Opioid withdrawal in adolescents

INTRODUCTION — 

Opioids are used medicinally for analgesic effects but can also cause euphoria and lead to substance use disorders and addiction. Abrupt cessation or reversal in a patient who is physiologically dependent upon opioids can produce a withdrawal syndrome. Untreated opioid withdrawal frequently results in relapse to opioid use.

The epidemiology, psychopharmacology, clinical manifestations, and management of opioid withdrawal in adolescents are reviewed here. The following related topics are discussed separately:

●Evaluation and treatment of substance and opioid use disorder in adolescents (see "Substance use disorder in adolescents: Epidemiology, clinical features, assessment, and diagnosis" and "Substance use disorder in adolescents: Treatment overview")

●Opioid withdrawal in adults (see "Opioid withdrawal in adults in the emergency setting" and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder")

●Evaluation and management of opioid use disorder (see "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment" and "Opioid use disorder: Treatment overview" and "Opioid use disorder: Pharmacologic management" and "Opioid use disorder: Psychosocial management")

EPIDEMIOLOGY — 

Opioid misuse and opioid use disorder are serious problems among adolescents. Nationally representative surveys estimate approximately 14 percent of United States (US) high school students had used prescription opioids for nonmedical purposes in their lifetime, while seven percent had misused prescription opioids in the current year [1]. The 2023 National Survey on Drug Use and Health found that 1.2 percent of adolescents aged 12 to 17 had an opioid use disorder in the past year, and 0.2 percent report use of illicitly manufactured fentanyl [2]. Overdose deaths among US adolescents more than doubled between 2019 and 2021; fentanyls were identified in three-quarters of 2021 fatalities [3].

In addition, between 2005 and 2015, an adolescent or young adult was prescribed a controlled medication from 15 percent of emergency department (ED) and three percent of outpatient clinic visits [4], but are less likely to receive an opioid prescription from a pediatric ED [5]. Furthermore, opioid dispensing has steadily declined since 2015 [6]. Approximately 8 percent of adolescents and young adults between the ages of 14 to 20 years surveyed at a university-based emergency department (ED) reported nonmedical use of prescription opioids [7]. Codeine, specifically cough syrup mixed with promethazine and soda ("purple drank" or "Lean"), has been misused by adolescents [8]. A study in a Virginia hospital system found that opioid-related ED visits for patients aged 12 to 21 increased sharply in 2021 to 2022 (correlating with the end of the COVID-19 pandemic); notably, the increase in adolescents aged 13 to 17 years was greater compared with patients aged 18 to 21 years [9].

Information on worldwide opioid use in adolescents is more limited. As examples, a 2017 survey of 10,163 Canadian high school students showed an 11 percent prevalence of nonmedical prescription opioid use [10]. In England between 2011 and 2018, 0.5 to 1 percent of children aged 11 to 15 reported use of any opioid [11]. The estimated number of patients (of all ages) in opioid substitution treatment programs in the European Union was approximately 654,000 in 2017. Opioids are the principal drug in approximately 35 percent of all drug treatment requests and are involved in approximately 85 percent of fatal overdoses [12]. According to the United Nations, opioid use among all ages has nearly doubled from 2010 to 2019 to approximately 62 million people annually. Opioid use appears to be rising in both Asia and Africa [13].

The epidemiology of prescription opioid misuse is discussed further elsewhere. (See "Prescription drug misuse: Epidemiology, prevention, identification, and management", section on 'Opioid analgesics'.)

TERMINOLOGY — 

Person-centered terminology should be used when caring for adolescents with opioid use disorder (OUD). Stigmatizing language (eg, "substance abuser," "addict") perpetuates negative perceptions and attitudes among clinicians and is a commonly cited barrier as to why people with OUD are not engaged in treatment [14-16].

●Tolerance – Describes the decrease of an individual's response to a given drug as the drug is administered repeatedly or for prolonged periods.

●Addiction – The American Society of Addiction Medicine (ASAM) defines addiction as a treatable, chronic medical illness involving complex interactions among neural circuits, genetics, the environment, and an individual's life experiences [17]. People with addiction suffer from a problematic pattern of substance use and compulsive behaviors that often continue despite harmful physical and/or psychosocial consequences.

