Opioid Withdrawal in Adolescents

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Opioid withdrawal in adolescents

AUTHOR: Shan Yin, MD, MPH
SECTION EDITOR: Michele M Burns, MD, MPH
DEPUTY EDITOR: Michael Ganetsky, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024.

This topic last updated: Mar 22, 2022.
INTRODUCTION
Opioids have analgesic and central nervous system (CNS) depressant effects and the
potential to cause euphoria. Morphine is the prototypic opioid. Heroin is a derivative of
morphine and is a commonly abused opioid.
Opioids are effective in the treatment of acute and chronic pain as analgesics and sedatives
and as anesthetic agents. They have the potential to be abused for these effects and the
associated feeling of euphoria.
The epidemiology, pharmacology, clinical manifestations, and management of opioid

withdrawal in adolescents are reviewed here. Opioid withdrawal in the neonate and opioid
use disorder in adolescents are discussed separately:
● (See "Prenatal substance exposure and neonatal abstinence syndrome (NAS):

Management and outcomes".)
● (See "Substance use disorder in adolescents: Treatment overview".)
EPIDEMIOLOGY
Opioid abuse and addiction is a serious problem among adolescents. As an example,

nationally representative surveys estimate approximately 17 percent of high school seniors
in the United States had used prescription opioids in their lifetime for medical purposes and
approximately 13 percent had used prescription opioids for nonmedical purposes [1].
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Approximately 8 percent of children between the ages of 14 to 20 surveyed at a university

based emergency department had reported nonmedical prescription opioid use [2]. In
addition, between 1994 and 2007, the proportion of ambulatory visits where an adolescent
or young adult was prescribed a controlled medication nearly doubled [3]. Lastly, per the
Substance Abuse and Mental Health Services Administration (SAMHSA), opioids represent
approximately 1 to 2 percent of all adolescent substance abuse treatment admissions and in
2008, 63 percent of these were due to prescription opioids [4].
Information on worldwide opioid use in adolescents is more limited but includes the
following:
● A 2007 survey of 2914 Canadian students aged 12 to 19 showed that approximately 20

percent had lifetime nonmedical use of prescription opioids [5].
● A 2010 nationwide survey of students in England aged 11 to 15 showed approximately

1 percent lifetime opioid use [6].
● The estimated number of patients (of all ages) in opioid substitution treatment
programs in the European Union has increased from approximately 450,000 in 2003 to
approximately 700,000 in 2010, which is believed to be largely due to increased abuse
of prescription opioids rather than heroin abuse [7].
● According to the United Nations, opioid use among all ages has been rising in Asia
since 2009 [8].
PHARMACOLOGY
Tolerance is defined as a decrease of an individual’s response to given drug as the drug is

administered repeatedly or for prolonged periods. A withdrawal state may occur as the body
adapts to higher and higher drug concentrations. Opioid withdrawal symptoms are thought
to primarily involve changes in the locus ceruleus (LC). Opioids inhibit the activity of LC
neurons. When opioids are continuously present, increased activity of the LC neurons
compensates for the inhibition. When opioids or their activity are abruptly removed, the
increased activity of the LC neurons results in withdrawal symptoms [9,10]. The mesolimbic
system is also important in mediating withdrawal symptoms [11,12].
SYMPTOMS OF OPIOID WITHDRAWAL
Tolerance and physical and psychologic dependence on opioids usually occur after three
weeks of daily usage. Higher tolerance is created as the user decreases the interval and
increases the dose to achieve euphoria. Tolerance does not develop to the following
physiologic effects: miosis and constipation.
Heroin, hydromorphone, and methadone have great addictive potential. Heroin provides a
"rush" because it easily crosses the blood brain barrier and can be used by multiple routes.
Hydromorphone is almost 100 times more potent than is codeine for analgesic effect.
Methadone is long-acting. Codeine, a prescription drug that must be ingested orally, has
weaker analgesic effects and a lower addictive potential.
The discontinuation of opioids leads to a constellation of withdrawal symptoms known as the

abstinence syndrome ( table 1). The severity of the abstinence syndrome depends upon
the type and frequency of the drug used. The abstinence syndrome usually is elicited if
opioid use is discontinued after several months of daily usage.
Withdrawal symptoms occur in stages, depending upon the time of the last dose and the
elimination time of the drug, the typical findings are as follows:
● 3 to 4 hours after blood levels decline – Drug craving, anxiety, fear of withdrawal
● 8 to 14 hours – Anxiety, restlessness, insomnia, yawning, rhinorrhea, lacrimation,

