Addressing Patient Opioid Use Disorder in Primary Care
September 1, 2025 30 minutes read
By Ellen Feldman, MD
Executive Summary
This issue emphasizes the critical role of primary care providers (PCPs) in diagnosing and initiating treatment for opioid use disorder (OUD), especially in the fentanyl era. It demonstrates that OUD is a chronic, treatable disease; underscores the importance of same-day induction with buprenorphine; and highlights reducing stigma as central to patient care. This issue also covers diagnostic criteria, treatment workflows, harm reduction, regulatory updates, and practical clinical tools to help PCPs confidently manage OUD in office-based settings.
- Use Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria to classify OUD severity; moderate OUD is diagnosed when four to five criteria are present.
- Standard buprenorphine induction should begin when the Clinical Opiate Withdrawal Scale (COWS) score is 12 or higher to reduce the risk of precipitated withdrawal.
- Since 2023, no X-waiver is required to prescribe buprenorphine; only an eight-hour substance use disorder training course is needed with Drug Enforcement Administration registration.
- Always co-prescribe naloxone and provide brief training for its use when starting medications for OUD.
- Implement universal or targeted screening, use non-stigmatizing language, integrate team-based care (including pharmacists and behavioral health), and consider tapering only after 12 or more months of stability.
Meet Maya
Maya, a 36-year-old local business owner, books a same-day visit for “a lingering stomach bug.” She is pale, yawning, mildly diaphoretic, with dilated pupils and a resting pulse of 104 bpm. Her chart looks benign at first glance — a few urinary tract infections in her 20s, an old prescription for 14 hydrocodone/acetaminophen tablets after an ankle fracture 10 months ago, and a recent emergency department visit for headache. A routine, single-question screen (“How many days in the past year have you used any opioid not exactly as prescribed?”) elicits, after a beat: “Honestly … every day for months. Sometimes the ‘blue 30s’ and sometimes my friend’s prescription. I am so tired of chasing pills, and I keep needing more to feel OK. Each time I stop I feel so bad that I go right back.” She pauses and looks up. “I decided this weekend would be it — no more. But I got so sick this time I couldn’t make it to work.” In less than five minutes, it becomes clear that Maya’s history and presentation satisfy multiple Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria: dose escalation, failed reduction attempts, withdrawal avoidance, and role impairment — consistent with moderate opioid use disorder (OUD).1
Maya’s physiologic discomfort most likely represents emerging withdrawal. When this is combined with the safety risk in taking illicit opioid tablets and expression of motivation (“I am just tired of chasing pills”), a narrow but actionable opportunity emerges. The question is not whether primary care should intervene, but will treatment begin today.
Primary care now sits at the forefront of the opioid epidemic. Synthetic opioids — chiefly illicit fentanyl analogues — have compressed the timeline from first exposure to physiologic dependence, blurred the distinction between “pill” and powder sources, and elevated overdose lethality even among intermittent users. At the same time, regulatory barriers that historically funneled patients toward specialties (such as the former DATA-Waiver/X-Waiver) have fallen, telehealth flexibilities have broadened geographic reach, and naloxone has entered mainstream community distribution.2,3 These shifts converge to make office-based identification and initiation of treatment for OUD not a niche extension of primary care, but core chronic disease management — akin to starting insulin for uncontrolled diabetes or a beta-blocker after a myocardial infarction.2
However, in many communities a persistent implementation gap remains. Patients with clear diagnostic criteria leave appointments without medication for OUD, are told to return when in “full withdrawal,” or are referred out (often to programs with weeks-long waits), leaving extended intervals when tolerance fluctuates, exposure risk accumulates, and motivation crumbles. Traditional linear sequences consisting of “screen, counsel, refer” are no match for the tempo or risk profile of fentanyl-era OUD. Instead, a parallel, same-day model provides at least a partial answer with documented better outcomes: brief normalized screening paired with rapid, criteria-based diagnosis (with careful use of non-stigmatizing language); immediate offering of buprenorphine via standard induction or the consideration of micro-induction pathways; concurrent harm reduction (naloxone, overdose prevention counseling); and early layering of supports (peer navigation, recovery groups, digital tools) without making these supports prerequisites for treatment.4
Stigma reduction remains a priority. Strategies such as use of person-first language and re-engagement protocols that treat return to use as clinical data and not a moral failure are illustrated through the fictional case presented in this article. Decision pathways are presented to assist clinicians with understanding typical workflows rather than memorizing isolated facts.
The overarching objective is confidence. Confidence to start lifesaving medicine today, to choose and explain induction strategies, to titrate based on craving/function metrics, to integrate harm reduction without signaling pessimism, and, ultimately, to form a comprehensive and integrated treatment team with the patient at the helm.
Historical Conceptualization of Substance Use
The principles of OUD treatment are embedded in an understanding of addiction medicine and how the medical conceptualization of substance use has evolved over time.
The early history of humanity is sprinkled with references to the use of substances with psychoactive properties. Properties of opium (extracted from the poppy flower) and alcohol (a fermented drink made from honey, rice, or grapes) were known as far back as 10,000 BCE. In ancient Greece, opium and its derivatives were used medicinally and for spiritual purposes, while there is evidence of recreational use of alcohol in the Middle East and China during this time.5,6
Cannabis, originally from Afghanistan, also is deeply rooted in early history. Although practical purposes, such as utility in rope making, fueled its spread through trade, medicinal use followed soon afterward in many areas, including ancient India and China.5,6
These substances spread across the world via trade and cultivation, with written records of specific properties and use in diverse civilizations attesting to a wide range of applications.