●Opioid use disorder – According to the DSM-5, a diagnosis of OUD is ascertained when at least 2 of 11 clinical criteria are met within a 12-month period (table 1). Tolerance and withdrawal are part of the diagnostic criteria for OUD but are not applicable to prescribed opioid use that is supervised under a clinician. Individuals with moderate or severe opioid use disorders have a greater likelihood of developing an opioid addiction.

●Medications for opioid use disorder – The term "medications for opioid use disorder" (MOUD) refers to the three opioid agonist or antagonist medications that are approved by the US Food and Drug Administration (FDA) to treat OUD: buprenorphine, methadone, or naltrexone. For the purpose of treating opioid withdrawal in adolescents, we will be using this term to refer to buprenorphine.

●Medically supervised withdrawal – The process of stopping opioid use often involves medications to manage withdrawal symptoms and reduce cravings with the goal of weaning until opioids are discontinued. This has been previously called "detox" or "detoxification", and the abrupt cessation of all opioids is called quitting "cold turkey." Medically supervised withdrawal on its own, without continued treatment in a substance use treatment program, carries a very high relapse rate for opioid use.

●Precipitated withdrawal – Withdrawal caused by an opioid antagonist (eg, naloxone) or partial agonist (eg, buprenorphine), which is typically more rapid and intense than withdrawal from interruption of opioid use.

●Cravings – A strong desire or urge to use a substance, which is a common reason for relapse of opioid use.

PSYCHOPHARMACOLOGY AND ADOLESCENCE — 

The psychopharmacology of opioid use and withdrawal is a complex process that is not completely understood. Some key principles include:

●Adolescence represents a unique period of brain development sensitive to environmental influences and vulnerable to the addictive effect of opioids [18]. (See "Substance use disorder in adolescents: Epidemiology, clinical features, assessment, and diagnosis", section on 'Pathogenesis'.)

●Opioid withdrawal is a predictable response to chronic opioid use but can also occur after short-term exposure to opioids [19]. In adults, the risk of transitioning to chronic opioid use begins to occur after the third day of acute use and rises in a dose-dependent fashion thereafter [20]. Exposure to opioids during adolescence increases the risk of addiction in adulthood. An observational study of 6220 adolescents found that high school students with an opioid prescription for medical purposes were 33 percent more likely to misuse opioids by 23 years of age [21]. A retrospective commercial-claims study found that 5 percent of opioid-naive adolescents and young adults who received an opioid prescription after surgery had developed long-term opioid use [22]. Another commercial-claims study found that 0.3 percent of adolescents and young adults who filled their first opioid prescription were diagnosed with an opioid use disorder or had an opioid-related overdose during the subsequent year [23]. (See "Risk of long term opioid use and misuse after prescription of opioids for pain".)

●Opioid withdrawal symptoms are thought to primarily involve changes induced by chronic opioid exposure to the locus ceruleus, the major brain noradrenergic center [24,25]. The mesolimbic system, specifically the amygdala, is also important in mediating withdrawal symptoms [26,27]. Minor opioid withdrawal symptoms can occur when opioids are discontinued after only short-term use; severity of withdrawal symptoms increases with higher doses and longer duration of opioid exposure [28,29]. (See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment", section on 'Pharmacology'.)

CLINICAL MANIFESTATIONS — 

The clinical presentation of opioid withdrawal in adolescents is similar to adults (table 2). Withdrawal from cessation of an opioid agonist is uncomfortable but not life-threatening, while precipitated withdrawal (eg, administration of an antagonist or in the setting of ultrarapid opioid detoxification) can produce sudden surges in catecholamines and hemodynamic instability that some patients (eg, those with chronic medical conditions such as diabetes) may not tolerate. In our experience, otherwise healthy adolescents are unlikely to experience life-threatening withdrawal symptoms from opioids.

●Onset and duration — After cessation of opioid use, the onset and duration of withdrawal symptoms can vary among the individual's tolerance to opioids and the duration of action of the opioid agent. Patients with withdrawal from agents with short duration of action (eg, heroin) will have shorter time to onset and duration of withdrawal symptoms as compared with agents with longer duration of action (eg, methadone) (table 3). Opioid withdrawal may begin immediately after receiving an antagonist (eg, naloxone, naltrexone, nalmefene) or partial agonist (eg, buprenorphine).

