Buprenorphine vs. Methadone

Buprenorphine and methadone, both being opioids, activate the opioid (mu) receptors on nerve cells. And both drugs have long half-lifes, meaning that they’re long-acting medications. The half-life can vary from 24 to 60 hours for buprenorphine, and from 8 to 59 hours for methadone. (The half-life is the amount of time a drug stays in the body before its concentration in the plasma drops by half. A drug’s half-life can vary from patient to patient.)

The long half-lifes of buprenorphine and methadone account for their usefulness in treating opioid dependence. Simply put, these drugs lack the peaks and troughs that are associated with short-term opioids, like heroin—swings in drug plasma levels that can cause overdose and withdrawal symptoms.

But there are key differences between buprenorphine and methadone.

Full Agonist vs. Partial Agonist

Buprenorphine is a partial agonist; methadone, like heroin, is a full agonist. It is by their actions on opioid receptors that opioids achieve their analgesic (pain-killing) as well as their addictive effects.

Methadone, as a full mu opioid agonist, continues to produce effects on the receptors until either all receptors are fully activated, or the maximum effect is reached.

Buprenorphine, as a partial agonist, does not activate mu receptors to the same extent as methadone. Its effects increase until they reach a plateau. At that level, opioid-addicted patients can discontinue opioid use without experiencing withdrawal. Buprenorphine reaches its ceiling effect at a moderate dose, which means that its effects do not increase after that point, even with increases in dosage.

Like all opioids, buprenorphine can cause respiratory depression and euphoria, but its maximal effects are less than those of full agonists. The benefits of this from an overdose perspective constitute the safety profile of buprenorphine—a lower risk of abuse, addiction, and side effects than with full agonists.

For people who are not addicted to or dependent on opioids, the effects of partial (buprenorphine) and full (methadone) agonists are indistinguishable. However, at a certain point, the increasing effects of partial agonists reach maximum levels. For this reason, people who are dependent on high doses of opioids are better suited to treatment with a full agonist, such as methadone.

Buprenorphine, like methadone, has a serious potential for drug-drug interactions. It must be used cautiously with other medications, in particular benzodiazepines, other sedatives, opioid antagonists like naltrexone, and opioid agonists.




Partial agonist Full agonist Full agonist
Long half-life (24 to 60 hours) Long half-life (8 to 59 hours) Short half-life
Ceiling effect; good safety profile No ceiling effect (useful in patients dependent on high doses of opioids) No ceiling effect

Formulations of Buprenorphine

In October 2002, the Food and Drug Administration (FDA) approved the buprenorphine monotherapy product, Subutex, and a buprenorphine/naloxone combination product, Suboxone, for treating opioid addiction.

Subutex is no longer sold in this country. It has been replaced by generic buprenorphine. Suboxone, a sublingual tablet (designed to dissolve under the tongue), comes in two dosage forms. Suboxone film was approved by the FDA in 2010. The sublingual film dissolves faster than the tablet, and is individually wrapped in unit-dose, child-resistant pouches. According to the manufacturer, Reckitt Benckiser, Suboxone film is clinically interchangeable with the tablet.

Last fall, Reckitt Benckiser voluntarily removed its Suboxone tablets from the market, citing a few pediatric overdoses. But it protected its hold on the Suboxone market by retaining the film formulation. The patent on the tablets had long expired; the patent on the film runs until 2023. Patients, of course, had to be switched to the film, unless their physicians wanted to switch them to generic buprenorphine. At the same time that Reckitt pulled the tablets, it filed a Citizen’s Petition with the FDA, calling on all buprenorphine products to be sold in childproof packaging.

