Open Access Open Access  Restricted Access Subscription or Fee Access

Patterns of care and side effects for patients prescribed methadone for treatment of chronic pain

Tara A. Macey, PhD, Melissa B. Weimer, DO, MCR, Elizabeth M. Grimaldi, BA, Steven K. Dobscha, MD, Benjamin J. Morasco, PhD


Objectives. This manuscript evaluates physician monitoring practices and incidence of cardiac side effects following initiation of methadone for treatment of chronic pain as compared to patients who began treatment for chronic pain with morphine sustained release (SR).

Design. We retrospectively reviewed medical record data on all new initiations of methadone and compared results of physician monitoring practices to patients with new initiations of morphine SR. A standardized chart tool was used to capture clinical data. Data related to health service utilization and clinical diagnoses were obtained from the VA clinical information system.

Setting. A single VA Medical Center in the Pacific Northwest.

Patients. Chronic pain patients prescribed methadone (n = 92) or morphine (n = 90) in the calendar year 2008.

Results. There was no difference between patients prescribed methadone versus patients prescribed morphine SR in the likelihood of receiving an electrocardiogram (ECG) prior to initiating medication (53 percent versus 54 percent) or in the year after opioid initiation (37 percent versus 40 percent). The two groups also did not differ in rates of developing prolonged rate-corrected (QTc) intervals (>450 ms) (11 percent versus 17 percent). Seventy-two percent of all patients discontinued their long-acting opioid regimens before 90 days due to adverse effects or insufficient pain relief.

Conclusion. Despite recommendations for standardized assessment and cardiac risk monitoring, few patients prescribed methadone received an ECG, and this occurred at a rate that did not differ from patients prescribed morphine SR. Patients discontinued both medications at high rates. Further research is needed to evaluate the clinical significance of QTc prolongation in patients treated with methadone.


chronic pain, opioids, veteran, pain/drug therapy, methadone, QTc prolongation, ECG, medication side effects

Full Text:



Manchikanti L, Abdi S, Atluri S, et al.: American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I–Evidence assessment. Pain Physician. 2012;15(3 Suppl): S1-S65.

Chou R: 2009 Clinical Guidelines from the American Pain Society and the American Academy of Pain Medicine on the use of chronic opioid therapy in chronic noncancer pain: What are the key messages for clinical practice? Polskie Archiwum Medycyny Wewnetrznej. 2009; 119(7-8): 469-477.

Von Korff M, Merrill JO, Rutter CM, et al.: Time-scheduled vs. pain-contingent opioid dosing in chronic opioid therapy. Pain. 2011; 152: 1256-1262.

Weschules DJ, Bain KT, Richeimer S: Actual and potential drug interactions associated with methadone. Pain Med. 2008; 9(3): 315-344.

Tan HL, Hou CJ, Lauer MR, et al.: Electrophysiologic mechanisms of the long QT interval syndromes and torsade de pointes. Ann Intern Med. 1995; 122(9): 701-714.

Krantz MJ, Martin J, Stimmel B, et al.: QTc interval screening in methadone treatment. Ann Intern Med. 2009; 150: 387-395.

Macey TA, Morasco BJ, Duckart JP, et al.: Patterns and correlates of prescription opioid use in OEF/OIF veterans with chronic noncancer pain. Pain Med. 2011; 12(10): 1502-1509.

Moss AJ: Measurement of the QT interval and the risk associated with QTc interval prolongation: A review. Am J Cardiol. 1993; 72(6): 23B-25B.

Krantz MJ, Lewkowiez L, Hays H, et al.: Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002; 137: 501-504.

Krook AL, Waal H, Hansteen V: Routine ECG in methadone-assisted rehabilitation is wrong prioritization. Tidsskr Nor Laegeforen. 2004; 124: 2940-2941.

Manchikanti L, Abdi S, Atluri S, et al.: American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2–Guidance. Pain Physician. 2012; 15(3 Suppl): S67-S116.

Kapur BM, Hutson JR, Chibber T, et al.: Methadone: A review of drug-drug and pathophysiological interactions. Crit Rev Clin Lab Sci. 2011; 48(4): 171-195.

