Pharmacotherapy Training

Buprenorphine is a controlled (Schedule III) medication that can be prescribed by any provider with a U.S. Drug Enforcement Administration (DEA) license. To prescribe controlled substances in the U.S., providers need a DEA license or "DEA Controlled Substances Registration,"¹ which most physicians already have. Those who do not can register with the DEA and apply for a DEA license without special training.² Non-physician prescribers, such as nurse practitioners and physician assistants, only need a DEA license to prescribe buprenorphine for OUD in most states. State-specific restrictions on non-physician MOUD provision are mostly due to scope-of-practice laws and requirements for additional supervision. More restrictive states include Kentucky, Missouri, Ohio, Tennessee, and West Virginia.³ Non-physicians should review and comply with any state-specific regulations pertaining to prescribing medications for OUD.

The Consolidated Appropriations Act (CAA) of 2023 was created to expand access to medications for OUD. Under CAA, the Medication Access and Training Expansion (MATE) Act mandates that providers who prescribe controlled substances (Schedules III-V) must complete one eight-hour training course in SUD treatment when they renew their DEA license or obtain their first DEA license. The CAA Mainstreaming Addiction Treatment (MAT) Act discontinued the need for providers to obtain an X-waiver to prescribe buprenorphine.

The Substance Abuse and Mental Health Services Administration (SAMHSA) and other federal partners have been promoting comprehensive SUD education for all health professions.⁴ DEA registrations must be renewed every three years, at which time the prescriber must have completed eight hours of training on OUD or other SUDs or become board certified in addiction medicine or addiction psychiatry.

The package inserts and various free training programs on buprenorphine include information on appropriate dosing. However, those dosing guidelines may have predated the emergence of fentanyl in the street drug supply. Patients who have been using fentanyl regularly may benefit from higher doses than recommended in some of the clinical guidelines. This emphasizes the importance of taking a person-centered approach to dosing^5-7 and recognizing that a higher dosage level may be appropriate. Recent research^8-11 also indicates that higher buprenorphine doses may be associated with longer retention in treatment.

Illicitly manufactured fentanyl often contains other drugs, typically unbeknownst to the person taking it. Prevalence of specific adulterants varies over time and by geographic area of the U.S. Common adulterants, excluding fentanyl analogs and precursors, include other opioids (heroin and tramadol), xylazine, methamphetamine, cocaine, acetaminophen, and diphenhydramine ^12,13 and most recently medetomidine.¹⁴

In addition, people who use opioids often use other drugs, such as cocaine, alcohol, benzodiazepines, and methamphetamine. Among people with an opioid use disorder, 60% had a current comorbid SUD and 72% had a comorbid lifetime SUD.¹⁵

The patient's clinical presentation will vary based on what substances are in their system. This is complicated by the fact that which drugs and the dose of the drug(s) used is often unknown to you and to the patient. Buprenorphine does not reduce the physiological dependence, withdrawal symptoms or craving associated with discontinuing other addictive non-opioid drugs. This unknown can make starting buprenorphine more challenging in an outpatient setting,¹⁶

Buprenorphine, a partial opioid agonist, is likely to be the medication you will prescribe most frequently. However, it is important to be familiar with the other medications approved for the treatment of OUD.

Long-acting injectable naltrexone (full opioid antagonist):¹⁷ A DEA license is not required to prescribe LAI naltrexone to treat OUD, as it is not a controlled substance. Naltrexone blocks the mu opioid receptors in the brain and therefore blocks the "high" or euphoric effects of opioids. Given this medication's high affinity (competitive binding) for mu opioid receptors, administration to a person who has recently ingested opioids will induce withdrawal. Naltrexone is also available in an oral formulation that is used to treat alcohol use disorder, but the oral form is not used to treat OUD.

Long-acting injectable naltrexone¹⁷ blocks the opioid "high" (i.e., rewarding effects) and can reduce cravings. However, it is more difficult to begin, as the patient must be completely abstinent from opioids. If the patient is in earlier stages of opioid withdrawal, administration of naltrexone may intensify withdrawal symptoms. The challenges with starting LAI naltrexone and the increased probability of early treatment exit have been associated with higher OD rates in some studies.¹⁸ Other studies indicate it can be a preferred treatment for certain groups of patients.¹⁹ While the Playbook focuses primarily on buprenorphine, you can learn more about treating OUD with naltrexone in SAMHSA's TIP 63: Medications for Opioid Use Disorder | SAMHSA.

