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Featured Clinical Topic: Opioid Use Disorder: Identification and Management in the Acute Setting

06 Apr 2022 5:02 PM | Anonymous

Opioid Use Disorder: Identification and Management in the Acute Setting

Madeline Taylor, BS, PharmD 2022 Candidate & Julianne Yeary, PharmD, BCCCP

Introduction

Opioid overdose deaths continue to increase in both urban and rural areas of Missouri, accounting for 1 out of every 56 deaths in 2018.1 The rise in patients suffering from opioid use disorder (OUD) is placing a great burden on the healthcare system. Establishing preventative measures and providing timely recognition and initiation of treatment for patients suffering from OUD is crucial.

 

Identification of Patients

In patients presenting with risk factors for OUD (e.g., personal or family history of OUD, related mental health or personality disorder, or a positive urine drug screen), clinicians should keep OUD on their differential diagnosis when particular signs and symptoms are present.2 Signs and symptoms can frequently involve the following domains: mood, physical, psychological, and behavior.2 The DSM-5 criteria should be used to make an official diagnosis in patients suspected to have OUD. Patients must meet at least two of the criteria to be eligible for pharmacological treatment.3

Acute withdrawal is seen when rebound hyperexcitability occurs after abrupt opioid cessation in opioid dependent patients.2 Opioid withdrawal symptoms (OWS) include anxiety or restlessness, diarrhea, fever, diaphoresis, nausea, vomiting, dilated pupils, tachycardia, and hypertension.4 Onset of withdrawal is dependent on the type of substance being used.5 For example, discontinuation of heroin, a short-acting opioid, will produce OWS in 8-12 hours. Alternatively, methadone, a long-acting opioid, may take up to 36 hours before OWS are apparent.5,6 The Clinical Opioid Withdrawal Scale (COWS) is a scale used in the inpatient setting to score the level of withdrawal as mild, moderate, moderately severe, or severe.5,7 The severity of OWS determined by COWS score guides treatment decisions.

 

Managing Opioid Use Disorder

The current Food and Drug Administration approved medications for OUD include methadone, buprenorphine, and naltrexone.2 Methadone and buprenorphine are agents commonly used in the inpatient setting. Naltrexone cannot be initiated until at least seven days since last opioid usage and is therefore not commonly used for the acute management of OUD.2 There are factors that should be considered when selecting optimal pharmacologic intervention for OUD in the hospital including any previous outpatient medication for addiction treatment (MAT), co-morbid conditions, current withdrawal symptoms, willingness to receive OUD treatment, and concomitant medications.

Opioid Withdrawal Symptom Management

 The opioid agonists buprenorphine and methadone are the primary treatment agents in OUD, while several non-opioid medications focus on OWS. Clonidine, an alpha-2 agonist, is the mainstay of non-opioid treatments for OWS, and is used off-label to manage specific symptoms, such as tachycardia, anxiety, and hypertension.4 Oral hydration, antiemetics, and antidiarrheals are also used for supportive care in OWS.4,5

Buprenorphine

Buprenorphine is a partial agonist at the mu opioid receptor which allows for maximal opioid effect with less risk of severe adverse reactions, such as respiratory depression, compared to full opioid agonists.2,5 Sublingual administration is preferred over the oral route to avoid first-pass effect and loss of bioavailability due to intestinal absorption. Peak effect occurs three to four hours after sublingual administration. Buprenorphine is metabolized by the liver, primarily via the cytochrome P450 (CYP) CYP3A4 enzyme, which can lead to drug interactions. Buprenorphine has an extremely high binding affinity and slowly dissociates from the mu opioid receptor providing the sublingual formulation with a long half-life of 38 hours. The only contraindication to its use is a known hypersensitivity to buprenorphine.2,5 Buprenorphine is typically initiated when a patient is in moderate withdrawal or COWS > 11 to avoid precipitating severe OWS (Table 1).2,5 New approaches are emerging to explore buprenorphine initiation strategies prior to OWS, however to date evidence is limited to case reports.15 The drug’s long half-life allows for a “self-taper” effect as it slowly dissociates from the opioid receptors.10,11,12 In two systematic reviews buprenorphine was more effective than clonidine for the management of opioid withdrawal and appeared to be equally effective to methadone.13,14 One systematic review found that buprenorphine may offer advantages over methadone in the inpatient setting for resolution of withdrawal symptoms; however more research is warranted for verification.14

Buprenorphine is often given in combination with naloxone, a full opioid receptor antagonist. This combination works to reduce adulteration and abuse rates when used for long term management in the outpatient setting and may be restarted when patients present to the acute care setting. Buprenorphine is a Schedule III medication, and prescribers need a waiver to prescribe this medication. Prescribing abilities for a 30-day prescription have also been extended to nurse practitioners and physician assistants, so long as their collaborative practice is with a physician who is waiver certified.16

Methadone

Methadone, a long-acting full agonist at the mu opioid receptor, works by dampening the rewarding effects of other opioids through its long-acting effect on the opioid receptors while preventing withdrawal symptoms.2,5 Methadone, which is metabolized in the liver primarily via the CYP2B6 enzyme, carries the risk for drug interactions as well as hypokalemia and QTc interval prolongation.5 Contraindications include current respiratory depression, severe bronchial asthma or hypercapnia, and paralytic ileus.2 A patient with lower opioid tolerance (e.g. re-initiating treatment after relapse) may require a lower initiation dose (Table 1).

