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    Opioid Withdrawal

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    Mar.20.2023

    Opioid Withdrawal

    Synopsis

    Key Points

    • Opioid withdrawal is a constellation of physical and psychological symptoms that occurs after abrupt cessation of (or significant dosage reduction of) opioids or after administration of an opioid antagonist
    • Patients with and without opioid use disorder can experience opioid withdrawal. Evaluate whether the patient has opioid dependence alone (without opioid use disorder) or with opioid use disorder (using DSM-5 criteria)
    • Treating opioid withdrawal is an opportunity to initiate long-term medications for opioid use disorder (eg, methadone, buprenorphine, naltrexone)
    • Elicit patient goals and use shared decision-making when counseling patients about medications for opioid use disorder
    • Treat most patients experiencing opioid withdrawal with opioid agonists (methadone or buprenorphine). Treat patients who wish to start naltrexone (an opioid antagonist) with nonopioid adjunctive medications
    • Use validated clinical scales (eg, Clinical Opiate Withdrawal Scale) to establish the severity of withdrawal and response to treatment
    • Any provider licensed to dispense controlled substances can dispense (but not prescribe) methadone and buprenorphine to treat opioid withdrawal and/or opioid use disorder in emergency departments, hospitals, and clinics
    • Provide harm reduction counseling and services to all patients after treating opioid withdrawal

    Pitfalls

    • Administering nonopioid adjunctive medications alone to treat opioid withdrawal is not the standard of care and is not appropriate treatment of opioid use disorder
    • Monitor patient withdrawal symptoms closely with a validated scale (such as Clinical Opiate Withdrawal Scale) while titrating methadone or buprenorphine
    • Explore patient goals and opioid use disorder treatment history when counseling about medications for opioid use disorder
    • Avoid stigmatizing language and be aware of biases against patients with opioid use disorder (as well as biases against treatments)
    • If a patient declines long-term medications for opioid use disorder treatment, counsel about the risks of untreated opioid use disorder and provide harm reduction counseling and services

    Terminology

    Clinical Clarification

    • Opioid withdrawal is a constellation of symptoms that occurs after abrupt cessation, therapeutic discontinuation, or dosage reduction of opioids (ie, μ-receptor agonists), or after administration of an opioid antagonist (naltrexone or naloxone) or in some cases partial opioid agonist (buprenorphine) to a person who is physically dependent on opioids as a result of persistent, regular use
    • Acute withdrawal symptoms may develop upon abrupt discontinuation of opioids after as few as 5 days of regular and uninterrupted opioid use r1
    • For short-acting opioids (eg, heroin, fentanyl, morphine immediate-release, oxycodone immediate-release), acute withdrawal symptoms usually begin within 12 hours after the last dose, peak in 24 to 48 hours, and diminish over the next 3 to 5 days r2r3
      • Illicitly manufactured fentanyl has contaminated the heroin supply throughout the United States r4
      • The pharmacokinetics of illicitly manufactured fentanyl have not been formally studied; however, fentanyl is highly lipophilic, and data suggest that regular fentanyl use may lead to protracted clearance and prolonged opioid effects r5r6
    • For longer-acting opioids (eg, methadone) or opioid formulations (eg, oxycodone extended-release, morphine extended-release), acute symptoms usually occur within 30 to 72 hours after last dose (although anxiety may occur before this) and resolve over the next 10 days r2r3
    • Among people who are opioid-dependent, antagonist-precipitated withdrawal can begin within 1 minute of an IV-administered dose of naloxone and last 30 to 60 minutes. Buprenorphine-induced withdrawal may occur if typical doses of buprenorphine are taken before the patient experiences mild to moderate opioid withdrawal symptoms. Withdrawal symptoms will occur within 90 minutes of sublingual buprenorphine dosage and may last for several days r2
    • Subacute symptoms of opioid withdrawal (eg, protracted abstinence syndrome, postacute withdrawal syndrome) follow the acute withdrawal period and may persist for weeks

    Classification

    • Spontaneous withdrawal follows abrupt cessation of or dramatic reduction in opioid use
    • Precipitated withdrawal follows administration of an antagonist (eg, naloxone, naltrexone) or in some cases a partial opioid agonist (eg, buprenorphine) to a patient who is physically dependent; symptoms may be more severe than those experienced during spontaneous withdrawal but are shorter lived
      • Symptoms caused by use of an antagonist are likely to be more severe than those induced by a partial opioid agonist

    Diagnosis

    Clinical Presentation

    History

    • Acute symptoms of opioid withdrawal are highly variable and may include some or all of the following:
      • Myalgia and arthralgia c1c2
      • Hyperalgesia c3
      • Gastrointestinal symptoms (eg, stomach cramping, nausea, loose stools) c4c5c6
      • Anxiety c7
      • Dysphoria c8
      • Irritability c9
      • Insomnia c10
      • Hot or cold flashes c11c12
      • Poor concentration c13
    • Subacute symptoms of opioid withdrawal (eg, postacute withdrawal syndrome, protracted abstinence syndrome) include:
      • Depression c14
      • Anhedonia c15
      • Insomnia c16
      • Fatigue c17
      • Anorexia c18
      • Impaired concentration c19
      • Sleep disturbances c20

    Physical examination

    • Signs of opioid withdrawal include:
      • Tachycardia c21
      • Hypertension c22
      • Diaphoresis c23
      • Rhinorrhea c24
      • Oscitation (ie, yawning) c25
      • Lacrimation c26
      • Muscle twitching c27
      • Restlessness c28
      • Vomiting c29
      • Diarrhea c30
      • Piloerection (ie, gooseflesh) c31
      • Tremor c32
      • Mydriasis c33

    Causes and Risk Factors

    Causes

    • Abrupt cessation of or dramatic reduction in opioid use among people physically dependent on opioids
    • Administration of an antagonist (eg, naloxone, naltrexone) or in some cases a partial opioid agonist (eg, buprenorphine) to a patient who is physically dependent

    Risk factors and/or associations r7

    Genetics
    • Some evidence supports a genetic component to severity of withdrawal, particularly involving OPRM1, a gene that encodes the μ-opioid receptor r8
      • Presence of the allele OPRM1 rs6848893 has been associated with worse withdrawal, especially abstinence-induced withdrawal c34
      • Presence of the allele OPRM1 rs6473797 has been associated with worse antagonist-induced withdrawal c35
    Other risk factors/associations
    • Environmental
      • Sudden cessation of opioid use during: hospitalization, incarceration, lack of access to opioids (prescribed or nonprescribed)
    • Drug-drug interactions
      • CYP450 inducers can cause reductions in methadone levels leading to withdrawal symptoms. Commonly prescribed CYP450 inducers include: r7
        • Various antimicrobials (eg, rifampin, azole class drugs)
        • Some HIV antiretrovirals (eg, efavirenz)
        • Antidepressants (eg, fluvoxamine)
        • Anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin)
        • Spironolactone
    • Pregnancy: owing to increased metabolic demands and volume expansion, a patient's usual dose of methadone may be insufficient, leading to opioid withdrawal r7c36
    • Opioid overdose followed by administration of naloxone (by a layperson, by an emergency medical technician, in an urgent care center, or in the emergency department or hospital)

