naltrexone again, and acamprosate.

The data is not really about comfort. It is about dying.

The largest analysis of this question pooled cohort studies following people in and out of treatment. Across 16 cohorts and 122,885 people on methadone, the all cause death rate was 11.3 per 1,000 person years while people were in treatment and 36.1 while they were out of it. Overdose deaths were 2.6 in treatment against 12.7 out. For buprenorphine, across 3 cohorts and 15,831 people, all cause deaths were 4.3 in treatment against 9.5 out (Sordo et al., The BMJ, 2017).

Read those pairs again. Being on the medication was associated with roughly a third of the death rate of being off it.

The same analysis found the two most dangerous stretches are the first four weeks after starting and the first four weeks after stopping. Stopping is the risky part, not staying.

Then there is the study families should probably see first. Researchers followed 40,885 people with opioid use disorder through six different treatment paths and compared what happened next. Only one path was associated with fewer overdoses: buprenorphine or methadone, with about a quarter of the overdose risk of no treatment at three months and about 40 percent of it at twelve (Wakeman et al., JAMA Network Open, 2020). Inpatient detox, residential treatment, intensive outpatient, counseling, and naltrexone did not show a significant reduction in overdose in that data.

That finding is uncomfortable, and we are not going to soften it. The 30 day residential admission is the thing most families are sold, sometimes at very high cost, and in this study it was not the thing that moved the overdose number. It does other work. It is not this.

One honest caveat: these are observational studies, not coin flips. People who stay on medication may differ from people who do not in ways the researchers could not fully adjust for. The findings are large, consistent, and repeated across countries, which is why they carry weight, but they are an association, not a guarantee.

About the substitution objection

Here is the fair version of it and the honest answer.

A person on a steady dose of methadone or buprenorphine is not high. The dose is level, so there is no peak to chase and no crash to survive. They can drive, work, parent, and remember the conversation. What changed is the shape of the exposure and, in the data above, whether they live.

But the objection is not silly. These are opioids. Stopping them causes withdrawal. Some people want to be off everything eventually, and that is a legitimate goal, not a failure of commitment. The research does not say never stop. It says the exit is the dangerous part, so it should be slow, planned, and supported, not improvised in a bad week.

If naltrexone is the goal, know the hurdle

Families often prefer naltrexone, because a blocker feels cleaner than an opioid. A large trial compared the monthly naltrexone shot against buprenorphine in 570 people. Twenty eight percent of the naltrexone group never managed to start the medication at all, against 6 percent of the buprenorphine group, because getting fully through withdrawal first is genuinely hard. Counting everyone assigned, buprenorphine came out ahead. But among the people who did get started on each one, the results were essentially the same (Lee et al., The Lancet, 2018).

So naltrexone works about as well, for the people who can get on it. Which means the practical question is where the person will be during that withdrawal window, and who is with them.

Alcohol has medications too, and almost nobody is offered them

For alcohol, a review of dozens of trials found that for every 12 people treated with acamprosate, one additional person avoided returning to drinking. For oral naltrexone at 50 mg a day, for every 12 treated, one additional person avoided returning to heavy drinking (Jonas et al., JAMA, 2014).

That is a modest effect and a real one. It is also rarely mentioned. If a family member is in treatment for alcohol and no one has raised medication, that is worth asking about.

The number that should bother everyone

Researchers tracked 17,568 adults in Massachusetts who survived an opioid overdose. In the twelve months afterward, 11 percent received methadone, 17 percent received buprenorphine, and 6 percent received naltrexone. For those who got methadone or buprenorphine, death rates were roughly cut in half (Larochelle et al., Annals of Internal Medicine, 2018).

Turn that around. Most people survive an overdose and are sent home with nothing.

Three questions to ask any program

You do not need to pick a medication. That is the doctor’s job and the person’s choice. But you can ask these, and the answers tell you a lot.

Does this program allow medication, or does it require people to be off it? Some abstinence based programs and many sober homes will not accept a resident who is taking buprenorphine. Ask before the deposit, not after.

Who prescribes it after discharge, and is that appointment already booked? A prescription that lapses in the gap between levels of care is the same as no prescription, and that gap is where plans break. We wrote about that seam in the gap between levels of care.

If the person ever chooses to come off it, what is the plan for the month after? The data says that month is the most dangerous one in the whole sequence. Nobody should reach it without a plan.

Where we fit

We are not a medical provider and we do not manage medication. What we do is keep the plan from falling apart between the people who do.

In practice that means recovery coaching supplying the weekly rhythm and making sure the appointment actually gets kept, and family coordination meaning one person is tracking whether the prescription got refilled while the treatment team changes around it. If you are still choosing a program, our guide to choosing a treatment center has the medication question built into the tour list. And if the brain science behind all of this is what you want next, what addiction does to the brain covers why the first year needs borrowed structure.

None of this settles what your family should do. It just means the decision gets made with the numbers in the room, which is more than most families are given.

Sources

• Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. The BMJ, 2017;357:j1550. bmj.com/content/357/bmj.j1550
• Wakeman SE, Larochelle MR, Ameli O, et al. Comparative effectiveness of different treatment pathways for opioid use disorder. JAMA Network Open, 2020;3(2):e1920622. jamanetwork.com
• Lee JD, Nunes EV, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT). The Lancet, 2018;391(10118):309-318. pmc.ncbi.nlm.nih.gov/articles/PMC5806119
• Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA, 2014;311(18):1889-1900. bumc.bu.edu
• Larochelle MR, Bernson D, Land T, et al. Medication for opioid use disorder after nonfatal opioid overdose and association with mortality: a cohort study. Annals of Internal Medicine, 2018;169(3):137-145. acpjournals.org/doi/10.7326/M17-3107