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Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.

Quilici S, Chancellor J, Löthgren M, Simon D, Said G, Le TK, Garcia-Cebrian A, Monz B - BMC Neurol (2009)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Health Economics & Outcomes Research, Uxbridge, UK. sibilia.quilici@gmail.com

ABSTRACT

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.

Conclusion: 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.

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Related in: MedlinePlus

Flow diagram of systematic review to identify eligible studies.
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Figure 1: Flow diagram of systematic review to identify eligible studies.

Mentions: Figure 1 presents the results of the literature search, screening and review for those studies deemed eligible for inclusion in the meta-analysis. From 91 potentially relevant publications, 11 were included in the meta-analysis. Of the four randomized studies of AMT potentially eligible, one had a very small sample (n = 25) with no sample size calculation and was, therefore, excluded[9] Two studies included benzotropine as an active placebo (to preserve blinding by mimicking the anticholinergic side-effects of amitriptyline). This precluded any tolerability comparison with no treatment. Of these two studies, one was a crossover study with no washout period. In the other, AMT was not directly compared to placebo. The sole remaining eligible study involving AMT was one of the studies of PGB (DPN-040), which included AMT as a control in addition to placebo. Due to the pre-specified minimum requirement for two eligible studies of any drug, AMT was eliminated from the meta-analysis. Hence, the meta-analysis included DLX (three unpublished studies at the time of searching, available as manufacturer's study reports)[10,11], GBP (two published studies)[12,13] and PGB (six studies, comprising four unpublished at the time of searching, available as EMEA Scientific Discussions, and two published studies) [14-16]. The three DLX studies included 679 patients on active treatment and 339 on placebo; the GBP studies included 114 patients on active treatment and 111 on placebo and the PGB studies included 988 patients on active treatment and 478 on placebo.


Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.

Quilici S, Chancellor J, Löthgren M, Simon D, Said G, Le TK, Garcia-Cebrian A, Monz B - BMC Neurol (2009)

Flow diagram of systematic review to identify eligible studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2663537&req=5

Figure 1: Flow diagram of systematic review to identify eligible studies.
Mentions: Figure 1 presents the results of the literature search, screening and review for those studies deemed eligible for inclusion in the meta-analysis. From 91 potentially relevant publications, 11 were included in the meta-analysis. Of the four randomized studies of AMT potentially eligible, one had a very small sample (n = 25) with no sample size calculation and was, therefore, excluded[9] Two studies included benzotropine as an active placebo (to preserve blinding by mimicking the anticholinergic side-effects of amitriptyline). This precluded any tolerability comparison with no treatment. Of these two studies, one was a crossover study with no washout period. In the other, AMT was not directly compared to placebo. The sole remaining eligible study involving AMT was one of the studies of PGB (DPN-040), which included AMT as a control in addition to placebo. Due to the pre-specified minimum requirement for two eligible studies of any drug, AMT was eliminated from the meta-analysis. Hence, the meta-analysis included DLX (three unpublished studies at the time of searching, available as manufacturer's study reports)[10,11], GBP (two published studies)[12,13] and PGB (six studies, comprising four unpublished at the time of searching, available as EMEA Scientific Discussions, and two published studies) [14-16]. The three DLX studies included 679 patients on active treatment and 339 on placebo; the GBP studies included 114 patients on active treatment and 111 on placebo and the PGB studies included 988 patients on active treatment and 478 on placebo.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Health Economics & Outcomes Research, Uxbridge, UK. sibilia.quilici@gmail.com

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus