Intramuscular Neridronate for the Treatment of Complex Regional Pain Syndrome Type 1: a Randomized, Double-blind, Placebo-controlled Study

Background: Complex regional pain syndrome type-1 (CRPS-1) is a severely disabling painful disease challenging to treat. This multicenter, randomized, double-blind placebo-controlled trial examined the efficacy of intramuscular (i.m.) neridronate in CRPS-1 patients.

Methods: A total of 78 patients diagnosed with CRPS-1 (aged 59.5 ± 10.3, 66.7% female) were randomly assigned to 25 mg (i.m.) neridronate ( = 41) given once daily for 16 consecutive days or placebo control ( = 37). Efficacy was assessed after 30 days using a visual analogue scale (VAS) pain score and the number of patients achieving ⩾50% reduction in VAS score. Change in clinical signs and symptoms, quality of life (QoL) using Short Form Health Survey (SF-36) and the McGill Pain Questionnaire were also assessed.

Results: After 30 days, VAS score decreased significantly to a greater extent in neridronate-treated patients placebo (31.9 ± 23.3 mm 52.3 ± 27.8 mm,  = 0.0003). Furthermore, the proportion of patients achieving a VAS reduction of ⩾50% was greater in the neridronate group (65.9% 29.7%,  = 0.0017). Clinical signs and symptoms were improved significantly in the neridronate group placebo for edema (72.5% 79.9%,  = 0.03), pain during motion (70% 83.3%,  = 0.0009), allodynia (20% 63.3%,  = 0.0004), and hyperalgesia (20% 56.7%,  = 0.0023). Whereas no difference was observed for QoL measures using the SF-36 questionnaire, three of the four pain variables using the McGill Pain Questionnaire improved significantly in the neridronate group. No serious drug-related adverse events were reported during the study.

Conclusion: In patients with acute CRPS-1, i.m. injections of 25 mg neridronate were associated with clinically relevant benefit compared with placebo controls.

Trial Registration: EU Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001156-28.