The rise of the church after the fall of the Roman Empire seemed to influence beliefs and attitudes toward intoxication significantly, in particular those involving alcohol. In 1647, Agapios, a Greek monk, was the first to document an association between excessive alcohol use and disease. Meanwhile, the “anti-opium” movement began to build, citing medical and moral objections to continued use (and focusing on some of the political implications of ending opium trade).5-7
By the mid-1800s, the addictive potential of opium became known, adding more fuel to the movement to end recreational and medicinal use of this substance. By the early 1900s, the term “addict” became widespread in the United States, and racial stereotypes, especially around cannabis use, emerged. Criminalization of “substances” soared with the passing of the 18th Amendment to the U.S. Constitution, ushering in an era of prohibition.5-7
The repeal of Prohibition in 1933 was followed closely by the establishment of Alcoholics Anonymous in 1935, perhaps a step toward looking at treatment outside of correctional institutions for individuals with disordered substance use.5-7
Yet, with the publication of the first DSM in 1952, through subsequent editions until 1980, substance use was not classified as a standalone disorder but viewed as most commonly arising from a separate disorder of mental health (such as a personality disorder). The third edition of the DSM began slowly to move away from this conceptualization. The 2013 and 2022 editions (DSM-5 and DSM-5-TR, respectively) dramatically demonstrated new perspectives on substance use disorder (SUD), basing diagnosis on an understanding of a biopsychosocial model, describing functional impairment, and recognizing that SUD presents on a spectrum from mild to severe according to the number of symptoms and degree of impairment.1,5-7
It is useful to note that societal influences, including political, spiritual, and socioeconomic forces, have contributed to a shifting perception of substance abuse over time, and contributed to our view of SUD and treatment direction today. It is unlikely that the current DSM classification and description of SUD is the final or most definitive word; very well, it may be that, as society moves forward, so will our understanding of this disorder, its underpinnings, and its treatment.
Reframing Addiction: A Brief Refresher
Addiction remains a treatable, chronic medical disease involving neurobiological dysregulation modulated by genetics (approximately 50% heritability), epigenetic influences, developmental adversity, mental health comorbidities, and social determinants (including housing instability, stigma, and limited access to treatment). Viewing addiction through the same longitudinal, relapse-remission lens used for hypertension or diabetes supports continuity, proactive monitoring, and deescalated moral framing.2,8
Imagine a patient taking an opioid for pain and who experiences an immediate rush of relief and well-being. This initial reaction is driven by a rapid flood of dopamine in the brain’s reward pathways paired with potentiated endogenous opioid signaling, forging a powerful link between the drug and pleasure. However, in time, the brain adapts, and baseline dopamine levels fall. Stress mediators (for example, corticotrophin-releasing factor) surge in response to the absence of the drug, and the prefrontal cortex’s ability to regulate impulses weakens, pushing the individual toward more use even when it conflicts with personal values or responsibilities. As tolerance builds, conditioned cues —such as seeing a pill bottle, or even the memory of relief — trigger negative reinforcement, so that taking the drug becomes more about avoidance of withdrawal symptoms or dysphoria and less about pleasure-seeking.8,9
But the neuroplastic brain can recalibrate. Effective medications that stabilize receptor activity and psychosocial supports that reduce chronic stress team up in this process. Over weeks to months, patients often reclaim cognitive control and emotional equilibrium, transforming what once felt like an unbreakable cycle into a manageable chronic condition amenable to long-term recovery.9,10
Why Focus on OUD Now?
Potent synthetic opioids (illicit fentanyl analogues) and polysubstance exposure (notably fentanyl and stimulants, as well as emerging sedative adulterants, such as xylazine) drive persistent overdose mortality.2,3,11 Primary care access points — medication initiation today, brief risk mitigation — measurably reduce mortality and improve retention compared with referral-only pathways.3,11
A Note on Epidemiology and Regulations
More than 100,000 Americans died from drug overdoses in 2023, a slight decrease from the year prior. Recently released provisional statistics from 2024 show a continuation of this downward trend, with a more substantial drop in 2024 to slightly more than 80,000 deaths. More than half of these deaths were attributable to synthetic opioids. Rates of polysubstance involvement, including stimulants and sedative adulterants, such as xylazine (a veterinary, alpha-2 agonist), are rising, further complicating presentations and amplifying overdose risk. These trends make early recognition and initiation of treatment in primary care even more central to efforts to curb morbidity and mortality.12
The Centers for Disease Control and Prevention (CDC) outlines three waves of this epidemic. The initial period began in the late 1990s, shortly after the introduction of oxycodone (approved by the Food and Drug Administration [FDA] in 1995 and the most prescribed pain pill in the United States by 2001); most of the overdose deaths were from prescription opioids marketed initially as “non-addicting.” As the habituating properties of these newer narcotic agents became clear, prescriptions declined, and many patients turned to the street for opioids. The second stage of this epidemic began in 2010 as overdoses with heroin rose. The third wave, beginning in 2013 and continuing to the present day, involves synthetic opioids, especially involving fentanyl (a very potent synthetic opioid marketed as Duragesic or Sublimaze, but also produced illegally).12,13
Recent policy and regulatory shifts have markedly expanded primary care’s ability to deliver OUD treatment. The Mainstreaming Addiction Treatment (MAT) Act in 2023, aimed at expanding access to SUD treatment, eliminated the X-waiver requirement to prescribe buprenorphine and enabled any Drug Enforcement Administration (DEA)-registered provider with Schedule III authority to initiate medications for opioid use disorder (MOUD). A new one-time, eight-hour SUD course to renew or obtain a DEA license now is required as well. However, providers are cautioned to be familiar with state laws regarding MOUD, which may have different requirements.2,3
Federal telehealth flexibilities, extended through at least 2025, permit both initiation and continuation of buprenorphine via virtual encounters without a prior in-person examination. Concurrently, naloxone’s transition to over-the-counter status and state-level standing orders have helped in equalizing overdose reversal access and streamlined co-prescribing. Together with streamlined training requirements (the one-time, eight-hour SUD CME course to renew or obtain a DEA license) and evolving reimbursement codes, these regulatory changes position primary care as the central front-line setting for evidence-based OUD management.2,3