    Diagnostic Procedures

    Primary diagnostic tools

    • Diagnosed through focused history and physical examination findings suggesting physical dependence on opioids, namely, repetitive exposure to opioids and uncomfortable and distressing symptoms upon interruption or reduction of opioid use or upon consumption of an opioid antagonist r9c37
    • Check the Prescription Drug Monitoring Program in your and surrounding states for controlled substances
    • Drug screening (eg, urine drug screen) can identify or confirm opioid use; however, screening does not confirm physical dependence or opioid use disorder c38
      • Use caution when interpreting urine drug screens, as 1 dose could cause a positive test result; patient history, clinician observation of withdrawal signs, or both are required to confirm physical dependence on opioids
      • Some commonly used opioids (eg, fentanyl, buprenorphine, methadone, oxycodone, tramadol), may not be detected on typical drug screens and may require specific testing r10
    • Test all patients of childbearing age for pregnancy r11c39
    • Validated withdrawal scoring systems may be used to help identify and determine the severity of opioid withdrawal: Opiate Withdrawal Scale, Clinical Opioid Withdrawal Scale, Subjective Opiate Withdrawal Scale, and Objective Opiate Withdrawal Scale r2
      • Monitor opioid withdrawal symptoms frequently (eg, every 2 hours) in patients who are at risk for opioid withdrawal and/or exhibiting opioid withdrawal symptoms

    Other diagnostic tools

    • Clinical Opiate Withdrawal Scale r12c40
      • Each item is scored for severity, and scores are totaled to reflect overall severity of the withdrawal syndrome:
        • Severe: higher than 36
        • Moderately severe: 25 to 36
        • Moderate: 13 to 24
        • Mild: 5 to 12
      • COWS: Clinical Opiate Withdrawal Scale.Score: 5-12, mild; 13-24, moderate; 25-36, moderately severe; more than 36, severe withdrawal.
        ScoreCriteria
        Resting pulse rate in beats per minute (after sitting or lying for 1 minute)
        0Pulse rate 80 or below
        1Pulse rate 81-100
        2Pulse rate 101-120
        4Pulse rate greater than 120
        Sweating (over previous 30 minutes, not accounted for by room temperature or patient activity)
        0No report of chills or flushing
        1Subjective report of chills or flushing
        2Flushed or observable moistness on face
        3Beads of sweat on brow or face
        4Sweat streaming off face
        Restlessness (observation during assessment)
        0Able to sit still
        1Reports difficulty sitting still but is able to do so
        3Frequent shifting or extraneous movements of legs/arms
        5Unable to sit still for more than a few seconds
        Pupil size
        0Pin size or normal size for room light
        1Possibly larger than normal for room light
        2Moderately dilated
        5So dilated that only rim of iris is visible
        Bone or joint aches (if patients was having pain previously, only the additional component attributed to opiates withdrawal is scored)
        0Not present
        1Mild diffuse discomfort
        2Patient reports severe diffuse aching of joints and muscles
        4Patient is rubbing joints or muscles and is unable to sit still owing to discomfort
        Runny nose or tearing (not accounted for by cold symptoms or allergies)
        0Not present
        1Nasal stuffiness or unusually moist eyes
        2Nose running or tearing present
        4Nose constantly running or tears streaming down cheeks
        Gastrointestinal upset (over the past 30 minutes)
        0No gastrointestinal symptoms
        1Stomach cramps
        2Nausea or loose stool
        3Vomiting or diarrhea
        5Multiple episodes of diarrhea or vomiting
        Tremor (observation of outstretched hands)
        0No tremor
        1Tremor felt by examiner but not observed
        2Slight observable tremor
        4Gross tremor or muscle twitching
        Yawning (observation during assessment)
        0No yawning
        1Yawning 1 or 2 times during assessment (approximately 2 minutes)
        2Yawning 3 or more times during assessment
        4Yawning several times per minute
        Anxiety or irritability
        0None
        1Reports increasing irritability or anxiousness
        2Obviously irritable or anxious
        4Participation in assessment is difficult due to irritability or anxiety
        Gooseflesh skin (piloerection)
        0Skin is smooth
        3Piloerection of skin can be felt or hairs standing up on arms
        5Prominent piloerection

    Differential Diagnosis

    Most common

    • Benzodiazepine or alcohol withdrawal c41d1
      • Early benzodiazepine or alcohol withdrawal symptoms are similar to opioid withdrawal: agitation, anxiety, increased vital signs, tremors, and gastrointestinal distress
        • As withdrawal develops further, symptoms of untreated or undertreated benzodiazepine or alcohol withdrawal are more severe and may be life-threatening (eg, seizures, cardiovascular instability and collapse, coma) compared with opioid withdrawal
      • History of sustained benzodiazepine or alcohol use, urine drug screening that supports benzodiazepine or alcohol use, or both helps to differentiate from opioid withdrawal; additionally, benzodiazepines will suppress benzodiazepine or alcohol withdrawal, whereas opioids will not
        • Do not use a single positive urine drug screen alone to support the diagnosis of benzodiazepine or alcohol (or other drug) withdrawal, because a screen could be positive after single use of a substance
    • Anxiety disorder c42
      • Co-occurring opioid use disorder and anxiety are common r13
      • Features similar to opioid withdrawal are present during a panic attack: physical signs and symptoms of anxiety (eg, sweating, palpitations, dizziness, tachycardia)
      • Differentiated from opioid withdrawal by relatively fast resolution of symptoms of panic, reaching a peak within minutes of onset
      • In most situations, urine drug screen will not show opioids
    • Gastroenteritis c43d2
      • Has features similar to opioid withdrawal: nausea and vomiting, diarrhea, and abdominal discomfort
      • Is differentiated by history of exposure to someone with similar symptoms and difference in clinical course
      • Urine drug screen for opioids typically yields a negative result in patients with gastroenteritis
      • Stool studies may be diagnostic, particularly if gastroenteritis is due to bacterial infection
    • Viral illness c44
      • Symptoms may overlap with those of opioid withdrawal (eg, rhinorrhea, myalgia and arthralgias, gastrointestinal symptoms)
      • Distinguishing features include fever and history of sick contacts
      • Urine drug screen for opioids typically yields a negative result in patients with influenza
    • Systemic infection c45d3
      • Generalized symptoms and signs are similar to those of opioid withdrawal: anxiety, chills, nausea, vomiting, tachycardia, agitation, and diaphoresis
      • Differentiated by findings of end-organ dysfunction (eg, acute renal dysfunction, delirium) and cardiovascular instability (eg, hypotension) with an infection source (eg, pneumonia, urinary tract) in septic patients