The effect of these moves by Reckitt on the buprenorphine marketplace are not clear, said Nicholas Reuter, MPH, who was senior public health analyst with SAMHSA’s Center for Substance Abuse Treatment (CSAT) when this story was written (he retired on January 31, 2013). “Submitting a Citizen’s Petition doesn’t mean the FDA has to accept it,” he said. In addition, in November 2012 the FDA accepted Orexo’s New Drug Application for Zubsolv, a buprenorphine-naloxone combination. Zubsolv could well be the first generic competition to Suboxone. And on December 17, 2012, Titan licensed Probuphine, its buprenorphine implant, to Braeburn Pharmaceutical for exclusive commercialization in the U.S. and Canada. “The buprenorphine marketplace is looking at different formulations,” noted Mr. Reuter. “There could be a generic competitor [for Suboxone] tomorrow.”

Making the Decision: Methadone vs. Buprenorphine

Aside from the dosage issue, there is no “cookie-cutter” approach for deciding what patient gets buprenorphine and what patient gets methadone. Philip L. Herschman, PhD, chief clinical officer of CRC Health Group, pointed out that different patients react differently to different medications. “Some feel better on buprenorphine, some feel better on methadone,” he said. CRC has been using generic buprenorphine in its OTPs on the same basis as methadone. The extent to which CRC will be able to give buprenorphine take-homes will depend in large part on state regulations—just because the federal government has approved the plan doesn’t mean states will.

“Buprenorphine is great, but it’s not for everybody,” said Walter Ginter, CMA, project director of the Medication Assisted Recovery Support (MARS) project. He doesn’t think the final rule is going to make a big difference for most patients. He noted that few patients go to methadone maintenance as their first course of treatment.

In fact, Mr. Ginter can speak as an expert on subjective effects in a personal way: he has been maintained on both medications—buprenorphine during its development in the 1990s, when he was a study subject, and then methadone. He has been on a high dose of methadone for years, and says “I don’t think I’m clouded out.” Indeed, he is one of the most energetic and articulate advocates in the field. It comes down to a matter of personal preference, he said. “With methadone, you’re never sick and you’re never high, but you do get the serum peaking four hours after the dose,” he said. “I think Suboxone is too much the same, with no ups or downs.”

Still, there are OTPs that do switch patients from methadone to buprenorphine, titrating very carefully downward for patients on doses of 80 milligrams or more of methadone before switching to buprenorphine, said Mark Parrino. MPA, president of the American Association for the Treatment of Opioid Dependence (AATOD). In general, if a patient has been using opioids for a longer period, or has a higher tolerance, methadone would be more appropriate. The reason is that buprenorphine’s ceiling limits those higher-dose equivalents.

Publishers Note: Nicholas Reuter, MPH joined Reckitt Benckiser in February 2013 as a Treatment Manager.


  1. Robert Newman, MD says

    February 13, 2013 SAMHSA recently announced a new rule providing flexibility in dispensing buprenorphine for opioid addiction treatment (http://www.ofr.gov/OFRUpload/OFRData/2012-29417_PI.pdf). The flexibility, which does not apply to methadone, is justified by SAMHSA on the basis of “differences in the abuse potential between methadone and buprenorphine, as well as the actual abuse and mortality rates (buprenorphine is lower in each instance).”

    Is there in fact evidence demonstrating that buprenorphine is misused, abused, and diverted to a lesser extent than methadone used in the management of addiction (as opposed to prescriptions for pain management)? Greater safety afforded by the “ceiling effect” attributed to buprenorphine is an important consideration, but would not seem to justify continuing a blanket, rigidly applied, no-exceptions-permitted set of restrictions on take-home of methadone, while allowing clinicians flexibility to determine on an individual basis whether to provide buprenorphine for self-administration, and, if so, for how many days. (It is not clear if OTPs will in future be permitted to prescribe buprenorphine, as office-based physicians may; if so, the ability to get medication from a local pharmacy would represent another enormously important—but difficult to justify—advantage over methadone.)

