Opioid use disorder is the persistent and compulsive self-administration of opioids for nonmedical purposes despite negative consequences. Treatment is with maintenance therapy using agonists or long-acting antagonists, sometimes preceded by medically supervised withdrawal, and social support.
The term opioid is used to refer to natural substances (originally derived from the opium poppy) and their semisynthetic and synthetic analogs, which bind to opioid receptors. Opioids are potent analgesics that are used and misused because of their wide availability and euphoriant properties. (See also Opioid Analgesics and Opioid Toxicity and Withdrawal. )
The problem of opioid use is a global concern, with an estimated worldwide age-standardized prevalence for opioid use disorder (OUD) of approximately 0.2%, or approximately 16 million people in 2021 (1). In the United States, deaths from opioid overdose increased significantly from 1999 through 2023 (2). The dramatic rise in overdose deaths during this period was in large part due to the infiltration of the illicit drug supply by high-potency synthetic opioids such as fentanyl and fentanyl analogs (3). Overall drug overdose death rates, the majority of which are opioid-related, fell 26% from 2023 to 2024 (4).
Misuse of prescription analgesic opioids (eg, morphine, oxycodone, codeine, hydrocodone, fentanyl) is the most common source of opioid misuse. According to national survey data from the United States, of the 7.8 million people age 12 and older who misused opioids in 2024 (decreased from 8.9 million in 2023), approximately 93% misused prescription opioid analgesics, approximately 4% misused both prescription opioid analgesics and heroin, and approximately 3% misused heroin only (5, 6).
Diagnosis of Opioid Use Disorder (OUD)
Psychiatric assessment
Opioid use disorder involves compulsive, long-term self-administration of opioids for nonmedical purposes with persistent opioid use despite negative consequences. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) considers OUD to be present if the pattern of use causes clinically significant impairment or distress as manifested by the presence of ≥ 2 of the following over a 12-month period (1):
Taking opioids in larger amounts or for a longer time than intended
Persistently desiring or unsuccessfully attempting to decrease opioid use
Spending significant time obtaining, using, or recovering from opioids
Craving opioids
Failing repeatedly to meet obligations at work, home, or school because of opioids
Continuing to use opioids despite having recurrent social or interpersonal problems because of opioids
Giving up important social, work, or recreational activities because of opioids
Using opioids in physically hazardous situations
Continuing to use opioids despite having a physical or mental problem caused or worsened by opioids
Tolerance to opioids (not a criterion when use is medically appropriate)
Opioid withdrawal symptoms or taking opioids because of withdrawal
Patients with chronic pain requiring long-term use of prescription opioids should not be routinely labeled as having an OUD until evaluated for negative consequences of opioid use. However, they commonly have signs of opioid tolerance and physiologic dependence. People who use opioids parenterally are at risk of all the complications of injection drug use.
Treatment and Management of Opioid Use Disorder (OUD)
Maintenance drug treatment (buprenorphine, methadone, or long-acting naltrexone)
Ongoing counseling and multimodal support (individual therapy, group therapy, 12-step programs, mutual help groups)
For patients who meet criteria for an OUD, starting maintenance drug treatment is the standard of care over medically supervised opioid withdrawal management alone. For maintenance treatment with opioid agonists, buprenorphine or methadone are used; long-acting naltrexone (an opioid antagonist) is also approved for OUD maintenance treatment.
Physicians must be fully aware of national, state, and local regulations concerning use of an opioid medication to treat someone with a substance use disorder. To comply, physicians must establish the existence of physical opioid dependence. In the United States, treatment is further complicated by stigma toward people with substance use disorders (including the attitudes of some law enforcement officers, physicians, and other health care practitioners) and toward treatment programs (1–3). Physicians should refer opioid-dependent patients to specialized treatment centers. If trained to do so, physicians may provide office-based treatment for selected patients.
Medically supervised opioid withdrawal (detoxification)
Medically supervised opioid withdrawal (previously called detoxification) can be an appropriate treatment for OUD when the patient elects to start long-acting naltrexone as maintenance therapy. This is because an opioid-free state is necessary prior to the use of long-acing naltrexone, an opioid antagonist. Outside of starting long-acting naltrexone, medically supervised opioid withdrawal without treatment with opioid agonists like buprenorphine or methadone is not recommended due to the high risk of relapse with this approach (4). (See Withdrawal Management and Detoxification for more details).
Maintenance treatment with medications
There are 3 medications for maintenance treatment of OUD: buprenorphine, methadone, and long-acting naltrexone.
Oral opioids such as buprenorphine (a partial agonist) and methadone (a full agonist) are both first-line treatments that can be used for opioid withdrawal management and continued as maintenance treatment. Treatment with these medications leads to more effective opioid withdrawal management and retention in treatment (5). Treatment with buprenorphine or methadone is also associated with a reduction in overdose risk and opioid-related acute care episodes at 3- and 12-month follow-up, when compared with outpatient, residential, or inpatient treatment without the use of maintenance medication (6). Treatment with buprenorphine or methadone reduces relapse rates and risk of fatal overdose compared to detoxication or psychological treatment alone (7, 8). Relapse to opioid use after detoxification alone approaches 90% within 1 year for individuals with OUD (9).
