1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
Copyright © 2023 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Class | Drugs | Mechanisms | RCTs | Outcomes for mean pain score | Dose | Effects | Adverse effects | FDA approval | Available in Korea |
---|---|---|---|---|---|---|---|---|---|
Gabapentinoids | Pregabalin | Inhibition of neurotransmitter release through binding to the α2δ subunit of calcium voltagegated channels | Rosenstock et al. (2004) [29] | NRPS: 6.5→4.0 (pregabalin) vs. 6.1→5.3 (placebo) | Initial 150 mg/day (max. 300 mg/day) | Pain relief in painful DPN, postherpetic neuralgia, fibromyalgia, and spinal cord injury | Dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, thinking abnormal | Painful DPN, postherpetic neuralgia, partial onset seizures, fibromyalgia, neuropathic pain associated with spinal cord injury | Yes |
Lesser et al. (2004) [30] | Difference at endpoint: −1.26 (300 mg/day); −1.45 (600 mg/day) | ||||||||
Gabapentin | Backonja et al. (1998) [24] | 11–point Likert scale: 6.4→3.9 (gabapentin) vs. 6.5→5.1 (placebo) | Initial 300 mg/ day (max. 1,800 mg/day) | Pain relief in painful DPN and postherpetic neuralgia | Dizziness, somnolence, peripheral edema | Postherpetic neuralgia, partial onset seizures | Yes | ||
Sandercock et al. (2009) [26] | Difference in ADP score at endpoint: –2.76 (gabapentin extended-release) vs. –1.38 (placebo) | ||||||||
Mirogabalin | Vinik et al. (2014) [37] | Difference in ADP score at endpoint: –0.94 (15 mg/day); –0.88 (20 mg/day); –1.01 (30 mg/day) | Initial 10 mg/day (max. 30 mg/day) | Pain relief in painful DPN and postherpetic neuralgia | Dizziness, somnolence, peripheral edema | None | No | ||
Merante et al. (2017) [38] | “Much improved” or “better” for the PGIC: 49.1% (5 mg/day); 54.5% (10 mg/day); 48.0% (15 mg/day); 48.1% (20 mg/day); 50.0% (30 mg/day) vs. 31.1% (placebo) | ||||||||
Baba et al. (2019) [39] | Difference in ADP score at endpoint: –1.81 (mirogabalin 30 mg/day) vs. –1.31 (placebo) | ||||||||
SNRIs | Duloxetine | Inhibition of reuptake of serotonin and norepinephrine | Goldstein et al. (2005) [46] | Difference from placebo at endpoint: –1.17 (95% CI, –1.84 to –0.50) (60 mg/day); –1.45 (95% CI, –2.13 to –0.78) (120 mg/day) | 60 mg/day | Pain relief in painful DPN, fibromyalgia and chronic musculoskeletal pain | Nausea, dry mouth, somnolence, fatigue, constipation, decreased appetite, hyperhidrosis | MDD, GAD, painful DPN, fibromyalgia, chronic musculoskeletal pain | Yes |
Venlafaxine | Rowbotham et al. (2004) [49] | Reduction in VAS-PI at endpoint: 50% (150–225 mg) vs. 27% (placebo) | Initial 37.5 mg/day (max. 225 mg/day) | Pain relief in painful DPN | Nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, erectile dysfunction, libido decreased | MDD, anxiety disorder, panic disorder | No | ||
TCA | Amitriptyline | Inhibition of reuptake of noradrenaline and serotonin in presynaptic neurons and antagonizing N-methyl-D-aspartate receptors | Max et al. (1987) [56] | Pain relief: 23/29 (amitriptyline) vs. 1/29 (placebo) | Initial 75 mg/day (max. 150 mg/day) | Pain relief in painful DPN, neuropathic pain and fibromyalgia | Dry mouth, somnolence, dizziness, constipation, weight gain | Depression | Yes |
Alphalipoic acid | Thiotic acid | Antioxidant | Ziegler et al. (1995) [66] | Decrease in total symptom score at endpoint: –58.6% (1,200 mg/day); –63.5% (600 mg/day); –38.4% (placebo) | 600 mg/day | Pain relief in painful DPN | Headache, hearburn, nausea, vomiting | None | Yes |
Sodium channel blockers | Carbamazepine | Inhibition of the secretion of neurotransmitters by blocking presynaptic voltage-sensitive sodium channels | Razazian et al. (2014) [51] | VAS score: 74.5→39.6 (carbamazepine) vs. 82.3→33.4 (pregabalin) vs. 74.5→46.6 (venlafaxine) | Initial 200 mg/day (max. 800 mg/day) | Pain relief in neuropathic pain | Dizziness, somnolence, unsteadiness, nausea, vomiting | Epilepsy, trigeminal neuralgia | Yes |
