Veterinary medicine suffers from a chronic lack of scientific evidence to identify safe and effective treatments. We are authorized to used medicines approved for human or animal use on an off-label basis in other species or conditions because the Food and Drug Administration (FDA) recognizes that there are so few properly tested and approved medications for our patients. Without this off-label authority, our ability to treat serious health problems would be crippled.1 Unfortunately, this means therapies are often widely used on the basis of low-quality or unreliable evidence, including in vitro or lab animal studies, extrapolation from human studies, clinical experience and anecdote, or weak clinical evidence.
One of the most critical unmet needs in companion animal medicine is for oral analgesics other than non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are the mainstay of our treatment for acute and chronic pain in dogs and cats. While they are safe and effective in many cases, sometimes they are contraindicated or the risks of NSAID use may outweigh the benefits.2–6 There is also an inappropriate level of anxiety among pet owners and veterinarians about using these drugs, especially in cats, that further limits their utility.
Many alternative oral analgesics are recommended and commonly used, but these typically lack the robust evidence regarding safety and efficacy we have for the NSIADs.7–11 In some cases, such therapies have been widely employed and then eventually found to be ineffective. Tramadol is perhaps the most well-known example of this.12 Despite promising evidence from human and preclinical research, the extensive use of this drug as a treatment for acute and chronic pain in dogs likely resulted in significant undertreatment and unnecessary suffering. Though the evidence for CBD is slightly better, the ubiquity of this remedy as an analgesic is also out of proportion to the strength of this evidence, and it remains to be seen if we will come to regret rapid and widespread adoption of this as an oral analgesic.13,14
The current leading non-NSAID oral analgesic appears to be gabapentin. I often encounter pet owners and veterinarians firmly convinced that this is a proven therapy for acute and chronic pain in dogs and cats. A recent survey of veterinarians found it the most popular prescription for chronic musculoskeletal pain in cats, ahead of much more extensively studied treatments such as meloxicam.8 Is this confidence justified? Let’s take a look at the evidence.
What is Gabapentin?
Gabapentin is a structurally similar to gamma-aminobutyric acid (GABA), though it is not a GABA receptor agonist.10It’s mechanisms of action are not well-understood, but it appears to operate by affecting pre-synaptic calcium channels in neurons.10,11 It is licensed as an anti-seizure medication in humans and for treatment of herpesvirus-associated neuralgia.10,11
Studies in Humans
Apart from its validated uses for seizures and herpetic neuralgia, gabapentin has been studies for many types of acute and chronic pain in humans. The evidence is mixed, low-quality, and inconclusive.15–23 Studies of perioperative gabapentin use in patients undergoing knee replacement19, hip replacement17, Cesarian section22, breast cancer23, and other surgical procedures16,18,20 are inconsistent. Some show reduction of opioid use and various measures of pain and others do not. In many of these reviews, some assessment tools for pain or discomfort may show beneficial effects from gabapentin while others do not. Even studies examining neuropathic pain in humans, which is considered the most reliable indication for gabapentin, find that many patients experience no benefit.21 Nearly all literature reviews emphasize that the evidence is of poor quality and that better quality research is needed to support firm conclusions.
Veterinary Evidence
Basic pharmacology and pharmacokinetic research indicates gabapentin given orally can be absorbed and achieve plasma levels associated with analgesia in humans.10 Because the drug has a very short half-life, it likely needs to be given every eight hours to achieve these levels.10
A few preclinical studies have been done in dogs and cats. Gabapentin did not affect thermal nociceptive response when given orally in cats. It also did not lower the minimum alveolar concentration (MAC) of isoflurane when given intravenously in this species.24,25 The MAC for isoflurane in dogs was decreased by oral gabapentin, though whether this reflects analgesia or some other effect, such as sedation, is unclear.26
Some case series, and the usual mountain of less formal anecdotal evidence, have suggested analgesic benefits from oral gabapentin in dogs and cats.27–30 However, these uncontrolled observations are at high risk of bias and error, and they frequently do not reflect the findings of better controlled clinical studies.