●Signs and symptoms – Patients experiencing opioid withdrawal may complain of or manifest the following:

•Craving for opioid, anxiety, fear of withdrawal

•Dysphoria and restlessness

•Rhinorrhea and lacrimation

•Myalgias, arthralgias, leg cramps

•Nausea, vomiting, abdominal cramping, increased bowel sounds, and diarrhea

•Mydriasis (pupillary dilation)

•Yawning

•Diaphoresis

•Piloerection (goosebumps)

Some or all of these symptoms may be present, and the severity depends on the individual's pattern of opioid use, the continued presence of the opioid in the serum and end organs, and the duration of time over which the withdrawal has occurred.

If the patient is in severe distress, their heart rate, blood pressure, and respiratory rate may be increased. Hypotension may be present in the setting of volume depletion from vomiting and diarrhea. Temperature is normal, and with the exception of very severe cases, mental status is preserved.

DIAGNOSIS — 

Opioid withdrawal is a clinical diagnosis in a patient with a history of cessation of opioid use or having received an opioid antagonist agent (eg, naloxone). Yawning, lacrimation, and piloerection are specific for opioid withdrawal, and their presence is helpful to confirm the diagnosis.

The Clinical Opioid Withdrawal Scale (COWS) (table 4) is a structured instrument that can be used to help determine the presence of symptoms and signs consistent with opioid withdrawal and the severity of withdrawal, but is not specifically a diagnostic tool [30]. (See 'Assess severity of withdrawal' below.)

DIFFERENTIAL DIAGNOSIS — 

Individuals with opioid withdrawal typically have preserved mental status, normal heart rate and blood pressure, and lack of seizures, in contrast to other withdrawal or intoxication syndromes that may appear similar. Although some individuals in opioid withdrawal have tachycardia that reflects their agitation or discomfort, only a minority manifest both hypertension and tachycardia. When present, these signs are almost always a result of a surge in catecholamines, such as from a sympathomimetic ingestion, withdrawal syndrome from a sedative-hypnotic agent, or precipitated opioid withdrawal. Specific disorders to consider in the differential diagnosis include:

●Concurrent medical or traumatic process – In a patient with abnormal vital signs or signs or symptoms atypical for opioid withdrawal, make sure to carefully evaluate for a concurrent medical or traumatic process that may be contributing (eg, infection, ischemia, hypovolemia, injury, hypothermia from environmental exposure). A thorough history should ascertain why the patient discontinued opioid use to ensure there is not another underlying medical condition that precluded them from continued opioid exposure.

●Ethanol or sedative-hypnotic withdrawal – These can present with a broad spectrum of severity and vital sign abnormalities, and markedly abnormal tachycardia and hypertension are more likely compared with opioid withdrawal. Hyperthermia, seizures, and altered mental status can occur with ethanol or benzodiazepine (eg, alprazolam) withdrawal, but not with opioid withdrawal. (See "Alcohol withdrawal: Epidemiology, clinical manifestations, course, assessment, and diagnosis" and "Benzodiazepine withdrawal".)

●Sympathomimetic toxicity – Mydriasis, agitation, tachycardia, and hypertension from sympathomimetic agents (eg, cocaine, amphetamines) are usually more severe than in opioid withdrawal. Severe sympathomimetic intoxication is associated with seizures and hyperthermia, which is not seen with typical opioid withdrawal. (See "Cocaine: Acute intoxication" and "Acute amphetamine and synthetic cathinone ("bath salt") intoxication" and "Methamphetamine: Acute intoxication".)

●Cholinergic (muscarinic) toxicity – Poisoning with cholinergic agents (eg, organophosphates or carbamates) may cause diarrhea and vomiting, but can be distinguished from opioid withdrawal by the presence of altered mental status, bradycardia, and salivation. In patients with organophosphate poisoning, fasciculations, muscle weakness, and seizures can occur in severe cases. (See "Organophosphate and carbamate poisoning".)

LABORATORY EVALUATION — 

Most patients with opioid intoxication and withdrawal can be managed without laboratory studies. If the patient presents with a history of significant vomiting or diarrhea, it is prudent to obtain a basic metabolic profile to help assess for fluid and electrolyte abnormalities.

