Minimizing Adverse Effects

The long-term use of opioids is associated with several adverse effects and clinicians should be prepared to anticipate, identify, and treat these occurrences. The most common opioid associated adverse effects include:

• Constipation
• Nausea and vomiting
• Sedation
• Sexual dysfunction
• Pruritus
• Myoclonus

Opioid-Induced Hyperalgesia
Opioid-induced hyperalgesia (OIH) can also severely impact the effectiveness of opioid treatment and can result in either increased sensitivity to pain, aggravation of pre-existing pain, or expression of novel pain symptoms. Some strategies to prevent OIH from occurring include:

• Use of adjuvant therapies for "opioid sparing" effect (e.g., use of anticonvulsants or antidepressants)
• Opioid rotation to take advantage of "incomplete cross tolerance"
• Use a combination of an opioid and low-dose mu receptor antagonist (e.g., buprenorphine and naltrexone)
• Blockade of the NMDA receptor (e.g., use of ketamine)

Methadone Monitoring
The use of methadone may prolong the rate-corrected QT interval and result in torsades de pointes. Therefore, clinicians should take precautions prior to initiating methadone treatment for their patients.

• Disclosure: Clinicians should inform patients of arrhythmia risk when they prescribe methadone
• Clinical History: Clinicians should ask patients about any history of structural heart disease, arrhythmia, and syncope
• Screening: Obtain a pretreatment electrocardiogram for all patients to measure the QTc interval and a follow-up EKG within 30 days and annually.
• Additional EKG is recommended if the methadone dose exceeds 100 mg/day or patients have unexplained syncope or seizures.
• Drug Interactions: Clinicians should be aware of interactions between methadone and other drugs that possess QT interval prolongation properties or slow the elimination of methadone

Suggested Reading:

• Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10:113-130. Abstract available at: www.ncbi.nlm.nih.gov/pubmed/19187889.
• Krantz MJ, Martin J, Stimmel B, et al. QTc interval screening in methadone treatment. Ann Intern Med. 2009;150:387-395. Article available at: www.annals.org/content/150/6/387.long.
• Silverman SM. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician. 2009;12:679-684. Article available at: www.painphysicianjournal.com/linkout_vw.php?issn=1533-3159&vol=12&page=679.