There are some clinical trial studies of oral gabapentin as an analgesic in dogs and cats. These have generally not been very encouraging, though they all have some methodological limitations, from ineffective blinding or other bias-control measures to administration of gabapentin every 12 hours, which is less than pharmacokinetic studies suggest is needed to achieve an effect.
In dogs, adding gabapentin to opioid or NSAID analgesia provided no additional pain benefit by most measures in dogs undergoing intervertebral disk surgery,31 mastectomy32, and forelimb amputation33. Studies involving dogs with neuropathic34,35 pain have also failed to find robust evidence of any benefit. One study in cats undergoing ovariohysterectomy found no analgesic benefit of oral gabapentin added to buprenorphine or meloxicam compared with a placebo.36 Reviews of the evidence uniformly conclude that the widespread use of gabapentin for acute and chronic pain in dogs and cats is not based on high-quality, robust scientific research.9–11
Is it Safe?
The potential risks of gabapentin are based almost entirely on anecdotal reports. Sedation, ataxia, and vomiting or diarrhea are commonly listed as potential adverse effects and have been reported in clinical trials, but there is virtually no research specifically investigating the potential risks of this drug in dogs or cats.37
Bottom Line
The widespread acceptance and use of gabapentin as a safe and effective treatment for acute and chronic pain in cats and dogs is not based on reliable scientific evidence. Extrapolation from preclinical research and the limited evidence available in humans is a common but poor foundation for clinical use of the drug in veterinary patients. The few studies so far published in dogs and cats have not been encouraging. It may turn out that gabapentin is a useful non-NSAID oral analgesic, but it seems equally likely that we will eventually realize we have been relying on yet another ineffective pain therapy. While we inevitably have to make the best effort we can to treat our patients in the information-poor context of veterinary medicine, we have ample reason to be wary of trusting therapies with such weak evidence behind them. Our patients deserve better than treatments we only hope will effectively treat their pain. Until better more definitive evidence is available, gabapentin should be regarded as no more than theoretically beneficial as an adjunctive treatment, and it should not be relied on as a sole therapy or an alternative to treatments with better evidence of real benefits, such as opioids and NSAIDs.
References
1. American Veterinary Medical Association. Extralabel Drug Use and AMDUCA: FAQ. https://www.avma.org/extralabel-drug-use-and-amduca-faq. Published 2021. Accessed January 7, 2021.
2. Monteiro B, Steagall P, Lascelles B, et al. Long-term use of non-steroidal anti-inflammatory drugs in cats with chronic kidney disease: from controversy to optimism. J Small Anim Pract. 2019;60(8). doi:10.1111/JSAP.13012
3. Sparkes A, Heiene R, Lascelles B, et al. ISFM and AAFP consensus guidelines: long-term use of NSAIDs in cats. J Feline Med Surg. 2010;12(7). doi:10.1016/J.JFMS.2010.05.004
4. Innes J, Clayton J, Lascelles B. Review of the safety and efficacy of long-term NSAID use in the treatment of canine osteoarthritis. Vet Rec. 2010;166(8). doi:10.1136/VR.C97
5. Luna S, Basílio A, Steagall P, et al. Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Am J Vet Res. 2007;68(3). doi:10.2460/AJVR.68.3.258
6. Monteiro-Steagall B, Steagall P, Lascelles B. Systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. J Vet Intern Med. 2013;27(5). doi:10.1111/JVIM.12127
7. Epstein ME, Rodan I, Griffenhagen G, et al. 2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats. J Feline Med Surg. 2015;17(3):251-272. doi:10.1177/1098612X15572062
8. Adrian DE, Rishniw M, Scherk M, Lascelles BDX. Prescribing practices of veterinarians in the treatment of chronic musculoskeletal pain in cats. J Feline Med Surg. 2019;21(6):495-506. doi:10.1177/1098612X18787910
9. Ruel H, Steagall P. Adjuvant Analgesics in Acute Pain Management. Vet Clin North Am Small Anim Pract. 2019;49(6). doi:10.1016/J.CVSM.2019.07.005
10. KuKanich B. Outpatient oral analgesics in dogs and cats beyond nonsteroidal antiinflammatory drugs: an evidence-based approach. Vet Clin North Am Small Anim Pract. 2013;43(5). doi:10.1016/J.CVSM.2013.04.007