Yet, the uptake of in-office MOUD by primary care remains hindered by lingering knowledge gaps, insufficient integrated behavioral-health support, workflow/time constraints, and basic access issues. For example, a February 2024 follow-up survey of clinicians who completed a MOUD training program found less than 50% actively prescribing or treating OUD, citing many of these factors as barriers.14 A June 2024 Journal of the American Medical Association (JAMA) study revealed that well over half of patients responding to a questionnaire were not aware a primary care provider (PCP) could treat OUD (although most thought that the PCP office was an appropriate setting for this treatment).15 Recommendations include practical ways to increase awareness that PCPs treat OUD, such as signage in offices, outreach, and messaging akin to campaigns for human immunodeficiency virus (HIV) treatment and cancer screening. Proactive OUD screening, as well as concrete administrative support, also are necessary elements.14-16
Stigma
Stigma is a powerful social mechanism shaped by attitudes and/or behaviors, including labeling, stereotyping, and separating, which contribute to discrimination and loss of status. Stigma in healthcare and in health facilities can be especially damaging, leading to poor outcomes for vulnerable individuals and affecting the healthcare workforce as well. Increasingly, it is becoming clear that recognition and correction of stigmatizing attitudes and behavior is essential to delivering quality healthcare.17,18
Individuals with mental illness, and particularly those with SUD, report that both overt stigma and perceived stigma are barriers to seeking treatment. In recognition of this, and as one of several concrete steps to encourage clinicians to recognize and correct stigmatizing behaviors, several prominent medical societies (including the American Medical Association) have joined forces to promote the use of accurate scientific terminology when discussing substance use and SUD.18
“Words matter,” noted Botticelli and Koh in JAMA in 2016, Slomski in JAMA in 2021, and Judd et al in 2023.19-21 All of these articles advocated for removing stigmatizing language from the everyday vocabulary of medical professionals, noting this can be an effective first step toward starting to change bias and the perceptions of other healthcare workers, patients, and the general public. For example, describing the patient as “a person with SUD” rather than labeling the individual a “drug abuser” or “addict” reinforces the concept that SUD is a treatable medical condition rather than a personal characteristic or failing. Other recommendations include avoiding the term “drug habit,” which may convey a sense of choosing to use (rather than use because of chronic brain disease) and to discuss individuals being “in recovery or relapse” rather than “clean or dirty.”18-21
Certainly, vocabulary changes alone must be matched with education and policy changes on many levels to defeat the stigma associated with SUD. However, the PCP can begin the process of defeating stigma and pull down some of the barriers surrounding access to treatment for patients with SUD by careful choice of medically accurate, neutral terms that portray SUD as a treatable, chronic medical condition.
Diagnostic Criteria
The DSM-5-TR provides concrete guidelines for the diagnosis of “Substance-Related and Addictive Disorders.” Note that none of these disorders are referred to “addictions,” but are classified as SUD. Substances specified in the DSM-5-TR include alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives/hypnotics, stimulants, and tobacco-related disorders.1 For most of these categories (apart from caffeine), the diagnostic criteria are as follows:
A problematic pattern of use leading to clinically significant impairment or distress, as manifested by at least two of the following over a 12-month period:1
- taking more than intended;
- inability to reduce or control use;
- spending a lot of time obtaining, using, or recovering from use;
- experiencing cravings;
- continued use despite failure to fulfill major obligations;
- continued use despite deterioration in interpersonal or social relations caused by use;
- giving up important social, occupational, or recreational activities because of use;
- recurrent use in a hazardous situation;
- continued use despite knowing use will worsen physical or psychological problems;
- tolerance to the effects of the substance; and/or
- withdrawal when reducing or stopping use.
Severity is determined by the number of criteria met: two to three criteria indicate a mild disorder, four to five criteria indicate a moderate disorder, and six or more criteria indicate a severe disorder. Early or sustained remission also may be documented. Note that there is no distinction made between “abuse” and “dependence.”1
Treatment
Treatment of SUD can fall into two general categories: pharmacologic and non-pharmacologic. In the best of worlds, these two modalities are intertwined into an individualized treatment program. However, many patients receive neither of these interventions.
It is estimated that there are fewer than 3,000 addiction specialists in the United States. Many communities simply do not have this resource available, and it falls to the PCP to initiate and/or continue medication treatment for patients with OUD.22
Before initiating treatment, it is useful for the PCP to develop a working understanding of the American Society of Addiction Medicine (ASAM) “dimensions,” which lend a structured approach to determining the level of care for an individual patient. These dimensions consider the complex, multifactorial nature of substance abuse. Dimensions 1-5 can be used to consider the level of care needed medically, while dimension 6 involves joint decision-making.23 (See Table 1.)
Table 1. ASAM Dimensions for Patient Care |
Dimension 1 Consider the state of intoxication, withdrawal stage, and addiction medications. A careful history can help determine if this patient can be treated safely as an outpatient. Dimension 2 Consider unstable comorbidities that require inpatient services, such as chronic liver disease, any pregnancy-related concerns, or sleep issues. Dimension 3 Consider psychiatric, cognitive, and behavioral comorbidities, such as mood disorder, psychosis, and/or suicidal threats that require psychiatric care. Dimension 4 Consider substance use-related risks, including the likelihood of risky behavior. Dimension 5 Consider recovery environment interactions, including safety and support in the patient’s current environment. Dimension 6 Consider patient-centered factors, including motivation, patient preferences, and barriers to care. |
ASAM: American Society of Addiction Medicine |
Considering each factor can help the PCP make a focused medical decision regarding whether the patient with SUD can be treated safely in an outpatient setting. If outpatient treatment is appropriate, the PCP next decides if the treatment is best initiated in the PCP office.23
Other options for more intensive care include intensive outpatient treatment (generally conducted by a licensed addiction counselor [LAC] several times weekly), a rehabilitation center, a psychiatric inpatient facility, or a medical center.4,23
It is important for the PCP to have a working knowledge of resources in the community and/or online offerings to provide to the patient to complement and enhance treatment and for referral, should a patient not tolerate initial treatment.
