Fast Fact and Concept #58: Neuroexcitatory Effects of Opioids: Treatment

Authors: Robin K. Wilson, Ph.D. and David E. Weissman, MD

2nd Edition

Fast Fact #57 reviewed the pharmacology and patient assessment aspects of opioid induced neurotoxicity, notably myoclonus. Decisions about the most appropriate treatment approach need to take into account features of the physical examination (the frequency and intensity of symptoms, hydration status, and estimated prognosis) and information from the medical record (temporal pattern of opioid use and dose escalation, other medications, and the presence of electrolyte abnormalities and major organ dysfunction). Whenever medically appropriate, easily treatable causes or exacerbating factors should be corrected (e.g. correct hypomagnesemia). The range of options for management of pain and direct opioid neurotoxic effects divides into strategies to treat the myoclonus and strategies to reduce the offending opioid.

1. Observation

Mild myoclonus may trouble family members more than the patient. If the patient is satisfied with current therapy, explaining the cause/progression of symptoms may be all that is necessary.

2. Opioid dose reduction

Myoclonus may resolve over a few days with a decrease in opioid dose. Note: Do not reduce the opioid dosage solely to control myoclonus at the expense of good pain control.

3. Rotate to a dissimilar opioid

Rotating to a lower dosage of a structurally dissimilar opioid will often reduce myoclonus and other neuroexcitatory effects within 24 hours, while achieving comparable pain control. Rotation is especially important in patients with opioid-induced hyperalgesia. As a general rule, decrease the morphine equianalgesic dose by at least 50% when switching to a new medication (see Fast Fact #36). For patients on very high doses, rotate to a new opioid at 20-25% of the morphine equianalgesic dose. Note: when switching to methadone, the reader should review recent methadone equianalgesic guidelines (see FFs #75, 86).

4. Adjuvant and other analgesic therapy

Adjuvant analgesics (e.g. anticonvulsants, antidepressants, corticosteroids) or non-drug therapies (e.g. acupuncture, TENS, heat, cold) may allow for opioid reduction, with preservation of analgesia.

5. Benzodiazepines and other drugs to reduce myoclonus

The addition of a benzodiazepine may reduce myoclonus without alteration of the opioid dose, although increasing sedation may be an unwanted side effect. Start with clonazepam 0.5-1mg qhs or 0.5mg BID or TID. Alternative agents include lorazepam orally or sublingually, starting at 1-2mg q8. Continuous infusion midazolam is an expensive but effective option. Alternatives to benzodiazepines include baclofen, gabapentin, and nifedipine. Start Baclofen at 5mg TID and increase as needed/tolerated to 20mg TID. Start gabapentin at 100mg TID and increase as needed to 900-3600mg PO/day; nifedipine (10mg TID) may be used.

References:

1. Abrahm J. Advances in pain management for older adult patients. Clinics in Geriatric Medicine 2000; 16: 269-311.
2. Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, Mercadante S, Pasternak G, and Ventafidda V. Strategies to manage the adverse effects of oral morphine: an evidence based report. JCO 2001. 19: 2542-2554.
3. Ferris D. Controlling myoclonus after high-dosage morphine infusions. American Journal of Health-System Pharmacy 1999; 56: 1009-1010.
4. Hagen N, Swanson R. Strychinine-like multifocal myoclonus and seizures in extremely high-dose opioid administration: treatment strategies. JPSM 1997; 14: 51-57.
5. Mercadante S. Pathophysiology and treatment of opioid-related myoclonus in cancer patients. Pain 1998; 74: 5-9.
6. Mercadante S. Gabapentin for opioid-related myoclonus in cancer patients. Support Care Cancer 2001; 9: 205-206.
7. Watanabe S. Methadone: the renaissance. J Pall Care 2001;117-120.

This Fast Fact was edited by David E. Weissman, MD; Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information: Users are free to d ownload and distribute Fast Facts for educational purposes only. Citation for referencing: Wilson RK and Weissman DE. Fast Facts and Concepts #58 Neuroexcitatory effect of opioids Part 2, 2 nd Edition. July 2006. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 1/2002

Purpose: Instructional Aid, Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain>opioids