    Treatment

    Goals

    • Medical stabilization and management of opioid withdrawal
    • Treat most patients who have opioid use disorder with opioid agonist medications for opioid use disorder (ie, methadone or buprenorphine)
    • Transition patients with opioid use disorder into long-term medications for opioid use disorder treatment according to patient goals
    • Provide harm reduction counseling and services to all patients after treating opioid withdrawal

    Disposition

    Admission criteria

    • Patients presenting with opioid withdrawal should generally be treated in the setting where they present, depending on their goals
    • Opioid withdrawal does not necessarily require inpatient or medically supervised management; however, many patients benefit from inpatient or medically supervised residential treatment where methadone or buprenorphine can be quickly initiated and titrated to response; patients can then be linked to long-term medications for opioid use disorder treatment
    • Inpatient or medically supervised management is also appropriate for patients with medical comorbidities that may require management, and for patients with severe withdrawal symptoms r14
    • In the absence of comparative effectiveness data on withdrawal management in outpatient versus inpatient settings, the factors of patient preference, comorbidities, and social circumstances, along with resource availability, should drive decisions about setting r2

    Recommendations for specialist referral

    • Refer to an addiction medicine physician, addiction psychiatrist, or medical toxicologist with addiction experience for evaluation, treatment recommendation, and ongoing management; look for subspecialty board certification in addiction medicine or addiction psychiatry when choosing a referral
      • Properly trained clinicians (eg, licensed alcohol/drug counselors, social workers) can assess patient and recommend appropriate level and location of care after withdrawal is completed or after patient has started taking methadone or buprenorphine

    Treatment Options

    The standard of care for treating opioid withdrawal is initiating medication for opioid use disorder with opioid agonist medications such as buprenorphine. Methadone or buprenorphine can be initiated to treat withdrawal symptoms only (started then tapered) or for ongoing opioid use disorder treatment (started then titrated to treat withdrawal symptoms and cravings)

    • Long-term medications for opioid use disorder reduces opioid use, risky opioid use (ie, injection), morbidity and mortality, and transmission of infectious diseases (eg, HIV, hepatitis C virus) r15r16r17r18r19
    • Initiating medications for opioid use disorder in the acute care setting:
      • Leads to increased engagement with outpatient medications for opioid use disorder treatment r20r21r22
      • Allows the patient to be comfortable enough to stay in the hospital to receive necessary medical treatment
      • Improves overall patient and staff experience r23
    • Managing opioid withdrawal only in the short term and without opioid agonist medications for opioid use disorder is not considered a treatment strategy for the patient with opioid use disorder and is not recommended r2

    History of present illness, earlier history, and shared decision-making

    • Take a detailed history of the patient's current opioid use and evaluate for opioid use disorder using DSM-5 criteria (history includes type of opioid and amounts used, frequency and route of administration, treatment history, and problems related to their use)
      • Medications for opioid use disorder are approved for patients with moderate-severe opioid use disorder by DSM-5 criteria r24
      • Iatrogenic physical dependence after prolonged controlled use of opioids in inpatient or outpatient settings can generally be managed by gradual opioid taper
    • Elicit patient goals regarding opioid use and opioid use disorder treatment (goals for abstinence versus reduction in use, interest in medications for opioid use disorder) and explore prior treatment experiences r25
    • Counsel patients on medication options for treating opioid use disorder. Know which medications for opioid use disorder are available locally
    • Be aware of stigma and bias
      • Preferred language includes: r26
        • "person with opioid use disorder" (instead of "addict or abuser")
        • "using opioids or abstaining from opioids" (instead of "dirty or clean")
      • Consider your own possible biases. Stigma toward substance use disorders is common among clinicians r27
      • Stigma toward opioid use disorder and medications for opioid use disorder is common among patients. Explore your patient's attitudes toward medications for opioid use disorder and be prepared to counter myths about opioid use disorder: r28r29r30
        • "Medications are just replacing one addiction with another"
        • "Methadone eats your bones"
        • "Being on medication isn't really being 'clean'"
      • "Meet patients where they're at"
        • Not all patients are ready to stop using opioids or other substances
          • Medication for opioid use disorder is beneficial even when patients don't abstain from all nonprescribed opioids
      • Counsel on benefits of medications for opioid use disorder and risks of untreated opioid use disorder, but accept your patient's decision if they decline medications for opioid use disorder

