Post-Amputation Pain: Combined Analyses of Randomized Controlled Trials Evaluating Opioids and Gabapentinoids versus Placebo

An estimated 185,000 patients per year undergo an extremity amputation in the United States (over 500 amputations/day). Prolonged postoperative opioid use, defined as the presence of a filled opioid prescription between 90 and 180 days following the operative amputation procedure, affects nearly 50% of amputees. Moreover, the use of preoperative benzodiazepines, muscle relaxants, anticonvulsants, and antidepressants is strongly linked to prolonged opioid use suggesting new therapeutic strategies are needed. The goal of this study was to better understand how well post-amputation pain is currently treated by selected pharmacologic agents and the success rates of these existing agents. The available literature on PubMed was screened for articles that used randomized-controlled trial (RCT) study designs and gabapentinoids (eg, gabapentin or pregabalin) or opioids (eg, morphine). Two morphine-related RCTs using at least 50% pain reduction responder criteria were combined and qualitatively compared with two gabapentin trials that were previously combined to understand the potential benefits of these drugs in post-amputation pain management compared with placebo. All 4 trials included measured post-amputation pain over a 4- to 6-week acute period. The combined opioid analysis demonstrated a treatment effect that favored morphine ( =0.02) over placebo and indicated the number needed to treat (NNT) of 3.9 (95% CI: 2.5, 9.3) patients. Similarly, the previously combined analysis of gabapentin trials favored gabapentin over placebo and indicated an estimated NNT of 8.9 (95% CI: 5.3, 27.8). Patients undergoing limb amputation have a clear unmet need for more adequate chronic pain control. Given that post-amputation pain is often diagnosed as a chronic condition, persisting for at least 90 days, our data highlight the need for larger sample sizes and longer-term controlled trials to better understand the advantages and disadvantages of chronic use of gabapentinoids and opioids/opioid combination drugs in this patient population.