Table III.
Summary of clinical studies on other topical agents for the treatment of DNP.
| Author, year | Topical agent(s) | Study design | No. of patients (% male) | Age, years (mean ± standard deviation) | Duration of pain | Outcomes | (Refs.) |
|---|---|---|---|---|---|---|---|
| Comparisons with topical 5% lidocaine and placebo | |||||||
| Ho et al, 2008 | 5% Amitriptyline cream | Double-blind, randomized, placebo-controlled crossover study | 35 (45.7) | 57.4±13.8 | ≥6 months | No significant change in pain intensity was observed with topical amitriptyline or placebo Topical lidocaine and placebo each reduced pain more than topical amitriptyline | (62) |
| Comparisons with topical 0.75% capsaicin cream | |||||||
| Kiani et al, 2015 | 2% Amitriptyline cream | Double-blind, 12-week, randomized, and non-inferiority trial | Amitriptyline: 51 (33.3) Capsaicin: 51 (31.4) | Amitriptyline: 57.5±10.8 Capsaicin: 55.4±10.6 | ≥3 months | Both drugs significantly relieved pain in 12 weeks compared with baseline values. Well tolerated | (24) |
| Comparisons with placebo | |||||||
| Campbell et al, 2009 and Wrzosek et al, 2015 | 0.1 and 0.2% Clonidine gels | Double-blind, 8-week, randomized placebo-controlled trial | 0.1% clonidine: 54 (NA) 0.2% clonidine: 54 (NA) Placebo: 57 (NA) | NA | NA | The reduction in mean aggregate pain score from week 8 to baseline in subjects who received 0.1% gel was significantly greater compared with the placebo group. The reduction in pain for the 0.2% group was less impressive Adverse events were similar between the three groups. | (25,87) |
| Campbell et al, 2012 | 0.1% Clonidine gel | Double-blind, 12-week, randomized, placebo-controlled, parallel-group, multi-center trial | Clonidine: 89 (49) Placebo: 90 (47) | Clonidine: 59.4±9.9 Placebo: 57.6±9.5 | ≥6 months | Significantly reduced the level of pain Safe and without the problematic side effects typically associated with systemic therapies | (88) |
| Motilal and Maharaj, 2013 | Nutmeg extract | Double-blind, 4-week, randomized, placebo-controlled trial. | Nutmeg extract: 37 (32.4) Placebo: 37 (32.4) | Nutmeg extracts: 60.7±11.5 Placebo: 59.7±8.1 | NA | Reduced worst and mean pain scores Improved QOL No statistically significant differences between the groups for all outcome measures | (26) |
| Heydari et al, 2016 | Topical Citrullus colocynthis extract oil | Two-arm, double-blind, randomized, placebo-controlled, parallel study | Citrullus colocynthis extract oil: 30 (39.3) Placebo: 30 (55.6) | Citrullus colocynthis extract oil: 57.4±10.0 Placebo: 52.7±10.5 | ≥3 months | Decreased mean pain score Improved nerve function Improved physical domain of QOL | (27) |
| Mahoney et al, 2012 | Topical ketamine cream | Double-blind, randomized, placebo-controlled, study | Ketamine: 10 (40.0) Placebo: 7 (57.1) | Ketamine: 64.0±9.5 Placebo: 65.4±15.0 | NA | No more effective than placebo | (100) |
| ClinicalTrials. govNCT00476151, 2006 | Topical 4% amitriptyline and 2% ketamine | Phase 2, multicenter, randomized, placebo-controlled, parallel group study | Ami/Ket: 114 (57.0) Placebo: 112 (50.9) | Ami/Ket: 56.1±9.4 Placebo: 55.1±11.0 | ≥6 months | Showed a strong trend toward pain reduction in painful diabetic neuropathy | (28) |
DNP, diabetic neuropathic pain; QOL, quality of life; NA, not available.