    Medications for opioid use disorder: selection and initiation

    • An overarching approach to withdrawal management with medications for opioid use disorder is presented in the accompanying Figure
    • Selection considerations and initial dosing for opioid agonist medications for opioid use disorder, methadone and buprenorphine, are laid out in the accompanying Table on opioid agonists. Use shared decision-making with the patient to guide selection
      • Opioid agonist medications for opioid withdrawal.QTc = QT corrected for heart rate.Data from many references, including the following: Torres-Lockhart KE et al: Clinical management of opioid withdrawal. Addiction. 117(9):2540-50, 2022; American Society of Addiction Medicine: The ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. ASAM website. Published June 1, 2015. Accessed April 27, 2021. https://www.asam.org/resources/guidelines-and-consensus-documents/npg; Substance Abuse and Mental Health Services Administration: Buprenorphine Practitioner Locator. SAMHSA website. Accessed October 21, 2022. https://www.samhsa.gov/medication-assisted-treatment/physician-program-data/treatment-physician-locator; Substance Abuse and Mental Health Services Administration: Medication-Assisted Treatment for Substance Use Disorders: Opioid Treatment Program Directory. SAMHSA website. Accessed October 21, 2022. https://dpt2.samhsa.gov/treatment/directory.aspx; Ajazi EM et al: Revisiting the X:BOT naltrexone clinical trial using a comprehensive survival analysis. J Addict Med. 16(4):440-6, 2022; World Health Organization (WHO): Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings. WHO website. Published 2009. Accessed October 18, 2022. https://apps.who.int/iris/bitstream/handle/10665/207032/9789290614302_eng.pdf?sequence=1&isAllowed=y.
        MedicationClassPreferred routeSelection considerationsDosing
        MethadoneFull opioid agonistOral• Outpatient treatment requires daily OTP attendance (opioid treatment program) for first 3 months
        • Can be dosed 2 or 3 times daily to help with pain management for
        hospitalized patient and will not block other opioid pain medications
        • Avoid if history of QTc more than 500 milliseconds or of torsades de pointes
        • Initial dose: 20-30 mg (10 mg if low opioid tolerance, risk of sedation)
        • Add 5-10 mg every 4-6 hours as needed
        • Recommended maximum day 1 dose: 40 mg
        • If dispensed for withdrawal management only, avoid exceeding 40 mg, then taper by 5-10 mg every 1-2 days as tolerated by the patient
        • If continuing treatment, increase by 5-10 mg every 3-5 days. Steady state may
        take 5 days to reach due to methadone's long half life
        Buprenorphine (mono-product,
        or co-formulated with naloxone, which is not absorbed when taken sublingually)
        Partial opioid agonistSublingual• Outpatient treatment typically in office-based setting. Prescriptions are generally for 1 week to 1 month in duration
        • Not ideal for patients who require full opioid agonists for chronic pain or who will experience severe, acute pain in the acute care setting
        • Initial dose: 2-4 mg when patient is experiencing moderate opioid withdrawal
        • Add 2-4 mg every 1-2 hours as needed
        • Typical day 1 dose: 8-16 mg
        • Maximum daily dose: 32 mg
        • If provided for withdrawal management alone, avoid exceeding 16 mg then taper gradually by 2 mg every 2-3 days as tolerated by the patient
        • If prescribing, counsel to store safely out of reach of children
    • Both methadone and buprenorphine are safe and effective treatments for opioid use disorder and opioid withdrawal
    • Methadone, a full opioid agonist with a long half-life, must be titrated more slowly than buprenorphine to avoid risk for opioid overdose
    • Buprenorphine is a partial opioid agonist with high affinity for the μ-opioid receptor. Buprenorphine's opioid effect plateaus with increased doses, referred to as the ceiling effect (ie, higher doses having no further effect), with less risk of overdose and lower bioavailability than methadone r31
      • Buprenorphine can displace full agonist opioids from the opioid receptor, which can lead to precipitated withdrawal. To prevent precipitated withdrawal, patients should be in moderate opioid withdrawal before receiving the first dose of buprenorphine
      • Low-dose buprenorphine initiation is an emerging practice that does not require patients to experience moderate withdrawal before receiving the first dose of buprenorphine
        • Small doses of buprenorphine are administered (or prescribed) while patients are still receiving (or using) full opioid agonists r25
        • There is currently no strong evidence to support using low-dose buprenorphine initiation over traditional initiation procedures r25
      • Treat patients who experience precipitated withdrawal during buprenorphine initiation with additional buprenorphine to saturate opioid receptors and minimize severe withdrawal symptoms as quickly as possible. Administer nonopioid adjunctive treatments r32
    • There is growing expert consensus that with the increasing prevalence of highly potent fentanyl in heroin, patients have higher opioid tolerance. Higher tolerance may lead to patients experiencing prolonged withdrawal symptoms when starting methadone or buprenorphine
      • While more data are required to establish best practices, patients who regularly use fentanyl may benefit from more rapid titration of methadone and buprenorphine r33
    • Naltrexone: An opioid antagonist administered as a monthly depot injection for moderate to severe opioid use disorder r34
      • Naltrexone does not treat opioid withdrawal
      • Mechanism of action is by blocking opioid receptors to prevent euphoria with opioid use and by affecting the dopaminergic system to reduce opioid cravings r34
      • Naltrexone does not have as robust an evidence-base as methadone and buprenorphine. Methadone and buprenorphine will be preferable to naltrexone for most patients r35r36r37r38
      • Naltrexone can be initiated 7 to 10 days after last opioid use among patients who are opioid dependent. Initiating before then may cause precipitated withdrawal r34
        • A low-dose naltrexone or naloxone challenge can be given to ensure no precipitation of withdrawal symptoms, before administration of the intramuscular injection
      • Manage opioid withdrawal in patients who wish to start naltrexone, to reduce time to starting naltrexone
        • Use nonopioid adjunctive medications
        • If patients have severe withdrawal symptoms, consider starting a short-acting opioid agonist taper and initiate naltrexone 7 to 10 days after the taper is complete
          • Nonopioid medications for opioid withdrawal management.*Availability varies by country.Data from many references, including the following: Torres-Lockhart KE et al: Clinical management of opioid withdrawal. Addiction. 117(9):2540-50, 2022; Substance Abuse and Mental Health Services Administration (SAMHSA): Detoxification and Substance Abuse Treatment. SAMHSA website. Published October 2015. Accessed November 2, 2022. https://store.samhsa.gov/sites/default/files/d7/priv/sma15-4131.pdf; National Institute for Health and Care Excellence: Drug Misuse in Over 16s: Opioid Detoxification. Clinical guideline CG52. NICE website. Published July 25, 2007. Accessed November 2, 2022. https://www.nice.org.uk/guidance/cg52; British Columbia Centre on Substance Use: A Guideline for the Clinical Management of Opioid Use Disorder. BCCSU website. Published June 5, 2017. Accessed November 2, 2022; Kampman K, Jarvis M: American Society of Addiction Medicine (ASAM) National Practice Guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med. 9(5):358–67.; Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder: For Healthcare and Addiction Professionals, Policymakers, Patients, and Families. 2018.
            Symptom(s) targetedMedicationClassPreferred routeDoseComments
            Autonomic hyperactivityClonidineAlpha-2 agonist
            Oral
            0.1-0.3 mg up to every 4 to 8 hours• Monitor blood pressure and heart rate after initial dose and before uptitration
            Autonomic hyperactivityLofexidine*Alpha-2 agonistOral0.54 mg up to four times daily• Monitor blood pressure and heart rate after initial dose and before uptitration
            • Lofexidine is FDA approved for opioid withdrawal management; clonidine is not
            • Lofexidine is very costly
            DiarrheaLoperamidePeripheral mu opioid agonistOral4
            mg followed by 2 mg as needed for loose stools
            • Maximum daily dose is 16 mg
            • Ensure adequate oral hydration
            InsomniaTrazodoneSedating antidepressantOral25-100 mg nightly
            InsomniaDoxepinSedating antidepressantOral10-50 mg nightly
            Muscle aches, joint pain, headacheIbuprofen
            Nonsteroidal antiinflammatory
            Oral
            400-600 mg up to every 6 hours
            • Avoid use in severe kidney disease and decompensated cirrhosis
            • Use with caution in liver disease
            Muscle aches, joint pain, headacheAcetaminophenAniline analgesicOral650-1000 mg up to every 6 hours• Avoid use in severe kidney disease and decompensated cirrhosis
            • Use with caution in liver disease
            Anxiety, restlessnessDiphenhydramineAntihistamineOral25-50 mg up to every 4 hours• Can help with
            nausea
            • Can be used in pregnancy
            • Can help with
            lacrimation and rhinorrhea