diaphoresis, stomach cramps, and mydriasis
● One to three days – Tremor, muscle spasms, vomiting, diarrhea, hypertension,

tachycardia, fever, chills, and piloerection
CLINICAL FEATURES AND DIAGNOSIS
Clinical features of opioid withdrawal in adolescents are similar to those seen in adults
( table 2).
● History — In individuals with opioid use disorder, opioid withdrawal may begin
immediately after receiving an antagonist, or after cessation of use. Partial agonists
(eg, buprenorphine) and agonist-antagonists (eg, pentazocine) can also produce
withdrawal, so for the purpose of this review, the term "antagonist" will be discussed in
relation to these drugs as well.
Signs and symptoms of withdrawal may begin 6 to 12 hours after the last dose of a
short-acting opioid and 24 to 48 hours after cessation of methadone. Withdrawal
symptoms typically peak within 24 to 48 hours of onset, but may persist for several
days with short-acting agents and up to two weeks with methadone.
Patients experiencing opioid withdrawal may complain of the following:
• Dysphoria and restlessness

• Rhinorrhea and lacrimation
• Myalgias and arthralgias
• Nausea, vomiting, abdominal cramping, and diarrhea
Some or all of these symptoms may be present, and the severity depends on the
individual's tolerance to opioids, the continued presence of opioid in the serum and end
organs, and the duration of time over which the withdrawal has occurred. As an
example, a person who is tolerant to 200 mg/day of methadone who was administered
two milligrams of naloxone intravenously would experience much more severe
symptoms than someone taking 10 mg of methadone daily who stopped abruptly (ie,
"cold turkey"). A thorough history should ascertain why the patient discontinued opioid
use to ensure there is not another underlying medical condition that precluded them
from obtaining the drug.
● Physical examination — Opioid withdrawal is characterized by mydriasis (pupillary

dilation), yawning, increased bowel sounds, and piloerection ( table 2). If the patient
is in severe distress, 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 – Most patients in opioid withdrawal have good insight into their problem,
and the diagnosis is usually established by history alone. When present, the findings of
yawning and lacrimation are helpful because of their specificity.
DIFFERENTIAL DIAGNOSIS
Opioid withdrawal may appear similar to other withdrawal or intoxication syndromes.

Patients with opioid withdrawal typically have a normal mental status and do not develop
seizures. In addition, significant tachycardia or hypertension is rare. Many patients in opioid
withdrawal have a pulse and blood pressure within normal limits. Although some in opioid
withdrawal have a tachycardia that reflects their agitation, discomfort, or hypovolemia, only
a small minority of patients manifest both hypertension and tachycardia. When present,
these signs are almost always a result of a surge in catecholamines from iatrogenically-
induced withdrawal. (See "Opioid withdrawal in the emergency setting", section on
'Differential diagnosis'.)
Ethanol withdrawal — Ethanol withdrawal may present with a broad spectrum of severity
and vital sign abnormalities. It is much more likely to cause tachycardia and hypertension
than opioid withdrawal. In contrast to opioid withdrawal, seizures and altered mental status
may be prominent.
A rapid overview of moderate and severe ethanol withdrawal is provided ( table 3). (See
"Management of moderate and severe alcohol withdrawal syndromes".)
Sedative-hypnotic withdrawal — Similar to ethanol withdrawal, patients with sedative-

hypnotic withdrawal are more likely to have tachycardia and hypertension than patients with
opioid withdrawal. Unlike typical opioid withdrawal, sedative-hypnotic withdrawal may cause
seizures and hyperthermia. (See "Benzodiazepine poisoning".)
Sympathomimetic intoxication — Cocaine, amphetamine, or other sympathomimetic

intoxication may produce mydriasis, agitation, tachycardia, and hypertension, but these
findings are usually much more severe than occur 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
"Methamphetamine: Acute intoxication" and "Acute amphetamine and synthetic cathinone
("bath salt") intoxication", section on 'Clinical features of overdose'.)
Cholinergic poisoning — 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 may occur,
which would further differentiate that clinical entity from opiate withdrawal. (See
"Organophosphate and carbamate poisoning", section on 'Clinical features'.)
A rapid overview for the treatment of organophosphate and carbamate poisoning is

provided ( table 4).
ACUTE MANAGEMENT OF OPIOID WITHDRAWAL
Approach — The approach to managing acute opioid withdrawal in adolescents is generally

