Opioids for chronic noncancer pain: A meta-analysis of effectiveness and side effects
Open accessAbstract
BACKGROUND: Chronic noncancer pain (CNCP) is a major health problem, for which opioids provide one treatment option. However, evidence is needed about side effects, efficacy, and risk of misuse or addiction. METHODS: This meta-analysis was carried out with these objectives: to compare the efficacy of opioids for CNCP with other drugs and placebo; to identify types of CNCP that respond better to opioids; and to determine the most common side effects of opioids. We searched MEDLINE, EMBASE, CENTRAL (up to May 2005) and reference lists for randomized controlled trials of any opioid administered by oral or transdermal routes or rectal suppositories for CNCP (defined as pain for longer than 6 mo). Extracted outcomes included pain, function or side effects. Methodological quality was assessed with the Jadad instrument; analyses were conducted with Revman 4.2.7. RESULTS: Included were 41 randomized trials involving 6019 patients: 80% of the patients had nociceptive pain (osteoarthritis, rheumatoid arthritis or back pain); 12%, neuropathic pain (postherpetic neuralgia, diabetic neuropathy or phantom limb pain); 7%, fibromyalgia; and 1%, mixed pain. The methodological quality of 87% of the studies was high. The opioids studied were classified as weak (tramadol, propoxyphene, codeine) or strong (morphine, oxycodone). Average duration of treatment was 5 (range 1-16) weeks. Dropout rates averaged 33% in the opioid groups and 38% in the placebo groups. Opioids were more effective than placebo for both pain and functional outcomes in patients with nociceptive or neuropathic pain or fibromyalgia. Strong, but not weak, opioids were significantly superior to naproxen and nortriptyline, and only for pain relief. Among the side effects of opioids, only constipation and nausea were clinically and statistically significant. INTERPRETATION: Weak and strong opioids outperformed placebo for pain and function in all types of CNCP. Other drugs produced better functional outcomes than opioids, whereas for pain relief they were outperformed only by strong opioids. Despite the relative shortness of the trials, more than one-third of the participants abandoned treatment.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sample size was calculated a priori with G*Power, expecting moderate between-group differences, with 80% power, alpha 0.05, Cohen's d of 0.5, yielding 50 participants needed per condition.
“Sample size was calculated a priori with the statistical software G*Power [49] considering previous studies on complications of pain treatments [30,50].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Assessing the quality of reports of randomized clinical trials: Is blinding necessary?
Jadad, A. R., Moore, R. A., Carroll, D., Jenkinson, C., Reynolds, D. J. M., Gavaghan, D. J., & McQuay, H. J. (1996) · Controlled Clinical Trials · doi:10.1016/0197-2456(95)00134-4 · Cited by 17,582 · see citing works
Zhang, Q., Wang, C., Zheng, M., Li, Y., Li, J., Zhang, L., Shang, X., & Yan, C. (2014) · Cerebrovascular Diseases · doi:10.1159/000369778 · Cited by 11,609 · see citing works
Moher, D., Cook, D. J., Eastwood, S., Olkin, I., Rennie, D., & Stroup, D. F. (1999) · The Lancet · doi:10.1016/s0140-6736(99)04149-5 · Cited by 4,826 · see citing works
Dong, Y., Hao, L., Shi, Z., Wang, G., Zhang, Z., & Han, C. (2013) · Urologia Internationalis · doi:10.1159/000351405 · Cited by 4,557 · see citing works
Competing interests: none declared.
Hirsch, L. (2006) · Cited by 1,396 · see citing works
Opioids in chronic non-cancer pain: systematic review of efficacy and safety
Kalso, E., Edwards, J. E., Moore, A. R., & McQuay, H. J. (2004) · Pain · doi:10.1016/j.pain.2004.09.019 · Cited by 1,216 · see citing works
The epidemiology of chronic pain in the community
