Pharmacotherapy

Every patient is different and will have their own needs and preferences related to medication. When choosing medication (i.e., buprenorphine monoproduct or buprenorphine/naloxone combination) and form (i.e., tablet, film, or LAI), balance the risks and benefits of the medication, along with lifestyle factors that can affect treatment adherence. Also consider referral to an OTP where methadone can be provided, or to a higher level of care, depending on the complexity of the patient's presentation. Keep in mind that some payers limit what medications and treatments are reimbursable, and treatment availability plays a role.

Consider the following when deciding which treatment to provide:¹

• Patient preference, including their prior history with and response to medications for OUD;
• Type of misused opioid (e.g., fentanyl, prescription opioids, heroin), the extent of physical dependence on the opioid, and use of other substances, whether intentionally or not;
• Side effects associated with medications;
• Patient characteristics and lifestyle (e.g., employment, scheduling limitations, pregnancy status, age, etc.); and
• Coverage, as payers may limit which forms of medication they cover.

Buprenorphine is a partial opioid agonist that does not fully activate the mu opioid receptors, resulting in less euphoria and fewer breathing problems than full agonists like methadone. However, buprenorphine still carries some small risk of misuse or lethal overdose when combined with other sedating substances.

There is also a significant risk of diversion with the oral formulations of buprenorphine. To reduce the risk of misuse or diversion, providers often prescribe a medication that combines buprenorphine with naloxone, an antagonist that blocks mu opioid receptors when injected intravenously. When these buprenorphine-naloxone combination products are taken properly--either as a sublingual tablet or as a film placed sublingually (under the tongue)—the naloxone is minimally active. However, if someone tries to inject or snort the medication, the naloxone becomes more bioavailable, reducing the effects of the buprenorphine. However, some scholars have argued that the addition of naloxone may only delay the onset of euphoric symptoms.² In addition, some clinicians have expressed concern that the negative side-effects of naloxone in the combined product are underestimated.

Buprenorphine treatment for OUD expands treatment access by enabling any medical provider with a DEA license to treat individuals with OUD in their practice. Different modes of administration provide flexibility to tailor treatment to the individual patient's needs. For example, long-acting buprenorphine injections can be administered weekly or monthly, which can improve adherence. These injections can be ideal and convenient for many patients, including those who are incarcerated or transitioning out of incarceration.

Long-acting injectable buprenorphine is a newer option, suitable for patients with moderate to severe OUD who struggle adhering to a daily buprenorphine schedule or prefer less-frequent dosing due to their personal circumstances and preferences. It is important to note that patients do not typically begin MOUD with injectable buprenorphine; patients are first stabilized on transmucosal buprenorphine before transitioning to the injectable form.⁴ Table 2 in the Playbook's Quick Start Guide summarizes the different types of medications for OUD available, including the forms and typical dose ranges. Sources for more information can be found in the Resources.

Know which pharmacies in your community will reliably fill your MOUD prescriptions. Patients typically need to visit local pharmacies to obtain the MOUD you prescribe, so it is worthwhile to know which pharmacies stock the medications. Some formulations are more challenging to procure, such as long-acting injectable (LAI) buprenorphine which is subject to Risk Evaluation and Mitigation Strategy (REMS) regulations.^5,6

Some pharmacies are reluctant to stock buprenorphine medications for fear of being identified in the Suspicious Opioid Reporting System^7,8 that was established to limit diversion of the medication. To address this national problem, the National Association of Boards of Pharmacy and the National Community Pharmacists Association have collaborated to develop The Pharmacy Access to Resources and Medication for Opioid Use Disorder (PhARM-OUD) Guideline (PDF - 606 KB). Also, online pharmacies are now available to fill in the gap when local options are limited. 

As with the type of medication you select for a given patient, you have choices about how you start the patient on the medication. You can start MOUD in your primary care setting or rely on specialty clinics or OTPs to do so, after which the patient may be a good candidate for maintenance treatment in primary care, as described in Phase III.