    It seems clear to me that the attendance demands, rigidly imposed by federal regulation on every patient who receives methadone, reflect the assumption that no methadone recipient, under any circumstances, can be trusted to take home the medication during the first 90 days, and that beyond those initial three months, no methadone recipient can be trusted with more than X days “take-home” after less than Y number of months in treatment. This extremely negative, universally applied, stereotype of patients being treated with methadone strikes me as unwarranted, and, frankly, reprehensible, and the significance of the official view of patients, purely by virtue of their treatment with methadone, will not be lost on staff, patients, and the community.

    Also, logic would seem to dictate that addiction-treatment components mandated (by governmental regulation, “standards” set by organizations such as JCAHO, or self-imposed by programs) should apply—or not apply—equally, regardless of medication utilized. In other words, if it is deemed imperative that a new methadone patient receive weekly individual and/or group counseling, then this should be imposed as well on buprenorphine recipient at the same frequency—or waived for all. If a program feels it’s “best practice” to do weekly (or monthly) random, unannounced urine testing, then presumably buprenorphine recipients should be obliged to have several visits per week (or per month) so that urine collection indeed can be random and unannounced—or (and this is my strong preference) urine-testing demands should be eliminated for all.

    Finally, it is difficult to imagine that patients—new or long-term—if given a choice between required clinic visits as infrequently as once monthly as opposed to daily (!) or five times a week, or . . . , would not overwhelmingly opt for the former regimen. The new rule (42 CFR Part 8, RIN 0930-AA14) states the case succinctly and compellingly in citing “commenters” who “noted that from the patient’s perspective the critical advantage of buprenorphine is the possibility of avoiding the long-term daily attendance for dosing that is required with methadone therapy.” Absolutely correct . . . but how can one perpetuate universal denial of this “critical advantage” to patients with the same medical condition, whose physicians decide that they may be best-served with methadone? And note that those patients, who together with their physicians, conclude that they are not achieving optimal therapeutic outcome with buprenorphine will be very strongly discouraged from switching to methadone, given the inflexible demands, regardless of individual clinical considerations, associated with such a change.

    I am aware of no evidence (evidence!) indicating that buprenorphine is more effective than methadone on subgroups of patients defined by age, duration of dependence, social stability, etc. So just who might one expect to request and be granted the “critical advantage” that will now be associated with buprenorphine treatment? I suspect it will depend on finances: the amount of money that can and will be charged the patient (by clinic or by pharmacist), and the amount that can and will be collected by the program, will be decisive. That does not seem a desirable basis for determining what mediation might be most suitable in individual cases.

    Again, I love the flexibility that will apply to required attendance by patients receiving buprenorphine. At the same time, I deplore the diametrically opposite standards that will govern treatment of patients receiving methadone, and the bias against them that I believe they reflect.

    Robert Newman, MD

    • Richard Christensen, PA, CAS says

      Hi Bob,
      Your comments are as always on the mark.
      Once again without any valid reason methadone patients have been thrown under the bus.
      CSAT and AATOD have been remiss in advocating for our methadone patients.
      CSAT for their biase toward Buprenorphine .
      AATOD for their unwilliness to rock the boat.
      Rick Christensen, P.A., CAS

    • pete green says

      You see, I have just come off 30 ml methadone, reduced from 50ml. I had been on methadone for 3 years… “With methadone, you’re never sick and you’re never high” – this is just WRONG for many experience a high on methadone. It made me happy and felt nice. I would also feel nausea and restlessness most mornings before dosage…Now I am on 4mg Subutex and feel nothing. I really miss methadone. Methadone did make me much more tired though….Everyone is different, some get high from subutex or suboxone but not nearly like heroin high.