Urine drug testing has no routine role in the diagnosis or management of opioid withdrawal. The prototypical urine opiate immunoassay detects morphine, which is a metabolite of heroin and codeine and does not detect synthetic opioids (eg, fentanyl, methadone) or semisynthetic opioids (eg, oxycodone, hydrocodone, buprenorphine). Specific screening assays for fentanyl, oxycodone, and buprenorphine are available but not offered by all clinical laboratories. Therefore, a negative test result should not be used to disprove opioid use in a patient complaining of withdrawal symptoms. If ordering a urine drug test, ensure that the appropriate assay is ordered; however, patients often do not realize to which opioid they may have been exposed (eg, many substances contain fentanyl). A positive urine drug test typically confirms exposure to the substance but does not provide any information regarding presence or absence of withdrawal. (See "Urine drug testing", section on 'Opioids'.)

MANAGEMENT — 

The approach to managing acute opioid withdrawal in adolescents is presented in the table (table 5) and described below.

All patients

Supportive care — Standard supportive care should be provided depending on signs and symptoms. For example, fluid and electrolyte repletion should be provided to a patient with significant losses (eg, 250 to 500 mL intravenous boluses of isotonic crystalloid may be repeated as needed).

Precipitated withdrawal (eg, following administration of an opioid antagonist) can produce sudden surges in catecholamines and hemodynamic instability. In our experience, otherwise healthy adolescents are unlikely to experience life-threatening precipitated withdrawal.

Assess severity of withdrawal — We use the Clinical Opioid Withdrawal Scale (COWS) (table 4) (calculator 1) to determine severity of withdrawal and guide therapy. It is a validated, simple-structured instrument that can help decide when to start opioid agonist therapy, evaluate therapeutic response with serial assessments, and provide a clear context for medical documentation and decision-making [30,31]. A COWS score >12 represents moderate to severe opioid withdrawal, and a score of 5 to 12 represents mild withdrawal. (See "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Monitoring'.)

Patients with withdrawal from interruption in opioid use

Buprenorphine — In an adolescent with opioid withdrawal (COWS score >5), we suggest treatment with buprenorphine. We use a low-dose buprenorphine initiation protocol, which involves frequent administration of small doses (eg, 2 to 4 mg) every one to two hours if symptoms persist. We start with a 2 mg dose and administer additional 2 to 4 mg doses based on the patient's COWS score. If the COWS score increases, we stop induction, treat symptoms with nonopioid adjunctive medications (eg, clonidine), and reassess in 24 hours. Many adolescents will stabilize at a daily buprenorphine dose of 4 to 8 mg, while some adolescents will require daily doses of 16 to 24 mg.

Clonidine can also be administered with buprenorphine to treat withdrawal symptoms while the buprenorphine dose is being titrated. (See 'Nonopioid adjunctive medications' below.)

We generally start buprenorphine after an appropriate amount of time following the most recent opioid exposure has passed (table 6) to avoid precipitating withdrawal. In an adolescent who presents with mild withdrawal symptoms (COWS score 5 to 12) or who has had recent opioid exposure, a reasonable option is nonopioid adjunctive medications (eg, clonidine) and symptom-specific medications (eg, acetaminophen) (table 7). These are temporizing measures until the patient is past the acute withdrawal period and can start maintenance treatment for opioid use disorder (OUD). If the adjunctive medications do not adequately control withdrawal symptoms or mild withdrawal becomes moderate to severe (COWS increases >12), we initiate buprenorphine.

Buprenorphine, a partial opioid agonist, is effective for treatment of acute withdrawal in the emergency setting and is preferred for medically supervised withdrawal in adults. Its advantages include a long duration of action, higher affinity for mu-opioid receptors than most opioids, slow dissociation from the receptor, and greater safety in overdose than full agonists such as methadone.

There are several reasons why we use a low-dose buprenorphine initiation protocol in adolescents. We try to minimize exposure to opioids (including buprenorphine) during this unique period of brain development. Thus, a reasonable approach is to start with low doses, just enough to treat withdrawal symptoms, and titrate up slowly to control cravings. Also, frequent low dosing avoids precipitated withdrawal that may otherwise occur with standard doses of buprenorphine if the adolescent has been misusing fentanyl or fentanyl analogs (possibly unintentionally) given the widespread supply. Evidence for this approach in adolescent patients is based on case reports, anecdotal experience, and use in adult patients [32,33]. (See "Opioid use disorder: Pharmacologic management", section on 'Alternative induction methods for specific circumstances'.)

