Day # 87: Opioid Withdrawal

We are continuing our current theme of emergency psychiatry. Today we will discuss opioid withdrawal. This post will include an introduction, signs/symptoms, and treatment.

Today's Content Level: All Levels (Beginner, Intermediate, Advanced)

INTRODUCTION

•What are opioids? Opioids are any chemical (natural, synthetic, or semi-synthetic) that interact with opioid receptors (mu, delta, kappa) in the nervous system. When stimulated these receptors reduce the intensity of pain signals but are also involved in sedation. Some opioids are legally prescribed for the treatment of pain (ex: oxycodone, hydrocodone, morphine, fentanyl), but also includes the illegal drug heroin. All opioids have the potential to cause euphoria (effects on the dopaminergic system) in addition to pain relief, so they can be misused and have potential for addiction.

•What is opioid withdrawal? Prolonged use of opioids (prescribed or not) will produce physiologic tolerance and dependence, which creates risk for opioid use disorder as well as withdrawal symptoms when someone suddenly stops or significantly reduces their use of opioids.

•Can opioid withdrawal be fatal? Unlike alcohol withdrawal, the symptoms of opioid withdrawal are not life threatening, however they lead to a very unpleasant constellation of symptoms (see below).

•Brief word on intoxication: Opioid intoxication causes drowsiness, nausea/vomiting, constipation, slurred speech, constricted pupils, seizures, and respiratory depression, which may progress to coma or death in overdose. Management includes administration of naloxone (opioid antagonist) and supportive airway management. Intoxication will be discussed in more detail during our substance use section (coming soon).

SIGNS AND SYMPTOMS

•Opioid withdrawal is not life-threatening but leads to a very unpleasant withdrawal syndrome. Symptoms include cravings, anxiety/irritability, insomnia, muscle aches, GI upset (nausea, vomiting, cramps), sweating, rhinorrhea, lacrimation, piloerection, yawning, shivering, and tremor.

•Duration of symptoms vary based on the half-life of the patients opioid of choice. For example, untreated heroin withdrawal symptoms typically begin after 5-10 hours after the last dose, reach their peak in 32-72 hours, and typically reduce significantly after 5 days. Untreated methadone withdrawal on the other hand typically reaches its peak between 4 and 6 days after last dose and symptoms don't subside for 10-12 days.

Symptom scales can be helpful in determining the level of opioid withdrawal as well as determining when/how much pharmacological support may be required. One of the most frequently used scales in the literature as well as my experience is the Clinical Opioid Withdrawal Scale (COWS). I have included the criteria categories for ease of reference, however feel free to visit here for the full scoring system.

• Resting pulse rate

• Sweating

• Restlessness

• Pupil size

• Bone or joint aches

• Runny nose or tearing

• GI upset

• Tremor

• Yawning

• Anxiety or irritability

• Gooseflesh skin (piloerection)

TREATMENT

General considerations of treatment

• Prior to treatment obtain a good history and ensure patient is dependent on opioids.

• Even though opioid withdrawal is not life-threatening it is very uncomfortable and it is not recommended that clinicians attempt to manage significant withdrawal symptoms without medication management.

• Offering treatment proactively can prevent patients leaving the hospital against medical advice. 1

• Ensure patients understand that after detox is completed the patient is at risk for overdose death if they continue to use opioids at the same pre-detox doses due to "loss of tolerance".

There are three general pharmacological approaches/options to treating opioid withdrawal:

• Methadone (long-acting opioid receptor agonist)

• Buprenorphine (partial opioid receptor agonist)

• Symptomatic treatment (ex: alpha agonists, NSAIDs, etc...)

•Both methadone and buprenorphine are effective in treating withdrawal symptoms and decreasing abuse of opioids. Recent systematic reviews find there is no significant evidence to support one over the other 2, 3. The decision for which agent to use is based on individual factors, particularly patient preference, and their long-term plans for maintenance treatment. *Maintenance treatment will be discussed during our substance use section (coming soon)*

Methadone

• Long-acting opioid receptor agonist.

• Consider for patients with plan to discharge to methadone clinic, as use is restricted to federally licensed substance abuse treatment programs.

• Significantly reduces morbidity and mortality in opioid-dependent persons, however is associated with increased mortality during the titration phase.

• Can cause QTc prolongation, thus a screening EKG is indicated.

• Compared to buprenorphine, plasma levels are more affected by drugs that inhibit/induce CYP450 enzymes such as anticonvulsants, SSRIs, HIV meds, antibiotics, etc.

• Compared to low-dose buprenorphine, it is associated with greater retention in outpatient maintenance treatment.

• Compared to buprenorphine, there is a greater risk of diversion.

• “Gold standard” treatment in pregnant opioid-dependent women.

• For specific dosing protocols see UpToDate.

Buprenorphine

• Partial opioid receptor agonist. High affinity to opioid receptors.

• More readily available since it can be prescribed from regular clinics as long as providers are trained.

• Sublingual preparation (Suboxone) combines buprenorphine and naloxone (opioid antagonist). Naloxone is activated if the medication is crushed in an attempt in inject intravenously. This prevents intoxication in this way.

• Unlike methadone, there is no association with increased mortality during titration. Also its effects reach a plateau and make overdose unlikely.

• Less severe neonatal withdrawal symptoms when used in pregnancy.

• It must be started when the patient is already in withdrawal, or else it will trigger withdrawal symptoms. Make sure it has been at least 12 hours since the last opioid use and they are experiencing definite symptoms. The first dose is typically given once COWS reach a score of 8-10.

• For specific dosing protocols see UpToDate.

Symptomatic Treatment

• Methadone and buprenorphine may be avoided in patients with less severe opioid dependency or those with only mild/moderate symptoms of withdrawal.

• Withdrawal symptoms: Alpha agonists such as clonidine can be effective to treat the autonomic symptoms of withdrawal as well as other symptoms of withdrawal (anxiety, agitation, insomnia, sweating, etc). Don't give with methadone or buprenorphine during the first day of dosing as it will reduce the COWS.

• GI effects: abdominal cramps (dicyclomine); nausea (ondansetron, metoclopramide, etc); diarrhea (loperamide).

• Muscle aches / headaches: NSAIDs or acetaminophen.

• Anxiety / insomnia: options include clonidine, hydroxyzine, benzodiazepines, and trazodone.

CONCLUSION

Great work today. In our next post we will discuss toxidromes.

Resources for today's post include the Maudsley Prescribers Guide, Pocket Psychiatry, First Aid for the Psychiatry Clerkship and the articles referenced in the post.

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