            Anxiety, restlessnessHydroxyzineAntihistamineOral25-100 mg up to every 6 hours• Can help with nausea
            • Can be used in pregnancy
            • Can help with lacrimation and rhinorrhea

    Regulations on prescribing and/or dispensing medications for opioid use disorder for opioid withdrawal:

    • For patients without opioid use disorder, there are no regulations on inpatient methadone or buprenorphine dispensing
    • For patients with opioid use disorder, methadone or buprenorphine can be prescribed or dispensed in most clinical settings by most providers, according to the following regulations:
      • Methadone or buprenorphine
        • For patients in emergency departments, hospitals, or clinics, any provider licensed to dispense controlled substances can dispense (but not prescribe) methadone or buprenorphine for:
          • An unlimited time as an adjunct to the management of conditions other than the opioid dependency (eg, myocardial infarction, surgical management) so that opioid withdrawal does not complicate a primary medical problem. This is most relevant to the acute care setting r39
          • A maximum of 72 hours while arranging referral for ongoing treatment, if the patient is only being treated for opioid use disorder and opioid withdrawal (and not a primary medical problem) r40
        • If the patient is enrolled in outpatient medication for opioid use disorder treatment, contact the program, refer to the state Prescription Drug Monitoring Program, or both to confirm the patient's dosage
      • Methadone
        • Methadone can be provided as long-term opioid use disorder treatment or opioid withdrawal management in federally approved opioid treatment programs. A complete listing of US opioid treatment programs that dispense methadone is available on the website of SAMHSA (Substance Abuse and Mental Health Services Administration)r41
      • Buprenorphine
        • Per SAMHSA, "All practitioners who have a current DEA registration [with Drug Enforcement Administration] that includes Schedule III authority, may now prescribe buprenorphine for Opioid Use Disorder in their practice if permitted by applicable state law, and SAMHSA encourages them to do so"; the former X-waiver requirement was ended by newer legislation r9r42
        • Listing of US buprenorphine providers by state is available on the website of SAMHSAr43

    Nonopioid adjunctive treatments for opioid withdrawal:

    • Nonopioid adjunctive treatments are useful while initiating methadone or buprenorphine, but they do not replace appropriate and timely initiation and titration of methadone or buprenorphine
    • α-Adrenergic agents may be used to mitigate autonomic withdrawal symptoms
    • Adjunctive treatments are also useful in treating precipitated withdrawal

    Drug therapy

    • Full opioid agonist r2
      • If this medication is provided for outpatient management, patient must ensure that medication is kept in a secure location that children cannot access
      • Buprenorphine r2r31c46
        • Buprenorphine Hydrochloride Sublingual tablet; Adults: 2 to 4 mg SL as needed to achieve clinical effectiveness as rapidly as possible, then titrate dose by 2 to 4 mg to a level that holds the person in treatment and suppresses opioid withdrawal signs and symptoms. Target maintenance dose: 16 mg SL once daily. Usual dose range: 4 to 24 mg/day. Max: 32 mg/day.
        • Outpatient treatment typically in office-based setting with certified provider. Prescriptions are generally for 1 week to 1 month in duration
        • Not ideal for patients who require full opioid agonists for chronic pain or who will experience severe acute pain in the acute care setting
        • Long-acting injectable buprenorphine is an emerging treatment for opioid use disorder. It is not a preferred medication for treating opioid withdrawal at this time r44r45r46
      • Methadone r47c47
        • Short-term detoxification
          • Methadone Hydrochloride Oral tablet; Adults: Up to 40 mg/day in divided doses to achieve an adequate stabilizing level. After 2 to 3 days, decrease dose by 20% every 1 to 2 days in hospitalized persons as tolerated; ambulatory persons may need a slower taper.
        • Routine detoxification
          • Methadone Hydrochloride Oral tablet; Adults: 20 to 30 mg PO once, initially; may administer an additional 5 to 10 mg after 2 to 4 hours if withdrawal symptoms have not been suppressed or if symptoms reappear, up to 40 mg/day on day 1. Use lower initial doses for persons whose tolerance is expected to be low at treatment entry. Adjust the dose over the first week of treatment based on control of withdrawal symptoms at 2 to 4 hours after dosing. Subsequently, titrate dose to a level that prevents opioid withdrawal symptoms for 24 hours, reduces drug hunger or craving, and blocks or attenuates the euphoric effects of self-administered opioids, ensuring tolerance to sedative effects. Usual dose range: 80 to 120 mg/day. During medically supervised withdrawal from methadone treatment, decrease dose by 10% every 10 to 14 days.
        • Outpatient treatment requires daily opioid treatment program attendance for first 3 months
          • Dose can be divided into 2 or 3 times daily dosing, to help with pain management for hospitalized patients; this medication will not block other opioid pain medications
          • Avoid if history of QTc more than 500 milliseconds or of torsades de pointes
    • α₂-Adrenergic agonists r2
      • Clonidine (off-label) c48
        • Clonidine Hydrochloride Oral tablet; Adults: 0.1 to 0.2 mg PO every 4 to 6 hours, initially, as needed or as a standing dose in cases of severe withdrawal. Adjust dose until withdrawal symptoms are reduced. Monitor blood pressure and withhold dose if blood pressure is 90/60 mmHg or lower. Dose range: 0.1 to 0.3 mg PO every 4 to 8 hours. Max: 1.2 mg/day on day 1, then 2 mg/day. To discontinue, taper dose over several days while monitoring for signs of withdrawal.
      • Lofexidine c49
        • Lofexidine Oral tablet; Adults: 0.54 mg PO 4 times daily for up to 14 days. Lower doses may be appropriate as opioid withdrawal symptoms wane. Max: 0.72 mg/dose and 2.88 mg/day. To discontinue, reduce dose by 0.18 mg/dose every 1 to 2 days over 2 to 4 days.