If an adolescent is experiencing withdrawal within the time window since last opioid use (table 6), we temporize symptoms with adjunctive medications (ie, clonidine) (table 7) until the appropriate time has passed and buprenorphine can be started. In general, we do not start buprenorphine in a patient who reports fentanyl use within the past 24 hours to limit the risk of precipitated withdrawal [34]. However, the timing of buprenorphine induction should be tailored to individual circumstances; these time windows are general guidelines to help decrease the risk of precipitated withdrawal.

Buprenorphine is also a first-line agent for treatment of opioid withdrawal and opioid use disorder (OUD) in the pregnant adolescent patient. (See "Opioid use disorder: Overview of treatment during pregnancy", section on 'MOUD or medically assisted withdrawal?'.)

Evidence specifically in adolescents supporting the use of medications for opioid use disorder (MOUD) is limited and mostly extrapolated from adult evidence that shows buprenorphine increases engagement in substance use treatment and reduces illicit opioid use compared with psychosocial treatment alone [35-39]. MOUD has been found to be superior to alpha-2 adrenergic agonists (eg, clonidine) during supervised withdrawal. (See "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Opioid agonists versus alpha-2 adrenergic agonists'.)

Efficacy data from clinical trials, either comparing buprenorphine with methadone or with controls, are insufficient to guide MOUD selection for adolescents who have an OUD. Only buprenorphine has been studied in a clinical trial in adolescents (presented below). Additional evidence influencing treatment decisions has been limited to trials of adults and decades of clinical experience with methadone. Several observational studies reported that many adolescents (48 to 62 percent) receiving methadone maintenance for heroin use disorders stayed engaged in treatment [40,41]. (See "Substance use disorder in adolescents: Treatment overview", section on 'Selecting maintenance treatment'.)

●A trial of 36 adolescents with opioid use disorders compared 28-day medically supervised withdrawal treatment with buprenorphine versus clonidine [42]. Both groups were provided behavioral treatment, allowed to take over-the-counter medications, and were offered naltrexone therapy at the end of the trial. Patients taking buprenorphine were more likely to complete the full duration of the treatment (72 versus 39 percent), provide opioid-negative urine samples (64 versus 32 percent), and transition to naltrexone therapy (61 versus 5 percent).

●A trial of 152 adolescents (83 percent were 18 to 21 years old) with opioid use disorders compared outpatient treatment with buprenorphine for 12 weeks (taper starting at week nine) versus two weeks (tapered during study period) [43]. Patients were instructed to avoid opioids for at least six hours and to have withdrawal symptoms prior to the first dose. Both groups received counseling. More patients in the rapid taper group had opioid-positive urine tests at four and eight weeks (61 versus 26 percent and 54 versus 23 percent respectively), but by week 12 there was no difference. Patients in the rapid taper group were also more likely to report opioid and other drug misuse. Patients in the longer buprenorphine treatment group were more likely to remain in treatment (84 versus 45 percent at four weeks and 70 versus 21 percent, OR 0.13, 95% CI 0.07-0.26 at 12 weeks).

●A trial of 53 patients ages 16 to 24 (11 younger than 18 years of age) with opioid use disorders were randomized to a buprenorphine taper of either 28 or 56 days. Both groups received behavioral counseling and opioid abstinence incentives. Patients in the 56-day taper period group had more opioid-negative urine tests (35 versus 17 percent) and longer retention in treatment (38 versus 26 days) [44].

Nonopioid adjunctive medications

●Clonidine – In patients with normal or elevated blood pressure, clonidine is a good option to treat withdrawal symptoms and can be administered with buprenorphine while the buprenorphine dose is being titrated. We administer 0.1 mg (0.05 mg in younger adolescents) orally every 6 to 8 hours with close monitoring for hypotension (table 7). It is an alpha-2 adrenergic receptor agonist that decreases withdrawal symptoms by blocking the release of norepinephrine. (See "Opioid withdrawal in adults in the emergency setting", section on 'Alpha-2 adrenergic receptor agonists' and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Alpha-2 adrenergic agonists'.)

●Others – Patients who are treated with buprenorphine can still receive nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, antiemetics, or antidiarrheals to specifically treat withdrawal symptoms (table 7). In adolescents with OUD, we generally do not use benzodiazepines for muscle cramping due to the risk of fatal overdose when coadministered with buprenorphine. (See "Opioid withdrawal in adults in the emergency setting", section on 'Non-opioid adjunctive medications' and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Adjunctive medications'.)