consistent with the approach in adult patients ( table 5). Commonly used medications in
this setting include buprenorphine, methadone, and clonidine ( table 6); evidence
supporting the use of these agents in adolescent patients is limited [13]. Acute treatment of
opioid withdrawal is discussed in detail separately. (See "Opioid withdrawal in the emergency
setting".)
Of note, ultrarapid opioid detoxification, which is a controversial procedure that has been
used in adult patients, is not used in adolescents because it has associated risks (ie, risks of
general anesthesia, seizures, hemodynamic instability) without a clear benefit. (See "Opioid
withdrawal in the emergency setting", section on 'Ultrarapid opioid detoxification'.)
Methadone is a reasonable alternative if buprenorphine is unavailable or unfamiliar.
Buprenorphine — Buprenorphine, a partial opioid agonist, is also effective for treatment of

acute withdrawal in the emergency setting and is preferred for medically supervised
detoxification in adults, but experience in adolescents is limited. Advantages to is use in
supervised withdrawal include a long duration of action, higher affinity for mu-opioid
receptor than all opioids except fentanyl, slow dissociation from the receptor, and greater
safety in overdose than full agonists such as methadone. However, careful administration is
needed to avoid precipitating or worsening withdrawal. (See "Opioid withdrawal in the
emergency setting" and "Opioid withdrawal: Medically supervised withdrawal during
treatment for opioid use disorder", section on 'Buprenorphine versus methadone'.)
Methadone — Methadone, a long-acting opioid with a half-life of 24 to 36 hours, is the

medical therapy sometimes used for opioid withdrawal in adults in the emergency setting
( table 6). Its use relieves opioid craving and withdrawal symptoms and when given in
sufficient doses, blocks the euphoric effects of opioids. However, buprenorphine is preferred
to methadone during medically supervised withdrawal after emergency treatment because
methadone poses a much greater risk of lethal overdose and intravenous abuse. (See
"Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use
disorder".)
A method of treating opioid withdrawal symptoms using methadone without causing over-
sedation or severe patient discomfort is discussed in detail elsewhere. (See "Opioid
withdrawal in the emergency setting".)
Other withdrawal symptoms (eg, pain, muscle spasm, diarrhea) can be treated with
nonsteroidal antiinflammatory drugs (NSAIDs), analgesics, muscle relaxants, and
antidiarrheals ( table 6).
Patients who need analgesia for coexisting medical problems during methadone treatment
should be treated with NSAIDs if possible. Narcotics with antagonist action (eg, pentazocine
[Talwin], nalbuphine [Nubain], and butorphanol [Stadol]) should be avoided because they
can precipitate immediate withdrawal.
Clonidine — Clonidine may be used as an alternative to methadone or buprenorphine

treatment. It decreases withdrawal symptoms by blocking the release of norepinephrine. It
can be used with methadone when methadone is tapered below 15 mg. In higher doses
(greater than 1.2 mg per day), clonidine can cause dry mouth, sedation, orthostasis, and
constipation. Patients taking clonidine should be monitored for hypotension. The use of
clonidine to manage acute withdrawal from opioids is discussed in detail elsewhere. (See
"Opioid withdrawal in the emergency setting".)
Rapid detoxification — Ultrarapid opioid detoxification has been extensively promoted as a

faster, more comfortable means of stopping use. In this practice, opioid antagonists are
administered under general anesthesia or heavy sedation with the intent of producing
withdrawal. The procedure is controversial in adults and is not used in adolescents because it
exposes people to the risks of general anesthesia, as well as seizures and hemodynamic
instability, without a clear benefit. (See "Opioid withdrawal in the emergency setting", section
on 'Ultrarapid opioid detoxification'.)
MEDICALLY SUPERVISED DETOXIFICATION
Medically supervised opioid withdrawal for adolescents is discussed in detail separately. (See
"Substance use disorder in adolescents: Treatment overview", section on 'Medically
supervised withdrawal'.)
Opioid detoxification of pregnant adolescents is discussed separately. (See "Opioid use

disorder: Overview of treatment during pregnancy", section on 'MOUD or medically assisted
withdrawal?'.)
Drug use disorder is pharmacologic (withdrawal symptoms occur when drug use is
discontinued) and psychologic (compulsive drug use despite problems related to use,
inability to reduce the frequency or intensity of use, preoccupation with drug-seeking
behavior). Thus, the treatment of adolescents with opioid addiction requires medical,
behavioral, and psychologic therapy. (See "Substance use disorder in adolescents: Treatment
overview".)
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".)
SUMMARY AND RECOMMENDATIONS
● Diagnosis
• The discontinuation of opioids leads to a constellation of withdrawal symptoms