Elliott, A. M., Smith, B. H., Penny, K. I., Smith, W. C., & Chambers, W. A. (1999) · The Lancet · doi:10.1016/s0140-6736(99)03057-3 · Cited by 1,208 · see citing works
Raffa, R. B., Friderichs, E., Reimann, W., Shank, R. P., Codd, E. E., & Vaught, J. L. (1992) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)11227-5 · Cited by 1,163 · see citing works
Trials to assess equivalence: the importance of rigorous methods: Fig 1
Jones, B., Jarvis, P., Lewis, J. A., & Ebbutt, A. F. (1996) · BMJ · doi:10.1136/bmj.313.7048.36 · Cited by 1,032 · see citing works
Opioid Therapy for Chronic Pain
Ballantyne, J. C., & Mao, J. (2003) · New England Journal of Medicine · doi:10.1056/nejmra025411 · Cited by 960 · see citing works
Efficacy of oxycodone in neuronathic pain
Watson, C. B., & Babul, N. (1998) · Neurology · doi:10.1212/wnl.50.6.1837 · Cited by 649 · see citing works
Opioids versus antidepressants in postherpetic neuralgia
Raja, S. N., Haythornthwaite, J. A., Pappagallo, M., Clark, M. R., Travison, T. G., Sabeen, S., Royall, R. M., & Max, M. B. (2002) · Neurology · doi:10.1212/wnl.59.7.1015 · Cited by 593 · see citing works
Double‐blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy
Harati, Y., Gooch, C. L., Swenson, M., Edelman, S. V., Greene, D., Raskin, P., Donofrio, P., Cornblath, D., Sachdeo, R., SIU, C. O., et al. (1998) · Neurology · doi:10.1212/wnl.50.6.1842 · Cited by 543 · see citing works
Watson, P. C. N., Moulin, D. E., Watt-Watson, J. H., GORDON, A. S., & Eisenhoffer, J. (2003) · Pain · doi:10.1016/s0304-3959(03)00160-x · Cited by 508 · see citing works
Controlled-release oxycodone for pain in diabetic neuropathy
Gimbel, J. S., Richards, P. T., & Portenoy, R. K. (2003) · Neurology · doi:10.1212/01.wnl.0000057720.36503.2c · Cited by 469 · see citing works
Efficacy and Safety of Opioid Agonists in the Treatment of Neuropathic Pain of Nonmalignant Origin
Eisenberg, E., McNicol, E. D., & Carr, D. B. (2005) · JAMA · doi:10.1001/jama.293.24.3043 · Cited by 406 · see citing works
Hypogonadism in men consuming sustained-action oral opioids
Daniell, H. W. (2002) · The Journal of Pain · doi:10.1054/jpai.2002.126790 · Cited by 401 · see citing works
Randomised trial of oral morphine for chronic non-cancer pain
Moulin, D. E., Amireh, R., Sharpe, W. K. J., Boyd, D. B., Merskey, H., & Iezzi, A. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90339-6 · Cited by 390 · see citing works
Moore, R. A., & McQuay, H. J. (2005) · Arthritis Research & Therapy · doi:10.1186/ar1782 · Cited by 377 · see citing works
Efficacy and safety of patient‐controlled opioid analgesia for acute postoperative pain
Walder, B., Schafer, M., Henzi, I., & Tramèr, M. (2001) · Acta Anaesthesiologica Scandinavica · doi:10.1034/j.1399-6576.2001.045007795.x · Cited by 365 · see citing works
Epidemiology of chronic non-malignant pain in Denmark
Eriksen, J., Jensen, M. K., Sjøgren, P., Ekholm, O., & Rasmussen, N. K. (2003) · Pain · doi:10.1016/s0304-3959(03)00225-2 · Cited by 364 · see citing works
Opioid Therapy for Chronic Noncancer Back Pain
Jamison, R. N., Raymond, S. A., Slawsby, E. A., Nedeljković, S. S., & Katz, N. P. (1998) · Spine · doi:10.1097/00007632-199812010-00014 · Cited by 301 · see citing works
Duehmke, R. M., Hollingshead, J., & Cornblath, D. R. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003726.pub3 · Cited by 269 · see citing works
Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial
Boureau, F., Legallicier, P., & Kabir-Ahmadi, M. (2003) · Pain · doi:10.1016/s0304-3959(03)00020-4 · Cited by 231 · see citing works
Caldwell, J. R., Rapoport, R. J., Davis, J. C., Offenberg, H. L., Marker, H. W., Roth, S. H., Yuan, W., Eliot, L., Babul, N., & Lynch, P. M. (2002) · Journal of Pain and Symptom Management · doi:10.1016/s0885-3924(02)00383-4 · Cited by 219 · see citing works
Caldwell, J. R., Hale, M. E., Boyd, R. E., Hague, J. M., Iwan, T., Shi, M., & Lacouture, P. G. (1999) · PubMed · Cited by 216 · see citing works
Efficacy of tramadol in treatment of chronic low back pain.
