A Practical Role for Long-Acting Buprenorphine in Opioid Use Disorder Care

SPECIAL REPORT: SUBSTANCE USE

For many health care providers, one of the greatest challenges when treating opioid use disorder (OUD) is helping patients stay engaged long enough to benefit from it.¹ Although daily transmucosal buprenorphine can be highly effective, everyday care is often derailed by missed doses, rural settings, transportation challenges, stigma, unstable housing, pharmacy barriers, diversion concerns, and loss of follow-up during transitions such as hospitalization, incarceration, residential treatment, or return to the community.^2,3

In the current fentanyl era, these types of interruptions often lead to greater clinical consequences, including severe physiological dependence, fluctuating tolerance, and sharply elevated overdose risk.^4-7 Long-acting injectable buprenorphine was developed to overcome some of these treatment barriers.² Instead of depending on daily self-administration, it provides sustained buprenorphine exposure over a clinically meaningful interval after administration by a health care professional. The appeal of sustained exposure is straightforward: fewer opportunities for missed doses, more stable medication exposure, less potential for diversion, and a treatment rhythm organized around follow-up care rather than around prescription logistics. For psychiatrists, that can translate into something deceptively simple but clinically important: a less fragile treatment experience.

A Patient Whom Psychiatrists Will Recognize

“Paul” is a 34-year-old man with OUD who uses fentanyl daily, cycles through emergency department visits, and repeatedly starts but does not remain on sublingual buprenorphine. He tells you the medication helps when he takes it but that he skips doses when work becomes chaotic and avoids pharmacies, where he feels judged. Paul also worries that an interruption in treatment will trigger withdrawal. Paul is the kind of patient for whom long-acting injectable buprenorphine could remove several day-to-day obstacles that keep an effective medication from working in real life.

Here is another familiar scenario: the patient who does reasonably well on daily buprenorphine when life is stable but destabilizes after a psychiatric admission, during a custody dispute, or after release from prison. In those moments, the clinical problem may be less about medication response and more about how easily a daily routine can collapse under stress. A long-acting formulation cannot solve every problem, but it may reduce one recurring point of failure.

More Than a Convenience

Buprenorphine is a partial agonist with high affinity and slow dissociation at the opioid μ receptor (μ-receptor), properties that support withdrawal suppression, craving reduction, and reduced responsiveness to other opioids.⁸ Development of monthly depot buprenorphine was guided by an exposure framework suggesting that plasma concentrations above 2 ng/mL are associated with substantial μ-receptor occupancy and meaningful opioid blockade.^9-12 In other words, the monthly formulation was designed to maintain the kind of sustained receptor engagement that may protect patients when adherence is otherwise fragile.

In practice, that sustained exposure can smooth out peaks and troughs, reduce the psychological burden of daily dosing, and create a more predictable treatment rhythm for both patients and clinicians. It can also be particularly useful in settings where continuity is frequently interrupted (eg, prisons, hospitals, residential programs, and busy outpatient clinics) because a patient can leave with ongoing medication coverage already in place.^13,14 That matters because many relapses are not failures of pharmacology; they are failures of continuity.

Available Long-Acting Buprenorphine Options

Two long-acting injectable buprenorphine products are currently approved in the United States: Sublocade and Brixadi. Both medications are administered as subcutaneous injections by a health care professional, are indicated for the treatment of moderate to severe OUD, and are available only through restricted Risk Evaluation and Mitigation Strategy programs.

Sublocade is the only once-monthly buprenorphine formulation that supports a rapid induction approach. This protocol involves administration of a single 4-mg dose of transmucosal buprenorphine to establish that buprenorphine is tolerated without precipitated withdrawal, followed by a first Sublocade injection, with the second monthly injection given as early as 1 week later. Findings from clinical studies have demonstrated that this rapid induction strategy is well tolerated and results in higher retention through the second injection compared with the traditional induction approach, which requires at least 7 days of transmucosal buprenorphine stabilization before the first Sublocade dose.^6,7 Improved retention was observed across the overall study population and was particularly notable among participants with positive results for fentanyl, supporting continued engagement in treatment during the critical early phase of care.^6,7

Brixadi is available in both weekly and monthly formulations. Weekly doses are available in strengths of 8, 16, 24, and 32 mg, whereas monthly doses are available as 64, 96, and 128 mg. The weekly and monthly products are not directly interchangeable on a milligram-to-milligram basis, and multiple weekly injections cannot be combined to achieve an equivalent monthly dose. For patients who are not currently receiving buprenorphine treatment, Brixadi may be initiated following a 4-mg transmucosal buprenorphine test dose, with treatment beginning with a weekly formulation that is followed by the monthly formulation. Patients who are already receiving transmucosal buprenorphine may transition to either the weekly or monthly Brixadi formulation, as determined by clinical judgment.