known as the abstinence syndrome ( table 1). The severity of the abstinence
syndrome depends upon the type and frequency of the drug used. The withdrawal
syndrome usually is elicited if opioid use is discontinued after several months of
daily usage (three to four times per day). (See 'Symptoms of opioid withdrawal'
above.)
• Most patients in opioid withdrawal have good insight into their problem, and the
diagnosis is usually established by history alone. When present, the findings of
yawning and lacrimation are helpful because of their specificity. Other findings of
opioid withdrawal are provided in the table ( table 2). (See 'Clinical features and
diagnosis' above.)
• Opioid withdrawal can be distinguished from other withdrawal or intoxication

syndromes in adolescents by a normal mental status and the absence of seizures.
Tachycardia or hypertension also tend to be less prominent in adolescents
presenting with opioid withdrawal. (See 'Differential diagnosis' above.)
● Treatment
• The approach to managing acute opioid withdrawal in adolescents is generally

consistent with the approach in adult patients ( table 5). Commonly used
medications in this setting include buprenorphine, methadone, and clonidine;
evidence supporting the use of these agents in adolescent patients is limited. Acute
treatment of opioid withdrawal is discussed in detail separately. (See "Opioid
withdrawal in the emergency setting" and "Substance use disorder in adolescents:
Treatment overview", section on 'Opioid use disorder'.)
• After treatment of withdrawal, initial and maintenance therapy for opioid use
disorder in adolescents is essential. The management of substance use disorder in
adolescents is discussed separately. (See "Substance use disorder in adolescents:
Treatment overview".)
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REFERENCES
1. McCabe SE, West BT, Teter CJ, Boyd CJ. Medical and nonmedical use of prescription
opioids among high school seniors in the United States. Arch Pediatr Adolesc Med 2012;
166:797.
2. Whiteside LK, Walton MA, Bohnert AS, et al. Nonmedical prescription opioid and
sedative use among adolescents in the emergency department. Pediatrics 2013;
132:825.
3. Fortuna RJ, Robbins BW, Caiola E, et al. Prescribing of controlled medications to

adolescents and young adults in the United States. Pediatrics 2010; 126:1108.
4. Substance Abuse and Mental Health Services Administration OoAS. Treatment Episode D
ata Set (TEDS). 1998 - 2008. National Admissions to Substance Abuse Treatment Service
s,. Rockville, MD: DASIS Series: S-50, HHS Publication No. (SMA) 09-4471; 2010.
5. Brands B, Paglia-Boak A, Sproule BA, et al. Nonmedical use of opioid analgesics among
Ontario students. Can Fam Physician 2010; 56:256.
6. UK Focal Point on Drugs. United Kingdom Drug Situation 2012 Edition. London. http://w
ww.nwph.net/ukfocalpoint/writedir/userfiles/file/Report%202012/REPORT2012FINAL.pd
f. (Accessed on March 06, 2014).
7. EMCDDA. Annual Report 2012. The State of the Drugs Problem in Europe. Luxembourg:
Publications Office of the European Union.
8. UNODC. World Drug Report 2013. Vienna, Austria: United Nations publication, Sales No
E.13.XI.6.
9. Williams JT, Christie MJ, Manzoni O. Cellular and synaptic adaptations mediating opioid
dependence. Physiol Rev 2001; 81:299.
10. Mazei-Robison MS, Nestler EJ. Opiate-induced molecular and cellular plasticity of ventral
tegmental area and locus coeruleus catecholamine neurons. Cold Spring Harb Perspect
Med 2012; 2:a012070.
11. Kosten TR, George TP. The neurobiology of opioid dependence: implications for
treatment. Sci Pract Perspect 2002; 1:13.
12. Kreek MJ, Koob GF. Drug dependence: stress and dysregulation of brain reward
pathways. Drug Alcohol Depend 1998; 51:23.
13. Minozzi S, Amato L, Davoli M. Detoxification treatments for opiate dependent

adolescents. Cochrane Database Syst Rev 2014; :CD006749.
Topic 6505 Version 25.0
GRAPHICS
Stages of opioid withdrawal syndrome
Stage Features
Stage I: Up to 8 Fear of withdrawal, anxiety, drug craving

