Opioid withdrawal resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2]; Vendhan Ramanujam M.B.B.S [3]

Overview

Opioid withdrawal refers to the arrays of signs and symptoms following the abrupt cessation of opioids among chronic users.

Shown below is a table indicative of time to withdrawal symptoms for different opioids:

Opioid	Peak withdrawal symptoms	Duration of symptoms
Heroin	36-72 hours	7-10 days
Methadone	72-96 hours	14 days or more
Buprenorphine	36-72 hours	Intermediate between 7-14 days

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Opioid withdrawal is a life-threatening condition and must be treated as such irrespective of the causes.

Common Causes

• Discontinuation of heroin
• Discontinuation of methadone
• Rapid detoxification with naloxone or naltrexone in opioid dependent subjects
• Use of partial agonists (buprenorphine) and/or agonist-antagonists (pentazocine) in subjects not known to be opioid dependent

Management

Shown below is an algorithm used for diagnosis and treatment of withdrawal from opioids, based on hospital concepts and treatment guidelines issued by Substance Abuse and Mental Health Services Administration (Center for Substance Abuse Treatment, US).

Diagnostic Approach

Characterize the symptoms: ❑ Flu like illness ❑ Lacrimation ❑ Rhinorrhea ❑ Sneezing ❑ Yawning ❑ Anorexia ❑ Nausea ❑ Vomiting ❑ Abdominal cramps ❑ Diarrhea ❑ Myalgia ❑ Arthralgia

Examine the patient: ❑ Increased or unchanged blood pressure ❑ Increased or unchanged heart rate ❑ Increased or unchanged respiratory rate ❑ Mydriasis ❑ Piloerection ❑ Tremor ❑ Increased bowel sounds

Consider alternative diagnosis: ❑ Alcohol withdrawal ❑ Sedative hypnotic withdrawal ❑ Cholinergic poisoning ❑ Sympathomimetic intoxication

Diagnostic criteria: ❑ A. Either of the following ❑ Cessation of or reduction in opioid use that has been heavy and for several weeks or longer ❑ Administration of an opioid antagonist after a period of opioid use ❑ B. Three or more of the following (developing within minutes to several days after criterion A) ❑ Diarrhea ❑ Dysphoric mood ❑ Fever ❑ Insomnia ❑ Lacrimation or rhinorrhea ❑ Muscle aches ❑ Nausea or vomiting ❑ Pupillary dilation, piloerection, or sweating ❑ Yawning

Opioid withdrawal

Consider treatment with: ❑ Opioid maintenance treatment or ❑ Medically supervised withdrawal (detoxification)

Treatment Approach

Induction-Day 1

Identify the opioid's the patient has been using

Short acting opioids

Long acting opioids

❑ Discontinue short acting opioids ❑ Look for withdrawal symptoms (12-24 hours after last dose)

❑ Taper long acting opioids (over a period of 1 week): ❑ Methadone to ≤ 30 mg/day ❑ LAAM† to ≤ 40 mg/48 hours ❑ Look for withdrawal symptoms: ❑ For methadone: 24+ hours after last dose ❑ For LAAM: 48+ hours after last dose

Withdrawal symptoms subside & return or still present: ❑ Administer buprenorphine 4 mg & naloxone 1 mg ❑ Observe for 2+ hours

Withdrawal symptoms absent: ❑ Reevaluate the suitability for induction

Withdrawal symptoms present: ❑ Administer buprenorphine 2 mg ❑ Observe for 2+ hours

Withdrawal symptoms not relieved: ❑ Repeat buprenorphine 4 mg (up to maximum of 8 mg/24 hours ❑ Naloxone 1 mg (up to maximum of 2 mg/24 hours)

Withdrawal symptoms relieved: ❑ Day 1 dose established ❑ Send patient home ❑ Schedule patient to return on day 2 for forward induction

Withdrawal symptoms not relieved: ❑ Repeat buprenorphine 2 mg (up to maximum of 8 mg/24 hours)

Withdrawal symptoms relieved: ❑ Day 1 dose established ❑ Send patient home ❑ Schedule patient to return on day 2 for forward induction

Withdrawal symptoms not relieved: ❑ Manage withdrawal symptoms symptomatically ❑ Clonidine 0.2 mg every 4 hours, tapered after day 3, or ❑ Lofexidine 0.2 mg BD daily, titrated to 1.2 mg BD daily ❑ Chlordiazepoxide as needed ❑ Return next day for repeat induction attempt

Induction-Day 2 & forward

On return withdrawal symptoms absent: ❑ Administer a daily dose = Total buprenorphine & naloxone or total buprenorphine administered on previous day ❑ For symptomatic relief ❑ W/o side effects: Increase subsequent doses of buprenorphine (in 2-4 mg increments daily; until a target dose of 12-16 mg/day) & naloxone (in 0.5-1 mg increments daily; until a target dose of 3-4 mg/day) ❑ W/ side effects: Maintain or lower buprenorphine & naloxone until side effects disappear

On return withdrawal symptoms present: ❑ Administer a daily dose = Total buprenorphine & naloxone or total buprenorphine administered on previous day + 4 mg of buprenorphine (up to maximum of 12 mg/24 hours) & 1 mg of naloxone (up to maximum of 3 mg/24 hours) ❑ Observe 2+ hours

Withdrawal symptoms relieved: ❑ Daily buprenorphine & naloxone dose established ❑ Continue for 5 more days

Withdrawal symptoms not relieved: ❑ Administer buprenorphine 4 mg (up to maximum of 16 mg/24 hours) & naloxone 1 mg (up to maximum of 4 mg/24 hours)

