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

• Published in: Journal of general internal medicine : JGIM 2009-02, Vol.24 (2), p.178-188
• Main Authors: Chou, Roger, Carson, Susan, Chan, Benjamin K. S.
• Format: Article
• Language: English
• Subjects: Amines - therapeutic use; Antidepressants; Antidepressive Agents, Tricyclic - therapeutic use; Biological and medical sciences; Comparative studies; Cyclohexanecarboxylic Acids - therapeutic use; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - epidemiology; Diabetic neuropathy; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; gamma-Aminobutyric Acid - therapeutic use; General aspects; Humans; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Meta-analysis; Neuralgia, Postherpetic - drug therapy; Neuralgia, Postherpetic - epidemiology; Neuropharmacology; Original; Original Article; Pain; Pharmacology. Drug treatments; Prescription drugs; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Randomized Controlled Trials as Topic - methods; Randomized Controlled Trials as Topic - standards; United States - epidemiology
• ISSN: 0884-8734; 1525-1497
• DOI: 10.1007/s11606-008-0877-5

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.