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Meta-Analysis
. 2009 Feb;24(2):178-88.
doi: 10.1007/s11606-008-0877-5. Epub 2008 Dec 17.

Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials

Roger Chou  1 , Susan Carson, Benjamin K S Chan
Affiliations
Meta-Analysis

Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials

Roger Chou et al. J Gen Intern Med. 2009 Feb.

Erratum in

  • J Gen Intern Med. 2009 Oct;24(10):1172

Abstract

Background: Previous systematic reviews concluded that tricyclics antidepressants are superior to gabapentin for neuropathic pain, but were based on indirect comparisons from placebo-controlled trials.

Purpose: To evaluate gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia, using direct and indirect comparisons.

Data sources: MEDLINE (1966 to March Week 4 2008), the Cochrane central register of controlled trials (1st quarter 2008), and reference lists.

Study selection: We selected randomized trials directly comparing gabapentin versus tricyclic antidepressants or comparing either of these medications versus placebo.

Data extraction: Studies were reviewed, abstracted, and quality-rated by two independent investigators using predefined criteria.

Data synthesis: We performed a meta-analysis of head-to-head trials using a random effects model and compared the results to an adjusted indirect analysis of placebo-controlled trials.

Results: In three head-to-head trials, there was no difference between gabapentin and tricyclic antidepressants for achieving pain relief (RR 0.99, 95% CI 0.76 to 1.29). In adjusted indirect analyses, gabapentin was worse than tricyclic antidepressants for achieving pain relief (RR = 0.41, 95% CI 0.23 to 0.74). The discrepancy between direct and indirect analyses was statistically significant (p = 0.008). Placebo-controlled tricyclic trials were conducted earlier than the gabapentin trials, reported lower placebo response rates, had more methodological shortcomings, and were associated with funnel plot asymmetry.

Conclusions: Though direct evidence is limited, we found no difference in likelihood of achieving pain relief between gabapentin and tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia. Indirect analyses that combine data from sets of trials conducted in different eras can be unreliable.

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Figures

Figure 1
Figure 1
Literature search results.
Figure 2
Figure 2
Relative risk for pain relief from head-to-head trials of gabapentin versus tricyclic antidepressants.
Figure 3
Figure 3
Relative risk for pain relief from placebo-controlled trials of gabapentin.
Figure 4
Figure 4
Relative risk for pain relief from placebo-controlled trials of tricyclic antidepressants.
Figure 5
Figure 5
Funnel plot, placebo-controlled trials of tricyclic antidepressants, on relative risk for pain relief.
Figure 6
Figure 6
L’Abbe plot, placebo-controlled trials of tricyclic antidepressants, on relative risk for pain relief.
See this image and copyright information in PMC

Comment in

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