A systematic review and comparative effectiveness network meta-analysis 2 assessing 27 pharmacologic interventions included 65 randomized, controlled trials involving 12 632 patients with painful diabetic neuropathy. Half of these studies had high or unclear risk of bias. 9 head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD] -0.34, 95% credible interval [CrI], -0.63 to -0.05) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD -1.36, CrI -1.77 to -0.95), topical capsaicin (SMD -0.91, CrI, -1.18 to -0.08), TCAs (SMD -0.78,CrI, -1.24 to -0.33), and anticonvulsants (SMD -0.67, CrI -0.97 to -0.37) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD -1.57, CrI -2.83 to -0.31), venlafaxine (SMD -1.53, CrI -2.41 to -0.65), duloxetine (SMD -1.33, CrI -1.82 to -0.86), and amitriptyline (SMD -0.72, CrI -1.35 to -0.08) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin.
A systematic review and Bayesian network meta-analysis 4 included 43 trials with 7 877patients. Statistically significant treatment difference for 50% pain reduction was reported for duloxetine vs. placebo (OR 2.50; CrI 1.62 to 3.91), mirogabalin vs. placebo (OR 3.25; CrI 1.16 to 9.35), pregabalin vs. placebo (OR 2.33; CrI 1.69 to 3.27), duloxetine vs. carbamazepine (OR 3.37; CrI 1.07 to 10.90), and pregabalin vs. nortriptyline (OR 4.10, CrI 1.13 to 5.28). Nortriptyline reported the highest possibility of achieving 30% and 50% pain reduction.
A systematic review and network meta-analysis 5 included 3 trials with 290 patients. No significant differences were observed between patients receiving duloxetine and gabapentin with respect to VAS (mean change difference -1.23, 95% CI -6.09 to 3.62; P = .62), Diabetic Neuropathy Symptom (DNS) score (mean change difference 0.14, 95% CI -0.35 to 0.63; P = .58), and Neuropathic Disability Score (NDS) (mean change difference 0.30, 95% CI -0.02 to 0.63; P = .07).
A Cochrane review [Abstract] 1 included 61 studies with a total of 3 293 subjects. Tricyclic antidepressants including amitriptyline, imipramine and desipramine had an NNT of 3.1 (95% CI 2.5 to 4.2) for the achievement of at least moderate pain relief. Venlafaxine (3 studies) has an NNT of 3.1 (95% CI 2.2 to 5.1) RR 2.2 (95% CI 1.5 to 3.1) with global improvement or pain relief measurements. For diabetic neuropathy the NNT for effectiveness of TCA was 1.3 (95% CI 1.2-1.5), RR 12.4 (95% CI 5.2-29.2; 5 studies); for postherpetic neuralgia 2.7 (95% CI 2 to 4.1), RR 2.2 (95% CI 1.6 to 3.1; 4 studies).
A Cochrane review [Abstract] 3 included 176 studies with a total of 28 664 subjects. The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (OR 1.91, 95% CI 1.69 to 2.17; 16 studies, n=4490) and continuous pain intensity (standardised mean difference (SMD) −0.31, 95% CI −0.39 to −0.24; 18 studies, n=4959). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD −0.22, 95% CI −0.39 to 0.06; 4 studies, n=1866).
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