Starting MOUD in patients who use fentanyl can be nuanced. Most of the existing literature on starting buprenorphine is based on people using heroin or prescription opioids. Starting buprenorphine following fentanyl misuse can involve a greater risk on patients entering precipitated withdrawal (see Managing Withdrawal Symptoms), which can make them more reluctant to continue treatment. Fentanyl purchased on the street is often illicitly manufactured and is unpredictable in both dosage and composition, frequently mixed with substances such as xylazine or stimulants.⁹

As described in Figure 2, one model for primary care providers is to specialize in buprenorphine maintenance and encourage and accept referrals from other settings (e.g., emergency departments, in-patient settings, jail/prison) after patients have started the medication.

There is no single agreed-upon protocol for starting MOUD. The most common approach is to begin buprenorphine when the patient is experiencing mild to moderate withdrawal symptoms. You can assess a patient's withdrawal symptoms throughout the process using the Clinical Opiate Withdrawal Scale (COWS) (PDF - 606 KB) in your office or the Subjective Opiate Withdrawal Scale (SOWS) (PDF - 225 KB) if the patient is at home. Buprenorphine initiation can last anywhere from several days to a week or more.¹⁰ Look at the Quick Start Guide for the most recent (2025) guidance from the American Academy of Family Physicians on starting buprenorphine in primary care settings.

Starting MOUD in the office or starting at home: MOUD can be started in an observed, office-based setting or at home by the patient. Most clinical trials of buprenorphine included office-based initiation, which led to longstanding recommendations that it must be started in a medical setting to be safe and effective. However, more recent evidence indicates patients can successful start the medication in either setting.¹¹ Many experts support starting the medication at home, in combination with telehealth,¹² which has been associated with improved retention early in buprenorphine treatment.

• Office-based inductions: Office-based initiation of MOUD can be difficult to schedule and may require a significant amount of provider and staff time, which can create delays and barriers to treatment initiation. In-office initiation can be reserved for more complex cases, such as patients transitioning from methadone or other long-acting opioids to buprenorphine, or those who have previously had problems starting buprenorphine.

• Home inductions: It can be advantageous to begin MOUD at home, particularly in uncomplicated cases, as it can be safe and appropriate for many patients.^13,14,25 There are no single agreed-upon protocols for starting buprenorphine but typically, you would schedule a visit (in-person or via telehealth) to discuss the protocol with the patient beforehand. Be sure to support patients throughout the process, by providing adequate education on what they should expect and by communicating via phone or text message.

  The protocol might include instructions for timing the medication start (i.e., the appropriate level of withdrawal), dosing (what dose to take at what interval or based on what factors, maximum dose, etc.), how to monitor to process (schedule telehealth check-in times during the start, determine after-hours availability if the patient has questions, etc.), and schedule your next visit (in-person or via telehealth).

  Be sure to support patients throughout the process, by providing adequate education on what patients should expect, communicating via phone or text message as needed during the process, and having follow-up visits soon afterward.

  Note that individuals who use fentanyl may be more likely to experience precipitated withdrawal (the rapid onset of withdrawal symptoms) when starting buprenorphine, which can complicate starting at home.

Many people with OUD fear the symptoms of withdrawal and even cite this as a reason for continued use, as exemplified in the following quotes:¹⁵

Symptoms: The symptoms of opioid withdrawal vary across individuals and are influenced by factors such as the type of opioid used and duration of use. Initially, withdrawal symptoms resemble those of the flu. According to DSM-5 (p. 547),¹⁷ withdrawal symptoms include the following:

• "Dysphoric mood;
• Nausea or vomiting;
• Muscle aches;
• Lacrimation or rhinorrhea;
• Pupillary dilation, piloerection, or sweating;
• Diarrhea;
• Yawning;
• Fever; an
• Insomnia.