Take Home Points
- Since 2023, any provider in the United States with a DEA license can prescribe MOUD. No waiver or special training is required, other than meeting the requirements to obtain the DEA license.
- Understanding the DSM-5-TR diagnostic criteria for SUD and the ASAM Dimensions system facilitate a structured approach to diagnosis and determination of treatment level.
- Use precise, nonjudgmental, person-first language and proactively identify and dismantle clinic or hospital-based sources of stigma, especially for patients who may fear judgment or repercussions when seeking care.
Back to Maya
Clinician: “I appreciate your honesty today. That couldn’t have been easy.”
Maya, with eyes downcast: “I feel very ashamed … like I am an addict.”
Clinician, nodding in understanding: “The symptoms you describe — including ‘chasing the pills’ — indicates you have a moderate OUD. This means your brain chemistry adapted to the opioids. The good news is that this is a chronic but treatable medical condition, and we may be able to start treatment today, to stabilize you and reduce cravings, if you are ready.”
Maya, looking up: “Today? Really?”
Clinician: “Yes. There also is an option for referral to a specialty clinic, if you prefer that route. Right now, the wait is at least two to three months, but the clinic has addiction specialists onsite. Most of my patients prefer to start here in the office and use the support services from the specialty clinic once they are available.
“But, regardless, the first step is to see where you are in terms of withdrawal. I use a tool called the Clinical Opiate Withdrawal Scale (COWS), which measures signs and symptoms of withdrawal. By my calculations, you score in the mild to moderate range, which indicates your body now depends on opiates to function.”
Maya, looking alarmed: “Yes, I know I am in withdrawal, with or without the scale! Do I just have to get through it? I don’t think I should wait a month or more — I think I would probably use again.”
Clinician: “I think we can help you out, but I want to make sure we can do this safely. Let me gather a little more history, check you out physically, and then we will go over some options. You will need some labs, also — but let’s take this step by step.”
After confirming that Maya has no unstable comorbidities, has no new prescriptions on the state database (Prescription Drug Monitoring Program; PDMP), and is in a stable home environment, the clinician feels ready to offer treatment options.
Some In-Office Tools for MOUD
Screens for OUD
The American Academy of Family Physicians (AAFP) recommends selective screening of all adults for OUD only when appropriate follow-up can be offered or referred. The Federal Substance Abuse and Mental Health Services Administration (SAMHSA) specifies routine screening of adults for substance misuse yearly, and especially at times of major life changes and when family members raise concerns.24,25
The National Institute for Drug Abuse (NIDA) provides a quick screen for substance misuse, accompanied with the reassurance that the information will be used for diagnostic and treatment purposes. The basic question, “In the past year, how often have you used the following substances?” can be modified for clinical purposes, as seen in the initial encounter with Maya.26
The 11-item Clinical Opiate Withdrawal Scale (COWS) rates clinical signs and symptoms of opiate withdrawal, such as pulse rate, nausea/vomiting, yawning, agitation, and tremor, and allows monitoring over time.27 Scores range from 0-47: 5 to 12 indicates mild withdrawal, 13 to 14 indicates moderate withdrawal, 25 to 36 indicates moderately severe withdrawal, and more than 36 indicates severe withdrawal. These scores often are used to decide when to initiate buprenorphine and subsequent dosing.
Prescription drug monitoring programs (PDMPs) are state-run electronic databases that collect information on all controlled medications dispensed to an individual.28 Accessing the PDMP allows clinicians to see dispensing history. This information is best used to provide safe treatment and not to judge a patient or refuse care. Sharing PDMP findings transparently can open a dialogue that builds trust. For example, “I see here you have recently filled a script from a different provider. Let’s talk through what is happening so we can safely manage your treatment.” (This can include more frequent visits, urine screens, or links to ancillary support.)
Most OUD treatment guidelines recommend checking PDMP at baseline and at every dose adjustment or another periodic interval to maintain oversight and patient safety.
Shared Decision-Making
The clinician explains to Maya the options for treatment:
- Standard induction: “We can start buprenorphine now while your withdrawal is moderate. This would be a dose of 2 mg under your tongue, and you would need to stay for monitoring for about 60 minutes. Then we will give you some more — up to about 8 mg total — in titrating doses, depending on if you still are in withdrawal. This should help you feel better quickly, but I want you to know there is a risk of feeling worse if our timing is off and you still have opioids on board.”
- Micro-induction: “This second option still is considered ‘off-label.’ This method uses very low doses of buprenorphine over several days while you taper your current opioids. This makes sense if you still have opioids in your system now and will help avoid significant withdrawal, but you need to check in daily for several days to weeks.”
Note: Buprenorphine’s high affinity for μ-opioid receptors means it can displace full agonists (such as fentanyl) and trigger sudden, intense withdrawal if these agonists still are present. To minimize this risk, patients should be in at least moderate withdrawal (COWS score of at least 12, but less than 20) before standard induction. The presence of fentanyl can heighten this risk, since this substance is highly lipophilic, often leading to prolonged receptor occupancy and, consequently, heightening susceptibility to precipitated withdrawal.29
Maya, looking away: “I want to feel better as quickly as possible, and I am committed not to use again. I promised my husband after he found my pills last week.” Taking a deep breath, she turns to face the clinician. “I think his disappointment was worse than any withdrawal,” she says. “I used fentanyl, but not for months — it scares me. Let’s do the first option.”
