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Gabapentin Versus Tricyclic Antidepressants for Diabetic Neuropathy and Post-Herpetic Neuralgia: Discrepancies Between Direct and Indirect Meta-Analyses of Randomized Controlled Trials

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Chou, Roger, Carson, Susan, Chan, Benjamin K. S.·2009·Journal of General Internal Medicine
DOI 10.1007/s11606-008-0877-5PMC PMC2628998
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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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  • The validity of indirect comparisons depends on how well they meet the critical assumption of consistent treatment effects across all of the trials.

    “The validity of indirect comparisons depends on how well they meet the critical assumption of consistent treatment effects across all of the trials.”

    From Comparative Efficacy and Harms of Duloxetine, Milnacipran, and Pregabalin in Fibromyalgia Syndrome (2010) · cites this paper as [14]

  • The assumption of consistent treatment effects can be violated by methodological shortcomings in the trials, differences in populations, interventions (eg, dosing), assessment of outcomes, or other factors.

    “This assumption can be violated by methodological shortcomings in the trials, differences in populations, interventions (eg, dosing), assessment of outcomes, or other factors.”

    From Comparative Efficacy and Harms of Duloxetine, Milnacipran, and Pregabalin in Fibromyalgia Syndrome (2010) · cites this paper as [14]

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Cited by

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Authors
Chou, R., Carson, S., & Chan, B. K. S.
Affiliations
Oregon Health & Science University (US)
Corresponding author
Chou, Roger
ORCID
Venue
Journal of General Internal Medicine
Publisher
Springer Science and Business Media LLC
Published
2008-12-17
Volume
24
Issue
2
Pages
178-188
ISSN
  • 0884-8734 (ISSN-L)
  • 1525-1497
DOI
10.1007/s11606-008-0877-5
PMC
PMC2628998
OpenAlex
W2014657120
Cited by
57
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 8 · 2014: 3 · 2013: 4 · 2012: 3
FWCI
2.98
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Journal of General Internal Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords
gabapentin, tricyclic antidepressants, diabetic neuropathy, postherpetic neuralgia, neuropathic pain, analgesia, placebo response, publication bias
MeSH terms
Gabapentin, Amines, Antidepressive Agents, Tricyclic, Cyclohexanecarboxylic Acids, Diabetic Neuropathies, gamma-Aminobutyric Acid, Humans, United States, Randomized Controlled Trials as Topic, Neuralgia, Postherpetic

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