For opioid addiction, treatment underdosing can lead to fentanyl overdosing – a physician explains

Imagine a patient named Rosa tells you she wakes up night after night in a drenching sweat after having very realistic dreams of smoking fentanyl.

The dreams seem crazy to her. Three months ago, newly pregnant, Rosa began visualizing being a good parent. She realized it was finally time to give up her self-destructive use of street fentanyl. With tremendous effort, she started treatment with buprenorphine for her opioid use disorder.

As hoped, she was intensely relieved to be free from the distressing withdrawal symptoms – restless legs, anxiety, bone pain, nausea and chills – and from the guilt, shame and hardship of living with addiction. But even so, Rosa found herself musing throughout the day about the rewarding rush of fentanyl, which seemed ever more appealing. And she couldn’t escape those dreams at night.

Rosa asks you, her doctor, for a higher dose of buprenorphine. You consider her request carefully. Your clinic follows the Food and Drug Administration prescribing guideline that has changed very little in over 20 years. It recommends her current prescription – 16 milligrams – as the “target” dose. You are aware of the prevailing view among medical providers that most patients don’t need a dose higher than that. Many believe that patients or others would use the extra pills to get high.

But after many visits, you feel that you know Rosa well. You believe in her sincerity. She is a responsible 25-year-old with a full-time job who never misses appointments. She now has stable housing with her parents after years of couch surfing. You reluctantly agree and raise her daily dose by one additional 8-milligram pill, totaling 24 milligrams.

At her next visit, Rosa tells you that the higher dose solved her daytime fentanyl craving, but the nightmares have continued. She would like to try an even higher dose.

How should you respond? The FDA guideline clearly states there is no evidence to support any benefit above her new dose. You begin to doubt Rosa’s sincerity and your own judgment.

Harms of low doses

This hypothetical scenario has played out countless times in the U.S. since 2002, when buprenorphine was first approved as a treatment for opioid use disorder. As a family physician specializing in addiction medicine, I have frequently encountered patients who still experience withdrawal symptoms at the “target dose” and even at the suggested maximum dose of 24 milligrams.

People like Rosa, plagued by uncontrolled fentanyl craving – either awake or in dreams – are at high risk of leaving treatment and returning to addiction. Yet from 2019 to 2020, only 2% of buprenorphine prescriptions were written for over 24 milligrams.

I was able to help some of those people in my work as co-founder and medical director of a low-barrier clinic, which is a clinic that makes it easier for people to get started with buprenorphine. I asked our clinicians to offer a higher dose when they believed the current one wasn’t meeting the patient’s needs.

The dose choice may be a life-or-death decision. Increasing it by one more pill – to 32 milligrams – often makes the difference between a patient staying in or leaving treatment. The risk of leaving treatment is particularly significant for the patients we typically see at low-barrier clinics, many of whom face severe life challenges. While patients do sometimes give away or sell extra pills, research consistently shows that illegally obtained pills are most commonly used for self-treatment – to control withdrawal and help quit opioids when treatment is unavailable.

Medicaid in my state of Washington began paying for prescriptions up to 32 milligrams in 2019. But clinicians may still encounter constraints from other health insurers and at pharmacies. Some states, such as Tennessee, Kentucky and Ohio, have dose restrictions cemented in law.

Finding the right dose

The challenge of finding the right treatment dose became more acute for clinicians and patients as fentanyl swept across the country starting in 2013. Fentanyl now dominates the unregulated opioid supply. Fifty times stronger than heroin, fentanyl overwhelms the ability of low doses of buprenorphine to counter its effects.

Buprenorphine – also known by the brand name Suboxone, which contains a mix of buprenorphine and naloxone – is an opioid medication with the quirk of both activating the brain’s opioid receptors and partially blocking them. It provides just enough opioid effects to prevent withdrawal symptoms and craving while also blocking the reward of euphoria. It relieves pain like other opioids but doesn’t cause breathing to stop. It can dramatically reduce the risk of overdose death by as much as 70%.