hours
Stage II: 8-24 Insomnia, restlessness, anxiety, yawning, stomach cramps, lacrimation,
hours rhinorrhea, diaphoresis, mydriasis
Stage III: Up to 3 Vomiting, diarrhea, fever, chills, muscle spasms, tremor, tachycardia, piloerection,
days hypertension, seizures*
* Only seen in neonates.
Graphic 78321 Version 4.0
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Clinical features of opioid withdrawal
Vital signs
Blood pressure increased or unchanged; decreased if hypovolemic
Heart rate increased or unchanged
Respiratory rate increased or unchanged
Temperature unchanged
Gastrointestinal
Nausea, vomiting
Diarrhea, increased bowel sounds
Neurological
Mental status usually normal, irritable
Restlessness
Seizures (neonates only)
Tremor
Yawning
Ophthalmologic
Lacrimation
Mydriasis
Skin
Piloerection
Diaphoresis
Other findings
Rhinorrhea
Moderate and severe alcohol withdrawal: Rapid overview of emergency

management
To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222
for the nearest regional poison control center. Contact information for poison control centers around
the world is available at the WHO website and in the UpToDate topic on regional poison control centers
(society guideline links).
Syndromes
Alcohol tremulousness – occurs early; characterized by hypertension, tachycardia, tremors, and
anxiety with normal mental status
Alcohol withdrawal seizures – occurs early; usually single or brief flurry of seizures with short
postictal period
Alcoholic hallucinosis – occurs early; no evidence of autonomic instability
Delirium tremens – occurs late; characterized by delirium and autonomic instability
History
Pattern of alcohol use, history of withdrawal symptoms; inquire about reasons for cessation of
alcohol
Physical examination
Vital signs, mental status, presence of tremor; examine for signs of trauma, abdominal tenderness,
other findings consistent with complications of chronic alcohol use
Laboratory testing
No test truly assesses withdrawal; ancillary data (eg, serum ethanol concentration, lumbar puncture
[CSF], head CT, lipase) frequently needed to assess patient and rule out coexistent illness
Treatment
Benzodiazepines
First-line therapy for ALL alcohol withdrawal syndromes
Most patients with symptoms require IV therapy initially
Give:
Diazepam, 5 to 10 mg IV, repeat every 5 to 10 minutes, OR
Lorazepam, 2 to 4 mg IV, repeat every 15 to 20 minutes
Massive doses (>2000 mg diazepam in 48 hours) may be required
Clinically stable patients with minimal symptoms may be treated with oral medications
Barbiturates
Synergistic with benzodiazepines; give if patient refractory to high-dose benzodiazepines
Phenobarbital 130 to 260 mg IV, repeat every 15 to 20 minutes
Intubation frequently required with concurrent benzodiazepine and barbiturate use
ALL patients requiring barbiturates are monitored in an intensive care unit
Propofol
Excellent agent if patient refractory to benzodiazepines and barbiturates
Intubation almost always required
1 mg/kg IV push as induction agent for intubation; titrate continuous infusion for sedation
Supportive care
Ensure adequate fluid and provide electrolyte replacement as needed
Give parenteral thiamine* 100 to 200 mg and glucose daily
Give multivitamin containing or supplemented with folic acid
Ensure adequate caloric support
CSF: cerebrospinal fluid; CT: computed tomography; IV: intravenous.
* The thiamine dose range provided is for the prevention of Wernicke encephalopathy (WE).
Treatment of diagnosed WE requires higher doses. Refer to UpToDate topic discussing WE for details.
Organophosphate and carbamate poisoning: Rapid overview of emergency

management
To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222
for the nearest regional poison control center. Contact information for poison control centers around
the world is available at the WHO website and in the UpToDate topic on regional poison control centers
(society guideline links).
Clinical syndromes
Acute toxicity
Generally manifests in minutes to hours
Evidence of cholinergic excess
SLUDGE = Salivation, Lacrimation, Urination, Defecation, Gastric Emptying
BBB = Bradycardia, Bronchorrhea, Bronchospasm
Respiratory insufficiency can result from muscle weakness, decreased central drive, increased
secretions, and bronchospasm
Intermediate syndrome
Occurs 24-96 hours after exposure
Bulbar, respiratory, and proximal muscle weakness are prominent features
Generally resolves in 1-3 weeks
Organophosphorus Agent-Induced Delayed Peripheral Neuropathy (OPIDN)
Usually occurs several weeks after exposure
Primarily motor involvement
May resolve spontaneously, but can result in permanent neurologic dysfunction
Diagnostic evaluation of acute toxicity
Atropine challenge if diagnosis is in doubt (1 mg IV in adults, 0.01 to 0.02 mg/kg in children)
Absence of anticholinergic signs (tachycardia, mydriasis, decreased bowel sounds, dry skin)
strongly suggests poisoning with organophosphate or carbamate
Draw blood sample for measurement of RBC acetylcholinesterase activity to confirm diagnosis
Treatment of acute toxicity

