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

doi:10.1007/s11606-008-0877-5

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 Chou¹, Susan Carson, Benjamin K S Chan

Affiliations

PMID: 19089502
PMCID: PMC2628998
DOI: 10.1007/s11606-008-0877-5

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.

. 2009 Feb;24(2):178-88.

doi: 10.1007/s11606-008-0877-5. Epub 2008 Dec 17.

Authors

Roger Chou¹, Susan Carson, Benjamin K S Chan

Affiliation

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

PMID: 19089502
PMCID: PMC2628998
DOI: 10.1007/s11606-008-0877-5

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 2**
Relative risk for pain relief from head-to-head trials of gabapentin versus tricyclic antidepressants.

**Figure 3**
Relative risk for pain relief from placebo-controlled trials of gabapentin.

**Figure 4**
Relative risk for pain relief from placebo-controlled trials of tricyclic antidepressants.

**Figure 5**
Funnel plot, placebo-controlled trials of tricyclic antidepressants, on relative risk for pain relief.

**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

Gabapentin versus tricyclics for neuropathic pain.
O'Connor AB. O'Connor AB. J Gen Intern Med. 2009 Jun;24(6):780-1; author reply 782. doi: 10.1007/s11606-009-0957-1. J Gen Intern Med. 2009. PMID: 19350332 Free PMC article. No abstract available.

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1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/j.pain.2007.08.033', 'is_inner': False, 'url': 'https://doi.org/10.1016/j.pain.2007.08.033'}, {'type': 'PubMed', 'value': '17920770', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17920770/'}]}
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1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1136/bmj.39213.565972.AE', 'is_inner': False, 'url': 'https://doi.org/10.1136/bmj.39213.565972.ae'}, {'type': 'PMC', 'value': 'PMC1914460', 'is_inner': False, 'url': 'https://pmc.ncbi.nlm.nih.gov/articles/PMC1914460/'}, {'type': 'PubMed', 'value': '17562735', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17562735/'}]}
2. Wong MC, Chung JW, Wong TK. Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ. 2007;335:87. - PMC - PubMed

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[1] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/j.pain.2007.08.033', 'is_inner': False, 'url': 'https://doi.org/10.1016/j.pain.2007.08.033'}, {'type': 'PubMed', 'value': '17920770', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17920770/'}]}

Dworkin RH, O’Connor AB, Backonja M. Pharmacologic management of neuropathic pain: Evidence-based recommendations. Pain. 2007;132:237–51. - PubMed

[2] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/j.pain.2007.08.033', 'is_inner': False, 'url': 'https://doi.org/10.1016/j.pain.2007.08.033'}, {'type': 'PubMed', 'value': '17920770', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17920770/'}]}

[3] Dworkin RH, O’Connor AB, Backonja M. Pharmacologic management of neuropathic pain: Evidence-based recommendations. Pain. 2007;132:237–51. - PubMed

[4] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1503/cmaj.060146', 'is_inner': False, 'url': 'https://doi.org/10.1503/cmaj.060146'}, {'type': 'PMC', 'value': 'PMC1513412', 'is_inner': False, 'url': 'https://pmc.ncbi.nlm.nih.gov/articles/PMC1513412/'}, {'type': 'PubMed', 'value': '16880448', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/16880448/'}]}

Gilron I, Watson CPN, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. CMAJ Can Med Assoc J. 2006;175:265–75. - PMC - PubMed

[5] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1503/cmaj.060146', 'is_inner': False, 'url': 'https://doi.org/10.1503/cmaj.060146'}, {'type': 'PMC', 'value': 'PMC1513412', 'is_inner': False, 'url': 'https://pmc.ncbi.nlm.nih.gov/articles/PMC1513412/'}, {'type': 'PubMed', 'value': '16880448', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/16880448/'}]}

[6] Gilron I, Watson CPN, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. CMAJ Can Med Assoc J. 2006;175:265–75. - PMC - PubMed

[7] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/j.pain.2005.08.013', 'is_inner': False, 'url': 'https://doi.org/10.1016/j.pain.2005.08.013'}, {'type': 'PubMed', 'value': '16213659', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/16213659/'}]}

Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118:289–305. - PubMed

[8] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/j.pain.2005.08.013', 'is_inner': False, 'url': 'https://doi.org/10.1016/j.pain.2005.08.013'}, {'type': 'PubMed', 'value': '16213659', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/16213659/'}]}

[9] Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118:289–305. - PubMed

[10] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/S0304-3959(99)00154-2', 'is_inner': False, 'url': 'https://doi.org/10.1016/s0304-3959(99)00154-2'}, {'type': 'PubMed', 'value': '10568846', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/10568846/'}]}

Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain. 1999;83:389–400. - PubMed

[11] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1016/S0304-3959(99)00154-2', 'is_inner': False, 'url': 'https://doi.org/10.1016/s0304-3959(99)00154-2'}, {'type': 'PubMed', 'value': '10568846', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/10568846/'}]}

[12] Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain. 1999;83:389–400. - PubMed

[13] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1136/bmj.39213.565972.AE', 'is_inner': False, 'url': 'https://doi.org/10.1136/bmj.39213.565972.ae'}, {'type': 'PMC', 'value': 'PMC1914460', 'is_inner': False, 'url': 'https://pmc.ncbi.nlm.nih.gov/articles/PMC1914460/'}, {'type': 'PubMed', 'value': '17562735', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17562735/'}]}

Wong MC, Chung JW, Wong TK. Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ. 2007;335:87. - PMC - PubMed

[14] {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1136/bmj.39213.565972.AE', 'is_inner': False, 'url': 'https://doi.org/10.1136/bmj.39213.565972.ae'}, {'type': 'PMC', 'value': 'PMC1914460', 'is_inner': False, 'url': 'https://pmc.ncbi.nlm.nih.gov/articles/PMC1914460/'}, {'type': 'PubMed', 'value': '17562735', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/17562735/'}]}

[15] Wong MC, Chung JW, Wong TK. Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ. 2007;335:87. - PMC - PubMed

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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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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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