Methadone Induction: Be Careful

Graphic illustrating how methadone blood level rises over five days with no dose change




This blog is written with gratitude to Thomas Payte M.D., a leader in the field of Addiction Medicine, who passed away in 2019.  Many years ago, I listened to an ASAM (American Society of Addiction Medicine) lecture by Dr. Payte (on cassette tape, which shows how long ago this was) that changed the way I did methadone induction.

At the time I started working at an opioid treatment program, I felt much empathy for the patients suffering opioid withdrawal when I admitted them to treatment. With the best intentions, I wanted to help them get out of withdrawal as quickly as possible, so I started them at doses higher than I probably should have and increased their doses daily. The other physicians I worked with practiced in a similar way, so I thought that was the way it should be done.

We had patient induction deaths. I learned some things the hard way, but also started going to ASAM conferences and listening to ASAM lectures, which was when I had the good fortune to hear Tom Payte.

Decades later, I can’t be sure exactly what he said, but this is what I remember:

He cautioned that induction deaths were relatively rare but devastating. If we start every patient on 30mg, eventually a patient will die during induction. That shook me up, because not only was I starting patients on 30mg, quite often I was dividing their dose on Day 1 to get a total of 40mg. He said patients inherently metabolize methadone at very different rates, and sooner or later a slow metabolizer would arrive for induction, and rapid increases in dosing during induction would be fatal.

Dr. Payte wasn’t unsympathetic to patient misery in opioid withdrawal. He just reminded me that we must temper compassion with science.

Today, induction guidelines look very different from the way I was practicing back when I started. I have changed my induction practices a great deal over the years as I’ve learned more.

Physicians who work at opioid treatment programs have so much more information available now than when I started in this field. It’s so easy to get colleague input about problems: at a national level, there’s the PCSS system, which stands for Providers Clinical Support System, a system for providing information and even mentors for providers who would like them (

At our state level, the North Carolina Governor’s Institute has contracted with me and with Dr. Eric Morse, so that we can be available for questions from providers at any opioid treatment program in the state at any time.

Recently, at an organizational level, our Acadia programs in North Carolina arranged for a monthly phone call for physicians and physician extenders to discuss problems and concerns on a monthly phone call.

ASAM has all sorts of guidelines and position statements ( SAMHSA has publications to help physicians (

Because of all this help that’s available, there’s no reason for any provider working at an opioid treatment program in the U.S. to be ignorant of current methadone induction recommendations.

I recently blogged about ASAM’s newly updated guidelines for the treatment of opioid use disorders. In those guidelines, initial dose of methadone, “ranges from 10 to 30mg, with reassessment as clinically indicated (typically in 2 to 4 hours)…” and then goes on to say, “methadone…generally should not be increased every day.” The guidelines recommend methadone be increased no more than 10mg approximately every 5 days.

If you are a provider who is starting every patient at 30mg and then increasing the dose daily, stop it. You are going to have an overdose sooner or later.

And although these guidelines did say that benzodiazepine use should not be a reason to suspend or withhold treatment with methadone or buprenorphine, they did make it clear that use of sedative-hypnotics with these medications increases the risk of serious side effects.

In other words, we shouldn’t deny treatment to patients with a co-occurring benzodiazepine use disorder, but we can’t admit them and carry on like their risk is the same as other patients who aren’t on benzodiazepines. Consider lower methadone starting doses and consider slower rates of induction for these more fragile patients. Consider closer observation and more frequent drug screening

The provider has a lot more work to do when a patient is using benzodiazepines. First, that provider needs to figure out, if possible, how extensive that patient’s use is, and decide the appropriate setting for methadone induction. That may need to be at an inpatient facility.

Second, since benzodiazepine prescribing guidelines recommend these medications not be prescribed for longer than three months, except for end-of-life care, an ongoing prescription must be explained. The prescribers of benzodiazepines must be talked to. In my area, most of the benzodiazepines are prescribed by a handful of practitioners.  When I talk to these prescribers, they say the patient complains of anxiety, indicating they think this justifies ongoing benzodiazepines.

That’s not good enough. Benzodiazepines aren’t first-line medications for anxiety disorders. Like opioids did for pain, it appears benzodiazepines make people more anxious when they are used long-term. Benzodiazepines make post-traumatic stress disorder worse, and they complicate ordinary grief reactions. Yet many patients are prescribed benzodiazepines for these reasons.

Third, a plan must be formulated to reduce the risk for the patient. In most cases, this means a reduction in benzodiazepine use by some method. If the patient can control their use of benzos, their prescriber can gradually lower their dose. Most of the time the patient can come off benzodiazepines, or at least get by with much less of these medications. In the meantime, a more appropriate medication for anxiety can be started for better treatment of anxiety.

In many cases, the patient needs trauma-focused therapy to address old issues. Many, perhaps most, of our patients have experienced serious physical, sexual, or emotional trauma in their lives. Appropriate counseling and medication can be just as life-changing for patients as can treatment for their opioid use disorder.

Since alcohol is as big a risk as benzodiazepines, the same cautions during methadone induction need to be taken for patients with alcohol use disorders. Start with lower doses and increase more slowly.