Schnitzer, T. J., Gray, W. L., Paster, R. Z., & Kamin, M. (2000) · PubMed · Cited by 206 · see citing works
Efficacy of Tramadol in Treatment of Pain in Fibromyalgia
Russell, J. I., Kamin, M., Bennett, R. M., Schnitzer, T. J., Green, J. A., & Katz, W. A. (2000) · JCR Journal of Clinical Rheumatology · doi:10.1097/00124743-200010000-00004 · Cited by 196 · see citing works
RUOFF, G. E., Rosenthal, N. R., Jordan, D. M., Karim, R., & Kamin, M. (2003) · Clinical Therapeutics · doi:10.1016/s0149-2918(03)80071-1 · Cited by 186 · see citing works
Bruera, E. D. (2003) · JAMA · doi:10.1001/jama.290.18.2476 · Cited by 185 · see citing works
Peloso, P. M., Bellamy, N., Bensen, W., Thomson, G. T. D., Harsanyi, Z., Babul, N., & Darke, A. C. (2000) · PubMed · Cited by 167 · see citing works
Arkinstall, W. W., Sandler, A. N., Goughnour, B. R., Babul, N., Harsanyi, Z., & Darke, A. C. (1995) · Pain · doi:10.1016/0304-3959(94)00262-d · Cited by 163 · see citing works
Peloso, P. M. J., Fortin, L., Beaulieu, A. D., Kamin, M., & Rosenthal, N. R. (2004) · PubMed · Cited by 157 · see citing works
Maier, C., Hildebrandt, J., Klinger, R., Henrich-Eberl, C., & Lindena, G. (2002) · Pain · doi:10.1016/s0304-3959(02)00020-9 · Cited by 148 · see citing works
Kjærsgaard‐Andersen, P., Nafei, A., Skov, O., Madsen, F., Andersen, H. M., Krøner, K., Hvass, I., Gjøderum, O., Pedersen, L., & Branebjerg, P. E. (1990) · Pain · doi:10.1016/0304-3959(90)90028-c · Cited by 126 · see citing works
Emkey, R. D., Rosenthal, N. R., Wu, S., Jordan, D. M., & Kamin, M. (2004) · PubMed · Cited by 113 · see citing works
Silverfield, J. C., Kamin, M., Wu, S., & Rosenthal, N. R. (2002) · Clinical Therapeutics · doi:10.1016/s0149-2918(02)85024-x · Cited by 107 · see citing works
Roth, S. H. (1998) · PubMed · Cited by 102 · see citing works
Duehmke, R. M., Cornblath, D. R., & Hollingshead, J. (2004) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003726.pub2 · Cited by 99 · see citing works
Chronic opioid therapy for non-cancer pain
Collett, B.-J. (2001) · British Journal of Anaesthesia · doi:10.1093/bja/87.1.133 · Cited by 89 · see citing works
Gordon, D. B., Dahl, J. H., Phillips, P., Frandsen, J. L., Cowley, C., Foster, R. L., Fine, P. G., Miaskowski, C. A., Fishman, S. M., & Finley, R. S. (2004) · Pain Management Nursing · doi:10.1016/j.pmn.2004.04.001 · Cited by 83 · see citing works
Slowing the Initial Titration Rate of Tramadol Improves Tolerability
RUOFF, G. E. (1999) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.19.1.88.30515 · Cited by 72 · see citing works
Joint pain and quality of life; results of a randomised trial.
Parr, G., Darekar, B., FLETCHER, A. E., & Bulpitt, C. (1989) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1989.tb05356.x · Cited by 69 · see citing works
Fleischmann, R., Caldwell, J. R., Roth, S. H., Tesser, J., Olson, W. H., & Kamin, M. (2001) · Current Therapeutic Research · doi:10.1016/s0011-393x(01)80021-7 · Cited by 54 · see citing works
Active-control equivalence trials and antihypertensive agents
McAlister, F. A., & Sackett, D. L. (2001) · The American Journal of Medicine · doi:10.1016/s0002-9343(01)00900-7 · Cited by 49 · see citing works
Pavelká, K., Peliskov, Z., kov, H. S., Ratcliffe, S. H., & Repas, C. (1998) · Clinical Drug Investigation · doi:10.2165/00044011-199816060-00002 · Cited by 42 · see citing works
Treatment of Pain Due to Postherpetic Neuralgia with Tramadol
Göbel, H., & Stadler, T. (1995) · Clinical Drug Investigation · doi:10.2165/00044011-199510040-00003 · Cited by 23 · see citing works
Opioids versus antidepressants in postherpetic neuralgia: A randomized, placebo-controlled trial
Manfredi, P. L. (2003) · Neurology · doi:10.1212/wnl.60.6.1052-a · Cited by 20 · see citing works
Glowinski, J. G., & Boccard, E. (1999) · Clinical Drug Investigation · doi:10.2165/00044011-199918030-00003 · Cited by 9 · see citing works
Evidence of self-synergism in the antinociceptive effect of tramadol in rats.
Pozos‐Guillén, A., Aguirre-Bañuelos, P., Arellano-Guerrero, A., Hoyo‐Vadillo, C., & Pérez‐Urizar, J. (2004) · PubMed · Cited by 7 · see citing works
Wilson (1999) · doi:10.1002/1529-0131(199907)42:7
Flagged first, then by citations
1 of the 52 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
- Bruera E, Kim HN. Cancer pain. JAMA 2003;290:2476-9.
- Schnitzer TJ, Gray WL, Paster RZ, et al. Efficacy of tramadol in treatment of chronic low back pain [comment]. J Rheumatol 2000;27:772-8.
- Schnitzer TJ, Kamin M, Olson WH. Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. Arthritis Rheum 1999;42:1370-7.
- Boureau F, Boccard E. Placebo-controlled study of analgesic efficacy of 500 mg paracetamol 30 mg codeine association combined with a low dose of diclofenac versus high dose of diclofenac in rheumatoid arthritis. Acta Ther 1991;17:123-36.
- Moran C. MST continus tablets and pain control in severe rheumatoid arthritis. Br J Clin Res 1991;2:1-12.
