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J Gen Intern Med. 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.

Author information

  • 1Oregon Evidence-based Practice Center, 3181 SW Sam Jackson Park Road, Mail code: BICC, Portland, OR 97239, USA. chour@ohsu.edu

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.

Comment in

PMID:
19089502
[PubMed - indexed for MEDLINE]
PMCID:
PMC2628998
Free PMC Article

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