    Nondrug and supportive care

    • For patients in a closed environment (eg, inpatient or residential care), provide a calm, quiet setting r47
      • Allow rest or moderate activities as desired c50c51
      • Offer opportunities to meditate or perform other calming activities c52
      • Do not force patients to engage in exercise until withdrawal is complete, because exercise may prolong and worsen withdrawal symptoms
      • Patients are often anxious and afraid and may respond well to accurate information regarding drugs and withdrawal c53
      • Patients may be confused and vulnerable; do not provide counseling or psychotherapy during moderate to severe acute withdrawal
    • Maintain hydration. Oral intake of sport drinks is usually adequate, and IV hydration is rarely necessary r3c54c55
    • Harm reduction
      • Counsel patients on overdose prevention:
        • If patients are likely to use opioids, they should use small amounts of opioids and titrate up slowly after periods of abstinence when tolerance is low
        • Avoid using opioids alone
        • Avoid mixing opioids with benzodiazepines, alcohol, and other sedatives
        • Have naloxone available when using opioids
      • Provide naloxone (formulated as nasal spray or intramuscular injection)
      • Refer to syringe services programs where available (for safer injection supplies and other harm reduction materials and services)
      • Prescribe sterile syringes and alcohol swabs, according to state laws

    Comorbidities

    • Significantly prolonged QTc interval (more than 500 milliseconds) or arrhythmia history are relative contraindications to use of methadone r48c56c57
      • Treating with methadone doses of 100 mg or less is not associated with QT prolongation r49
      • There is insufficient evidence to guide ECG screening among patients receiving methadone treatment
      • Risks of arrhythmia must be weighed against the risks of untreated or undertreated OUD, which include ongoing risky opioid use and opioid overdose r50
        • Counsel patients on risks and benefits of methadone and use a shared decision-making approach
    • Severe asthma or chronic hypercapnic respiratory failure may increase the risk of methadone in an unmonitored (eg, outpatient) setting beyond the inpatient unit r48c58c59

    Special populations

    • Pregnant patients with opioid use disorder who are taking buprenorphine or methadone treatment should continue taking these medications during pregnancy to avoid the physiologic stress that withdrawal has on the developing fetus and the additional risk of maternal relapse, which threatens the well-being of both mother and fetus r11d4
      • Buprenorphine (in a sublingual tablet or film with or without naloxone) or methadone are used for treatment of opioid use disorder during pregnancy and while breastfeeding r51
      • When initiating buprenorphine in pregnant patients, special care must be taken to avoid precipitating withdrawal, which can negatively impact the mother and fetus
      • ASAM guidelines (American Society of Addiction Medicine) recommend that hospitalization during initiation of treatment with buprenorphine may be advisable due to the potential for adverse events, especially in the third trimester. The decision of whether to hospitalize a patient for initiation of methadone should consider the experience of the clinician as well as comorbidities and other risk factors for the individual patient r2
      • Neonates of mothers who use opioids regularly or who are monitored and treated for emergence of neonatal opioid withdrawal syndrome r52
        • Opioid withdrawal may begin as early as 24 to 72 hours after delivery, and subacute symptoms and signs of opioid withdrawal may last up to 6 months r52
        • Neonates with chronic fetal opioid exposure should be observed to monitor for development of withdrawal; duration of monitoring is at least 72 hours (ie, if exposure to immediate-release opioids) and is 4 to 7 days if exposure to buprenorphine or methadone has occurred r52
        • Neonatal withdrawal may require treatment with morphine, methadone, or buprenorphine if it cannot be controlled by nonpharmacologic measures r52r53
        • Breastfeeding is associated with reduced neonatal hospital stay and requirements for pharmacologic treatment r54
    • Opioid withdrawal also may occur in breastfed infants of opioid-using mothers when maternal use of opioids is reduced or abruptly discontinued r11
      • Opioid-using patients who are breastfeeding but wish to stop are advised to gradually reduce breastfeeding to lessen withdrawal symptoms in their nursing children
    • Chronic pain
      • Patients with chronic pain (called persistent pain by some authorities) are at risk of opioid withdrawal when there is a disruption in their long-term opioid therapy
      • Patients with chronic pain receiving long-term opioid therapy may benefit from switching from full agonist opioids to buprenorphine, depending on their goals and preferences and the balance of risks/benefits with their current treatment r55r56r57
        • FDA-approved buprenorphine formulations for chronic pain include the buccal formulation and transdermal patch
        • Buprenorphine-naloxone can be used for patients with chronic pain and opioid use disorder, or off-label for patients with chronic pain alone who require higher opioid dosage r56
      • Methadone may be effective for chronic pain among people with opioid use disorder if dosed 2 or 3 times daily r58
        • Patients with chronic pain and opioid use disorder must receive methadone treatment in an opioid treatment program
          • Methadone programs can offer twice daily dosing for chronic pain, but this should be established before referring patients
    • Mental health problems
      • Comorbid mental health problems are common with opioid use disorder, including anxiety, depression, and posttraumatic stress disorder; link to mental health treatment as needed r13
      • Patients with severe, persistent mental illness may benefit from the intensive structure of opioid treatment programs over less-intensive office-based buprenorphine treatment
    • Adolescents
      • Buprenorphine and naltrexone are effective in reducing opioid use among adolescents with opioid use disorder and should be offered to all adolescents in combination with behavioral therapy r59r60r61
      • Federal policies specify that adolescents must have 2 failed attempts at behavioral treatment for opioid use disorder before being eligible for methadone treatment r59

    Monitoring

    • Closely monitor patients who potentially may begin experiencing withdrawal (eg, every 4 hours, or 1-2 hours after administering first dose of methadone or buprenorphine); use a validated clinical scale (eg, Clinical Opiate Withdrawal Scale)
    • If the methadone dose required to suppress withdrawal exceeds 120 mg daily, if the patient has a history of prolonged QT interval or arrhythmias, or if the patient is taking other medications that may prolong the QT interval (as seen with methadone) and increase the risk of arrhythmia, consider using ECG to assess the QT interval r41

    Complications and Prognosis

    Complications

    • Sustained tachycardia r2c60
    • Electrolyte imbalance r2c61
    • Hypovolemia r2c62
    • Increased risk of overdose if patient resumes opioid use, owing to decreased tolerance r2c63

    Prognosis

    • Severe distress can occur when withdrawal is rapidly precipitated by administering an antagonist r62c64
    • Opioid withdrawal is highly uncomfortable, but it is not life-threatening for most patients

    Screening and Prevention

    Screening c65

    At-risk populations

    • Patients who abruptly discontinue opioids after as few as 5 days of regular and uninterrupted opioid use
    • Patients with known opioid use who present to the emergency room or hospital
    • Patients with interruptions in long-term opioid therapy