Pharmacotherapy for OUD
For additional information about pharmacotherapy for OUD, see Table 2.
Table 2. Pharmacotherapy Agents for OUD |
Buprenorphine, with or without naloxoneBarrier to Initiation: Low (standard/micro) Overdose Risk: Low (ceiling) Primary Care Setting Suitability: Optimal for office-based induction and maintenance |
MethadoneBarrier to Initiation: Very high; requires specialized treatment setting Overdose Risk: Moderate (dose-related) Primary Care Setting Suitability: No; requires specialized treatment clinic |
XR NaltrexoneBarrier to Initiation: Very high (detox first) Overdose Risk: None (antagonist) Primary Care Setting Suitability: Limited use |
OUD: opioid use disorder; XR: extended release |
Buprenorphine (Partial μ-Agonist and κ-Antagonist)30,31
This agent lightly activates the same opioid receptors that full opioids (such as fentanyl or morphine) stimulate, reducing cravings and withdrawal without producing the same high. At the same time, it blocks other opioid effects (κ-antagonism), which can help decrease dysphoria and lower the risk of misuse.
- Formulations: Sublingual films/tablets (with or without naloxone), monthly depot injection, six-month implant for select stable patients
- Initiation: Standard induction is 2 mg to 4 mg sublingually at COWS score > 12; titrate to 8 mg on day 1 based on relief of withdrawal symptoms. On day 2, beginning with the total dose from the day prior and taper up in 2 mg to 4 mg increments to 16 mg as clinically indicated (according to symptoms of withdrawal). The typical daily dose is 16 mg to 24 mg, with evidence that< 16 mg daily is less effective than higher doses at suppressing opioid misuse. There is emerging evidence that doses up to 32 mg may be necessary to successfully retain individuals in treatment, especially those previously exposed to fentanyl.
- Management of precipitated withdrawal: Precipitated withdrawal looks like opiate withdrawal and should be managed symptomatically. Avoid benzodiazepines. Stop induction and have the patient return soon to try again.
- Micro-induction: Gradual, low-dose schedule over five to seven days for patients exposed to fentanyl. Note: micro-induction protocols remain off-label, since these have not received formal FDA approval, but they are supported by emerging clinical evidence and expert consensus to mitigate precipitated withdrawal risk.
- Side effects: Usually less intense than full agonists, but may include sweating, tongue pain, vomiting, and agitation.
- Maintenance dosing: The goal is once-daily dosing up to 16 mg daily with no withdrawal between doses; higher doses may be needed to suppress fentanyl-driven cravings.
- Laboratory monitoring: Order baseline laboratory values immediately; the results will inform follow-up care, but do not delay treatment or the first dose to wait for results. Recommendations include urine drug screen, complete blood count (CBC), liver enzymes, serum bilirubin, serum creatinine, pregnancy test, and tests for hepatitis B, hepatitis C, and HIV.
- Safety monitoring: The “ceiling effect” (increasing dose does not increase side effects, including respiratory depression or euphoria) reduces overdose risk. Always monitor for sedation. Taper benzodiazepines if these are present, since this combination may lead to significant respiratory depression.
- Combination with naloxone: Co-formulating buprenorphine with naloxone (e.g., Suboxone) is designed to deter misuse by injection. If taken as prescribed sublingually, naloxone has minimal systemic effect; however, if dissolved and injected, naloxone precipitates acute withdrawal, reducing the incentive for intravenous diversion. Despite this safeguard, diversion still occurs. Clinicians should council patients on secure medication storage, safe handling, and the legal implications of sharing or selling their prescription. Consider QTc monitoring with higher doses and any predisposing comorbidities (including taking other medications that could increase QTc) and baseline electrocardiogram (ECG).
- Management of ancillary symptoms during induction and stabilization: Short courses of non-opioid medications, including clonidine for autonomic symptoms, hydroxyzine for anxiety, ondansetron for nausea, loperamide for diarrhea, nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for pain, and trazodone for sleep, can enhance comfort during these stages.
Methadone
- Formulation: Multiple forms are available, most commonly oral (tablets or liquid), but also available for injectable or subcutaneous administration.32,33
- Initiation: This opioid agonist is highly effective for the treatment of OUD. In the United States, methadone is permitted to be prescribed only within an opioid treatment program (such as a methadone clinic).32,33
- Caveats: If a PCP is treating a patient with methadone maintenance, be mindful of drug interactions and the risk of overdose and methadone toxicity, especially if methadone is combined with sedative-hypnotics. There also are medical risks if patients involved in a methadone program combine this substance with illicit drugs. For example, the use of cocaine combined with methadone may lead to clinically significant prolongation of the QT interval.32,33
Extended-Release Naltrexone (μ-Antagonist)
- Formulation: Extended-release naltrexone is available as a monthly intramuscular injection. 2,33
- Initiation: The initiation requires full opioid detox (seven to 10 days) with a high precipitated withdrawal risk if residual opioids remain.32,33
- Ideal candidate: The ideal candidate is a highly motivated patient post-detox, with co-occurring alcohol use disorder.32,33
A Word About Naloxone Alone
This opioid antagonist rapidly reverses an opioid overdose. This does not treat OUD but can be lifesaving should an overdose occur. Prescriptions for this agent include a “naloxone kit,” and formulations include injectable, intranasal, and auto-injector. Prescribe two: one for the patient to keep with them and one to give to a trusted friend.32-34
In 2023, the FDA approved the first nasal spray naloxone available over the counter. Although this has improved access to this potentially lifesaving medication, stigma and cost continue to be barriers.32-34
Back to Maya
Clinician: “We will start with a 2-mg sublingual dose. In about one hour, the nurse will recheck your pulse and blood pressure, and I will take a look to see how you are doing.”