More cautious induction must be considered for medically fragile patients: those with underlying pulmonary disease, lower body weight, those on multiple medications, and the “elderly” over fifty years old. And be sure to ask about opioid use over the preceding week. If a patient was admitted to a detoxification unit, or just got out of jail or a hospital, their opioid tolerance will be lower, and the patient needs a lower methadone starting dose.

If their admission drug screen is negative for opioids, stop for a moment to consider what this means. Does the patient really have opioid use disorder? Has the patient taken an opioid recently that doesn’t show on your drug screen? Or has the patient been unable to use opioids for the last several days? If the latter is true, consider a lower starting dose.

Don’t do cookie-cutter inductions. Carefully evaluate each new patient and gather all the data that you can, including history and physical, old records, the prescription monitoring program, and other treating physicians to help you make the best decisions possible. There will always be that pull…trying to get the patient out of opioid withdrawal so they can stop using dangerous illicit opioids….while trying to provide safe methadone induction.

I’ve written mostly about methadone induction because it’s much trickier than buprenorphine. Methadone is much less forgiving during induction than buprenorphine. With buprenorphine induction, just make sure you don’t start too soon and make your patient sick. At times I wish all my patients could do well on buprenorphine, but that’s not possible. We will never have one medication that works well for everyone. Many patients never feel right on buprenorphine, or it isn’t strong enough to treat their opioid use disorder.

I’m more cautious with methadone induction prescribing now than when I started many years ago. This is from a combination of experience and learning from experts. I strongly recommend the latter form of learning; it’s much less painful.

8 responses to this post.

  1. Posted by william taylor MD on May 28, 2020 at 1:41 am

    Thank you for your very sobering post. For patients who have been on methadone before, one additional piece of data that can be helpful is the patient’s prior maximum methadone dose . A patient previously stable on 25 is very different from someone previously on 250.


  2. Posted by Stuart Gitlow on May 28, 2020 at 1:57 am

    An excellent post. For benzodiazepine tapers, the key to success is not to rush. Each time the dose is decreased, particularly in a long-time recipient, there will be a concurrent increase in perceived anxiety. And even if the patient is compliant with the newly prescribed lower dose, they might simultaneously increase their alcohol use to make up for the difference. So the second key to success is to decrease the dose by small amounts. How to do it: give your patient a full 12 months to come off the benzodiazepine entirely. Reduce the dose by a small fraction and wait at least two weeks or until any perceived worsening of anxiety symptoms have dissipated. Then reduce the dose by another small fraction. Repeat. The last few reductions will be the most difficult. Teach your patient how the curve works: if they start with an anxiety level of 10, when the dose is decreased, their anxiety will go to 11 briefly, but will then come down to 9. Then at the next dose decrease, their anxiety will go to 10 briefly, but then come down to 8. Ultimately they will feel much better off the medication, but that won’t be their acute perception.


  3. Posted by bpmurraymd on May 28, 2020 at 3:04 am

    i have seen all this “start low and go slow” induction recommendations– and they have some merit is some high risk patients — but patients using a ‘gram to two grams of heroin’ which in my area is mostly fentanyl are very tolerant and not patient — you are balancing the issue of methadone overdose which every one admits is rare — to the very real and common problem of overdose with illicit heroin and fentanyl. The patients will leave treatment if they don’t feel progress is being made and that is not good for anyone. They don’t understand why they should pay the OTP and do all the counseling and UDS etc for and still pay the dope man. It is a problem. While we can be risk adverse and ‘go slow’ we will loose more patients that way to OD’s and leaving treatment then to loosing patients to methadone OD in my opinion. But as the experts say ‘go slow’ must be done it makes it difficult not to do that , and protect ourselves rather than the patients


  4. Posted by bpmurraymd on May 28, 2020 at 12:28 pm

    I agree with the previous comment — a history of MAT and the previous methadone dose is so helpful in giving you a benchmark.
    When i ask the experts at ASAM about this , they say : ” well, dosing can be individualized” , but then they seem to set the standard of care at the same time .


  5. I was fired for following titration guidelines. My employer feels with potent fentanyl clients must be at hi dose ; previous employee medical practioner had them at 400, 500 , 600 mg methadone .
    I practiced addiction as per ABAM. ASAM. SAMSHA


    • It’s awful that you were fired for following current guidelines! And I’ll bet I know which national chain of opioid treatment programs you probably worked for.
      This claim that “Nowadays, patients need much higher doses,” has been around for ten or twenty years. Back when patients were using OxyContin, it was commonly said that patients needed higher doses of methadone because they were using medical-grade, high-potency pain pills. These days, it’s because patients are using the highly potent fentanyl.
      I’m not discounting this idea, but I’d like to see some data about doses above 400mg per day. Are there better outcomes? Are there higher complication rates?
      Reading the literature, “high dose” methadone means the 80-120 range. We have enough data to show clearly that doses of 80-120 work better than capping the dose at 60 or 70mg. But do we have any data at all to support going to 400mg on many if not most patients? Not that I know of.
      I’ve had patients on 200-360mg per day, rarely. But those doses were checked with peak and trough levels, and I also did EKGs to watch for prolonged QT. Around 1% of the population will metabolize methadone extremely quickly, and need unusually high doses. But when you take a majority of patients to very high doses, I wonder about the safety of the patients.
      Keep doing the right thing. It sucks to get fired for doing the right thing, but that happens to many of us somewhere along the way.


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