Deliver 100% oxygen via facemask; early intubation often required; avoid succinylcholine
Decontamination if ingestion within 1 hour give single dose activated charcoal, adult 50 g (1 g/kg in
children) unless airway not protected or other contraindication. Aggressive dermal and ocular
irrigation as needed. Bag/discard clothing.
Atropine 2 to 5 mg IV/IM/IO bolus (0.05 mg/kg IV in children)
Escalate (double) dose every 3-5 minutes until bronchial secretions and wheezing stop
TACHYCARDIA AND MYDRIASIS ARE NOT CONTRAINDICATIONS TO ATROPINE USE
Hundreds of milligrams may be needed over several days in severe poisonings
Inhaled ipratropium 0.5 mg with parenteral atropine may be helpful for bronchospasm; may
repeat
Pralidoxime (2-PAM) 2 g (25 mg/kg in children) IV over 30 minutes; may repeat after 30 minutes or
give continuous infusion if severe
Continuous infusion at 8 mg/kg/hour in adults (10 mg/kg/hour in children)
If no IV access, give pralidoxime 600 mg IM (15 mg/kg in children <40 kg). Rapidly repeat as
needed to total of 1800 mg or 45 mg/kg in children.
Pralidoxime is given with atropine
Benzodiazepine therapy
Diazepam 10 mg IV (0.1 to 0.2 mg/kg in children), repeat as necessary if seizures occur. Do not
give phenytoin.
Opioid withdrawal in adults: Rapid overview of diagnosis and management
To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222,
or the nearest international regional poison center. Contact information for regional poison centers
around the world is available at Society guideline links: Regional poison control centers.
Clinical and laboratory features

Individuals with opioid use and tolerance typically experience withdrawal after administration of an
antagonist or within 4 to 48 hours of cessation of opioid use.
Withdrawal from cessation of an opioid agonist is not life-threatening, but withdrawal that is
untreated or undertreated places the patient at risk of overdose from self-treating with illicit opioids
Precipitated withdrawal (eg, administration of antagonist) is potentially life threatening.
Common signs and symptoms of opioid withdrawal include mydriasis, yawning, diaphoresis,
increased bowel sounds, and piloerection. Mental status is usually normal.
Other signs and symptoms can include dysphoria, restlessness, rhinorrhea, lacrimation, myalgias,
arthralgias, nausea, vomiting, abdominal cramping, diarrhea, tachycardia, and hypertension.
Patients may describe themselves as sick from not using opioids.
Diagnostic evaluation
Opioid withdrawal is a clinical diagnosis in a patient with a history of cessation of opioid use or
having received an opioid antagonist or partial agonist (eg, naloxone, buprenorphine).
Laboratory evaluation is helpful only to assess associated conditions (eg, serum electrolyte
concentrations in the setting of significant vomiting or diarrhea).
Treatment
If withdrawal is naturally occurring, the clinician may opt to manage the patient with either opioid o
non-opioid adjunctive medication. Whenever possible, we use a single class of medication for
treatment of acute withdrawal. Methadone or buprenorphine is a good choice.
We typically administer buprenorphine 8 mg SL for acute withdrawal. If symptoms persist 30 to 60

minutes after initial dose, a second and subsequent doses can be given up to 32 mg total in 24
hours, but higher doses are occasionally required.
Fluid resuscitation is given if needed due to losses. 250 to 500 mL intravenous boluses of isotonic
crystalloid may be repeated as needed.
Adjunctive medications* may include alpha-2 adrenergic agonists, benzodiazepines, antiemetics,

and antidiarrheals.
Clonidine is the first-line non-opioid medication for patients with normal or elevated blood
pressure. Administer clonidine 0.1 to 0.3 mg orally every hour (0.8 mg maximum total daily
dose) with close monitoring for hypotension.
Other useful medications may include:

