A study was conducted to determine whether amantadine in addition to NSAIDs would relieve refractory osteoarthritic pain better than an NSAID alone. Lameness and activity impairment had to have been present for at least 3 months despite use of an NSAID over that period. The NSAIDs used before the study were aspirin, carprofen, deracoxib, etodolac, firocoxib, and meloxicam. On day 0, analgesic medications were discontinued. On day 7, all dogs were started on meloxicam (0.1 mg/kg once daily PO after a 0.2-mg/kg initial dose on the first day). On day 21, dogs were randomly allocated to receive amantadine (3-5 mg/kg Q 24 H PO) or placebo for 21 days, in addition to meloxicam. The primary outcome measure was blinded owner assessments of activity on days 0, 7, 21, and 42. In this study, neither group significantly deteriorated when the original NSAID therapy was stopped, and both groups improved over the 14-day period on meloxicam. These results suggest that changing NSAIDs as a strategy can be effective when trying to manage refractory OA pain, although this part of the study was not placebo-controlled. All dogs were still impaired and considered to be in pain at day 21 when amantadine or placebo was added. The focus of the statistical analysis was to determine whether there were differences between the groups over the period from days 21 to 42. During that period, there was time by treatment effect (P = .009), indicating that amantadine might be a useful adjunctive therapy for clinical management of pain in dogs with OA.

Finally, a well-controlled, properly blinded clinical trial evaluating the efficacy of amantadine as an adjunct to NSAIDs in treating canine OA. These data, although limited, provide strong, credible evidence that amantadine has an additive, positive effect in eliminating clinical signs. The data beg completion of similar blinded, controlled trials evaluating the efficacy of other drugs, such as tramadol and gabapentin, as adjunctive therapies to NSAIDs in canine OA. Currently tramadol and gabapentin are widely used with NSAIDs in a similar fashion as amantadine with NSAIDs without a shred of clinical efficacy data.

Amantadine in a multimodal analgesic regimen for alleviation of refractory osteoarthritis pain in dogs. Lascelles BDX, Gaynor JS, Smith ES, et al. J VET INTERN MED 22:53-59, 2008.