# 057 Neuroexcitatory Effects of Opioids: Patient Assessment, 2nd ed


Author(s): Robin K Wilson PhD and David E Weissman MD

Background Everyone recognizes the common opioid side effects: constipation, nausea, pruritis, and urinary retention. Less well appreciated are the neuroexcitatory effects, commonly seen among patients on chronic opioids. Among these, myoclonus is typically the herald symptom. This Fast Fact will discuss risk factors and patient assessment of the neuroexcitatory opioid side effects, particularly myoclonus; Fast Fact #58 will discuss treatment options.

Physiology and Risk Factors Myoclonus can occur in patients on chronic therapy with most opioids including morphine, hydromorphone, fentanyl, meperidine, and sufentanil. Higher doses more frequently result in myoclonus, but the dose relationship is variable. Myoclonus can occur with all routes of administration. Current research implicates the 3-glucuronide opioid metabolites as one likely cause of neuroexcitatory side effects, although current understanding is limited. Co-morbid factors including renal failure, electrolyte disturbances, and dehydration can also contribute to myoclonus development.

Clinical Scenarios Myoclonus – the uncontrollable twitching and jerking of muscles or muscle groups – usually occurs in the extremities, starting with only an occasional random jerking movement. A patient's spouse may be the first to recognize this symptom. With continued administration, the jerking may increase in frequency; at the extreme, there is constant jerking of random muscle groups in all extremities. As myoclonus worsens, patients may develop other neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with hallucinations, and eventually grand mal seizures. Well meaning clinicians may misinterpret the hyperalgesia as increasing pain, leading to a vicious cycle of increasing dose, increasing hyperalgesia, increasing dose, worsening delirium, and finally seizures. After identifying a patient with possible opioid toxicity, the clinician should complete a physical examination and chart review.

Physical Examination

  • Assess frequency of myoclonic jerks. Stand at the bedside and observe a patient for 30-60 seconds. Watch for and count the number of uncontrolled jerking movements.
  • Determine if there is evidence of a new or worsening delirium. Complete a bedside mini-mental assessment.
  • Assess hydration status.
  • Estimate prognosis: hours, days, weeks, months or years? A longer prognosis demands a more definitive change in treatment.

Chart review

  • Review the recent opioid analgesic history. What is the current drug and dose? How has the dose changed over the past few days and weeks?
  • Review the medication list for potentially exacerbating drugs. (e.g. haloperidol, phenothiazines)
  • Review recent laboratory studies if available. Check renal and liver function, and for low magnesium, glucose or sodium.


  1. Cherny N, Ripamonti C, Pereira J, et al. Strategies to manage the adverse effects of oral morphine: an evidence based report. J Clin Oncol. 2001; 19:2542-2554.
  2. Mercadante S. Pathophysiology and treatment of opioid-related myoclonus in cancer patients. Pain. 1998; 74:5-9.
  3. Smith M. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. Clinical and Experimental Pharmacology and Physiology. 2000; 27:524-528.
  4. Wright A, Mather L, Smith M. Hydromorphone-3-glucuronide, a more potent neuro-excitant than its structural analogue morphine-3-glucuronide. Life Sciences. 2001; 69:409-420.

Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.

Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published July 2006. Current version re-copy-edited April 2009.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Wilson RK, Weissman DE. Neuroexcitatory Effects of Opioids: Patient Assessment, 2nd Edition. Fast Facts and Concepts. July 2006; 57. Available at: http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_057.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a 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.

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain – Evaluation; Pain – Opioids