In medicine, there is a general concern that too high a dose may have toxic effects. However, as many clinicians and researchers have observed, using too low a dose of some treatments can also lead to harm, including death from patients going back to fentanyl.

After observing so many patients responding well to higher doses, my colleagues and I looked in the medical literature for more information. We discovered over a dozen reports as far back as 1999 providing evidence that buprenorphine’s benefits steadily increase up to at least 32 milligrams.

At higher doses, patients stay on treatment longer, use illicit opioids less often, have fewer complications such as hepatitis C, have fewer emergency room visits and hospitalizations, and suffer less from chronic pain. Brain scans show that buprenorphine at 32 milligrams occupies more opioid receptors – over 90% of receptors in some brain regions – compared with lower doses. One study even showed that a high enough dose of buprenorphine can directly prevent fentanyl overdose.

Patients with some health conditions may especially benefit from higher doses. During pregnancy, as in Rosa’s case, withdrawal symptoms can grow more intense because of metabolism changes that reduce the blood concentration of most medications. A higher dose may be needed to maintain the level of effects they had before pregnancy. Additionally, I found that the patients in my clinic with chronic pain, post-traumatic stress disorder or longtime opioid use were most likely to find relief at a dose above 24 milligrams.

The American Society of Addiction Medicine recommends
four goals of treatment: suppressing opioid withdrawal, blocking the effects of illicit opioids, stopping opioid cravings and reducing the use of illicit opioids, and promoting recovery-oriented activities.

Similarly, patients seek a comfortable and effective dose – that is, one that avoids withdrawal symptoms and craving, and allows them to avoid illicit drug use and the associated worry and stress. Many patients also yearn to feel trusted, accepted and understood by their clinician. Achieving that goal requires shared decision-making.

A clinician can never be sure a patient is meeting all the goals of treatment. But a patient who reports positive life changes – such as stable housing and improved relationships – and reports low or no craving while awake or dreaming will likely be satisfied with the current dose. For a patient who does not make progress with a dose increase to 32 milligrams, the clinician might consider a different treatment plan, such as a 30-day buprenorphine injection, which can provide an even higher dose, or transition to methadone, the other highly effective FDA-approved medication for opioid use disorder.

The FDA guideline change

In August 2022, a team of addiction physicians attempted to move the FDA to change dosing guidelines for buprenorphine. They submitted a petition asking for a modernized guideline that based dosing on how a patient responds to buprenorphine – including symptom relief and reduced illicit drug use – rather than a fixed “target” dose. They asked to remove language that incorrectly denied evidence that patients benefited from doses above 24 milligrams.

The FDA listened. In December 2023, it convened a public meeting with leading addiction clinicians, researchers and policymakers to review the evidence on buprenorphine dosing. The group came to an overwhelming consensus that there was extensive research showing benefit at doses above 24 milligrams. Moreover, they doubted whether the guideline’s dosing conclusions, made before fentanyl infiltrated the drug supply, applied today.

Then, the FDA responded. In December 2024, it announced a new buprenorphine recommendation that would not mention a target dose and would not deny the existence of evidence of benefits above 24 milligrams. Only time will tell whether and when the FDA’s new guideline will meaningfully alter prescribing patterns, insurance and pharmacy restrictions, and state laws.

To maintain the national trend toward lower overdose deaths, the best possible use of each effective treatment is critical. Yet the Trump administration’s proposed cuts to Medicaid – which covers nearly half of all buprenorphine prescriptions – put access seriously at risk. Most people with untreated addiction would be blocked from accessing treatment altogether, let alone at an effective dose or with the behavioral health, social work and recovery support services needed for the best outcomes. Research shows that a sharp reduction in buprenorphine prescriptions occurred following 2023 Medicaid coverage restrictions.

Opioid use disorder is treatable. Buprenorphine works well and saves lives when given at the right dose. An inadequate dose can directly harm patients who are simply trying to survive and improve their lives.