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


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


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


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


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


RESULTS
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.
Chou
Roger
R
Oregon Evidence-based Practice Center, 3181 SW Sam Jackson Park Road, Mail code: BICC, Portland, OR 97239, USA. chour@ohsu.edu
Carson
Susan
S
Chan
Benjamin K S
BK
D000588:Amines / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000453:epidemiology; D000077206:Gabapentin; D006801:Humans; D051474:Neuralgia, Postherpetic / Q000188:drug therapy* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards; D014481:United States / Q000453:epidemiology; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
D000588:Amines; D000929:Antidepressive Agents, Tricyclic; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin