Table 1.
Randomized controlled trials of pharmacologic interventions for the treatment of postamputation pain
| Study | N | Treatment/placebo | Chronicity | Adverse events | Follow-up | Effecta |
|---|---|---|---|---|---|---|
| NMDA antagonists | ||||||
| Memantine | ||||||
| Maier et al68 | 36 | 1. Oral memantine 30 mg/d × 3 weeks 2. Placebo |
> 12 months | Vertigo, fatigue, headache, nausea, restlessness, excitation, cramps | 3 weeks | − |
| Wiech et al69 | 8 | 1. Oral memantine titrated to 30 mg/d × 4 weeks 2. Placebo |
Chronic | Fatigue, agitation, dizziness, nausea, headache | 30 days | − |
| Schwenkreis et al70 | 16 | 1. Oral memantine titrated to 30 mg/d 2. Placebo |
> 12 months | Not described | 3 weeks | − |
| Dextromethorphan | ||||||
| Abraham et al67 | 10 | 1. Oral dextromethorphan 120 mg/d × 10 days 2. Oral dextromethorphan 180 mg/d × 10 days 3. Placebo |
Mean duration of pain 4.8 months |
None reported | 10 days | + |
| Ketamine | ||||||
| Nikolajsen et al65 | 11 | 1. IV ketamine 0.5 mg/kg infusion × 45 minutes 2. Placebo |
Mean duration of pain 4 years | Insobriety, mood elevation, discomfort | 45 minutes | + |
| Eichenberger et al66 | 20 | 1. IV ketamine 0.4 mg/kg infusion × 1 hour 2. IV calcitonin 200 IU infusion × 1 hour 3. Combination ketamine/calcitonin 4. Placebo |
Mean duration of pain 12 years | Loss of consciousness, light sedation, light visual hallucination, hearing impairment, position/feeling impairment | 48 hours | + |
| Anticonvulsants | ||||||
| Gabapentin | ||||||
| Bone et al76 | 19 | 1. Oral gabapentin titrated to 2400 mg or maximum tolerable 2. Placebo |
>6 months | Somnolence, dizziness, headache, nausea | 6 weeks | + |
| Smith et al77 | 24 | 1. Oral gabapentin titrated to 3600 mg or maximum tolerable 2. Placebo |
>6 months | Not described | 6 weeks | − |
| Antidepressants | ||||||
| Amitriptyline | ||||||
| Robinson80 | 39 | 1. Oral amitriptyline 10 mg/d titrated to maximum 125 mg/d 2. Oral benztropine 0.5 mg/d |
>3 months | Dry mouth, dizziness | 6 weeks | − |
| Calcitonins | ||||||
| Jaeger and Maier79 | 21 | 1. IV calcitonin 200 IU X 20-minute infusion 2. Saline |
0-7 days following amputation | Headache, vertigo, nausea, vomiting, augmented phantom sensations, drowsiness, hot flashes | 1 year | + |
| Opioids | ||||||
| Huse et al72 | 12 | 1. Oral morphine titrated to 300 mg/d or maximum tolerable 2. Placebo |
Chronic | Constipation | 4 weeks | + |
| Wu et al73 | 31 | 1. IV morphine 0.2 mg/kg infusion × 40 minutes 2. IV lidocaine 4 mg/k influsion × 40 minutes 3. Diphenhydramine placebo |
>6 months | Sedation (nonsignificant) | 30 minutes | + (morphine and lidocaine groups versus placebo) |
| Local anesthetics | ||||||
| Casale et al63 | 8 | 1. Contralateral myofascial inj with bupivacaine 2.5 mg/mL 2. Placebo |
>6 months | None | 60 minutes | + |
Notes:a“+” designates studies that show a statistically significant improvement of the study drug over placebo in the treatment of postamputation pain, and “−“ designates studies that do not
Abbreviations: IV, intravenous; NMDA, N-methyl-D-aspartate.