Clonidine

Clonidine stimulates alpha-2 adrenoceptors in the brain, activating an inhibitory neuron, which results in reduced central nervous system (CNS) sympathetic outflow and ultimately decreases heart rate and blood pressure.8 In a systematic review, clonidine was superior to placebo in reducing withdrawal symptoms.9 Clonidine is metabolized in the liver, however, it does not carry the risk of CYP drug interactions. Patients using clonidine may experience hypotension and bradycardia.2,10 The only contraindication to its use is a known hypersensitivity to clonidine.

Outpatient MAT

Both behavioral and medical screening is necessary to determine which patients would be good candidates for MAT at time of discharge. Goals of initial screening include access for crisis intervention, federal and state eligibility requirements, a patient’s ability to understand and accept program responsibilities including benefits and drawbacks of MAT, and recognition of barriers that might hamper a patient’s ability to meet treatment requirements (e.g. lack of transportation, other substance abuse, and commitment concerns).

 

Conclusion

The focus of caring for patients with OUD in the inpatient setting should be on both acute treatment as well as prevention. Patients initiated on MAT while inpatient will require follow-up post discharge in the outpatient setting for continued management. Educating clinicians on symptoms of OUD, the importance of providing MAT, and evidence-based treatment options employed to alleviate OWS may improve timely diagnosis and treatment.

References:

  1. Missouri Department of Health and Senior Services. Missouri Opioids Information. https://health.mo.gov/data/opioids/ (accessed 2021 June 20).
  2. 2020 Focused Update Guideline Committee. The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. J Addict Med. 2020; 14(2S Suppl1):1-91.
  3. American Psychiatric Association. Opioid Use Disorder. https://www.psychiatry.org/patients-families/addiction/opioid-use-disorder (accessed 2021 July 15).
  4. Kosten TR, Baxter LE. Review article: effective management of opioid withdrawal symptoms: a gateway to opioid dependence treatment. Am J Addict. 2019; 28:55-62.
  5. Koehl JL, Zimmerman DE, Bridgeman PJ. Medications for the management of opioid use disorder. Am J Health-Syst Pharm. 2019; 76:1097-1104.
  6. American Addiction Centers. Opiate withdrawal timeline, symptoms, and treatment. (2021). https://americanaddictioncenters.org/withdrawal-timelines-treatments/opiate (accessed 2021 July 16).
  7. Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003; 35:253-259.
  8. Catapres (clonidine hydrochloride) package insert. Ridgefield, CT: Boehringer Ingelheim Corporation; 2009 Oct.
  9. Gowing L, Farrell MF, Ali R, White JM. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev. 2016; 3:CD002024.
  10. Toce MS, Chai PR, Burns MM, Boyer EW. Pharmacological treatment of opioid use disorder: a review of pharmacotherapy, adjuncts, and toxicity. J Med Toxicol. 2018; 14:306-322.
  11. Sigmon SC, Bisaga A, Nunes EV et al., Opioid detoxification and naltrexone induction strategies: recommendations for clinical practice. Am J Drug Alcohol Abuse. 2012; 38:187-99.
  12. Fishbain DA. Opioid tapering/detoxification protocols, a compendium: narrative review. Pain Med. 2021; 22(7):1676-1697.
  13. Gowing L, Ali R, White JM, Mbewe D. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017; 2:CD002025.
  14. Gowing L, Ali R, White JM. Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst Rev. 2009; 3:CD002025.
  15. Adams KK, Machnicz M, Sobieraj DM. Initiating buprenorphine to treat opioid use disorder without prerequisite withdrawal: a systematic review. Addict Sci Clin Pract. 2021;16(1):36. Published 2021 Jun 8. doi:10.1186/s13722-021-00244-8
  16. State of Missouri. 630.875 Citation of Law. Missouri Revisor of Statutes - Revised Statutes of Missouri, RSMo, Missouri Law, MO Law, Joint Committee on Legislative Research. https://revisor.mo.gov/main/OneSection.aspx?section=630.875&bid=47957&hl=buprenorphine%25u2044. Accessed March 19, 2022.

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