Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.
BACKGROUND
Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator.


METHODS
We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5-13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs, and response rate (>or= 50% pain reduction) and Patient Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed - and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation.


RESULTS
Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences.


CONCLUSIONS
From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition.
Quilici
Sibilia
S
Health Economics & Outcomes Research, Uxbridge, UK. sibilia.quilici@gmail.com
Chancellor
Jeremy
J
Löthgren
Mickael
M
Simon
Dominique
D
Said
Gérard
G
Le
Trong Kim
TK
Garcia-Cebrian
Ana
A
Monz
Brigitta
B
D000588:Amines / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D001499:Bayes Theorem; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D000068736:Duloxetine Hydrochloride; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017933:Peripheral Nervous System / Q000503:physiopathology*; D000069583:Pregabalin; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D013876:Thiophenes; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000068736:Duloxetine Hydrochloride