Guidelines for effective management of OUD strongly advocate initiation of agonist therapy with either buprenorphine or methadone, taking into account individualized factors such as patient preference, history of prior treatment, comorbid medical conditions, and psychosocial circumstances (5, 10). However, it is ultimately the patient's choice whether to initiate maintenance treatment and which medication is used; however, patients should be advised about the likelihood of relapse and risk of overdose if undergoing withdrawal management without transitioning to maintenance treatment so that they can make an informed decision. Stabilizing someone with OUD in opioid withdrawal with adjuvant medications (clonidine, acetaminophen, loperamide, ondansetron) without offering maintenance treatment for OUD is considered substandard care.
Maintenance treatment of pregnant people with OUD using agonist therapy—methadone or buprenorphine—is safe and the standard of care over detoxification alone (11).
Buprenorphine is used for maintenance treatment of OUD. It is a partial agonist at the mu opioid receptor, which produces a ceiling effect on the potentially dangerous side effects of opioids such as respiratory depression and sedation. The high binding affinity of buprenorphine for the mu receptor makes it very effective in protecting against overdose when other opioids are used while buprenorphine is at steady state (12). Buprenorphine can be prescribed for office-based treatment. Since December 2022, U.S. regulations around prescribing buprenorphine, including additional training requirements, were relaxed, but evidence is mixed as to whether prescribing has increased significantly (13, 14).
The typical daily dose range is 8 to 24 mg of the sublingual formulation, which can be dosed once, or in divided doses 2 or 3 times daily. Dosing protocols vary according to clinical need (15). Low-dose induction protocols allow for buprenorphine to be started at low doses and gradually increased while a concomitant full agonist is used to treat withdrawal symptoms. The intent of the low-dose induction method is to avoid precipitating opioid withdrawal. A high-dose induction method also exists and is most likely to be successful when someone is already experiencing severe opioid withdrawal.
Naloxone is often added to buprenorphine in a combined formulation to discourage misuse in people who may crush the pill and use it in nonsublingual modes of administration, such as by intravenous injection. Naloxone is inactive when the combination of buprenorphine and naloxone is taken sublingually but precipitates acute withdrawal if taken intravenously. The combination formulation is used in office-based treatment. Buprenorphine is also available as a monoproduct without naloxone and is used on a case-by-case basis based on a patient's response to the combined formulation. Historically, the monoproduct formulation was recommended for managing OUD in pregnancy. However, a study published in 2024 on the comparative safety of monoproduct buprenorphine versus combined buprenorphine-naloxone showed no increased risk of worse fetal or maternal outcomes when the combination product is used (16).
Long-acting injectable formulations of buprenorphine for supervised use have been developed; these formulations lead to equivalent or higher serum concentration levels at steady state, on average, than the sublingual or buccal formulations (15, 17).
Methadone, an opioid agonist used for maintenance treatment of OUD, must be supervised in a licensed opioid treatment program (OTP) when used in the United States. Use of methadone has increased since 2020, primarily due to increased public insurance coverage (18). The expansion of mobile methadone clinics and loosening of regulations around take-home methadone doses since the COVID pandemic has also led to increased access (19, 20).
Due to the pharmacokinetics of methadone at steady state, methadone prevents withdrawal symptoms and opioid cravings without providing a significant euphoria or oversedation when given at a therapeutic dose. This eliminates potentially destabilizing forces from an individual's life—craving, use of other potentially dangerous opioids, withdrawal, risk of overdose from a contaminated drug supply, and intravenous use—which can enable people with OUD to function better.
Methadone is given at a typical daily dose of 60 to 120 mg after initiation and titration; however, dosing is highly individualized depending on an individual's opioid tolerance and use history (10).
Methadone has been reported to be associated with QTc prolongation and serious arrhythmias, including torsades de pointes (see also Long QT Syndrome and Torsades de Pointes). Thus, it should be used very carefully with appropriate patient evaluation and monitoring of EKGs during initiation and dose titration.
Naltrexone, an opioid antagonist at the mu opioid receptor, blocks the effects of full agonist opioids. A monthly depot intramuscular formulation is available and is the preferred method of administration for OUD maintenance treatment. Because naltrexone is an opioid antagonist, it cannot be within 7 days of the last full dose of another opioid agonist to avoid precipitating withdrawal. Studies have shown lower treatment retention rates in patients with OUD treated with intramuscular naltrexone compared to opioid agonist therapy with buprenorphine or methadone (5, 6). Naltrexone may be useful for patients with less severe dependence, early-stage opioid dependence, and comorbid alcohol use disorder.
Psychosocial treatments and support
Multimodal treatment can include office-based medication management, individual and group therapy, mutual help and peer support groups, and therapeutic communities. These modalities can be helpful in different combinations depending on the individual's treatment goals and preferences. Patients can move between varying levels of treatment ranging from outpatient treatment consisting of periodic visits with clinicians, to more intensive outpatient treatment, to inpatient or residential treatment depending on the phase of treatment and the stage of recovery. Inability of an individual to meet their treatment goals at a less intense level of care necessitates altering treatment to include other forms of multimodal support or moving to a higher level of care.
The therapeutic community concept, pioneered by such centers as Samaritan Daytop Village and Phoenix House, involves treatment in communal residential centers, where people with substance use disorders receive vocational training, education, and social feedback to help them build new lives. Length of stay in a therapeutic community is typically more than 12 months. Therapeutic communities are rooted in peer-based treatment models with "community as method." Initial dropout rates can be higher than short-term treatments; however, studies have shown that successful completion of treatment in a therapeutic community model can lead to sustained change, including sobriety from substances and success in achieving personal or vocational goals (21).
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