For nausea and vomiting, ondansetron 4 mg IV or IM; 8 mg ODT or orally every 4 to 8 hours as
needed
For diarrhea, loperamide 4 mg orally or octreotide 50 mcg subcutaneously
For anxiety or dysphoria or muscle cramps, diazepam 5 to 10 mg orally, IV, or IM
In a patient who declines buprenorphine and is not taking methadone, 10 mg intramuscularly or 20

mg orally of methadone is usually sufficient to relieve symptoms of acute withdrawal without
producing intoxication.
For precipitated withdrawal (eg, from an opioid antagonist), buprenorphine and/or non-opioid
adjunctive medications are reasonable options. The buprenorphine dose should be tailored to the
agent and the dose that precipitated the withdrawal.
SL: sublingually; IV: intravenous; IM: intramuscular; ODT: orally disintegrating tablet.
* Additional information about adjunct therapy can be found in the UpToDate topic discussing
emergency management of acute opioid withdrawal and the accompanying table listing useful
medications.
Medications for management of acute opioid withdrawal in adults in the

emergency setting
Medication Initial dose (adult) Indication
Opioid
Methadone 10 mg IM or 20 mg orally (for patient Acute opioid withdrawal.*

not currently taking methadone) Not recommended for
May give an additional half-dose if management of acute withdrawal
significant withdrawal symptoms triggered by an opioid antagonist
persist 1 hour after IM dose or 2 (naloxone, naltrexone, nalmefene)
hours after oral dose; maximum in May prolong QTc interval; refer to
first 24 hours: 20 mg IM or 40 mg clinical topic for ECG screening
orally indications.
Buprenorphine Standard initiation (NOTE: Before Acute opioid withdrawal.*

beginning this regimen, patient needs Alternative low-dose initiation may
to have entered mild-moderate be preferred for treating
withdrawal generally with COWS score individuals who are not yet having
>8): starting dose is typically 8 mg signs of withdrawal, with high
sublingually ¶ ; if withdrawal persists levels of opioid dependence,
30 to 60 minutes later, can give cannot abstain from opioid use
additional 8 mg doses every 1 or more long enough to tolerate a standard
hours, up to 32 mg total in 24 hours, induction, or when transitioning
but higher doses are occasionally from methadone to
required buprenorphine.
or If used to manage acute
withdrawal triggered by an opioid
0.3 to 0.9 mg IV every 6 to 12 hours
antagonist (naloxone, naltrexone,
Alternative low-dose initiation nalmefene), the buprenorphine
"microdosing" (NOTE: Can begin dose should be tailored to the
without waiting for onset of agent and the dose that
withdrawal signs): 0.5 to 2 mg SL with precipitated the withdrawal.
frequent (eg, every 1 to 2 hours)
redosing ¶
Non-opioid adjunctive medications*
Clonidine 0.1 to 0.3 mg orally every hour with Anxiety, restlessness, dysphoria
monitoring of blood pressure and with elevated or normal blood
heart rate (0.8 mg maximum total pressure and heart rate.
daily dose); check blood pressure
prior to each dose and hold the dose
if hypotension is present
Lofexidine 0.54 mg orally every 5 to 6 hours as

needed; maximum 2.88 mg/24 hours
Diazepam 5 to 10 mg orally or IV; may repeat Hypertension and tachycardia

after 5 to 10 minutes until symptoms precipitated by long-acting
subside antagonist (eg, naltrexone,
Alternative benzodiazepines if nalmefene).
diazepam not available: Anxiety, restlessness, dysphoria,
Lorazepam 1 to 2 mg IV may be insomnia, muscle cramping.
given every 10 minutes until
symptoms subside
Midazolam 2 mg IV may be given
every 5 to 10 minutes until
symptoms subside
Hold doses if patient does not remain

hemodynamically stable
Ondansetron 4 to 8 mg IV or IM; 8 mg ODT or orally; Nausea, vomiting.

every 4 to 8 hours as needed
Diphenhydramine 50 mg IV, IM, or orally every 6 hours

as needed
Hydroxyzine 50 to 100 mg IM or orally every 6

hours as needed
Loperamide 4 mg orally, followed by 2 mg every Diarrhea, stomach cramps.

loose stool; maximum: 16 mg/24
hours
Octreotide 50 micrograms SUBQ every 6 hours as

needed
Bismuth 524 mg orally every 30 to 60 minutes

subsalicylate as needed; maximum 4200 mg/24
hours
Acetaminophen 650 to 1000 mg orally every 4 to 6 Pain, myalgia.

hours as needed; maximum 4000
mg/24 hours
Ibuprofen 600 mg orally every 6 to 8 hours as

needed; maximum 2400 mg/24 hours
Baclofen 5 to 10 mg orally up to three times per Muscle cramping.