Cited by
Sorted by citations
Chou, R., Qaseem, A., Snow, V., Casey, D., Cross, J. T., Shekelle, P., Owens, D. K., & for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians and the American College of Physicians/American Pain Society Low Back Pain Guidelines Panel* (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-147-7-200710020-00006 · Cited by 2,718 · see citing works
Zhang, W., Moskowitz, R. W., Nuki, G., Abramson, S., Altman, R. D., Arden, N., Bierma-Zeinstra, S., Brandt, K. D., Croft, P., Doherty, M., et al. (2008) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2007.12.013 · Cited by 2,796 · see citing works
Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain
Chou, R., Fanciullo, G. J., Fine, P. G., Adler, J. A., Ballantyne, J. C., Davies, P., Donovan, M. I., Fishbain, D. A., Foley, K. M., Fudin, J., et al. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2008.10.008 · Cited by 2,192 · see citing works
Pharmacologic management of neuropathic pain: Evidence-based recommendations
Dworkin, R. H., O’Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jensen, T. S., Kalso, E. A., Loeser, J. D., Miaskowski, C., Nurmikko, T. J., et al. (2007) · Pain · doi:10.1016/j.pain.2007.08.033 · Cited by 2,126 · see citing works
OARSI recommendations for the management of hip and knee osteoarthritis
Zhang, W., Nuki, G., Moskowitz, R. W., Abramson, S. B., Altman, R. D., Arden, N., Bierma‐Zeinstra, S., Brandt, K. D., Croft, P. R., Doherty, M., et al. (2010) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2010.01.013 · Cited by 1,687 · see citing works
Chou, R., Turner, J. A., Devine, E. B., Hansen, R. N., Sullivan, S. D., Blazina, I., Dana, T., Bougatsos, C., & Deyo, R. A. (2015) · Annals of Internal Medicine · doi:10.7326/m14-2559 · Cited by 1,606 · see citing works
Opioid Prescriptions for Chronic Pain and Overdose
Dunn, K. M., Saunders, K. W., Rutter, C. M., Banta‐Green, C. J., Merrill, J. O., Sullivan, M. D., Weisner, C. M., Silverberg, M. J., Campbell, C. I., Psaty, B. M., et al. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-2-201001190-00006 · Cited by 1,265 · see citing works
Opioid Epidemic in the United States
Manchikanti, L. (2012) · Pain Physician · doi:10.36076/ppj.2012/15/es9 · Cited by 1,180 · see citing works
Pharmacological Management of Persistent Pain in Older Persons
American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons, R. W. P. F. T. A. G. S. O. A. A. I. J. A. G. S. 2. (2009) · Pain Medicine · doi:10.1111/j.1526-4637.2009.00699.x · Cited by 916 · see citing works
Long-term opioid management for chronic noncancer pain
Noble, M., Treadwell, J. R., Tregear, S., Coates, V. H., Wiffen, P. J., Akafomo, C., Schoelles, K. M., & Chou, R. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006605.pub2 · Cited by 728 · see citing works
Treatment of chronic non-cancer pain
Turk, D. C., Wilson, H. D., & Cahana, A. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60402-9 · Cited by 716 · see citing works
De Facto Long-term Opioid Therapy for Noncancer Pain
Korff, M. V., Saunders, K. W., Ray, G. T., Boudreau, D. M., Campbell, C. I., Merrill, J. O., Sullivan, M. D., Rutter, C. M., Silverberg, M. J., Banta‐Green, C. J., et al. (2008) · Clinical Journal of Pain · doi:10.1097/ajp.0b013e318169d03b · Cited by 663 · see citing works
Opioids and the treatment of chronic pain: Controversies, current status, and future directions.
Rosenblum, A., Marsch, L. A., Joseph, H., & Portenoy, R. K. (2008) · Experimental and Clinical Psychopharmacology · doi:10.1037/a0013628 · Cited by 648 · see citing works
Manchikanti, L. (2008) · Pain Physician · doi:10.36076/ppj.2008/11/s63 · Cited by 642 · see citing works
THE EFFECTS OF SPINAL CORD STIMULATION IN NEUROPATHIC PAIN ARE SUSTAINED
Kumar, K., Taylor, R. S., Jacques, L. G., Eldabe, S. S., Meglio, M., Molet, J., Thomson, S., O’Callaghan, J., Eisenberg, E., Milbouw, G., et al. (2008) · Neurosurgery · doi:10.1227/01.neu.0000325731.46702.d9 · Cited by 638 · see citing works
Evidence for Improving Palliative Care at the End of Life: A Systematic Review
Lorenz, K., Lynn, J., Dy, S. M., Shugarman, L. R., Wilkinson, A., Mularski, R. A., Morton, S. C., Hughes, R. G., Hilton, L. K., Maglione, M., et al. (2008) · Annals of Internal Medicine · doi:10.7326/0003-4819-148-2-200801150-00010 · Cited by 590 · see citing works
Chou, R., & Huffman, L. H. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-147-7-200710020-00008 · Cited by 583 · see citing works