Patients with precipitated withdrawal (eg, from opioid antagonist) — In an adolescent with precipitated withdrawal due to an opioid antagonist (eg, naloxone, nalmefene, or naltrexone), it may be difficult to administer enough opioid to overcome the antagonist, or rebound opioid intoxication could ensue following treatment with short-acting antagonists (naloxone and nalmefene). Buprenorphine itself can also precipitate withdrawal, which may be more common with increasing fentanyl use. We prefer buprenorphine in an adolescent with opioid withdrawal symptoms who is agreeable to opioid agonist therapy. Precipitated withdrawal from buprenorphine is typically treated with higher doses of buprenorphine. Experience with using buprenorphine to treat precipitated withdrawal in adolescents is limited because it uncommonly occurs; the use and doses in adults are discussed elsewhere. (See "Opioid withdrawal in adults in the emergency setting", section on 'Precipitated withdrawal (eg, from opioid antagonist)'.)

Clonidine and/or other nonopioid adjunctive medications (table 7) are reasonable alternatives and adjuncts for managing precipitated withdrawal. (See "Opioid withdrawal in adults in the emergency setting", section on 'Non-opioid adjunctive medications' and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Adjunctive medications'.)

Declining or not a candidate for buprenorphine — An adolescent patient with opioid withdrawal who declines buprenorphine (eg, wants to use naltrexone for long-term management of OUD) or is not a candidate for buprenorphine (eg, co-occurring severe alcohol or sedative use disorder) should be treated with nonopioid adjunctive medications targeted to control the withdrawal symptoms. Options and dosing are presented in the table (table 7) and discussed in detail elsewhere. (See "Opioid withdrawal in adults in the emergency setting", section on 'Non-opioid adjunctive medications' and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Adjunctive medications'.)

Therapies we avoid

●Benzodiazepines – In adolescents with opioid withdrawal, we generally do not use benzodiazepines for muscle cramping due to the potential for substance use disorder.

●Methadone – We do not routinely use methadone for treatment of opioid withdrawal in adolescents. Methadone may be a reasonable alternative in patients who have previously used methadone or if buprenorphine is unavailable. However, in the United States, methadone is typically not available for adolescent use and is dispensed through a federally regulated clinic system. Methadone is not approved in adolescents younger than 18 years old unless they have failed two prior withdrawal management attempts. In many other countries, methadone is available by prescription and utilizes pharmacy-based dispensing. (See "Opioid use disorder: Pharmacologic management", section on 'Methadone: Opioid agonist'.)

●Ultrarapid opioid detoxification — We recommend against using ultrarapid opioid detoxification in adolescents because it exposes patients to the risks of general anesthesia, as well as seizures and hemodynamic instability, without a clear benefit. In this approach, opioid antagonists are administered under general anesthesia or heavy sedation with the intent of producing withdrawal. The procedure has been extensively promoted as a faster, more comfortable means of stopping use and is controversial in adults, with numerous associated case reports of severe adverse events and deaths. (See "Opioid withdrawal in adults in the emergency setting", section on 'Ultrarapid opioid detoxification' and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Ultra-rapid or anesthesia-assisted opioid withdrawal'.)

FOLLOW-UP CARE — 

All adolescents with an opioid use disorder (OUD) (table 1) should be referred to substance use disorder treatment following stabilization from the withdrawal. Maintenance pharmacotherapy is often continued after the withdrawal phase to decrease cravings and reduce the risk of relapse. The choice of maintenance therapy depends on the severity of the OUD (table 1) and is discussed separately. Options include naltrexone, which may be appropriate for adolescents with a mild OUD who are motivated to achieve abstinence, and buprenorphine for adolescents with moderate to severe OUD. (See "Substance use disorder in adolescents: Treatment overview", section on 'Opioid use disorder'.)

Adolescents with OUD benefit from behavioral and psychologic therapy in addition to medications. (See "Opioid use disorder: Psychosocial management".)

Options for patients who decline medication for OUD are discussed separately. (See "Opioid use disorder: Treatment overview", section on 'Individuals who decline medication for opioid use disorder'.)

ADDITIONAL RESOURCES

Regional poison centers — Regional poison centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Opioid use disorder and withdrawal" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use" and "Society guideline links: Poisoning prevention".)

