Table 1.
Randomized clinical studies for neuropathic pain following spinal cord injury
| References | Treatment | Dosage | Study design | Sample size | Active substance | Placebo |
|---|---|---|---|---|---|---|
| Antidepressants | ||||||
| Cardenas et al. [37] | Amitriptyline vs placebo | 10–25 mg | Randomized controlled Trial | 84 | 44 | 40 |
| Rintala et al. [36] | Amitriptyline vs active placebo vs gabapentin | 150 mg amitriptyline vs 3600 mg gabapentin | Randomized, controlled, double blind, triple crossover | 38 | 38 | 38 |
| Yang et al. [38] | Lithium vs placebo | 0.6–1.2 mmol/l | Randomized, double-blind, placebo-controlled trial | 40 | 20 | 20 |
| Davidhoff et al. [39] | Trazodone hydrochloride vs placebo | 50–150 mg | Randomized, double-blind, placebo-controlled trial | 18 | 9 | 9 |
| Vranken et al. [40] | Duloxetine vs placebo | 60-120 mg | Randomized, double-blind, placebo-controlled trial | 48a | 24 | 24 |
| Antiepileptics | ||||||
| Rintala et al. [36] | Gabapentin vs active placebo | 900–3600 mg | Randomized, controlled, double blind, triple crossover trial | 38 | 38 | 38 |
| Levendoglu et al. [43] | Gabapentin vs placebo | 1800 mg | Randomized, double blind, placebo-controlled, crossover trial | 20 | 20 | 20 |
| Tai et al. [45] | Gabapentin vs placebo | 150–600 mg | Prospective, randomized, double-blind, crossover trial | 7 | 7 | 7 |
| Ahn et al. [47] | Gabapentin | 1800 mg | Evaluation study | 31 | 31 | |
| Siddall et al. [48] | Pregabalin | 150–600 mg | Randomized, placebo-controlled, multicentre trial | 137 | 70 | 67 |
| Vranken et al. [49] | Pregabalin vs placebo | 150-600 mg | Randomized, double-blind, placebo-controlled trial | 40a | 20 | 20 |
| Cardenas et al. [50] | Pregabalin vs placebo | 150–600 mg | Randomized, double-blind, placebo-controlled trial | 220 | 112 | 108 |
| Finnerup et al. [52] | Lamotrigine vs placebo | 200–400 mg | Randomized double blind, placebo-controlled, crossover trial | 30 | 27 | 28 |
| Drewes et al. [53] | Valproate vs placebo | 600–2400 mg | Double-blind, cross-over, placebo-controlled trial | 20 | 20 | 20 |
| Finnerup et al. [54] | Levetiracetam | 500–3000 mg | Randomized, double-blind, placebo-controlled, crossover, multicentre trial | 36 | 18 | 18 |
| Salinas et al. [55] | Carbamazepine vs placebo | 600 mg | Randomized, double-blind, placebo-controlled trial | 46 | 24 | 22 |
| Opioids | ||||||
| Norrbrink et al. [58] | Tramadol | 150 mg | Randomized, double-blind, placebo-controlled trial | 35 | 23 | 12 |
| Attal et al. [59] | Morphine vs placebo | 2 mg morphine every 10 min intravenous | Double-blind, placebo-controlled, crossover trial | 16 | 8 | 8 |
| Siddall et al. [60] | Morphine and clonidine vs placebo | Individual dosage | Randomized, double-blind, placebo-controlled trial | 15 | 15 | 15 |
| Cannabinoids | ||||||
| Rintala et al. [68] | Dronabinol vs placebo | 5–20 mg | Randomized, controlled, double-blind, crossover trial | 7 | 7 | 5 |
| Wade et al. [69] | Cannabis vs placebo | 2.5–120 mg | Double-blind, placebo-controlled, crossover trial | 24a | 24 | 24 |
| Karst et al. [70] | Synthetic cannabinoid vs placebo | 40 mg | Randomized, double-blind, placebo-controlled trial | 21a | 21 | 21 |
| Others | ||||||
| Eide et al. [66] | Ketamine, alfentanil and placebo | 60 + 6 µg/kg and alfentanil (7 + 0.6 µg/kg) | Continuous and evoked pain was examined before and after the intravenous infusion of either ketamine, alfentanil or placebo | 9 | 9 | 9 |
| Amr et al. [65] | Ketamine + gabapentin vs gabapentin + placebo | 80 mg ketamine + 900 mg gabapentin | Randomized, controlled, double blind trial | 40 | 29 | 29 |
| Kvarnstrom et al. [67] | Lidocaine vs ketamine vs placebo | 0.4 mg/kg ketamine vs 2.5 mg/kg lidocaine | Randomized, double-blind, three period, three-treatment, cross-over trial | 10 | 10 | 10 |