Fishbain, D. A., Cole, B., Lewis, J. E., Rosomoff, H. L., & Rosomoff, R. S. (2007) · Pain Medicine · doi:10.1111/j.1526-4637.2007.00370.x · Cited by 565 · see citing works
Therapeutic Use, Abuse, and Nonmedical Use of Opioids: A Ten-Year Perspective
Manchikanti, L. (2010) · Pain Physician · doi:10.36076/ppj.2010/13/401 · Cited by 535 · see citing works
Trends in long‐term opioid therapy for chronic non‐cancer pain
Boudreau, D. M., Korff, M. V., Rutter, C. M., Saunders, K. W., Ray, G. T., Sullivan, M. D., Campbell, C. I., Merrill, J. O., Silverberg, M. J., Banta‐Green, C. J., et al. (2009) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1833 · Cited by 522 · see citing works
Seal, K. H., Shi, Y., Cohen, G., Cohen, B. E., Maguen, S., Krebs, E. E., & Neylan, T. C. (2012) · JAMA · doi:10.1001/jama.2012.234 · Cited by 515 · see citing works
Reid, K. J., Harker, J., Bala, M. M., Truyers, C., Kellen, E., Bekkering, G. E., & Kleijnen, J. (2011) · Current Medical Research and Opinion · doi:10.1185/03007995.2010.545813 · Cited by 476 · see citing works
Trends and predictors of opioid use after total knee and total hip arthroplasty
Goesling, J., Moser, S. E., Zaidi, B., Hassett, A. L., Hilliard, P., Hallstrom, B., Clauw, D. J., & Brummett, C. M. (2016) · Pain · doi:10.1097/j.pain.0000000000000516 · Cited by 461 · see citing works
Humphreys, K. N., Shover, C. L., Andrews, C. M., Bohnert, A. S. B., Brandeau, M. L., Caulkins, J. P., Chen, J. H., Cuéllar, M.-F., Hurd, Y. L., Juurlink, D. N., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(21)02252-2 · Cited by 463 · see citing works
Opioid dependence and addiction during opioid treatment of chronic pain
Ballantyne, J. C., & LaForge, S. K. (2007) · Pain · doi:10.1016/j.pain.2007.03.028 · Cited by 445 · see citing works
Manchikanti, L. (2008) · Pain Physician · doi:10.36076/ppj.2008/11/s5 · Cited by 430 · see citing works
Cannabinoids for treatment of chronic non‐cancer pain; a systematic review of randomized trials
Lynch, M. E., & Campbell, F. (2011) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2011.03970.x · Cited by 397 · see citing works
ASIPP, A. (2012) · Pain Physician · doi:10.36076/ppj.2012/15/s67 · Cited by 426 · see citing works
Chou, R., Ballantyne, J. C., Fanciullo, G. J., Fine, P. G., & Miaskowski, C. A. (2009) · Journal of Pain · doi:10.1016/j.jpain.2008.10.007 · Cited by 384 · see citing works
Opiates and elderly: use and side effects
Chau, D. (2008) · Clinical Interventions in Aging · doi:10.2147/cia.s1847 · Cited by 383 · see citing works
Sullivan, M. D., Edlund, M. J., Fan, M.-Y., DEVRIES, A. R., Braden, J. B., & Martin, B. C. (2008) · Pain · doi:10.1016/j.pain.2008.04.027 · Cited by 374 · see citing works
Chou, R., Fanciullo, G. J., Fine, P. G., Miaskowski, C. A., Passik, S. D., & Portenoy, R. K. (2009) · Journal of Pain · doi:10.1016/j.jpain.2008.10.009 · Cited by 365 · see citing works
Efficacy of Opioids for Chronic Pain: A Review of the Evidence
Ballantyne, J., & Shin, N. S. (2008) · The Clinical Journal of Pain · doi:10.1097/ajp.0b013e31816b2f26 · Cited by 361 · see citing works
Opiate Therapy in Chronic Cough
Morice, A. H., Menon, M. S., Mulrennan, S. A., Everett, C. F., Wright, C., Jackson, J., & Thompson, R. L. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200607-892oc · Cited by 361 · see citing works
Opioid Prescribing: A Systematic Review and Critical Appraisal of Guidelines for Chronic Pain
Nuckols, T. K., Anderson, L., Popescu, I., Diamant, A. L., Doyle, B. J., Capua, P. D., & Chou, R. (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-160-1-201401070-00732 · Cited by 349 · see citing works
Oral or transdermal opioids for osteoarthritis of the knee or hip
da Costa, B. R., Nüesch, E., Kasteler, R., Husni, M. E., Welch, V. A., Rutjes, A. W., & Jüni, P. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003115.pub4 · Cited by 348 · see citing works
Bender, A., Scheiber, J., Glick, M., Davies, J. W., Azzaoui, K., Hamon, J., Urbán, L., Whitebread, S., & Jenkins, J. L. (2007) · ChemMedChem · doi:10.1002/cmdc.200700026 · Cited by 324 · see citing works
Ambulatory Diagnosis and Treatment of Nonmalignant Pain in the United States, 2000–2010
Daubresse, M., Chang, H., Yu, Y., Viswanathan, S., Shah, N. D., Stafford, R. S., Kruszewski, S. P., & Alexander, G. C. (2013) · Medical Care · doi:10.1097/mlr.0b013e3182a95d86 · Cited by 318 · see citing works