    Prevention c66

    Galinkin J et al: Recognition and management of iatrogenically induced opioid dependence and withdrawal in children. Pediatrics. 133(1):152-5, 201424379233American Society of Addiction Medicine: ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update. ASAM website. Updated December 18, 2019. Accessed March 7, 2023. https://www.asam.org/quality-care/clinical-guidelines/national-practice-guidelinehttps://www.asam.org/quality-care/clinical-guidelines/national-practice-guidelineSigmon SC et al: Opioid detoxification and naltrexone induction strategies: recommendations for clinical practice. Am J Drug Alcohol Abuse. 38(3):187-99, 201222404717CDC: Synthetic Opioid Overdose Data. CDC website. Updated June 6, 2022. Reviewed June 6, 2022. Accessed March 7, 2023. https://www.cdc.gov/drugoverdose/deaths/synthetic/index.htmlhttps://www.cdc.gov/drugoverdose/deaths/synthetic/index.htmlAntoine D et al: Method for successfully inducting individuals who use illicit fentanyl onto buprenorphine/naloxone. Am J Addict. 30(1):83-7, 202132572978Huhn AS et al: Protracted renal clearance of fentanyl in persons with opioid use disorder. Drug Alcohol Depend. 214:108147, 202032650192Kapur BM et al: Methadone: a review of drug-drug and pathophysiological interactions. Crit Rev Clin Lab Sci. 48(4):171-95, 201122035341Jones JD et al: Searching for evidence of genetic mediation of opioid withdrawal by opioid receptor gene polymorphisms. Am J Addict. 25(1):41-8, 201626692286Department of Health and Human Services: Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder. Federal Register website. Published April 28, 2021. Accessed March 7, 2023. https://www.federalregister.gov/documents/2021/04/28/2021-08961/practice-guidelines-for-the-administration-of-buprenorphine-for-treating-opioid-use-disorderhttps://www.federalregister.gov/documents/2021/04/28/2021-08961/practice-guidelines-for-the-administration-of-buprenorphine-for-treating-opioid-use-disorderMoeller KE et al: Clinical interpretation of urine drug tests: what clinicians need to know about urine drug screens. Mayo Clin Proc. 92(5):774-96, 201728325505Mozurkewich EL et al: Buprenorphine and methadone for opioid addiction during pregnancy. Obstet Gynecol Clin North Am. 41(2):241-53, 201424845488Wesson DR et al: The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 35(2):253-9, 200312924748Santo T Jr et al: Prevalence of mental disorders among people with opioid use disorder: a systematic review and meta-analysis. Drug Alcohol Depend. 238:109551, 202235797876Mee-Lee D et al, eds: The ASAM Criteria. Treatment Criteria for Addictive, Substance-Related, and Co-Occurring Conditions. 3rd ed. The Change Companies; 2013Sordo L et al: Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 357:j1550, 201728446428Santo T Jr et al: Association of opioid agonist treatment with all-cause mortality and specific causes of death among people with opioid dependence: a systematic review and meta-analysis. JAMA Psychiatry. 78(9):979-93, 202134076676MacArthur GJ et al: Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis. BMJ. 345:e5945, 201223038795Karki P et al: The impact of methadone maintenance treatment on HIV risk behaviors among high-risk injection drug users: a systematic review. Evid Based Med Public Health. 2, 201627066590Platt L et al: Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs. Cochrane Database Syst Rev. 9:CD012021, 201728922449Liebschutz JM et al: Buprenorphine treatment for hospitalized, opioid-dependent patients: a randomized clinical trial. JAMA Intern Med. 174(8):1369-76, 201425090173D'Onofrio G et al: Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 313(16):1636-44, 201525919527Caldiero RM et al: Inpatient initiation of buprenorphine maintenance vs. detoxification: can retention of opioid-dependent patients in outpatient counseling be improved? Am J Addict. 15(1):1-7, 200616449087Calcaterra SL et al: Opioid use disorder treatment initiation and continuation: a qualitative study of patients who received addiction consultation and hospital-based providers. J Gen Intern Med. 37(11):2786-94, 202234981359American Psychiatric Association: Opioid-related disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013:540-9Torres-Lockhart KE et al: Clinical management of opioid withdrawal. Addiction. 117(9):2540-50, 202235112746National Institute on Drug Abuse: Words Matter--Terms to Use and Avoid When Talking About Addiction. NIDA website. Updated November 29, 2021. Accessed March 7, 2023. https://nida.nih.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-terms-to-use-avoid-when-talking-about-addictionhttps://nida.nih.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-terms-to-use-avoid-when-talking-about-addictionvan Boekel LC et al: Stigma among health professionals towards patients with substance use disorders and its consequences for healthcare delivery: systematic review. Drug Alcohol Depend. 131(1-2):23-35, 201323490450Schwartz RP et al: Attitudes toward buprenorphine and methadone among opioid-dependent individuals. Am J Addict. 17(5):396-401, 200818770082Gryczynski J et al: Patient perspectives on choosing buprenorphine over methadone in an urban, equal-access system. Am J Addict. 22(3):285-91, 201323617873Providers Clinical Support System: Myths and Misconceptions: Medications for Opioid Use Disorder (MOUD). PCCS website. Updated June 10, 2021. Accessed March 7, 2023. https://pcssnow.org/resource/myths-and-misconceptions-medications-for-opioid-use-disorder-moud/https://pcssnow.org/resource/myths-and-misconceptions-medications-for-opioid-use-disorder-moud/Substance Abuse and Mental Health Services Administration: Detoxification and Substance Abuse Treatment. A Treatment Improvement Protocol. TIP 45. SAMHSA website. Published October 2015. Accessed March 7, 2023. https://store.samhsa.gov/product/TIP-45-Detoxification-and-Substance-Abuse-Treatment/SMA15-4131https://store.samhsa.gov/product/TIP-45-Detoxification-and-Substance-Abuse-Treatment/SMA15-4131Spadaro A et al: Buprenorphine precipitated opioid withdrawal: prevention and management in the ED setting. Am J Emerg Med. 58:22-6, 202235623179Buresh M et al: Adapting methadone inductions to the fentanyl era. J Subst Abuse Treat. 141:108832, 202235870437Clinical Pharmacology powered by ClinicalKey: Naltrexone. Drug Monograph. ClinicalKey website. Accessed March 7, 2023. https://www.clinicalkey.com/pharmacology/monograph/426https://www.clinicalkey.com/pharmacology/monograph/426Jarvis BP et al: Extended-release injectable naltrexone for opioid use disorder: a systematic review. Addiction. 