Maya: “So I just sit here?”
Clinician: “Actually, you will be busy. The orders are in for your lab, just across the hall, and I have some information for you to read about support groups and therapy options. I encourage you to pursue a therapy option along with the medication. Our OUD health coach also will be checking in with you to explain the program, the follow-up schedule, and our off-hour availability. We work with partners, so you can call for help around the clock. Then it will be time to meet Dr. L, our OUD pharmacist, who will explain the naloxone kit. I prescribed two of these for you — one to keep with you and one to give to someone you trust.”
About 45 minutes later, Maya’s COWS score reassessment has dropped to 6. The laboratory tests have been completed, and although most results are not available, her pregnancy test is negative. She gets an additional 4 mg sublingual dose of bupherorphine/naloxone and remains stable. Before leaving the clinic, she picks up naloxone as instructed. She is given another 2-mg tablet of the agent to take home if withdrawal symptoms increase. She is scheduled to return the next day for a quick check, a calculation of her ongoing dose (based on her cumulative dose day 1), and to pick up her medication.
Follow-up appointments are scheduled (in person and via telehealth) weekly for two weeks, then every other week for two appointments, and then monthly until her stability is confirmed and appointments can be stretched out further.
Take-Home Points
- COWS provides a standardized way to time induction; aim for a score > 8 but < 20 for standard protocol.
- Initiate buprenorphine without waiting for laboratory results or counseling enrollment.
- Dispense naloxone with brief training before discharge.
- Provide a clear handout and 24/7 contact for questions.
- Order baseline labs immediately: CBC, pregnancy test (if applicable), liver enzymes, serum creatinine, and screening tests for hepatitis B, hepatitis C, and HIV. Draw blood during the observation period so the results inform follow-up care, but do not delay the first dose of buprenorphine.
Team-Based Care: Pharmacist Integration in MOUD
Although formal prevalence data are limited, surveys suggest that less than one-quarter of primary care clinics offering MOUD report onsite pharmacist involvement. However, integrating pharmacists into MOUD delivery has been associated with improved retention, fewer medication errors, and increased clinician capacity for patient-facing care. Models range from co-located pharmacists to telepharmacy support.35 In such settings, roles of the pharmacist typically include:
- Dispensing and medication management: Verifying prescriptions and dispensing formulations.
- Patient counseling and education: Providing in-depth medication counseling on induction expectations, proper administration techniques, safe storage, and diversion prevention, and offering brief proactive follow-up contacts to assess adherence and side effects.
- Clinical monitoring and coordination: Monitoring for drug-drug interactions, reviewing lab data, and flagging abnormal results for provider review.
- Workflow: Managing prior authorizations, navigating insurance, setting up refill alerts and naloxone co-prescribing prompts.
- Quality improvement: Tracking metrics such as adherence rates, naloxone distribution, 30-day retention, etc.35,36
Note that SAMHSA Treatment Improvement Protocol (TIP) 63 recommends that providers establish formal relationships or referral pathways with pharmacies to ensure patients can receive medication without delay.37
Follow-Up Appointment: Two Months Later
Maya: “I came today thinking I want to tell you that I continue to do well, and no, before you ask, I haven’t used again. You have my drug screen! But I think I should tell you that I don’t feel completely like me, either.”
Clinician: “That must be unsettling.”
Maya: “It is. When I was using, I was caught in a cycle and barely had time to think. Now, I think all the time … and feel ashamed, which makes everything worse. My husband asks all these questions and tells me he wants to help, but I just shut down. Ironically, my business is going well, but inside I feel like a failure.”
Clinician, nodding: “I’m sorry you are experiencing this, but I am glad you told me. Your Patient Health Questionnaire-9 score, the depression questionnaire you complete at the beginning of each appointment, has been creeping up into mild to moderate levels of depression. We see that a lot during recovery. Depression is tough, and one concern with rising depression is self-harm. Have you felt down enough to consider hurting or killing yourself?”
Maya: “No — maybe giving up, but I would never hurt or try to kill myself. Depression? I hope that doesn’t mean another pill. One is enough.”
Clinician: “Let’s keep monitoring before we decide on medication. Remember those therapy options we discussed? Our health coach can walk you through them and help you choose what fits your lifestyle. In the meantime, maybe we can discuss a few ways to help you feel better. What has worked in the past when you felt sad?”
Maya, pausing: “Cooking helps me feel better. My husband and I used to cook together every weekend. I bet doing that again could help us reconnect, and maybe then we could talk. Thinking about it, that’s one of the hardest parts of this whole experience — just feeling so alone.”
Clinician: “That sounds like a good plan. You’re not alone in this -- you have the team here, and it sounds like your husband wants to be there, even if it’s hard to let him in. Maybe getting back to something you both enjoy will help you feel more comfortable opening up.”
Maya: “Yes, and maybe you are right — I will think about giving therapy a try, too. I guess it couldn’t hurt to let someone else in.”