Towards a mechanism-based approach to pain management in osteoarthritis
Malfait, A., & Schnitzer, T. J. (2013) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2013.138 · Cited by 310 · see citing works
Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews
Kroenke, K., Krebs, E. E., & Bair, M. J. (2009) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2008.12.006 · Cited by 308 · see citing works
Challenges in Using Opioids to Treat Pain in Persons With Substance Use Disorders
Savage, S. R., Kirsh, K. L., & Passik, S. D. (2008) · Addiction Science & Clinical Practice · doi:10.1151/ascp08424 · Cited by 291 · see citing works
Pharmacologic interventions for treating phantom limb pain
Alviar, M. J. M., Hale, T., & Dungca, M. L. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006380.pub3 · Cited by 288 · see citing works
Use and misuse of opioids in chronic pain
Volkow, N., Benveniste, H., & McLellan, A. T. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-011817-044739 · Cited by 279 · see citing works
Noble, M., Tregear, S., Treadwell, J. R., & Schoelles, K. M. (2008) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2007.03.015 · Cited by 274 · see citing works
Opioids for chronic noncancer pain
Franklin, G. M. (2014) · Neurology · doi:10.1212/wnl.0000000000000839 · Cited by 272 · see citing works
The Comparative Safety of Opioids for Nonmalignant Pain in Older Adults
Solomon, D. H. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.450 · Cited by 251 · see citing works
Goplen, C. M., Verbeek, W., Kang, S. H., Jones, C., Voaklander, D. C., Churchill, T. A., & Beaupré, L. A. (2019) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-019-2619-8 · Cited by 249 · see citing works
Manchikanti, L., Abdi, S., Atluri, S. L., Balog, C. C., Benyamin, R. M., Boswell, M. V., Brown, K. R., Bruel, B. M., Bryce, D. A., Burks, P. A., et al. (2012) · PubMed · Cited by 243 · see citing works
The Impact of Virtual Reality on Chronic Pain
Jones, T., Moore, T., & Choo, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167523 · Cited by 241 · see citing works
Cantrill, S. V., Brown, M. D., Carlisle, R. J., Delaney, K. A., Hays, D. P., Nelson, L. S., O’Connor, R. E., Papa, A. R., Sporer, K. A., Todd, K. H., et al. (2012) · Annals of Emergency Medicine · doi:10.1016/j.annemergmed.2012.06.013 · Cited by 240 · see citing works
Papaleontiou, M., Henderson, C., Turner, B. J., Moore, A. A., Olkhovskaya, Y., Amanfo, L., & Reid, M. C. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02920.x · Cited by 231 · see citing works
Opioid therapy for chronic pain in the United States: Promises and perils
Sullivan, M. D., & Howe, C. Q. (2013) · Pain · doi:10.1016/j.pain.2013.09.009 · Cited by 231 · see citing works
Afilalo, M., Etropolski, M. S., Kuperwasser, B., Kelly, K., Okamoto, A., Hove, I. V., Steup, A., Lange, B., Rauschkolb, C., & Häeussler, J. (2010) · Clinical Drug Investigation · doi:10.2165/11533440-000000000-00000 · Cited by 228 · see citing works
Diabetic Neuropathies: Diagnosis and Management
Deli, G., Bosnyák, E., Pusch, G., Komoly, S., & Fehér, G. (2013) · Neuroendocrinology · doi:10.1159/000358728 · Cited by 229 · see citing works
National Drug Control Policy and Prescription Drug Abuse: Facts and Fallacies
Manchikanti, L. (2007) · Pain Physician · doi:10.36076/ppj.2007/10/399 · Cited by 220 · see citing works
Osteoarthritis- a systematic review of long-term safety implications for osteoarthritis of the knee
Charlesworth, J., Fitzpatrick, J., Perera, N. K. P., & Orchard, J. W. (2019) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-019-2525-0 · Cited by 219 · see citing works
Tapering Long-term Opioid Therapy in Chronic Noncancer Pain
Berna, C., Kulich, R. J., & Rathmell, J. P. (2015) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2015.04.003 · Cited by 217 · see citing works
Trends in Long-term Opioid Therapy for Non-Cancer Pain among Persons with a History of Depression
Braden, J., Sullivan, M., Ray, G., Saunders, K. W., Merrill, J., Silverberg, M., Rutter, C., Weisner, C., Banta-Green, C. J., Campbell, C. I., et al. (2009) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2009.07.003 · Cited by 209 · see citing works
Thompson, T., Oram, C., Correll, C. U., Tsermentseli, S., & Stubbs, B. (2017) · The Journal of Pain · doi:10.1016/j.jpain.2016.11.009 · Cited by 202 · see citing works
