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#103 Duloxetine (Cymbalta®): Jack of All Trades, Master of None?


CLINICAL QUESTION
How safe and effective is duloxetine for the treatment of chronic painful conditions?

BOTTOM LINE
Compared to placebo, duloxetine appears efficacious in neuropathic pain, improving pain by 50% or more for one in six people. One in 18 people (over placebo) will have to quit due to adverse events. 


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EVIDENCE
Compared to placebo: meta-analysis1 of three Randomized Controlled Trials (RCTs) with 1,139 diabetic peripheral neuropathy patients over 12 weeks. 
  • ≥50% improvement in pain: duloxetine 47% vs. placebo 29% (Number Needed to Treat (NNT) 6). 
    • Mean pain scores improved 2.66 with duloxetine and 1.62 on placebo (on 0–10 scale). 
  • Adverse events leading to discontinuation: duloxetine 60 mg/day 13.9% vs. placebo 8.3% (Number Needed to Harm (NNH) 18). 
    • Adverse events included nausea (NNH 9), somnolence (NNH 14), dry mouth (NNH 17), and dizziness (NNH 21). 
  • Increasing dose no advantage: no difference in response but more adverse events. 
Compared to other neuropathic pain medications: 
  • RCT2 of 804 diabetic peripheral neuropathy patients treated with either duloxetine 60 mg/day or pregabalin 300 mg/day for eight weeks.    
    • ≥50% improvement in pain: duloxetine 40% vs. pregabalin 28% (NNT 9). 
    • ~12% discontinued treatment due to adverse effects in both groups. 
    • Trial sponsored by manufacturer of Cymbalta®. 
  • Previous small trials showed no conclusive difference between duloxetine and amitriptyline3,4 or pregabalin4,5 in neuropathic pain. 
  Context: 
  • Duloxetine is also efficacious in other chronic painful conditions, including fibromyalgia6 (NNT 8), chemotherapy-induced neuropathic pain (NNT ~9),7 and osteoarthritis of the knee (NNT 6–8).8,9  
  • For depression, duloxetine has similar efficacy and overall safety to other second generation antidepressants, with no clear advantages compared to other agents.10 
  • Duloxetine trials are at moderate-to-high risk of bias: industry funding, short duration, high risk of selective outcome reporting, high drop-out rates, multiple outcomes without adjustment and possible selective publication.     
 

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Author(s):

  • G. Michael Allan MD CCFP
  • Ricky D. Turgeon BSc(Pharm) ACPR PharmD

1. Lunn MP, Highes RA, Wiffen PJ. Cochrane Database Syst Rev. 2009; (4):CD007115.

2. Tesfaye S, Wilhelm S, Lledo A, et al. Pain. 2013; 154(12):2616–25.

3. Kaur H, Hota D, Bhansali A, et al. Diabetes Care. 2011; 34:818–22.

4. Boyle J, Eriksson ME, Gribble L, et al. Diabetes Care. 2012; 35:2451–8.

5. Tanenberg RJ, Irving GA, Risser RC, et al. Mayo Clin Proc. 2011; 86:615–24.

6. Hauser W, Urrutia G, Tort S, et al. Cochrane Database Syst Rev. 2013; (1):CD010292.

7. Lavoie Smith EM, Pang H, Cirrincione C, et al. JAMA. 2013; 309:1359–67.

8. Frakes EP, Risser RC, Ball TD, et al. Curr Med Res Opin. 2011; 27:2361–72.

9. Hochberg MC, Wohlreich M, Gaynor P, et al. J Rheumatol. 2012; 39:352–8.

10. Cipriani A, Koesters M, Furukawa TA, et al. Cochrane Database Syst Rev. 2012; (10):CD006533.

Authors do not have any conflicts of interest to declare.