SUMMARY AND RECOMMENDATIONS

●Psychopharmacology – Opioid misuse and opioid use disorder (OUD) are serious problems among adolescents. Adolescence represents a unique period of brain development sensitive to environmental influences and vulnerable to the addictive effect of opioids. (See 'Epidemiology' above and 'Psychopharmacology and adolescence' above.)

The evaluation and management of opioid withdrawal in adolescents is summarized in the table (table 5).

●Clinical manifestations – The clinical manifestations of opioid withdrawal in adolescents are similar to adults and summarized in the table (table 2). Otherwise healthy adolescents are unlikely to experience life-threatening withdrawal. Withdrawal from cessation of an opioid agonist is uncomfortable but not life-threatening, while precipitated withdrawal (eg, following administration of an opioid antagonist) can produce sudden surges in catecholamines and hemodynamic instability that some patients (eg, those with chronic medical conditions) may not tolerate. The onset and duration of withdrawal symptoms can vary based on the individual's tolerance to opioids and the duration of action of the opioid (table 3). (See 'Clinical manifestations' above.)

●Laboratory evaluation – Most adolescents with isolated opioid withdrawal do not need laboratory studies. Urine drug testing has no routine role; the prototypical urine opiate immunoassay detects morphine (a metabolite of heroin and codeine), and does not detect synthetic opioids (eg, fentanyl, methadone) or semisynthetic opioids (eg, oxycodone, hydrocodone, buprenorphine). (See 'Laboratory evaluation' above.)

●Diagnosis – Opioid withdrawal is a clinical diagnosis in a patient with a history of cessation of opioid use or having received an opioid antagonist agent (eg, naloxone). Yawning, lacrimation, and piloerection are specific for opioid withdrawal and their presence is helpful to confirm the diagnosis. (See 'Diagnosis' above.)

●Severity assessment – The Clinical Opioid Withdrawal Scale (COWS) is used to assess the severity of withdrawal (table 4) (calculator 1). (See 'Assess severity of withdrawal' above.)

●Management of withdrawal from interruption of opioid use – In an adolescent with opioid withdrawal (COWS >5), we suggest treatment with buprenorphine rather than solely nonopioid adjunctive medications (Grade 2C). We use a low-dose buprenorphine initiation protocol, which involves frequent administration of small doses (eg, 2 mg) every one to two hours if symptoms persist. Clonidine can be administered with buprenorphine to treat withdrawal symptoms while the buprenorphine dose is being titrated. (See 'Patients with withdrawal from interruption in opioid use' above.)

We generally start buprenorphine after an appropriate amount of time following the most recent opioid exposure has passed (table 6) to avoid precipitating withdrawal. In an adolescent who presents with mild withdrawal symptoms (COWS score 5 to 12) or who has had recent opioid exposure, a reasonable option is nonopioid adjunctive medications (table 7). These are temporizing measures until the patient is past the acute withdrawal period and can start treatment for OUD. If the adjunctive medications do not adequately control withdrawal symptoms or mild withdrawal becomes moderate to severe (COWS increases >12), we initiate buprenorphine.  

●Management of precipitated withdrawal due to an opioid antagonist – In an adolescent with precipitated opioid withdrawal due to an opioid antagonist, we suggest buprenorphine (Grade 2C). When withdrawal is triggered by a full antagonist (such as naloxone, nalmefene, or naltrexone), it may be difficult to administer enough opioid to overcome the antagonist, or rebound opioid intoxication could ensue following treatment with short-acting antagonists (naloxone and nalmefene). The buprenorphine dose should be tailored to the agent and the dose that precipitated the withdrawal. Clonidine and other adjunct nonopioid medications (table 7) are reasonable alternatives. (See 'Patients with precipitated withdrawal (eg, from opioid antagonist)' above.)

●Patient declining or is not a candidate for buprenorphine – This may include an adolescent who wants to use naltrexone for long-term management of OUD or an adolescent with a co-occurring severe alcohol or sedative use disorder. These patients can be treated with nonopioid adjunctive medications (eg, clonidine) and symptom-specific medications (eg, acetaminophen) (table 7). (See 'Declining or not a candidate for buprenorphine' above.)

●Follow-up care for OUD treatment – All adolescents with an opioid use disorder (OUD) (table 1) should be referred to substance use disorder treatment following stabilization from the withdrawal. (See 'Follow-up care' above.)