Opioids for the Treatment of Chronic Pain: Mistakes Made, Lessons Learned, and Future Directions
Ballantyne, J. C. (2017) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000002500 · Cited by 203 · see citing works
Genetic predictors of human chronic pain conditions
Zorina-Lichtenwalter, K., Meloto, C. B., Khoury, S., & Diatchenko, L. B. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.04.041 · Cited by 192 · see citing works
Integrative Medicine Therapies for Pain Management in Cancer Patients
Deng, G. E. (2019) · The Cancer Journal · doi:10.1097/ppo.0000000000000399 · Cited by 195 · see citing works
The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain
Chou, R., Deyo, R. A., Devine, B., Hansen, R. N., Sullivan, S., Jarvik, J. G., Blazina, I., Dana, T., Bougatsos, C., & Turner, J. E. (2014) · doi:10.23970/ahrqepcerta218 · Cited by 186 · see citing works
Opioids for chronic noncancer pain: A position paper of the American Academy of Neurology
Katz, J. A. (2015) · Neurology · doi:10.1212/wnl.0000000000001485 · Cited by 186 · see citing works
Urine Drug Testing In Chronic Pain
Christo, P. J. (2011) · Pain Physician · doi:10.36076/ppj.2011/14/123 · Cited by 180 · see citing works
A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury
Teasell, R. W., Mehta, S., Aubut, J.-A. L., Foulon, B. L., Wolfe, D. L., Hsieh, J., Townson, A. F., & Short, C. (2010) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2010.01.022 · Cited by 182 · see citing works
Karanges, E. A., Blanch, B., Buckley, N. A., & Pearson, S. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12937 · Cited by 181 · see citing works
Opioids for chronic noncancer pain: a new Canadian practice guideline
Furlan, A. D., Reardon, R., Weppler, C., & for the National Opioid Use Guideline Group (NOUGG) (2010) · Canadian Medical Association Journal · doi:10.1503/cmaj.100187 · Cited by 180 · see citing works
Holman, J., Stoddard, G. J., & Higgins, T. F. (2013) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.l.00619 · Cited by 178 · see citing works
Kahan, M., Mailis, A., Wilson, L., & Srivastava, A. (2011) · Europe PMC (PubMed Central) · Cited by 177 · see citing works
Opioid system and human emotions
Nummenmaa, L., & Tuominen, L. (2018) · British Journal of Pharmacology · doi:10.1111/bph.13812 · Cited by 178 · see citing works
Morasco, B. J., Duckart, J. P., Carr, T. P., Deyo, R. A., & Dobscha, S. K. (2010) · Pain · doi:10.1016/j.pain.2010.08.002 · Cited by 176 · see citing works
A Pilot Cohort Study of the Determinants of Longitudinal Opioid Use After Surgery
Carroll, I. R., Barelka, P. L., Wang, C. K. M., Wang, B. M., Gillespie, M., McCue, R., Younger, J., Trafton, J. A., Humphreys, K. N., Goodman, S. B., et al. (2012) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e31825c049f · Cited by 175 · see citing works
Interventions for the reduction of prescribed opioid use in chronic non-cancer pain
Eccleston, C., Fisher, E., Thomas, K. H., Hearn, L., Derry, S., Stannard, C., Knaggs, R., & Moore, A. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010323.pub3 · Cited by 173 · see citing works
Chapman, C. R., Lipschitz, D. L., Angst, M. S., Chou, R., Denisco, R. C., Donaldson, G. W., Fine, P. G., Foley, K. M., Gallagher, R. M., Gilson, A. M., et al. (2010) · Journal of Pain · doi:10.1016/j.jpain.2010.02.019 · Cited by 172 · see citing works
Neuromodulatory treatments for chronic pain: efficacy and mechanisms
Jensen, M. P., Day, M. A., & Miró, J. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.12 · Cited by 172 · see citing works
Opioids for chronic low-back pain
Deshpande, A., Furlan, A. D., Mailis, A., Atlas, S. J., & Turk, D. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004959.pub3 · Cited by 171 · see citing works
Effectiveness of opioids in the treatment of chronic non-cancer pain
Trescot, A. M. (2008) · Pain Physician · doi:10.36076/ppj.2008/11/s181 · Cited by 169 · see citing works
Efficacy and safety of opioids for osteoarthritis: a meta-analysis of randomized controlled trials
Avouac, J., Gossec, L., & Dougados, M. (2007) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2007.02.006 · Cited by 165 · see citing works
A Systematic Review of Randomized Trials of Long-Term Opioid Management for Chronic Non-Cancer Pain
Manchikanti, L. (2011) · Pain Physician · doi:10.36076/ppj.2011/14/91 · Cited by 176 · see citing works
Trends in opioid use and dosing among socio-economically disadvantaged patients.