Methadone (full opioid agonist): Methadone is a full opioid agonist that fully binds to mu opioid receptors in the brain, which activates the receptors and helps reduce withdrawal symptoms. Methadone is a Schedule II controlled medication. Schedule II controlled medications are "defined as drugs with a high potential for abuse, with use potentially leading to severe psychological or physical dependence."²⁰ Methadone cannot be prescribed or administered by primary care practices for the treatment of OUD.

Opioid-Treatment Programs: Only SAMHSA-certified OTPs are authorized to treat OUD with methadone,²¹ as it is a Schedule II controlled substance subject to strict federal regulations. OTPs are also able to treat with buprenorphine and naltrexone. OTPs are federally certified and accredited entities that provide comprehensive services for individuals with OUD.²¹ They treat opioid withdrawal and stabilize individuals with OUD. Many OTPs also offer medical care and non-pharmacological behavioral health services such as counseling and other interventions, peer support, care management, and referrals to community recovery organizations where patients can find additional recovery supports. Without specific regulatory approval, methadone must be administered directly to patients by an OTP, rather than being dispensed at a pharmacy. Since OTPs are specialty substance use treatment programs with a multidisciplinary team of healthcare professionals, they may be an appropriate referral option for your patients who need more intensive treatment.

Be Familiar with Overdose Reversal Medication: It is essential to be prepared to address potential overdose situations. While medications like buprenorphine and methadone can help manage OUD, individuals with OUD remain at risk for overdose, particularly in the early stages of treatment or during recurrence of use (relapse). Therefore, it is important to familiarize yourself with overdose reversal medication, such as naloxone, which can save lives in an emergency.

Naloxone (full opioid antagonist, common brand name Narcan)²² is a standalone medication that rapidly reverses overdose symptoms. This life-saving medication can be purchased, carried, and administered by anyone in case of emergency. Naloxone is available without a prescription over the counter and online as a nasal spray or injection. A helpful approach is to encourage anyone with an OUD and their family to carry naloxone with them, regardless of whether they receive medications for OUD. If possible, provide your patients with naloxone when you first detect their OUD.

In the implementation planning process, you will determine the level of care that suits your practice, the simplest of which is providing maintenance MOUD treatment. Patients receiving MOUD maintenance may have been receiving medications and other treatment at a specialty clinic such as a residential treatment program, an OTP, or other higher level of addiction care, are progressing well in their recovery and are ready to transition to a lower level of care. Alternatively, patients may have started buprenorphine in another setting, such as an ED or carceral setting, then been referred to you for maintenance. Primary care clinics have the advantage of being able to provide routine medical care that may not be available in the specialty setting.

You may choose to begin providing MOUD treatment by starting patients on buprenorphine. As you gain experience with MOUD treatment, you may choose to adjust the services and level of care you provide. Whatever services you provide, some patients with OUD will need to be referred to a higher level of care, such as a specialized SUD treatment setting, to meet more complex treatment needs. Depending on their needs, they could be referred to an OTP or an intensive outpatient, partial hospitalization, or residential treatment program.

The State of Vermont developed a hub and spoke model, which builds on collaboration between office-based opioid treatment providers and OTPs. The concept of the hub and spoke system is that patients who need a higher intensity of care may be referred to the OTP or "hub" while patients who have less complex treatment needs may receive care in office-based clinic settings or "spokes". The model emphasizes care coordination between care settings, recognizing that the hub OTP staff are specialists in substance use treatment. Hub staff serve as consultants to the spoke clinic team, and responsibility for patient care may shift back and forth between hub and spoke as needed. For example, initial medication induction might be conducted by the hub OTP, and then the patient could be transferred to the spoke clinic for ongoing management.

You might investigate whether a hub and spoke model is possible in your area. As of 2022, there are approximately 1,900 OTPs in the U.S., including DC, Puerto Rico, and the Virgin Islands, covering every state except for Wyoming.²³ To find an OTP near you, search Find Help and Treatment for Mental Health, Drug, Alcohol Issues | SAMHSA. Learn more about the hub and spoke model at Vermont.gov (PDF - 855 KB).