| Finnerup et al. [63] | Lidocaine vs placebo | 5 mg/kg | Randomized, double-blind, placebo-controlled, crossover trial | 24 | 24 | 24 |
| Chiou-Tan et al. [64] | Mexiletine vs placebo | 450 mg | Randomized, placebo-controlled, double-blind, crossover trial | 15 | 11 | 11 |
| References | Time | Outcomes | Adverse effect active substance | Adverse effect placebo | Dropout |
|---|---|---|---|---|---|
| Antidepressants | |||||
| Cardenas et al. 37] | 6 weeks | No significant between amitriptyline and placebo | 43 | 36 | 0 |
| Rintala et al. [36] | 8 weeks |
Amitriptyline > gabapentin Amitriptyline > diphenhydramine No significant difference between gabapentin and diphenhydramine |
28 completed the amitriptyline phase 25 completed the active placebo phase 16 completed all 3 phases |
||
| Yang et al. [38] | 6 weeks | Lithium > placebo | 16 | 14 | 2 in each group |
| Davidhoff et al. [39] | 6 weeks | No significant difference between trazodone hydrochloride and diphenhydramine | 4 | 1 | 5 in active drug group, 1 in placebo group |
| Vranken et al. [40] | No significant difference between duloxetine vs placebo | 30 AE in total | 10 AE in total | 0 | |
| Antiepileptics | |||||
| Rintala et al. [36] | 8 weeks | No significant difference between gabapentin and diphenhydramine | 26 completed the gabapentin phase | ||
| Levendoglu et al. [43] | 18 weeks | Gabapentin > placebo | 30 AE in total | 6 | |
| Tai et al. [45] | 10 weeks | Gabapentin > placebo | NA | ||
| Ahn et al. [47] | 8 weeks | Effect of Gabapentin | 15 | NA | |
| Siddall et al. [48] | 12 weeks | Pregabalin > placebo | 15 | 9 | 21 in active group, 30 in placebo group |
| Vranken et al. [49] | 4 weeks | Pregabalin > placebo | 3 | 3 | 3 in active group, 4 in placebo group |
| Cardenas et al. [50] | 17 weeks | Pregabalin > placebo | 75 | 50 | 6 in active group, 5 in placebo group |
| Finnerup et al. [52] | 21 weeks | No significant difference between lamotrigine and placebo | 1 | 2 | 3 in active group, 5 in placebo group |
| Drewes et al. [53] | 8 weeks | No significant difference between valproate and placebo | 4 | 0 | 0 |
| Finnerup et al. [54] | 12 weeks | No significant effect | 7 | 2 | 9 in active group, 3 in placebo group |
| Salinas et al. [55] | 1 month | Carbamazepine > placebo only after 1 monthb | 23 | 21 | 1 in active group, 1 in placebo group |
| Opioids | |||||
| Norrbrink et al. [58] | 4 weeks | Tramadol > placebo | 21 | 7 | 10 in active group, 1 in placebo group |
| Attal et al. [59] | 20 min each | Morphine > placebo after 1 month | 5 | 0 | 1 |
| Siddall et al. [60] | 3 days each | Morphine + clonidine > morphine or clonidine or placebo | Morphine 25 AE, Clonidine 27 AE, Morphine/clonidine 27 AE | 4 AE | 0 |
| Cannabinoids | |||||
| Rintala et al. [68] | 17 weeks | No significant difference between dronabinol and placebo | 30 AE | 18 AE | 2 in active group, 0 in placebo group |
| Wade et al. [69] | 10 weeks | Cannabis > placebo | 24 | 21 | 3 in active group |
| Karst et al. [70] | 3 weeks | Synthetic cannabinoid > placebo | 2 | 0 | 2 in active group, 0 in placebo group |
| Others | |||||
| Eide et al. [66] | 2 h each | Ketamine + alfentanil > alfentanil or ketamine or placebo | – | – | – |
| Amr et al. [65] | 1 week | Ketamine + gabapentin > gabapentin + placebo | – | – | – |
| Kvarnstrom et al. [67] | 2 weeks | Ketamine > lidocaine or placebo | Ketamine 9, Lidocaine 5 | 1 | – |
| Finnerup et al. [63] | 2 weeks | Lidocaine > placebo | 9 | 1 | 0 |
| Chiou-Tan et al. [64] | 10 weeks | No significant difference between mexiletine and placebo | – | – | 4 |
AE adverse events, NA not applicable
aPatients with several diagnoses were included in the study
bCarbamazepine was used as prophylactic treatment