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]

Definition

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 management of withdrawal from opioids, based on treatment guidelines issued by Substance Abuse and Mental Health Services Administration (US).

Diagnostic Approach

Shown below is an algorithm depicting the management of opioid withdrawal.

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

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 ❑ 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 present: ❑ Administer buprenorphine/naloxone 4/1 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 4mg (up to maximum of 8mg/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 2mg (up to maximum of 8mg/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 established equal to total buprenorphine & naloxone administered on previous day

On return withdrawal symptoms present: ❑ Administer dose equal to total amount of buprenorphine & naloxone administered on previous day + 4mg of buprenorphine (up to maximum of 12mg on day 2) & 1mg of naloxone (up to maximum of 3mg on day 2) ❑ Observe 2+ hours

Withdrawal symptoms relieved: ❑ Daily buprenorphine & naloxone dose established

Withdrawal symptoms not relieved: ❑ Administer buprenorphine 4 mg (up to maximum of 16mg on day 2) & naloxone 1 mg (up to maximum of 4 mg on day 2)

Withdrawal symptoms relieved: ❑ Daily buprenorphine & naloxone dose established

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 ❑ On subsequent induction days, if the patient returns experiencing withdrawal symptoms, continue increasing dose (up to a maximum of buprenorphine 32 mg/day & naloxone 8 mg/day

Stabilization phase (1-2 months): ❑ Transition when patient has: ❑ No withdrawal symptoms ❑ Minimal or no side effects ❑ No uncontrollable craving for opioid agonists ❑ 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 8mg 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

Do's

• Start stabilization phase, when patient is asymptomatic, suffering minimal or no side effects and no longer craving for opioids.
• For initiating buprenorphine induction, ensure that the patient is exhibiting signs of early withdrawal and has stopped using all illicit 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 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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