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- Title
Gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia: discrepancies between direct and indirect meta-analyses of randomized controlled trials.
- Authors
Chou, Roger; Carson, Susan; Chan, Benjamin; Chan, Benjamin K S
- Abstract
<bold>Background: </bold>Previous systematic reviews concluded that tricyclics antidepressants are superior to gabapentin for neuropathic pain, but were based on indirect comparisons from placebo-controlled trials.<bold>Purpose: </bold>To evaluate gabapentin versus tricyclic antidepressants for diabetic neuropathy and post-herpetic neuralgia, using direct and indirect comparisons.<bold>Data Sources: </bold>MEDLINE (1966 to March Week 4 2008), the Cochrane central register of controlled trials (1st quarter 2008), and reference lists.<bold>Study Selection: </bold>We selected randomized trials directly comparing gabapentin versus tricyclic antidepressants or comparing either of these medications versus placebo.<bold>Data Extraction: </bold>Studies were reviewed, abstracted, and quality-rated by two independent investigators using predefined criteria.<bold>Data Synthesis: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
ANTIDEPRESSANTS; DIABETIC neuropathies; NEURALGIA; SYSTEMATIC reviews; MEDLINE; ANALGESIA
- Publication
JGIM: Journal of General Internal Medicine, 2009, Vol 24, Issue 2, p178
- ISSN
0884-8734
- Publication type
journal article
- DOI
10.1007/s11606-008-0877-5