Withdrawal symptoms can begin immediately (in response to administration of an antagonist) or emerge gradually over the course of several hours to days. The temporal onset, duration and severity of symptoms vary based on multiple factors, including the type and amount of non-prescribed opioid used, the extent of physical dependence, and individual patient characteristics. Clinical Opiate Withdrawal Scale (COWS) (PDF - 606 KB) can be used to assess the severity of withdrawal symptoms.

Symptom Relief: Several medications can be used in to ease the discomfort of withdrawal symptoms while starting MOUD, such as:

• Alpha 2 agonists (e.g., clonidine) for anxiety, agitation, and muscle aches;
• Non-opioid analgesics (e.g., ibuprofen, acetaminophen) for minor aches and discomfort;
• Antispasmodics (e.g., dicyclomine) to treat abdominal cramps;;
• Anxiolytics (e.g., hydroxyzine, gabapentin) for nervousness, agitation, and nausea;
• Hypnotics (e.g., trazodone) for anxiety, insomnia, and agitation;
• Antiemetics (e.g., ondansetron) for nausea; and
• Anti-diarrheal (e.g., loperamide) for diarrhea.^14,18

Keeping patients as comfortable as possible while starting MOUD will decrease the likelihood of premature treatment attrition.¹⁸

Use medication management visits to monitor your patient's progress, functional status, and the appropriateness of their treatment plan. These visits are also an opportunity to assess the risk of recurrence of use and to administer any screenings or assessments not conducted earlier. This is also a good time to link patients with resources and supports. Use these visits to assess:

• Medication adherence;
• Cravings and withdrawal symptoms;
• Substance use;
• Life and social stressors;
• Any other relevant medical issues;
• Mental health issues, suicidal thoughts — consider providing psychiatric medications, if appropriate, and/or referral to a mental health provider;
• Social support, engagement with recovery supports or counseling; and
• Results of laboratory tests.

If medication management visits indicate a patient is at risk of or has resumed using non-prescribed opioids, take appropriate steps. Learn more in Prevention and Response to Recurrence of Use.

Frequency of Visits: The following signs may indicate a patient is ready to decrease visit frequency:²⁵

• Several weeks of no opioid use;
• Continued attendance at scheduled appointments and adherence to the treatment plan; and
• Engagement in treatment to address co-occurring mental health or medical concerns.

Patients who are ready to decrease the frequency and intensity of treatment visits will also show no evidence of the following:

• Co-occurring substance use that may pose significant risk to their safety;
• Significant side effects from medication; or
• Signs of diversion (e.g., early refill requests, unexpected prescriptions from other providers in the prescription drug monitoring program, no buprenorphine in the urine drug screen).

Brief Supportive Counseling: If your practice has begun to integrate behavioral health and primary care so that you have behavioral health professionals on site or in a collaborative relationship, additional counseling or therapy may be possible in-house. Medication management visits also offer an opportunity for you or other members of the care team to provide brief supportive counseling, as you would with any other chronic disease. You can use the following strategies for brief counseling:²⁵

• Identify triggers and manage stressors;
• Listen empathically and have discussions with patients in a nonjudgmental manner;
• Assess progress against treatment goals and revise these goals as needed using shared decision-making techniques (See Resources);
  • Provide medical care for co-occurring physical health conditions;
  • Identify patient needs and refer to other providers as needed (including mental health treatment, substance use counseling, case management, and community-based recovery support);
  • Have patients invite family and friends to medication management visits to discuss how they can support the patients and to educate those who are reluctant to accept the use of medication to treat OUD. This may also be an opportunity to engage the support persons if they display evidence of OUD; and
  • Advocate for patients if their retention in treatment is challenged by their employer, housing provider, insurance company, or the criminal justice system.

Patients may be surprised by the level of emotions they experience once non-prescribed opioids and other substances are out of their systems. It is not uncommon for unresolved trauma, guilt, and shame to surface once active addiction subsides. This can be a valuable time for the patient to seek counseling and other supports, if they have not already.