What the Evidence Means in Practice

Findings from randomized trials established that extended-release buprenorphine improves opioid abstinence, treatment success, craving, and withdrawal outcomes compared with placebo, and findings from long-term studies have shown durable benefit without new major safety signals.^15-18 Patient-centered analyses are especially relevant for psychiatric practice because they move beyond urine toxicology alone. Participants receiving monthly injectable buprenorphine reported improvements in health-related quality of life, medication satisfaction, and other functional outcomes.^19,20

That broader lens matters. Patients do not define recovery as a function of negative results from urine screening. Rather, they talk about sleeping through the night, showing up at work, having fewer crises, reconnecting with family, and spending less mental energy on taking medication. Clinical programs suggest that longer treatment exposure is associated with better multidimensional recovery trajectories.^21-24 For psychiatrists, this supports a familiar principle: Pharmacotherapy is most powerful when it lowers the daily cognitive and logistical burdens enough for patients to rebuild functioning.

Emerging fentanyl-era data add another practical layer. Findings from studies suggest that sustained buprenorphine exposure can attenuate fentanyl-induced respiratory depression, and findings from newer trials support more rapid initiation pathways and individualized higher maintenance exposure for select high-risk patients, including some with frequent fentanyl use.^6,7,25 These findings do not eliminate overdose risk, especially when sedatives or alcohol are involved. They do, however, strengthen the case for reducing gaps in medication coverage whenever possible.

Which Patients May Benefit Most?

Patient preference should be a central consideration when evaluating treatment options. In practice, patients who repeatedly miss doses despite wanting treatment, those with ongoing fentanyl exposure or high overdose risk, patients leaving controlled settings such as hospitals or prisons, those with concerns about diversion or medication security, and patients who plainly say they want treatment to feel less burdensome are often strong candidates for a conversation about this option.

Psychiatrists should also think about co-occurring illnesses. For patients with severe depression, psychosis, posttraumatic stress disorder, cognitive impairment, chronic pain, or unstable living situations, simplifying the medication routine may free up clinical attention for the psychiatric and social drivers of relapse. Long-acting treatment will not fix those problems by itself, but it can reduce one avoidable source of instability.

The Table summarizes common clinical situations in which psychiatrists may consider discussing long-acting injectable buprenorphine. The emphasis should remain on shared decision-making. In settings where power differentials are pronounced (eg, corrections, residential care, child welfare, or mandated treatment), clinicians should be especially careful to explain alternatives and make clear that long-acting treatment is being offered as a choice, not as a condition of care.

Implementation

A few operational lessons stand out. First, treat transitions of care as opportunities. Hospital discharge, release from incarceration, or exit from residential treatment are moments when adherence barriers are predictable and overdose risk may be high. Second, build workflows before the first prescription. Successful implementation usually depends on support for prior authorization, reliable procurement and storage, appointment reminders, and a clear plan for missed visits. Third, monitor the same clinical domains you would monitor with any buprenorphine treatment: withdrawal, craving, opioid use, adverse effects, co-occurring psychiatric symptoms, pain, and social stressors. Long-acting medication simplifies dosing, but it does not replace ongoing clinical assessment. Fourth, use the visit to practice recovery-oriented psychiatry. Because patients are not preoccupied with daily dosing, encounters with health care providers can shift toward sleep, anxiety, depression, trauma, housing, work, and family functioning. That is often where psychiatrists add the most value. Fifth, pay attention to team roles. Clinics that implement long-acting formulations well usually involve nursing, pharmacy, front-desk staff, and case management rather than leaving the logistics entirely to the prescriber. Finally, plan ahead for discontinuation. Long-acting buprenorphine has a long apparent terminal half-life, so exposure declines gradually, but patients still need counseling about what to expect and how to reengage quickly if cravings, stress, or relapse risk return.

What Psychiatrists Should Watch For

As with any OUD treatment, follow-up should include more than a brief check-in about opioid use. Ask about anxiety, depression, insomnia, trauma symptoms, pain, suicidal ideation, stimulant or benzodiazepine use, and whether daily life is becoming easier or harder. In many cases, improvement appears first in routine functioning rather than in dramatic milestones. A patient who keeps appointments, returns to work, sleeps better, and has fewer crises may be showing meaningful recovery even before every outcome is fully stabilized.

It is also worth addressing expectations. Some patients hope a monthly injection will make OUD disappear quickly. Others worry it means they are “sicker” or less independent. Clear psychoeducation helps; this is still buprenorphine treatment, simply delivered in a way that may protect continuity when daily routines are difficult to maintain.

Important Cautions

Patients still need access to overdose prevention, harm-reduction counseling, psychiatric care, and treatment for co-occurring medical and substance use conditions. Cost, access, workflow demands, and local availability also influence whether the treatment is feasible in a given setting. Emerging data for pregnancy, corrections, and health-system implementation are encouraging and will benefit from further prospective studies.^26-29

Bottom Line

For practicing psychiatrists, the chief advantage of long-acting injectable buprenorphine is the ability to turn an effective medication into a more continuous and less fragile treatment experience. When used thoughtfully, it can reduce treatment friction, improve continuity during high-risk transitions, and support the broader goals patients usually care about most: fewer crises, better functioning, and a more stable recovery. In daily practice, long-acting buprenorphine is worth considering precisely because the clinical problem is not willingness to be treated but rather the difficulty of staying in treatment.

Dr Heidbreder is the chief scientific officer of Indivior Pharmaceuticals. He is also an affiliate professor at Virginia Commonwealth University School of Medicine in Richmond.

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