In the first part of this series I described my experiences working in methadone-assisted treatment, including aspects of that industry that, in my opinion, warrant serious consideration. In the second part I described steps that potential patients can take that might help them avoid spending their entire lives attached to their local clinic. In this final section I will describe how treatments for opioid use disorder using buprenorphine (aka Suboxone) differ from methadone. TLDR: Get buprenorphine, not methadone.

Methadone is an opioid agonist with typical opioid actions, primarily at the mu opioid receptor. Methadone has dose-related effects on cardiac function in some people, prolonging the QT interval and increasing, theoretically at least, the risk of sudden death from ventricular fibrillation. Buprenorphine is an opioid with partial agonist effects. Partial agonists or ‘agonist/antagonists’ have a mixture of blocking and activating effects that create a ceiling on their action. Sublingual doses of buprenorphine above 16-24 mg/day do not result in further increases in opioid tone.

Methadone

Buprenorphine rarely causes overdose in adults. To die from buprenorphine a person generally must 1. have a low tolerance to opioids, and 2. use a second respiratory depressant to which the individual also lacks tolerance. About 50 people die from buprenorphine overdose each year in the US, compared to over 100,000 overdoses overall. A typical buprenorphine overdose occurs in a person whose first use of opioids is buprenorphine combined with benzodiazepines. Awareness that overdose to buprenorphine is possible if benzodiazepines are also used led to significant confusion where pharmacists and some doctors thought buprenorphine was uniquely dangerous combined with benzodiazepines. That is not true. Combinations of benzodiazepines with an opioid agonist like methadone are much more dangerous than with buprenorphine.

The first and largest difference between treatments is regulatory. Methadone can be prescribed for pain by any physician with a DEA license covering schedule II medications. But methadone cannot be used to treat opioid use disorder outside of clinics that are regulated by state and federal agencies. On the other hand, any physician with a valid DEA license and DATA 2000 waiver can prescribe buprenorphine products for the treatment of opioid use disorder.

The waiver requires an 8-hr course and is doled out over time, permitting the treatment of 30 patients the first year, up to 100 the next year, and eventually up to 275 patients per waived physician. Buprenorphine meds can be prescribed by family practice docs, psychiatrists, addictionologists, surgeons, ER docs, and providers from any other specialty. Nurse practitioners were recently given the ability to prescribe buprenorphine if they have the waiver.

These regulatory differences mean that patients on methadone are firmly attached to methadone clinics. Moving to an area not served by methadone requires tapering off the medication, a difficult process that can take several years or more. Many patients at methadone programs must attend the clinic every day except Sundays. Some state medicaid agencies reimburse travel expenses. but the time lost attending a daily program is never regained.

Patients on buprenorphine, on the other hand, receive prescriptions for medication that can be filled at any pharmacy. Most prescribers work on a trust system where patients who do well are gradually allowed longer intervals between office visits. Many long-term buprenorphine patients, after demonstrating abstinence through urine drug testing, eventually get to the point of quarterly visits.

More important is that patients on buprenorphine can change physicians as easily as patients with any other health concerns. More and more physicians have the waiver, and a growing number of online companies prescribe buprenorphine medications through telemedicine programs.

The difference in regulations for the two medications is why I strongly advise any patient seeking ‘methadone-assisted treatment’ to demand buprenorphine instead. Many methadone programs offer either medication, but methadone companies have a strong business interest in pushing the methadone option as those patients will become dependent on the clinic. Patients who demand buprenorphine can leave the program at their discretion and find a new doctor.

There are significant differences between the effects of buprenorphine and methadone. Buprenorphine is a partial agonist with a ‘ceiling’ on the drug’s opioid effect. A patient who maintains a blood level above that ceiling develops almost perfect tolerance and feels nothing or almost nothing upon dosing and throughout the day. Methadone is an agonist like oxycodone, heroin, or morphine. Patients on methadone have peak blood levels, causing peak sedation, about six hours after dosing. Many patients on methadone experience mild withdrawal the morning before receiving their next dose.

Discontinuing regular use of any opioid is difficult because of withdrawal, a collection of symptoms that most opioid users eventually dread. The severity of withdrawal is directly related to the degree of opioid tolerance, and the offset of the opioid used to maintain that tolerance. Both buprenorphine and methadone have long half-lives that reduce the severity of withdrawal during the first seven days. After that, drug half-life plays less of a role.

Patients on buprenorphine have opioid tolerances that are about equal to patients on 35 mg of methadone per day. In other words, a patient on 35 mg of methadone/day would have withdrawal symptoms comparable to a patient on buprenorphine, if both stopped the medications abruptly. But most patients on methadone are on far-greater doses, up to 500 mg/day in some clinics. Discontinuing methadone from that level of tolerance can cause months and months of severe withdrawal.

Over the past 15 years I have helped about 500 patients taper off buprenorphine. The process is feared by most patients, but the comment I hear most is ‘it wasn’t as hard as I thought’. I describe a process that allows most patients to cut their dose in half within 2-3 months, and discontinue buprenorphine completely over the course of a year without missing a day of work. It typically takes a year or more to taper off only 50 mg of methadone. Which would you rather be on?

Both medications are relatively safe long-term. Studies have shown a greater incidence of testosterone suppression by methadone compared to buprenorphine, probably because of the ultimate dose range chosen by many clinics. Some people gain significant weight on methadone for reasons that are not fully understood. But safety isn’t everything, as I explained in prior posts. Patients on methadone often fear full employment as that could remove Medicaid payments that cover the cost of attendance. Buprenorphine patients generally face far less cost and may even find a provide in the health networks covered by their employers. I charge long-term patients less than $900 per year, whereas methadone-assisted treatment usually costs more than $500 every month.

There are times when buprenorphine treatment is not the best approach. The first dose of buprenorphine must be taken after opioid agonists have been metabolized, meaning after about 24 hours for users of heroin or oxycodone. People using methadone must wait longer before starting buprenorphine, making conversions from methadone to buprenorphine difficult. A person presenting to methadone-assisted treatment who isn’t in withdrawal is best advised to accept methadone, rather than leaving and trying to return another day. Every day out there presents considerable risk. In those cases, patients would serve themselves well by making every effort to limit dose escalation once their use is in remission.

Medication-assisted treatments are by far the most effective approach for treating opioid use disorder. If you are struggling with an attachment to opioids, get help. I have been there myself, and I know the isolation, depression, and despair that grow over time. Medication-assisted treatment can stabilize your symptoms almost immediately, without a long and painful detox. Find treatment, but demand buprenorphine over methadone so that you have options in the future.


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