  2. Richard Moore says

    I read the above comments with great interests, I am currently a 58-yr-old male patient on Buprenorphine (24mg/day) after having been on methadone for over two years (60/mg day). The two weeks during switching from methadone to Buprenorphine was horrific to say the least. I want to go back to Methadone treatment but have no medical knowledge if this is even possible and at what dose.I have noticed a marked rise in my desire to be fixated on depressive issues and suicide (I’ve not acted on the latter due to family support). But what should/could I do about the medicine question at hand?
    Rich Moore

    • syner says

      Hello. I was on methadone for three years…switched to sub…3 8 mg per day… Went to one a day and done switch back to done after 36 hours of last dose. First dose did not make me sicker but did not kick withdraw…second dose felt full affect…. Hope this helps

  3. Mike says

    I have been on bupe for 8 years… Suboxone made me sick and subutex has completely stopped working for me a couple years ago. I would prefer to be on a full agonist like methadone yet the restrictions as mentioned stop me. I believe there should be more options for people like myself who are going to be on opiate replacement for life.

  4. melissa Vanherwaarden says

    I was placed on methadone 20+ years ago by a pain management Dr.for chronic back and neck pain. When the new restrictions went into effect the beginning of 2014 my Dr.cut my rx by 20mg. I started having withdrawal symptoms and had to start going to a methadone clinic. The rules you have to adhere to are so strict. Going everyday to dose puts your life in hold. You can’t work because you go in to dose and if they are doing “random ” ua’s you will be late. How do you plan for that? I so wish I would have never choose this route. Now I am on 125mg daily! Where else would I go? STUCK!!

  5. Mary A. Dionne says

    “I believe there should be more options for people like myself who are going to be on opiate replacement for life.” I’ts sad when treatment has left someone feeling like this is all there is….what about some cognitive, spiritual changes?? Has anyone tried 12 step programs? Meditation? Exercise ? Yoga? God forbid, other psych meds? I know opiates are tough, so is booze, ,it’s every friggin’ where…you want to be chained to methadone for the rest of your life…I still say it is a horrible capitalist money maker on the backs of addicts…yes it does help some…those who have not gone too far down, but I have seen too many stay in the miserable life of addiction on methadone and not being clean. Good luck to all.

  6. jeremy says

    Ive been on opiates for years for agonizing pain after surviving being hit by a car doing 50. I have a rod in my leg that can never come out. Ive taken almost any opiod prescription pills you can think off. I was back and forth between oxycodone,opana and methadone pills. I finally discovered that I could get decent pain control without needing to constantly increase me dose with Suboxone. However I would get headaches and the naloxone does decrease the effects of the buprenorphine, I dont care what the “experts” say. Since switching to generic Subutex, my average chronic pain has decreased by 30% of the level it was at with Suboxone. I put Subutex at just less than methadone but just more than Suboxone in terms of pain control. Its good enough for me. I dont want to be on a huge dose of a powerful opiate like opana or fentanyl. Ill suffer with some of my pain to prevent being a mindless Zombie.

  7. Jeff Bisaga, PhD says

    As a psychologist leading a recovery group in a local methadone clinic here in California for the past seven years, I read over the above comments and questions with great interest and concern. As the various comments illustrate so well, we are all so very different, especially in our reactions both physiologically and psychologically, to the various medications and approaches being used to treat opiate addiction. Therefore, take what I say with more than a grain of salt, it may not apply to you. My experience over these years has taught me what an especially vicious thing opiate addiction is, because it not only involves the psychological snares of any addiction, but also causes such intense physiological symptoms when withdrawn, that escape feels impossible. The necessity of personal counseling and group support is unquestionable. Either medication can be effective in containing the physical distress, but if those psychological/emotional (and spiritual) issues that helped start or maintain the addiction are not addressed, then recovery is truly a nearly impossible task. What I have come to call the “wisdom of methadone treatment” is that the extensive amount of time it takes to determine a therapeutic dosage, establish and maintain some stability at that dose, then gradually taper off the medication entirely (where possible) buys one the time to make the emotional, psychological, and social changes/growth necessary to maintain recovery. This is not to criticize the use of buprenorphine, for clearly many have benefitted greatly from that treatment as well. It’s just that, as stated above, we’re all so different and for many individuals those changes or adjustments to their thinking and behavior take time, courage and significant effort.

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