Duloxetine May Be Helpful for Diabetic Peripheral Neuropathic Pain

Laurie Barclay, MD

February 23, 2009

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February 23, 2009 — Duloxetine has comparable efficacy and tolerability vs gabapentin and pregabalin in the treatment of diabetic peripheral neuropathic pain (DPNP), according to the results of a meta-analysis reported in the February 10 Online First issue of BMC Neurology.

"Few direct head-to-head comparisons have been conducted between drugs for the treatment of...DPNP," write Sibilia Quilici, from Health Economics & Outcomes Research at i3 Innovus in Uxbridge, United Kingdom, and colleagues. "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."

The investigators searched PubMed, EMBASE, CENTRAL databases, and regulatory Web sites for appropriate studies of duloxetine, pregabalin, gabapentin, and amitriptyline in DPNP. Inclusion criteria were double-blind, placebo-controlled, parallel-group, or crossover-design randomized clinical trials that used approved dosages with evaluations after 5 to 13 weeks.

Response was defined as more than a 50% reduction in pain. Efficacy criteria in included trials were reduction in 24-hour pain severity (24h PS) for all drugs, and response rate and Patient Global Impression of Improvement/Change (PGI-I/C) for duloxetine and pregabalin only. Tolerability outcomes were discontinuation of study drug, diarrhea, dizziness, headache, nausea, and somnolence.

For endpoints reported in at least 2 studies of each drug, the investigators performed direct comparisons vs placebo with pooled fixed-effects and random-effects analyses. Using Bayesian simulation, they performed indirect comparisons between duloxetine and each of pregabalin and gabapentin.

The number of identified studies meeting inclusion criteria was 3 for duloxetine, 6 for pregabalin, 2 for gabapentin, and none for amitriptyline. Random-effects and fixed-effects analyses showed that duloxetine, pregabalin, and gabapentin were each superior to placebo for all efficacy parameters but with less tolerability in some adverse events.

When duloxetine was indirectly compared vs pregabalin, there were no differences in 24h PS. However, there were significant differences in PGI-I/C, favoring pregabalin, and in dizziness, favoring duloxetine. No statistically significant differences were found between duloxetine and gabapentin.

"From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP," the study authors write. "Duloxetine provides an important treatment option for this disabling condition."

Limitations of this study include those inherent in the included trials, small number of trials meeting inclusion criteria, exclusion of amitriptyline and opioids from the meta-analysis, use of indirect adjusted comparisons, and possible study selection bias.

"The summary reporting of trial results tends to conceal that response and tolerability to the various types of pharmacological treatment may be highly individual," the study authors conclude. "In neuropathic pain, the empirical approach to treatment and the common use of off-label treatments attests to the clinical need for a wide range of drug choices."

Two study authors are employees of Eli Lilly and Co, and another study author is an employee of Boehringer Ingelheim, both of which companies market duloxetine in the European Union. Lilly reimbursed i3 Innovus for payment of the Journal's article processing charge. i3 Innovus, which employs or employed 3 of the study authors, is a business unit of Ingenix Pharmaceutical Services Limited,which carried out this meta-analysis under a commercial contract with Lilly. Three other study authors have disclosed various financial relationships with Lilly.

BMC Neurol. Published online February 10, 2009.


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