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#149 Burning Issues and Aching Questions: Tramadol for osteoarthritic and neuropathic pain


CLINICAL QUESTION
Is tramadol effective for neuropathic or osteoarthritic pain?

BOTTOM LINE
Compared to placebo, tramadol reduces neuropathic and osteoarthritic pain by ≥50% for one in five people with one in 8-12 stopping for adverse effects. Although comparisons are limited, pain control with tramadol appears to be similar to gabapentin (neuropathic pain) and maybe similar or better than opioids or diclofenac (osteoarthritis).   


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EVIDENCE
  • For neuropathic pain: 
    • Tramadol alone: Two systematic reviews [6-7 Randomized Controlled Trials (RCTs)]:1,2 
      • ≥50% pain reduction: 46% tramadol, 27% placebo, Number Needed to Treat (NNT)=5 over 4-9 weeks.1 
        • Other found NNT=4 at ~6 weeks.2  
      • Adverse effects causing withdrawal:1,2 Number Needed to Harm (NNH)=8-12. 
    • Tramadol with acetaminophen:  
      • RCT (313 diabetic neuropathy patients) versus placebo:3  
        • Achieved 30% pain reduction: NNT=6.  
      • Open-label RCT (163 diabetic neuropathy patients): No difference in pain intensity versus gabapentin.4  
    • Tramadol increased nausea/vomiting, NNH=12. Issues: Possible publication bias,1 high loss to follow-up,2,4 some studies too flawed for meaningful interpretation,2 underpowered.4 
  • For osteoarthritis: 
    • Systematic review (11 RCTs),5,6 targeting ≥50% pain reduction at ~35 days: 
      • Versus placebo (four RCTs): 
        • 71% versus 51%, NNT=5. 
        • More stopping due to adverse effects, NNH=8. 
      • Versus other opioids or diclofenac (three RCTs): 
        • 63% versus 47%, NNT=7. 
        • Adverse effects causing withdrawal higher with tramadol in two of three comparisons (including diclofenac). 
      • Limitations: Systematic review author employed by manufacturer, most studies manufacturer sponsored, randomization process often not described. 
    • Two small RCTs tramadol versus diclofenac: No efficacy difference.7,8 Adverse effects higher with tramadol.   
Context: 
  • Systematic review of neuropathic pain found NNT and NNH similar for most drugs versus placebo.1 
  • Osteoarthritis response with opioids: NNT=10, with NNH to stop drug due to adverse effects=21.9 
  • Underpowered and potentially biased study found tramadol had similar rates of “abuse” with NSAIDs, and lower rates than hydrocodone.10  
    • Reports of abuse and deaths from tramadol are increasing.11,12 
  • Cohort data suggests seizures are rare (<1%), but more likely in those predisposed.13-15 
  • Tramadol delayed release costs ~$75/month (200mg daily). Tramacet (two tabs QID) costs ~$185/month.16 
    • Not covered in many jurisdictions due to insufficient evidence of superiority over less expensive agents.17 
October 26, 2015

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Author(s):

  • Adrienne J Lindblad BSP ACPR PharmD
  • Lisa Freeman MD CCFP

1. Finnerup NB, Attal N, Haroutounian S, et al. Lancet Neurol. 2015; 14:162-73.

2. Duehmke RM, Hollinshead J, Cornblath DR. Cochrane Database Syst Rev. 2006; 3:CD003726.

3. Chaparro LE, Wiffen PJ, Moore RA, et al. Cochrane Database Syst Rev. 2012; 7:CD008943.

4. Ko SH, Kwon HS, Yu JM, et al. Diabet Med. 2010; 27:1033-1040.

5. Cepeda MS, Camargo F, Zea C, et al. Cochrane Database Syst Rev. 2006; 3:CD005522.

6. Cepeda MS, Camargo F, Zea C, et al. J Rheumatol. 2007; 34:543-55.

7. Pavelka K, Pelisková Z, Stehliková H, et al. Clin Drug Investig. 1998; 16(6):421-9.

8. Beaulieu AD, Peloso PM, Haraoui B, et al. Pain Res Manag. 2008; 13(2):103-10.

9. da Costa BR, Nüesch E, Kasteler R, et al. Cochrane Database Syst Rev. 2014; 9:CD003115.

10. Adams EH, Breiner J, Cicero TJ, et al. J Pain Symptom Manage. 2006; 31:465-76.

11. Randall C, Crane J. J Forensic Leg Med. 2014; 23:32-6.

12. Winstock AR, Borschmann R, Bell J. Int J Clin Pract. 2013; 68:1147-51.

13. Gardner JS, Blough D, Drinkard CR, et al. Pharmacotherapy. 2000; 20:1423-31.

14. Gasse C, Derby L, Vasilakis-Scaramozza C, et al. Pharmacotherapy. 2000; 20:629-34.

15. Jick H, Derby LE, Vasilakis C, et al. Pharmacotherapy. 1998; 18:607-11.

16. Regier L. Chronic Non-cancer Pain: General Considerations. RxFiles drug comparison charts. RxFiles 10th ed. Saskatoon, SK. Saskatoon Health Region; 2014. p. 95-97. Available from: www.Rxfiles.ca. Last accessed: July 9, 2015.

17. Canadian Agency for Drugs and Technology in Health. CEDAC Final recommendation and reasons for recommendation: tramadol hydrochloride/acetaminophen. Available at: https://www.cadth.ca/media/cdr/complete/cdr_complete_Tramacet_May17-07.pdf. Last accessed: June 8, 2015.

Authors do not have any conflicts of interest to declare.