day
For additional information on managing symptoms of withdrawal in patients cared for in a non-
emergency setting, refer to the UpToDate topics discussing treatment of opioid use disorder. The
approach to treatment of iatrogenic withdrawal (eg, weaning from prolonged opioid infusions) is
reviewed separately; refer to UpToDate topic reviews of opioid withdrawal in critically ill patients.
IM: intramuscular; ECG: electrocardiogram; COWS: Clinical Opiate Withdrawal Scale; IV: intravenous;
SUBQ: subcutaneous; SL: sublingual; ODT: orally disintegrating tablet.
* Opioids are generally more effective than non-opioid adjunctive medications and should be offered
to patients with opioid withdrawal. Refer to UpToDate topics on opioid withdrawal in adults.
¶ Buprenorphine buccal film has greater bioavailability compared with sublingual tablets and film.
450 mcg buccal buprenorphine ≈ 1 mg SL buprenorphine.

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21/2/24, 19:53 Opioid withdrawal in adolescents - UpToDate

Official reprint from UpToDate®

Opioid withdrawal in adolescents

Literature review current through: Jan 2024.

The epidemiology, pharmacology, clinical manifestations, and management of opioid

● (See "Prenatal substance exposure and neonatal abstinence syndrome (NAS):

● (See "Substance use disorder in adolescents: Treatment overview".)

Opioid abuse and addiction is a serious problem among adolescents. As an example,

Approximately 8 percent of children between the ages of 14 to 20 surveyed at a university

● A 2007 survey of 2914 Canadian students aged 12 to 19 showed that approximately 20

● A 2010 nationwide survey of students in England aged 11 to 15 showed approximately

Tolerance is defined as a decrease of an individual’s response to given drug as the drug is

SYMPTOMS OF OPIOID WITHDRAWAL

The discontinuation of opioids leads to a constellation of withdrawal symptoms known as the

● 8 to 14 hours – Anxiety, restlessness, insomnia, yawning, rhinorrhea, lacrimation,

● One to three days – Tremor, muscle spasms, vomiting, diarrhea, hypertension,

CLINICAL FEATURES AND DIAGNOSIS

Patients experiencing opioid withdrawal may complain of the following:

• Dysphoria and restlessness

● Physical examination — Opioid withdrawal is characterized by mydriasis (pupillary

Opioid withdrawal may appear similar to other withdrawal or intoxication syndromes.

Sedative-hypnotic withdrawal — Similar to ethanol withdrawal, patients with sedative-

Sympathomimetic intoxication — Cocaine, amphetamine, or other sympathomimetic

Cholinergic poisoning — Poisoning with cholinergic agents (eg, organophosphates or

A rapid overview for the treatment of organophosphate and carbamate poisoning is

ACUTE MANAGEMENT OF OPIOID WITHDRAWAL

Approach — The approach to managing acute opioid withdrawal in adolescents is generally

Methadone is a reasonable alternative if buprenorphine is unavailable or unfamiliar.

Buprenorphine — Buprenorphine, a partial opioid agonist, is also effective for treatment of

Methadone — Methadone, a long-acting opioid with a half-life of 24 to 36 hours, is the

Clonidine — Clonidine may be used as an alternative to methadone or buprenorphine

Rapid detoxification — Ultrarapid opioid detoxification has been extensively promoted as a

MEDICALLY SUPERVISED DETOXIFICATION

Opioid detoxification of pregnant adolescents is discussed separately. (See "Opioid use

SOCIETY GUIDELINE LINKS

SUMMARY AND RECOMMENDATIONS

• The discontinuation of opioids leads to a constellation of withdrawal symptoms

• Opioid withdrawal can be distinguished from other withdrawal or intoxication

• The approach to managing acute opioid withdrawal in adolescents is generally

Use of UpToDate is subject to the Terms of Use.

3. Fortuna RJ, Robbins BW, Caiola E, et al. Prescribing of controlled medications to

13. Minozzi S, Amato L, Davoli M. Detoxification treatments for opiate dependent

Stages of opioid withdrawal syndrome

Stage I: Up to 8 Fear of withdrawal, anxiety, drug craving

* Only seen in neonates.

Graphic 78321 Version 4.0

Clinical features of opioid withdrawal

Blood pressure increased or unchanged; decreased if hypovolemic

Heart rate increased or unchanged

Respiratory rate increased or unchanged

Diarrhea, increased bowel sounds

Mental status usually normal, irritable

Seizures (neonates only)

Graphic 81045 Version 6.0

Moderate and severe alcohol withdrawal: Rapid overview of emergency

Alcoholic hallucinosis – occurs early; no evidence of autonomic instability

Delirium tremens – occurs late; characterized by delirium and autonomic instability