How Does One Approach the Patient With an Opioid Use Disorder?

Opioid Use Disorder

Addiction is a chronic, primary disease of the brain, influenced by genetics and environment, with cycles of relapse and remission, and manifests as a compulsive drive to use a substance despite harmful consequences. About 2 million Americans have an OUD, including 1.7 million persons with prescription pain reliever use disorder, contributing to 72,000 deaths from accidental overdose and becoming the leading cause of death for Americans under the age of 50 before the COVID-19 pandemic. Advances in neurobiology, genetics, and brain imaging have deepened our understanding of how normal brain functions in processing reward, emotional memories, motivation, and decision making become maladapted in addiction. Drugs of addiction elicit and enhance the rewarding, pleasurable response of dopamine manifold over natural rewards (e.g., eating a donut or having sex), and increasing amounts of the drug are required over time just to feel “normal” as the brain adapts to these disruptions. Addiction is a highly treatable, though incurable, chronic disease (like diabetes), with recovery in brain function and behavior after prolonged abstinence.

A diagnosis of mild, moderate, or severe OUD is made using the DSM-5 when at least two criteria are met over 12 months ( Table 12.1 ). Notably, the DSM-5 recognizes tolerance and dependence as natural physiological adaptations for any person with consistent opioid exposure. Therefore tolerance and dependence alone in a patient on long-term opioids taking their medication as directed do not satisfy criteria for OUD. The 4 Cs of addiction (Craving, lack of Control, Consequences, Compulsive use) is a mnemonic to simplify DSM-5 criteria.

Opioid/Medication Misuse

Some patients in palliative care may have higher risk behavior while taking opioids, or “misuse” behaviors, that do not clearly satisfy DSM-5 criteria for an OUD. The CDC refers to medication misuse as “the use of drugs or medications in a manner other than as directed by a doctor, such as use in greater amounts, more often, or longer than told to take a drug, or using someone else’s prescription.” In the National Survey on Drug Use and Health, 9.9 million people reported past-year misuse of prescription opioids, with 63.6% reporting physical pain as the driver for misuse.

Treatment of OUD

Medications for OUD (MOUD), including the opioids methadone and buprenorphine (referred to as opioid agonist treatment [OAT]), undeniably save lives, reduce drug use, and diminish human immunodeficiency virus (HIV) and hepatitis C virus transmission. OAT does not include the MOUD naltrexone, an opioid antagonist. OAT suppresses cravings for opioids and reduces the reinforcing cycle of euphoria–withdrawal that drives ongoing drug use, which allows the faulty reward pathways of addiction to reestablish homeostasis, restore emotional and decision-making capacity, and improve health and situational stability. Detoxification alone is not OUD treatment, as it is associated with both greater mortality and lower treatment retention compared to MOUD.

MOUD in the United States includes methadone, buprenorphine, and naltrexone. Despite the widely documented effectiveness of methadone maintenance treatment (MMT), it remains a Schedule II drug with federal regulations limiting its use as MOUD to approved outpatient treatment programs (OTPs), which exacerbates a treatment gap of nearly 1 million people with OUD without treatment. The FDA approved buprenorphine as a Schedule III drug in 2002 and federal policies allowing certified (the “X-waiver”) physicians, nurse practitioners, and physician assistants the ability to prescribe buprenorphine brought treatment of OUD into office-based settings. However, as of 2023 the X-waiver is no longer required for buprenorphine prescribing, such that all practitioners with a DEA registration that includes schedule III authority can prescribe buprenorphine for OUD. The educational training is still required to prescribe for more than 30 patients at once. Naltrexone blocks the euphoric and analgesic effect of opioids, but is not widely used as MOUD given less efficacy and adherence, and will have rare use in palliative care as it precludes use of agonist opioids.

Given the context of practicing amid an overdose epidemic, and the fact that myriad referrals to specialty palliative care for complex pain management involve opioids, palliative care providers will benefit from (1) knowledge of MOUD ( Table 12.3 ) and (2) the ability to offer buprenorphine to select patients with pain, OUD/misuse, and life-limiting serious illness.

Buprenorphine

Sublingual (SL) buprenorphine is a tightly binding, mu-opioid receptor partial agonist with a long half-life that, when used as MOUD, reduces opioid cravings, opioid withdrawal, and the euphoric effects of nonmedical opioid use. Formulations that include buprenorphine and naloxone are preferred over buprenorphine alone in MOUD, as naloxone is intended to deter intravenous misuse and is otherwise inactive if taken sublingually as prescribed ( Table 12.4 ). SL buprenorphine has been used off-label to treat chronic pain in patients with higher analgesic dosing needs or higher risk for opioid misuse. Though buprenorphine no longer requires additional education, it is recommended that prescribers review training materials to expand their knowledge of OUD and use of buprenorphine in situations where suspicion for opioid misuse is high.

Buprenorphine has two unique properties: it acts as a partial agonist at the mu-opioid receptor and has a high affinity for the receptor with a long half-life of 24 to 60 hours, facilitating its use as MOUD. The partial agonism means that in contrast to full agonists, increasing beyond moderate doses of buprenorphine typically does not result in greater opioid effects on respiratory depression and sedation. Buprenorphine also outcompetes other opioids with lower affinity (e.g., heroin, oxycodone) from binding, thereby blunting the effects of other opioids on euphoria and offering partial protection from accidental overdose. Despite this high affinity, treating pain is possible and will be discussed later in this chapter. Buprenorphine has an analgesic half-life of 6 to 8 hours, has wide individual variation in pharmacokinetics, is excreted in the urine, is extensively metabolized by cytochrome P450 (CYP450) in the liver, and generally has fewer drug–drug interactions than methadone.

Precipitated Withdrawal and Initiation

Rotation to buprenorphine for a patient on full agonist requires forethought to account for either a washout period from the prior full agonist, or a planned timeline for administration of microdoses (explained shortly). If buprenorphine is introduced when opioid receptors are occupied by full agonists, buprenorphine will outcompete the full agonist to exert a partial opioid effect, with the resultant shift from full opioid effect to partial opioid effect manifesting as opioid withdrawal. This precipitated withdrawal can be treated by reducing the relative opioid deficit (i.e., adding more buprenorphine), or by pausing initiation and using non-opioid “comfort medications” to alleviate withdrawal symptoms. These include acetaminophen and NSAIDS, antidiarrheal agents, antiemetics, and clonidine or quetiapine for anxiety and agitation.

Buprenorphine is increasingly initiated at home (rather than in-office or inpatient) by (1) a traditional regimen that instructs patients to stop full agonist opioids and enter opioid withdrawal prior to initiation, or (2) a microdosing regimen with gradual cross-taper of full agonist and buprenorphine. Microdosing introduces buprenorphine at very small doses with monitored frequency to minimize shifts in opioid effect until a steady concentration is established. Multiple microdosing regimens have been described, and it is our recommended approach for most patients in palliative care where withdrawal from full agonist would likely cause great distress.