Withdrawal symptoms relieved: ❑ Daily buprenorphine & naloxone dose established ❑ Continue for 5 more days

Withdrawal symptoms not relieved: ❑ Manage withdrawal symptoms symptomatically ❑ Clonidine 0.2 mg every 4 hours, tapered after day 3, or ❑ Lofexidine 0.2 mg BD daily, titrated to 1.2 mg BD daily ❑ Chlordiazepoxide as needed ❑ If patient returns with withdrawal symptoms: Continue increasing buprenorphine up to a maximum of 32 mg/day & naloxone up to a maximum of 8 mg/day on subsequent induction days

❑ No withdrawal symptoms ❑ Minimal or no side effects ❑ No uncontrollable cravings for opioid agonists

Stabilization phase (1-2 months): ❑ Begin with buprenorphine/naloxone combination, increasing dose by 2/0.5-4/1 mg per week till stabilization is achieved, most stabilizing at 16/4-24/6 mg ❑ As patient stabilizes, transition to alternate day or every third day regimen by doubling and tripling daily doses respectively

Maintenance phase: ❑ Maintain at same dose as daily stabilization dose ❑ Decide total treatment duration based on: ❑ Stable housing & income ❑ Patients motivation, doctors comfort in tapering ❑ Presence of psychosocial support ❑ Absence of legal support ❑ Other drugs & alcohol abuse

Detoxification (Medically Supervised Withdrawal) With Buprenorphine

Detoxification

Short acting opioids

OAT† (methadone/LAAM)

Induction phase: ❑ Take patient off offending agent, inducing withdrawal ❑ Administer 1st dose of buprenorphine/naloxone 4/1 mg, when patient shows initial symptoms of withdrawl ❑ Repeat once after 2-4 hours if indicated ❑ ↑ dose to 12/3 - 16/4 mg over next 2 days, to establish stabilization dose

Induction phase: ❑ Taper methadone to ≤ 30 mg/day Taper LAAM ≤ 40 mg/48 hour ❑ Induce by buprenorphine monotherapy 2 mg, repeated after 2-4 hours to a maximum dose of 8 mg in 24 hour period

Dose reduction phase: ❑ Begin only if documented negative toxicology results, or patient admitted to hospital Long period reduction: ❑ Reduce dose by 2 mg every week Moderate period reduction: ❑ Perform detoxification over 10-14 days ❑ Reduce dose by 2 mg every 2-3 days Short period reduction: Perform over 3 days Dose reduction by half every day

Dose reduction phase

Rapid discontinuation: ❑ Taper buprenorphine monotherapy over 3-6 days, then discontinue

Gradual dose reduction: ❑ Switch to buprenorphine/naloxone combination therapy ❑ Stabilize combination dosage over 1 week ❑ Taper gradually over next 2 weeks, then discontinue

† OAT: Opioid agonist therapy; LAAM: Levo-α-acetylmethadol

Do's

• A signed release of information from patients who are currently enrolled in Opioid Treatment Programs (OTPs) or other programs should be obtained before initiating buprenorphine treatment.
• Initiation of buprenorphine treatment should be carefully timed such that the patients should be in the early stages of withdrawal.
• Patients should be carefully explained regarding the advantages of waiting and should be urged to wait until they begin to experience the symptoms of withdrawal.
• Consider patients history and concerns and counsel about potential side effects from buprenorphine overdosing or underdosing before initiation.
• Buprenorphine should be administered as sublingual tablets.
  • Asses the dose taken.
  • Assess the amount of time the medication is allowed to dissolve under the tongue.
• After initiation, periodic reassessment regarding the patient’s motivation for treatment should be done in order to assess the duration for various aspects of treatment.
• During induction, patients should be advised to avoid driving or operating other machinery until they are familiar with the effects of buprenorphine and until their dose is stabilized.
• Pregnant women and patients on long-acting opioids should be inducted and maintained on buprenorphine monotherapy, and the number of doses should be limited.
• Non pregnant women started on buprenorphine monotherapy for induction should be switched to a buprenorphine and naloxone combination on day 2 to minimize the possibility of abuse.
• A lowest possible dose of (2/0.5 mg) of buprenorphine/naloxone for induction treatment can be considered in patients who are not physically dependent on opioids but who have a known history of opioid addiction, have failed other treatment modalities, and have a demonstrated a need to cease the use of opioids.
• Doses should be increased more rapidly, or to a higher maintenance dose level along with intensive psychosocial treatments in patients who experience withdrawal symptoms during induction or who feel compelled to use illicit drugs. Strongly warn those who continue to take illicit opioids.
• To determine the adequacy of clinical response, toxicology testing for drugs of abuse should be done.
• Start stabilization phase, when patient is asymptomatic, suffering minimal or no side effects and no longer craving for opioids.
• Toxicology screens must be performed atleast once a month to assess progress.
• Frequency of visits should be as follows:

• During stabilization phase atleast once a week.
• During maintenance phase, anywhere from biweekly to monthly visits is considered satisfactory, however must be tailored to meet patients needs.

• Use following measures to assess efficacy of treatment:

• No evidence of ongoing drug abuse of any kind.
• Toxicity from opioid use is absent.
• Adverse effects due to medical treatment are absent or minimal.
• Patient is stable with respect to psycho-social elements.
• Treatment adherence is good.

Dont's

• Do not initiate induction until the patients have symptoms of withdrawal.
• Do not abruptly stop drugs that are being used to treat withdrawal.
• Do not prefer, short term (3 day) reduction for detoxification unless there is a strong reason for the same such as impending incarceration, foreign travel, job requirement etc.

References

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