Gomes, T., Juurlink, D. N., Dhalla, I. A., Mailis, A., Paterson, J. M., & Mamdani, M. (2011) · Europe PMC (PubMed Central) · Cited by 161 · see citing works
Consenso brasileiro do tratamento da fibromialgia
Heymann, R. E., Paiva, E. D. S., Helfenstein, M., Pollak, D. F., Martinez, J. E., Provenza, J. R., de Paula, A. P., Althoff, A. C., Souza, E. J. R., Neubarth, F., et al. (2010) · Revista Brasileira de Reumatologia · doi:10.1590/s0482-50042010000100006 · Cited by 160 · see citing works
Busse, J. W., Bartlett, S. J., Dougados, M., Johnston, B. C., Guyatt, G. H., Kirwan, J., Kwoh, K. C., Maxwell, L. J., Moore, A., Singh, J. A., et al. (2015) · The Journal of Rheumatology · doi:10.3899/jrheum.141440 · Cited by 157 · see citing works
Effectiveness of Long-Term Opioid Therapy for Chronic Non-Cancer Pain
Manchikanti, L. (2011) · Pain Physician · doi:10.36076/ppj.2011/14/e133 · Cited by 154 · see citing works
Kaplovitch, E., Gomes, T., Camacho, X., Dhalla, I. A., Mamdani, M., & Juurlink, D. N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134550 · Cited by 153 · see citing works
Oxycodone: a review of its use in the management of pain
Riley, J. L., Eisenberg, E., Müller-Schwefe, G. H. H., Drewes, A. M., & Arendt‐Nielsen, L. (2007) · Current Medical Research and Opinion · doi:10.1185/030079908x253708 · Cited by 153 · see citing works
Trends in Prescription of Opioids From 2003–2009 in Persons With Knee Osteoarthritis
Wright, E. A., Katz, J. N., Abrams, S. K., Solomon, D. H., & Losina, E. (2014) · Arthritis Care & Research · doi:10.1002/acr.22360 · Cited by 152 · see citing works
Opioids and endocrine dysfunction
Seyfried, O., & Hester, J. (2012) · British Journal of Pain · doi:10.1177/2049463712438299 · Cited by 149 · see citing works
Pain Treatment in Arthritis-Related Pain: Beyond NSAIDs
van de Laar, M. A. F. J., Pergolizzi, J. V., Mellinghoff, H.-U., Merchante, I. M., Nalamachu, S., O'Brien, J., Perrot, S., & Raffa, R. B. (2012) · The Open Rheumatology Journal · doi:10.2174/1874312901206010320 · Cited by 149 · see citing works
Chronic pain, opioid prescriptions, and mortality in Denmark: A population-based cohort study
Ekholm, O., Kurita, G. P., Hjsted, J., Juel, K., & Sjøgren, P. (2014) · Pain · doi:10.1016/j.pain.2014.07.006 · Cited by 147 · see citing works
Argoff, C. E., & Silvershein, D. I. (2009) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(11)60749-0 · Cited by 141 · see citing works
Chou, R. (2009) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.741 · Cited by 140 · see citing works
Wolfert, M. Z., Gilson, A. M., Dahl, J. L., & Cleary, J. F. (2009) · Pain Medicine · doi:10.1111/j.1526-4637.2009.00761.x · Cited by 137 · see citing works
Pain mechanisms and their implication for the management of pain in farm and companion animals
Viñuela-Fernández, I., Jones, E., Welsh, E. M., & Fleetwood-Walker, S. M. (2007) · The Veterinary Journal · doi:10.1016/j.tvjl.2007.02.002 · Cited by 135 · see citing works
Hale, M. E., Upmalis, D. H., Okamoto, A., Lange, C., & Rauschkolb, C. (2009) · Current Medical Research and Opinion · doi:10.1185/03007990902816970 · Cited by 133 · see citing works
Chronic morphine use does not induce peripheral tolerance in a rat model of inflammatory pain
Zöllner, C., Mousa, S. A., Fischer, O., Rittner, H. L., Shaqura, M. A., Brack, A., Shakibaei, M., Binder, W., Urban, F., Stein, C., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci25911 · Cited by 130 · see citing works
Psychiatry and Pain Management: at the Intersection of Chronic Pain and Mental Health
Goesling, J., Lin, L. A., & Clauw, D. J. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0872-4 · Cited by 130 · see citing works
Manchikanti, L., Abdi, S., Atluri, S. L., Balog, C. C., Benyamin, R. M., Boswell, M. V., Brown, K. R., Bruel, B. M., Bryce, D. A., Burks, P. A., et al. (2012) · PubMed · Cited by 129 · see citing works
Townsend, C. O., Kerkvliet, J. L., Bruce, B. K., Rome, J. D., Hooten, M. W., Luedtke, C. A., & Hodgson, J. E. (2008) · Pain · doi:10.1016/j.pain.2008.08.005 · Cited by 128 · see citing works
Goesling, J., Henry, M. J., Moser, S. E., Rastogi, M., Hassett, A., Clauw, D., & Brummett, C. (2015) · Journal of Pain · doi:10.1016/j.jpain.2015.05.010 · Cited by 110 · see citing works
- Authors
- Furlan, A. D.
- Affiliations
- Toronto Western Hospital (CA)
- Corresponding author
- Furlan, A. D.
- ORCID
- Furlan, A. D.
- Venue
- Canadian Medical Association Journal
- Publisher
- CMA Impact Inc.
- Published
- 2006-05-23
- Volume
- 174
- Issue
- 11
- Pages
- 1589-1594
- ISSN
- 0820-3946 (ISSN-L)
- 1488-2329
- PMC
- PMC1459894
- OpenAlex
- W2160172135
- Cited by
- 873
- References
- 52
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 36 · 2023: 23 · 2022: 26 · 2021: 21 · 2020: 43 · 2019: 38 · 2018: 30 · 2017: 63 · 2016: 50 · 2015: 65 · 2014: 59 · 2013: 53 · 2012: 65
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Canadian Medical Association Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Toronto
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Keywords
- chronic non-cancer pain, opioids, opioid efficacy, opioid side effects, strong opioids, weak opioids, tramadol, morphine, oxycodone, constipation, nausea, fibromyalgia, neuropathic pain, nociceptive pain, back pain, osteoarthritis, rheumatoid arthritis, postherpetic neuralgia, treatment discontinuation
- MeSH terms
- Analgesics, Opioid, Chronic Disease, Humans, Pain, Pain Measurement, Placebos, Randomized Controlled Trials as Topic, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