Flockhart D: Cytochrome P450 drug interaction table, 2007. Available at Accessed May 20, 2013.

Warner M, Chen LH, Makuc DM, et al.: Drug poisoning deaths in the United States, 1980-2008. NCHS Data Brief. 2011; (81): 1-8.

Krebs EE, Becker WC, Zerzan J, et al.: Comparative mortality among Department of Veterans Affairs patients prescribed methadone or long-acting morphine for chronic pain. Pain. 2011; 152: 1789-1795.

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.

Furlan AD, Sandoval JA, Mailis-Gagnon A, et al.: Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects. CMAJ. 2006; 174: 1589-1594.

Bohnert AS, Valenstein M, Bair MJ, et al.: Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305: 1315-1321.

Deyo RA, Smith DH, Johnson ES, et al.: Prescription opioids for back pain and use of medications for erectile dysfunction. Spine. 2013; 38(11): 909-915.

Dunn KM, Saunders KW, Rutter CM, et al.: Opioid prescriptions for chronic pain and overdose: A cohort study. Ann Intern Med. 2010; 152: 85-92.

Saunders KW, Dunn KM, Merrill JO, et al.: Relationship of opioid use and dosage levels to fractures in older chronic pain patients. J Gen Intern Med. 2010; 25(4): 310-315.

Braden JB, Russo J, Fan MY, et al.: Emergency department visits among recipients of chronic opioid therapy. Arch Intern Med. 2010; 170: 1425-1432.

Kidner CL, Mayer TG, Gatchel RJ: Higher opioid doses predict poorer functional outcome in patients with chronic disabling occupational musculoskeletal disorders. J Bone Joint Surg Am. 2009; 91: 919-927.

Gomes T, Mamdani MM, Dhalla IA, et al.: Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011; 171: 686-691.

Veterans Health Administration: Pain as the 5th Vital Sign Toolkit, revised. Geriatrics and Extended Care Strategic Healthcare Group, National Pain Management Coordinating Committee, 2000. Available at Accessed August 1, 2012.

International Association for the Study of Pain: Classification of chronic pain. Pain Suppl. 1986; 3: S1–S226.

US Food and Drug Administration. Methadone use for pain control may result in death and life-threatening changes in breathing and heart rate, 2006. Available at Accessed April 20, 2012.

Morasco BJ, Duckart JP, Carr TP, et al.: Clinical characteristics of veterans prescribed high doses of opioid medications for chronic non-cancer pain. Pain. 2010; 151: 625-632.

Pollock AB, Tegeler ML, Morgan V, et al.: Morphine to methadone conversion: An interpretation of published data. Am J Hosp Palliat Care. 2011; 28: 135-140.

Mayet S, Gossop M, Lintzeris N, et al.: Methadone maintenance, QTc and torsade de pointes: Who needs an electrocardiogram and what is the prevalence of QTc prolongation? Drug Alcohol Rev. 2011; 30(4): 388-396.

Krantz MJ: Heterogeneous impact of methadone on the QTc interval: What are the practical implications? J Addict Dis. 2008; 27(4): 5-9.

Anchersen K, Clausen T, Gossop M, et al.: Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: A mortality assessment study. Addiction. 2009; 104: 993-999.

Roy AK, McCarthy C, Kiernan G, et al.: Increased incidence of QT interval prolongation in a population receiving lower doses of methadone maintenance therapy. Addiction. 2012; 107(6): 1132-1139.

Krantz MJ, Kutinsky IB, Robertson AD, et al.: Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Pharmacotherapy. 2003; 23(6): 802-805.

Martell BA, Arnsten JH, Ray B, et al.: The impact of methadone induction on cardiac conduction in opiate users. Ann Intern Med. 2003; 139: 154-155.

Noble M, Tregear SJ, Treadwell JR, et al.: Long-term opioid therapy for chronic noncancer pain: A systematic review and meta-analysis of efficacy and safety. J Pain Symptom Manage. 2008; 35: 214-228.



  • There are currently no refbacks.