A systematic review and comparative effectiveness network meta-analysis 3 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 5 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 to3.91), 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), mirogabalin vs. carbamazepine (OR 4.39; CrI 1.01 to 19.63), mirogabalin vs. lamotrigine (OR 4.05: CrI 1.07 to 15.77), pregabalin vs. lamotrigine (OR 2.90, CrI 1.19 to 7.22) 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. Sodium valproate and benztropine reported the highest probability of total withdrawals and withdrawals due to adverse drug events, respectively
A systematic review and network meta-analysis 6 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 A Cochrane review [Abstract] 4 included 37 studies with a total of 5914 subjects. Gabapentin was studied at daily doses of 1200 mg or more in different neuropathic pain conditions, predominantly postherpetic neuralgia and painful diabetic neuropathy.In painful diabetic neuropathy, more participants (38%) had substantial benefit (at least 50% pain relief or PGIC very much improved) with gabapentin at 1200 mg daily or greater than with placebo (21%) (RR 1.9 (95% CI 1.5 to 2.3); NNT 5.9 (4.6 to 8.3); 6 studies, n=1277). More participants (52%) had moderate benefit (at least 30% pain relief or PGIC much or very much improved) with gabapentin at 1200 mg daily or greater than with placebo (37%) (RR 1.4 (95% CI 1.3 to 1.6); NNT 6.6 (4.9 to 9.9); 7 studies, 1n=439).Serious adverse events were no more common with gabapentin (3.2%) than with placebo (2.8%) (RR 1.2 (95% CI 0.8 to 1.7); 19 studies, n=3948); there were 8 deaths. Participants experiencing at least one adverse event were more common with gabapentin (63%) than with placebo (49%) (RR 1.3 (95% CI 1.2 to 1.4); NNH 7.5 (6.1 to 9.6); 18 studies, n=4279). Individual adverse events occurred significantly more often with gabapentin. Participants taking gabapentin experienced dizziness (19%), somnolence (14%), peripheral oedema (7%), and gait disturbance (14%).
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