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#25 Gabapentin & Chronic Pain: Missing Evidence and Real Effect?


CLINICAL QUESTION
QUESTION CLINIQUE
What is the evidence to support gabapentin (or pregabalin) in chronic peripheral neuropathic pain?


BOTTOM LINE
RÉSULTAT FINAL
The apparent benefit of gabapentin in chronic pain was exaggerated by publication and reporting biases. In carefully selected patients with peripheral neuropathic pain, gabapentin may offer moderate or more pain relief for 1 in every 6-8 patients but causes adverse events in a similar number. There is no trial evidence pregabalin is superior to gabapentin.   



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EVIDENCE
DONNÉES PROBANTES
Review of 20 Randomized Controlled Trials (RCTs) of gabapentin for off-label use (primarily 17/20 for pain).1   
  • Eight were never published (40%). 
  • Reporting of outcomes in 12 published studies:  
    • Only four used the planned primary outcome.   
    • Of 180 predefined secondary, 122 (68%) not reported.  
Meta-Analysis of all trials conducted up to 2009 (including unpublished).2  
  • Moderate-marked improvement in pain occurs in 13-17.5% more patients than placebo.  
    • Number Needed to Treat (NNT) = 6-8 (two weeks). 
    • Efficacy greatest in post-herpetic neuralgia.   
    • No benefit for acute pain or in dose escalation beyond 900mg (but more adverse events). 
  • Adverse events: NNH 8 (dizziness, somnolence, gait disturbance, peripheral edema, etc.).
Cochrane review of 37 studies (5,914 patients) of gabapentin for 12 chronic pain conditions (78% neuropathic pain types).3 
  • NNT for moderate benefit was 5-7 and for substantial benefit was 6-7.
Context:   
  • An older Cochrane review4 (of published studies only) reported a more optimistic estimate of pain relief in chronic pain, NNT 3-4.  
    • Another review5 found similar. 
  • Pregabalin best case: Effective peripheral chronic pain relief is NNT ~8 based on published plus unpublished studies.6 
    • Common Drug Review7 reported pregabalin was intermittently (but not consistently) better than placebo.  
      • No direct clinical trial evidence for superiority over gabapentin.  
      • One trial had an active comparator:  Pregabalin not superior to placebo but tricyclic antidepressant was. 
  • Other reviews suggest tricyclic antidepressants are similar8 or perhaps superior8,9 to gabapentin or pregabalin.  This evidence may be biased by time and trial quality.8  
  • While publication bias and selective reporting likely occur more in industry funded research, non-profit funded RCTs also selectively report outcomes.10   
updated dec 16 2017 by ricky


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Author(s)
Auteur(s)
  • G. Michael Allan MD CCFP
  • Ken L. Basset MD PhD

1. Vedula SS, Bero L, Scherer RW, et al. N Engl J Med. 2009; 361:1963-71.

2. Therapeutics Letter 2009; 75. Available at: http://www.ti.ubc.ca/PDF/75.pdf Accessed November 21, 2013.

3. Wiffen PJ, Derry S, Bell RF, et al. Cochrane Database System Rev. 2017;6:CD007938.

4. Wiffen PJ, McQuay HJ, Edwards JE, et al. Cochrane Database Syst Rev. 2005 Jul 20; (3):CD005452.

5. Therapeutics Letter 2000; 33. Available at: http://www.ti.ubc.ca/PDF/33.PDF Accessed November 21, 2013.

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

7. Pregabalin resubmission. CDR 2009. Available at: http://www.cadth.ca/media/cdr/complete/cdr_complete_Lyrica%20Resubmission_September_25-2009.pdf Accessed November 21, 2013.

8. Chou R, Carson S, Chan BK. J Gen Intern Med. 2009; 24(2):178–88.

9. Wong MC, Chung JW, Wong TK. BMJ. 2007; 335(7610):87.

10. Chan AW, Krieza-Jerić K, Schmid I, et al. CMAJ. 2004; 171(7):735-40.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 16/12/2017

By: Ricky D Turgeon BSc(Pharm) ACPR PharmD

Comments:

Evidence Updated: Updated Cochrane review, unpublished pregabalin data added to context; Bottom Line: Unchanged.

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