Depression in OUD
Depression is one of the most common psychiatric comorbidities among patients receiving medications for OUD. Lifetime prevalence estimates of major depressive disorder (MDD) in this population range from 40% to 75%, with literature reviews citing rates up to 75% and cross-sectional analyses indicating that approximately 44% of individuals entering buprenorphine or methadone treatment meet criteria for MDD. Untreated depression during MOUD treatment may be linked to poorer outcomes.38,39
Primary care clinicians should incorporate routine depression screening (such as the Patient Health Questionnaire [PHQ]-9) at MOUD initiation and follow-up visits, engage in collaborative management with behavioral health partners, and consider evidence-based antidepressant therapy or psychotherapy to optimize both mood and opioid-related outcomes.38,39
A Word About Motivational Interviewing
The clinician working with Maya demonstrates an interview style with many components of motivational interviewing (MI). Fittingly, MI was developed by psychologists William Miller and Stephan Rollnick in the 1980s as an approach to talking with individuals about substance use that differed significantly from techniques in use at that time, such as shame and confrontation. MI recognizes that change is more likely when a person decides for themselves to change.40
The principles of this technique demonstrate respect and a desire to understand the patient’s ideas about behavioral change. The approach is collaborative rather than unilateral, goal-directed, and geared toward motivating by encouraging patients to voice their own arguments for change. During a clinical interview conducted via MI, the patient is encouraged to examine values, principles, fears, and hopes.40
Although a mastery of MI is a complex undertaking, understanding some of the guiding principles may be helpful in conducting brief interventions. The OARS model, shown in Table 3, may be particularly helpful.40,41
Table 3. The OARS Model |
O: Open-ended questions. These are questions that are not able to be answered with a single yes/no response. Try to avoid “why” questions, since these can promote defensiveness. A: Affirmations. Find and acknowledge true internal strengths of the patient. This differs fundamentally from praise and relies on the interviewer to note positive characteristics elicited by the interview. (For example: “Coming here today must have been difficult after you had such a bad experience at your appointment two years ago.”) R: Reflective listening. Listen and voice back to the patient the concept, idea, or theme the patient is attempting to convey. S: Summarizing. Summarizing statements can be used midway and toward the conclusion of the interview. |
Take-Home Points
- Create a multidisciplinary treatment team — include the pharmacist and mental health specialists.
- Meet frequently with the patient in the early months of treatment.
- Monitor for comorbid conditions, with an eye on any emerging psychiatric disorders.
- Use MI when speaking with patients about behavioral change.
A Word About Deprescribing
Although no minimum or maximum duration of buprenorphine therapy is universally recommended, data suggest that courses shorter than 90 days are associated with higher rates of relapse. Generally speaking, discontinuation should be considered only after a period of sustained stability, which typically is defined as at least 12 months of continuous abstinence, minimal cravings, and with strong psychosocial supports in place.4
When a patient and clinician agree to taper, the recommended process is gradual and monitored, with a dose taper of 2 mg to 4 mg per month. This pace can be adjusted depending on any emergence of withdrawal symptoms, stressors, and life stability. Throughout and following taper completion, harm-reduction measures (e.g., naloxone co-prescribing, overdose education) should be offered. Access to reinitiation of rapid induction of buprenorphine should be maintained if relapse risk increases.4
Individuals with a history of severe OUD, multiple overdoses, or unstable environments may require indefinite maintenance therapy.4
Summary
Take-Home Points
- Apply a chronic disease framework and nonstigmatizing language when diagnosing and managing OUD; use principles of MI to help patients express motivation.
- Implement efficient universal or targeted screening for unhealthy substance use and differentiate risky use from SUD using DSM-5-TR criteria.
- Rapidly assess OUD severity and determine the level of care using practical adaptations of ASAM Dimensions.
- Initiate and continue (or refer, if indicated) evidence-based pharmacotherapies for OUD, including office-based induction.
- Integrate harm-reduction into routine care.
- Coordinate psychosocial and wraparound support without delaying lifesaving medications.
- Evaluate for taper after at least 12 months of sustained abstinence with minimal cravings and strong psychosocial support in place.
Ellen Feldman, MD, is with Altru Health System, Grand Forks, ND.
References
1. Center for Substance Abuse Treatment. Managing Chronic Pain in Adults with or in Recovery from Substance Use Disorders. Treatment Improvement Protocol (TIP) Series, No. 54. Substance Abuse and Mental Health Services Administration; 2012. https://www.ncbi.nlm.nih.gov/books/NBK92053/table/ch2.t5/
2. Krupp J, Hung F, LaChapelle T, et al. Impact of policy change on access to medication for opioid use disorder in primary care. South Med J. 2023;116(4):333-340.
3. 90 Fed Reg 13410 (March 24, 2025)
4. American Society of Addiction Medicine (ASAM). The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. ASAM; 2020.
5. Crocq MA. Historical and cultural aspects of man’s relationship with addictive drugs. Dialogues Clin Neurosci. 2007;9(4):355-361.
6. Nathan PE, Conrad M, Skinstad AH. History of the concept of addiction. Annu Rev Clin Psychol. 2016;12:29-51.
7. Robinson SM, Adinoff B. The classification of substance use disorders: Historical, contextual, and conceptual considerations. Behav Sci (Basel). 2016;6(3):18.
8. Alcaro A, Brennan A, Conversi D. The SEEKING drive and its fixation: A neuro-psycho-evolutionary approach to the pathology of addiction. Front Hum Neurosci. 2021;15:635932.
9. Heilig M, MacKillop J, Martinez D, et al. Addiction as a brain disease revised: Why it still matters, and the need for consilience. Neuropsychopharmacology. 2021;46(10):1715-1723.
10. Lomas C. Neurobiology, psychotherapeutic interventions, and emerging therapies in addiction: A systematic review. J Addict Dis. 2024; Dec 17:1-19. doi: 10.1080/10550887.2024.2440184. [Online ahead of print].
11. U.S. Food and Drug Administration. Primary care providers can prescribe with confidence. Dec. 18, 2024. https://www.fda.gov/drugs/prescribe-confidence/primary-care-providers-can-prescribe-confidence
12. Centers for Disease Control and Prevention. U.S. overdose deaths decrease almost 27% in 2024. May 14, 2025. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2025/20250514.htm
13. Centers for Disease Control and Prevention. Understanding the opioid overdose epidemic. June 9, 2025. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdose-epidemic.html
14. Nyaku AN, Zerbo EA, Chen C, et al. A survey of barriers and facilitators to the adoption of buprenorphine prescribing after implementation of a New Jersey-wide incentivized DATA-2000 waiver training program. BMC Health Serv Res. 2024;24(1):179.