113(7):1188-209, 201829396985Lim J et al: Relative effectiveness of medications for opioid-related disorders: a systematic review and network meta-analysis of randomized controlled trials. PLoS One. 17(3):e0266142, 202235358261Morgan JR et al: Overdose following initiation of naltrexone and buprenorphine medication treatment for opioid use disorder in a United States commercially insured cohort. Drug Alcohol Depend. 200:34-9, 201931082666Ajazi EM et al: Revisiting the X:BOT naltrexone clinical trial using a comprehensive survival analysis. J Addict Med. 16(4):440-6, 202235960214Electronic Code of Federal Regulations: Title 21--Food and Drugs. Chapter II--Drug Enforcement Administration, Department of Justice. Part 1306--Prescriptions. Controlled Substances Listed in Schedule II. Sec. 1306.11 Requirement of Prescription. eCFR website. Updated May 14, 2021. Accessed October 21, 2022. https://www.ecfr.gov/current/title-21https://www.ecfr.gov/current/title-21Electronic Code of Federal Regulations: CFR 1306.07: Administering or Dispensing of Narcotic Drugs. eCFR website. Accessed March 7, 2023. https://www.ecfr.gov/current/title-21/chapter-II/part-1306/subject-group-ECFR1eb5bb3a23fddd0/section-1306.07https://www.ecfr.gov/current/title-21/chapter-II/part-1306/subject-group-ECFR1eb5bb3a23fddd0/section-1306.07Substance Abuse and Mental Health Services Administration: Medication-Assisted Treatment for Substance Use Disorders: Opioid Treatment Program Directory. SAMHSA website. Accessed March 7, 2023. https://dpt2.samhsa.gov/treatment/directory.aspxhttps://dpt2.samhsa.gov/treatment/directory.aspxSubstance Abuse and Mental Health Services Administration: Removal of DATA Waiver (X-Waiver) Requirement. SAMHSA website. Updated January 25, 2023. Accessed March 7, 2023. https://www.samhsa.gov/medications-substance-use-disorders/removal-data-waiver-requirementhttps://www.samhsa.gov/medications-substance-use-disorders/removal-data-waiver-requirementSubstance Abuse and Mental Health Services Administration: Buprenorphine Practitioner Locator. SAMHSA website. Accessed March 7, 2023. https://www.samhsa.gov/medication-assisted-treatment/physician-program-data/treatment-physician-locatorhttps://www.samhsa.gov/medication-assisted-treatment/physician-program-data/treatment-physician-locatorLee JD et al: Comparison of treatment retention of adults with opioid addiction managed with extended-release buprenorphine vs daily sublingual buprenorphine-naloxone at time of release from jail. JAMA Netw Open. 4(9):e2123032, 202134495340Lofwall MR et al: Weekly and monthly subcutaneous buprenorphine depot formulations vs daily sublingual buprenorphine with naloxone for treatment of opioid use disorder: a randomized clinical trial. JAMA Intern Med. 178(6):764-73, 201829799968Peckham AM et al: Real-world outcomes with extended-release buprenorphine (XR-BUP) in a low threshold bridge clinic: a retrospective case series. J Subst Abuse Treat. 126:108316, 202134116808WHO Regional Office for the Western Pacific: Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings. WHO website. Published 2009. Accessed March 7, 2023. https://apps.who.int/iris/handle/10665/207032https://apps.who.int/iris/handle/10665/207032Theisen-Toupal J et al: Inpatient management of opioid use disorder: a review for hospitalists. J Hosp Med. 12(5):369-74, 201728459909Stallvik M et al: Corrected QT interval during treatment with methadone and buprenorphine--relation to doses and serum concentrations. Drug Alcohol Depend. 129(1-2):88-93, 201323084592New York Office of Addiction Services and Supports: Medical Advisory Panel Position on QTc Interval Screening in Methadone Treatment. OASAS website. Published 2009. Accessed March 7, 2023. https://oasas.ny.gov/news/medical-advisory-panel-position-qtc-interval-screening-methadone-treatmenthttps://oasas.ny.gov/news/medical-advisory-panel-position-qtc-interval-screening-methadone-treatmentSubstance Abuse and Mental Health Services Administration: Advisory: Sublingual and Transmucosal Buprenorphine for Opioid Use Disorder: Review and Update. SAMHSA website. Published March 2016. Accessed March 7, 2023. https://store.samhsa.gov/product/Advisory-Sublingual-and-Transmucosal-Buprenorphine-for-Opioid-Use-Disorder-/SMA16-4938https://store.samhsa.gov/product/Advisory-Sublingual-and-Transmucosal-Buprenorphine-for-Opioid-Use-Disorder-/SMA16-4938Patrick SW et al: Neonatal opioid withdrawal syndrome. Pediatrics. 146(5):e2020029074, 202033106341McPhail BT et al: Opioid treatment for neonatal opioid withdrawal syndrome: current challenges and future approaches. J Clin Pharmacol. ePub, 202033382111Wachman EM et al: Neonatal abstinence syndrome: advances in diagnosis and treatment. JAMA. 319(13):1362-74, 201829614184Lazaridou A et al: Is Buprenorphine effective for chronic pain? A systematic review and meta-analysis. Pain Med. 21(12):3691-9, 202032330264Chou R et al: Rethinking opioid dose tapering, prescription opioid dependence, and indications for buprenorphine. Ann Intern Med. 171(6):427-9, 201931450240Department of Health and Human Services: HHS Guide for Clinicians on the Appropriate Dosage Reduction or Discontinuation of Long-term Opioid Analgesics. NIH website. Published October 2019. Accessed March 7, 2023. https://nida.nih.gov/nidamed-medical-health-professionals/opioid-crisis-pain-management/hhs-guide-clinicians-appropriate-dosage-reduction-or-discontinuation-long-term-opioidhttps://nida.nih.gov/nidamed-medical-health-professionals/opioid-crisis-pain-management/hhs-guide-clinicians-appropriate-dosage-reduction-or-discontinuation-long-term-opioidBrown R et al: Methadone: applied pharmacology and use as adjunctive treatment in chronic pain. Postgrad Med J. 80(949):654-9, 200415537850Society for Adolescent Health and Medicine: Medication for adolescents and young adults with opioid use disorder. J Adolesc Health. ePub, 202133485735McCarty D et al: Effectiveness of and access to medications for opioid use disorder for adolescents and young adults: a scoping review. J Addict Med. 16(3):e157-64, 202234282085American Academy of Pediatrics Committee on Substance Use and Prevention: Medication-assisted treatment of adolescents with opioid use disorders. Pediatrics. 138(3), 201627550978Chalana H et al: Predictors of relapse after inpatient opioid detoxification during 1-year follow-up. J Addict. 2016:7620860, 201627722007
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