Amantadine update

There are a couple of recent publications worth discussing relating to amantadine. The first is a publication titled "Amantadine as a therapeutic option for neuropathic pain in dogs with degenerative lumbosacral stenosis."

Objective

To evaluate whether amantadine improves neuropathic pain associated with degenerative lumbosacral stenosis (DLSS) in dogs, using objective force-plate gait analysis, and to assess whether adding amantadine improves outcomes in dogs previously unresponsive to meloxicam alone. 

Study Design

• Prospective randomized clinical trial.

• 20 client-owned dogs with confirmed DLSS.

• All dogs had previously failed to respond adequately to meloxicam therapy. 

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Treatment groups

Group A (n=10)

• Meloxicam:

  • 0.2 mg/kg loading dose

  • then 0.1 mg/kg SID for 7 days

• Amantadine:

  • 3 mg/kg SID for 21 days

Group B (n=10)

• Amantadine alone:

  • 3 mg/kg BID for 21 days 

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Outcome Measures

Objective force-plate analysis at:

• Baseline (T0)

• Day 7 (T1)

• Day 21 (T2)

Measured:

• Peak Vertical Force (PVF)

• Vertical Impulse (VI)

• Stance Time (ST) 

Key Results

1. Significant improvement with amantadine

Both treatment groups showed statistically significant increases in:

• Peak Vertical Force (PVF)

• Vertical Impulse (VI)

after 21 days, indicating improved limb loading and reduced pain-associated gait abnormalities. 

Group A (Meloxicam + Amantadine)

• VI improved significantly:

  • T0 → T1 (p=0.012)

  • T0 → T2 (p=0.008)

• PVF improved significantly:

  • T0 → T1

  • T0 → T2

  • T1 → T2 

Group B (Amantadine Alone)

• VI improved significantly:

  • T0 → T2 (p=0.0012)

  • T1 → T2 (p=0.0034)

• PVF improved significantly at all time points. 

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2. Amantadine alone appeared effective

Dogs receiving amantadine without NSAIDs showed similar objective improvement to those receiving combination therapy, supporting a direct analgesic benefit of amantadine for neuropathic pain associated with DLSS. 

3. No significant change in stance time

Stance time did not change significantly, likely because enrolled dogs had mild-to-moderate disease and improvements were reflected primarily in force generation rather than gait timing. 

Clinical Interpretation

The authors suggest that amantadine's NMDA receptor antagonism may reduce central sensitization and chronic neuropathic pain, allowing dogs to load affected limbs more normally. 

Importantly, this study specifically enrolled dogs considered refractory to meloxicam alone, making the findings clinically relevant for difficult chronic pain cases. 

Limitations

• Small sample size (20 dogs).

• No meloxicam-only control group.

• Follow-up limited to 21 days.

• Force-plate outcomes improved, but long-term clinical durability remains unknown. 

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Clinical Take-Home Message

This 2025 randomized trial provides objective evidence that amantadine can improve gait kinetics and likely reduce neuropathic pain in dogs with degenerative lumbosacral stenosis, including dogs previously unresponsive to NSAID therapy. Both amantadine alone and amantadine combined with meloxicam produced significant improvements in limb function over 21 days. The authors conclude that amantadine is a useful addition to multimodal management of canine DLSS-associated neuropathic pain

Practical dosing from the study:

• Amantadine 3 mg/kg PO BID (monotherapy), or

• Amantadine 3 mg/kg PO SID with meloxicam. 

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Notably, the study cites a previous veterinary case report by Madden, Gurney, and Bright (2014) describing successful use of amantadine for chronic neuropathic pain in a dog. 

Our view:

The study design of amantadine/meloxicam vs amantadine is good because it answers a long-held question – is amantadine effective alone – which does seem to be the case in this study. Can we extrapolate that from DLSS to osteoarthritis? Are the pain types the same or similar? Neuropathic pain is a feature of DLSS, but not really in OA so I would hesitate to say yes to this question.

Amantadine has been part of my treatment options for these cases and it’s good to have some further information, albeit a study with small numbers.

New reported potential adverse effect:

The second update pertains to a case report in which a dog treated with amantadine developed hypoglycaemia which resolved after discontinuation of treatment. You can read that report here – it’s certainly worth knowing this is a potential adverse effect.

References

Caterino C, Della Valle G, Aragosa F, Cavalli S, Lamagna F, Fatone G. Amantadine as a therapeutic option for neuropathic pain in dogs with degenerative lumbosacral stenosis. BMC Vet Res. 2025 Jul 16;21(1):469. doi: 10.1186/s12917-025-04911-9.

Shahira A, Medina-Serra R, Adam F, Zoff A. Suspected amantadine-induced hypoglycaemia in a dog treated for chronic lumbosacral pain. Vet Anaesth Analg. 2026 Jul 28;53(5):101290. doi: 10.1016/j.vaa.2026.101290.

Telemedicine

Did you know we offer a telemedicine service for chronic pain advice? If you have a DLSS case that you are struggling to control, you can request advice here.