Oxcarbazepine | Dogra et al. (2005) [69] | >50% reduction in VAS score at endpoint: 35.2% (oxcarbazepine) vs. 18.4% (placebo) | Initial 600 mg/day (max. 2,400 mg/day) | Pain relief in neuropathic pain | Dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, headache, nystagmus, tremor, abnormal gait | Partial seizures | |||
Topical agent | Capsaicin 8% patch | Removal of substance P from vanilloid nerve receptors | Simpson et al. (2017) [75] | Difference in ADP score at endpoint: –27.4% (capsaicin 8% patch) vs. –20.9% (placebo) | Max. 4 patches for 30 min- utes | Relief of neuropathic pain associated with postherpetic neuralgia and DPN | Site erythema, application site pain, application site pruritus | Postherpetic neuralgia, painful DPN of the feet | No |
Study | Intervention | Control treatment | Study population; follow-up duration | Outcomes (mean±SD or mean [95% CI] or number [%]): Intervention vs. Control (P value) |
---|---|---|---|---|
De Vos et al. (2014) [101] | LF-SCS | Medical therapy | 40 (intervention) vs. 20 (control); 6 months | Percentages of patients with 50% pain reduction: 25 (60%) vs. 1 (5%) (P<0.001) |
VAS: 73±16→31±28 vs. 67±18→67±21 (P<0.001) | ||||
MPQ NWC-T: 13±5→8±7 vs. 13±3→13±4 (P<0.01) | ||||
MPQ PRI-T: 27±13→15±14 vs. 24±9→26±10 (P<0.01) | ||||
MPQ QoL: 16±5→8±7 vs. 15±6→14±6 (P<0.001) | ||||
EQ-5D VAS: 50±19→61±22 vs. 46±17→41±20 (P<0.01) | ||||
PGIC pain: 29 (73%) vs. 3 (17%) (P<0.01) | ||||
Satisfaction with treatment: 8/10 vs. 4/10 (P<0.001) | ||||
Slangen et al. (2014) [102] | LF-SCS | Medical therapy | 22 (intervention) vs. 14 (control); 6 months | Percentage of patients with 50% pain reduction (day): 9 (41%) vs. 0 (0%) (P<0.001) |
Percentages of patients with 50% pain reduction (night): 8 (36%) vs. 1 (7%) (P<0.01) | ||||
NRS during the day: –3.1 points vs. no change (P<0.001) | ||||
NRS during the night: –2.4 points vs. –0.9 points (P<0.003) | ||||
EQ-5D Utility score: 0.25±031→0.50±0.33 vs. 0.33±0.32→0.33±0.29 (NS) | ||||
EQ-5D Current health: 53.9±18.5→57.6±24.3 vs. 54.6±16.7→56.5±14.2 (NS) | ||||
PGIC for pain: 12 (55%) vs. 0 (0%) (P<0.001) | ||||
PGIC for sleep: 8 (36%) vs. 0 (5%) (P<0.05) | ||||
Treatment successa: 13 (59%) vs. 1 (7%) (P<0.01) | ||||
Petersen et al. (2021) [103] | HF-SCS | Medical therapy | 113 (intervention) vs. 103 (control); 6 months | Combination of 50% pain reduction and no deterioration on neurological examination: 75 (79%) vs. 5 (5%) (P<0.001) |
Percentages of patients with 50% pain reduction: 74 (85%) vs. 5 (5%) (P<0.001) | ||||
VAS: 7.6 [7.3–7.9]→1.7 [1.3–2.1] vs. 7.0 [6.7–7.3]→6.9 [6.5–7.3] (P<0.001) | ||||
Percentages of patients with VAS ≤3: 53 (60%) vs. 1 (1%) (P<0.001) | ||||
EQ-5D-5L index: 0.130±0.159 vs. –0.031±0.127 (P<0.001) | ||||
EQ-5D-5L health VAS: 15.9±21.6 vs. –1.7±23.0 (P<0.001) |
RCT, randomized controlled trial; FDA, U.S. Food and Drug Administration; NRPS, numeric pain rating scale; DPN, diabetic peripheral neuropathy; ADP, average daily pain; PGIC, patient global impression of change; SNRI, serotonin–norepinephrine reuptake inhibitor; CI, confidence interval; MDD, major depressive disorder; GAD, generalized anxiety disorder; VAS-PI, VAS pain intensity; TCA, tricyclic antidepressant; VAS, visual analogue scale.
SD, standard deviation; CI, confidence interval; LF, low-frequency; SCS, spinal cord stimulation; VAS, visual analogue scale; MPQ, McGill Pain Questionnaire; NWC-T, the total number of words chosen from the McGill Pain Questionnaire; PRI-T, pain rating index; QoL, quality of life; EQ-5D, EuroQoL-5D; PGIC, patient global impression of change; NRS, numeric rating scale; NS, not statistically significant; HF, high-frequency. Treatment success means ≥50% reduction in pain intensity during the daytime or nighttime or an improvement in pain and sleep of ≥6 in the PGIC score.