15. Del Pozo B, Park JN, Taylor BG, et al. Knowledge, attitudes, and beliefs about opioid use disorder treatment in primary care. JAMA Netw Open. 2024;7(6):e2419094.
16. Satyasi SK, Stewart C, Parimi K, et al. Barriers in office-based opioid treatment in rural United States. Cureus. 2024;16(11):e73373.
17. Nyblade L, Stockton MA, Giger K, et al. Stigma in health facilities: Why it matters and how we can change it. BMC Med. 2019;17(1):25.
18. Witte TH, Wright A, Stinson EA. Factors influencing stigma toward individuals who have substance use disorders. Subst Use Misuse. 2019;54(7):1115-1124.
19. Botticelli MP, Koh HK. Changing the language of addiction. JAMA. 2016;316(13):1361-1362.
20. Slomski A. The lingua franca of addiction — stigmatizing words that wound. JAMA. 2021;326(15):1468-1470.
21. Judd H, Yaugher AC, O’Shay S, Meier CL. Understanding stigma through the lived experiences of people with opioid use disorder. Drug Alcohol Depend. 2023;249:110873.
22. McNeely J, Schatz D, Olfson M, et al. How physician workforce shortages are hampering the response to the opioid crisis. Psychiatry Online. Sept. 15, 2021. https://psychiatryonline.org/doi/10.1176/appi.ps.202000565
23. American Society of Addiction Medicine. The ASAM Criteria, 4th Edition. https://www.asam.org/asam-criteria
24. American Academy of Family Physicians. Opioid use disorder (OUD): Screening. Clinical Preventive Service Recommendation. https://www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/oud.html
25. Duggirala R, Khushalani S, Palmer T, et al. Screening for and management of opioid use disorder in older adults in primary care. Clin Geriatr Med. 2022;38(1):23-38.
26. National Institute on Drug Abuse. Screening for drug use in general medical settings: Quick reference guide. https://nida.nih.gov/sites/default/files/pdf/screening_qr.pdf
27. American Society of Addiction Medicine. Clinical Opiate Withdrawal Scale (COWS). https://www.asam.org/docs/default-source/education-docs/cows_induction_flow_sheet.pdf?sfvrsn=b577fc2_2
28. Centers for Disease Control and Prevention. Prescription Drug Monitoring Programs (PDMPs). May 6, 2024. https://www.cdc.gov/overdose-prevention/hcp/clinical-guidance/prescription-drug-monitoring-programs.html
29. Silverstein SM, Daniulaityte R, Martins SS, et al. “Everything is not right anymore”: Buprenorphine experiences in an era of illicit fentanyl. Int J Drug Policy. 2019;74:76-83.
30. Auvity S, Goutal S, Caille F, et al. Pharmacokinetic neuroimaging to study the dose-related brain kinetics and target engagement of buprenorphine in vivo. Neuropsychopharmacology. 2021;46(6):1220-1228.
31. Substance Abuse and Mental Health Services Administration. Buprenorphine quick start pocket guide. https://www.samhsa.gov/sites/default/files/quick-start-pocket.pdf
32. Substance Abuse and Mental Health Services Administration. CSAT’s Knowledge Application Program: KAP Keys for Clinicians. Based on TIP 43: Medication-assisted treatment for opioid addiction in opioid treatment programs. https://library.samhsa.gov/sites/default/files/sma12-4108.pdf
33. American Society of Addiction Medicine. The ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. https://www.asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/asam-national-practice-guideline-pocketguide.pdf
34. Saari TI, Strang J, Dale O. Clinical pharmacokinetics and pharmacodynamics of naloxone. Clin Pharmacokinet. 2024;63(4):397-422.
35. McLeman B, Gauthier P, Lester LS, et al. Implementing a pharmacist-integrated collaborative model of medication treatment for opioid use disorder in primary care: Study design and methodological considerations. Addict Sci Clin Pract. 2024;19(1):18.
36. Wu LT, John WS, Ghitza UE, et al. Buprenorphine physician-pharmacist collaboration in the management of patients with opioid use disorder: Results from a multisite study of the National Drug Abuse Treatment Clinical Trials Network. Addiction. 2021;116(7):1805-1816.
37. Substance Abuse and Mental Health Services Administration. Medications for opioid use disorder. Treatment Improvement Protocol: TIP 63. https://library.samhsa.gov/sites/default/files/pep21-02-01-002.pdf
38. Ghabrash MF, Bahremand A, Veilleux M, et al. Depression and outcomes of methadone and buprenorphine treatment among people with opioid use disorders: A literature review. J Dual Diagn. 2020;16(2):191-207.
39. Vest N, Wenzel K, Choo TH, et al. Trajectories of depression among patients in treatment for opioid use disorder: A growth mixture model secondary analysis of the XBOT trial. Am J Addict. 2023;32(3):291-300.
40. Cole S, Sannidhi D, Jadotte YT, Rozanski A. Using motivational interviewing and brief action planning for adopting and maintaining positive health behaviors. Prog Cardiovasc Dis. 2023;77:86-94.
41. Substance Abuse and Mental Health Services Administration. Chapter 3: Motivational interviewing as a counseling style. In: Enhancing Motivation for Change in Substance Use Disorder Treatment: Updated 2019. Treatment Improvement Protocol: TIP 35. Substance Abuse and Mental Health Services Administration; 2019.
Primary care providers (PCPs) play a critical role in diagnosing and treating opioid use disorder (OUD). By approaching OUD as a chronic disease, using non-stigmatizing language, and integrating team-based care, PCPs can provide accessible, effective treatment.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content