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Microdosing Buprenorphine and Evolving Approaches to Medication-Assisted Treatment

The microinduction process – as part of MAT for opioid use disorder – makes it possible to overlap buprenorphine with ongoing use of full-agonist opioids, thereby avoiding the precipitation of severe opioid withdrawal.

with Saeed Ahmed, MD and Michael R. Clark, MD, MPH, MBA

Buprenorphine, an FDA-approved medication-assisted treatment (MAT) to treat opioid use disorder (OUD), can be given in physician offices, so it significantly increases access to those in need – especially since President Biden expanded the X-waiver for prescribing buprenorphine in the spring of 2021. However, buprenorphine’s high-binding affinity as a partial u-opioid agonist displaces pre-existing full agonists, causing precipitated withdrawal. This mechanism can make the induction of buprenorphine a difficult experience for many patients due to that withdrawal.1

A newer approach called “microinduction” has emerged with the goal of easing this challenge.

What is Microinduction?

“Microinduction is a procedure that involves the administration of small, frequent doses of buprenorphine and removes the need for a period of withdrawal prior to the start of treatment," explains Saeed Ahmed, MD, an addiction psychiatrist and medical director of West Ridge Center at Rutland Regional Medical Center in Vermont. He and colleagues conducted a review of the literature on the concept,2 which was introduced in the medical literature in 2016, when a study out of Switzerland presented two cases of buprenorphine induction overlapping with full opioid agonist use.3

Microdosing involves the administration of small, frequent doses of buprenorphine with a goal of removing withdrawal symptoms before starting medication-assisted treatment for opioid use disorder. (iStock)


"By using a microdosing process, it is possible to overlap buprenorphine induction with the ongoing use of prescribed full-agonist opioids or street heroin without experiencing severe opioid withdrawal," Dr. Ahmed tells PPM.

"Traditionally, you have had to wait for a certain period to transition to buprenorphine/naloxone, especially if someone is using a full agonist such as methadone or street heroin/fentanyl," Dr. Ahmed explains. That's because the buprenorphine displaces pre-existing full agonist opioids like methadone from their receptors through competitive inhibition, which leads to the precipitation of opioid withdrawal and that is a very uncomfortable experience for patients."

The experience also often leads to patients discontinuing their treatment or relapsing, he says. In these situations, microdosing ''is a reasonable alternative.”

Says Dr. Ahmed, ''people usually ask us, ‘why buprenorphine over methadone?’ Because it has some advantages, including lower risk of overdose due to ceiling effects, fewer drug-drug interactions, and other pluses.”

Buprenorphine Microdosing: What the Literature Shows

In their review, Dr. Ahmed and colleagues analyzed 18 papers covering 63 patients who were successfully transitioned to buprenorphine using microdosing. While different techniques were used, the inpatient setting was a primary approach.

Initial doses ranged from 0.2 to 0.5 mg of buprenorphine and the timeframes for various schedules ranged from 3 to 112 days, but most people transitioned over a period of 4 to 8 days. Most patients completed the cross titration at 8 to 16 mg.

"There is currently no consensus on a single microdosing approach,” says Dr. Ahmed. “Many methods have been published in case reports and case series, however, any microdosing method may be used as long as the basic principles of small, incremental doses are followed."

Sublingual buprenorphine appears to be the most commonly used formulation for this purpose, but transdermal may also be an option, he says.

Comparing Microdosing to Conventional MAT Approaches

Most commonly in MAT, very low doses of buprenorphine (0.5 to 1 mg) are initiated alongside full opioid agonists. The buprenorphine is then gradually increased as the full opioid agonist dose is gradually decreased and eventually discontinued.  The 4-to-8-day transition is typical. Patients usually complete the cross-titration at 8 to 16 mg. "Then some clinicians and hospitals also perform rapid induction, which also seems to be safer and smoother," Dr. Ahmed tells PPM.

According to Michael R. Clark, MD, MPH, MBA, an associate professor of psychiatry at Johns Hopkins School of Medicine in Baltimore and a member of the PPM editorial board, Dr. Ahmed’s literature review will hopefully ''encourage clinicians to go beyond the [typical] algorithm and tailor their care to the individual needs of patients.”

Dr. Clark adds, "In the old version [of giving buprenorphine], if you put [patients] on the usual dose of buprenorphine and they are taking opioids, you can precipitate withdrawal.” Dr. Ahmed’s work is showing that “you can start with low doses and get some buprenorphine on board without precipitating that withdrawal, while you are trying to get someone to lower the dose of whatever opioid they are using and abusing." It's cross-taper, cross-titration approach, he says.

Microdosing: Identifying Patients for MAT

"Clinicians should consider microdosing in patients who have failed a conventional induction due to the inability to tolerate moderate withdrawal," advises Dr. Ahmed, adding that this approach might be especially useful in those individuals experiencing great anxiety about withdrawal.

Avoiding severe withdrawal might also be especially appreciated and important for patients with opioid use disorder (OUD) who are in chronic pain (see Latif ZH et al).4

Before beginning microinduction, it is crucial to inform patients that the microdosing approach is still off-label, Dr. Ahmed says.  However, '”the benefits likely outweigh the significant risk of patients with opioid addiction not receiving standard of care and lifesaving treatment with buprenorphine maintenance."

That said, the microinduction method has grown in popularity in the past 4 or 5 years. Dr. Ahmed observes that it is more popular in Canada than in the US. However, that might be changing. "The good news is that most clinicians in the United States are now aware of this method, particularly those who deal with addiction and pain management." Some major academic hospitals in the US have developed their own microdosing protocols, he notes.

Microdosing and Practical Takeaway

Tailoring care to individual patient's needs, such as with the microdosing approach, "might take more time, but you will have more success," Dr. Clark says. Further, when using microinduction to manage opioid use disorder, there will likely be less withdrawal issues and greater chances the patient will stay in treatment.



Last updated on: October 12, 2021
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Tapering Opioids May Drive Overdose, Mental Health Crises
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