11. Moore S. Managing Neuropathic Pain in Dogs. Front Vet Sci. 2016;3. doi:10.3389/FVETS.2016.00012
12. McKenzie BA. Is tramadol an effective analgesic for dogs and cats? Vet Pract News. June 2018:32-33.
13. McKenzie B. A conclusion on cannabis? Vet Pract News. July 2019:26-27.
14. McKenzie BA. Cannabis-based remebdies: No reliable clinical research evidence. Vet Pract News. August 2017:38.
15. Fabritius M, Wetterslev J, Mathiesen O, Dahl J. Dose-related beneficial and harmful effects of gabapentin in postoperative pain management – post hoc analyses from a systematic review with meta-analyses and trial sequential analyses. J Pain Res. 2017;10. doi:10.2147/JPR.S138519
16. Fabritius M, Geisler A, Petersen P, Wetterslev J, Mathiesen O, Dahl J. Gabapentin in procedure-specific postoperative pain management – preplanned subgroup analyses from a systematic review with meta-analyses and trial sequential analyses. BMC Anesthesiol. 2017;17(1). doi:10.1186/S12871-017-0373-8
17. Mao Y, Wu L, Ding W. The efficacy of preoperative administration of gabapentin/pregabalin in improving pain after total hip arthroplasty: a meta-analysis. BMC Musculoskelet Disord. 2016;17(1). doi:10.1186/S12891-016-1231-4
18. Egunsola O, Wylie C, Chitty K, Buckley N. Systematic Review of the Efficacy and Safety of Gabapentin and Pregabalin for Pain in Children and Adolescents. Anesth Analg. 2019;128(4). doi:10.1213/ANE.0000000000003936
19. Han C, Li X, Jiang H, Ma J, Ma X. The use of gabapentin in the management of postoperative pain after total knee arthroplasty: A PRISMA-compliant meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016;95(23). doi:10.1097/MD.0000000000003883
20. Fabritius M, Geisler A, Petersen P, et al. Gabapentin for post-operative pain management – a systematic review with meta-analyses and trial sequential analyses. Acta Anaesthesiol Scand. 2016;60(9). doi:10.1111/AAS.12766
21. Wiffen P, Derry S, Bell R, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane database Syst Rev. 2017;6(6). doi:10.1002/14651858.CD007938.PUB4
22. Felder L, Saccone G, Scuotto S, et al. Perioperative gabapentin and post cesarean pain control: A systematic review and meta-analysis of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol. 2019;233. doi:10.1016/J.EJOGRB.2018.11.026
23. Rai A, Khan J, Dhaliwal J, et al. Preoperative pregabalin or gabapentin for acute and chronic postoperative pain among patients undergoing breast cancer surgery: A systematic review and meta-analysis of randomized controlled trials. J Plast Reconstr Aesthet Surg. 2017;70(10). doi:10.1016/J.BJPS.2017.05.054
24. Pypendop B, Siao K, Lkiw J. Thermal antinociceptive effect of orally administered gabapentin in healthy cats. Am J Vet Res. 2010;71(9). doi:10.2460/AJVR.71.9.1027
25. Reid P, Pypendop B, Ilkiw J. The effects of intravenous gabapentin administration on the minimum alveolar concentration of isoflurane in cats. Anesth Analg. 2010;111(3). doi:10.1213/ANE.0B013E3181E51245
26. Johnson B, Aarnes T, Wanstrath A, et al. Effect of oral administration of gabapentin on the minimum alveolar concentration of isoflurane in dogs. Am J Vet Res. 2019;80(11). doi:10.2460/AJVR.80.11.1007
27. Davis L V, Hellyer PW, Downing RA, Kogan LR. Retrospective Study of 240 Dogs Receiving Gabapentin for Chronic Pain Relief. J Vet Med Res. 2020;7(4):1194. https://www.jscimedcentral.com/VeterinaryMedicine/veterinarymedicine-7-1194.pdf. Accessed January 7, 2021.
28. Steagall P, Monteiro-Steagall B. Multimodal analgesia for perioperative pain in three cats. J Feline Med Surg. 2013;15(8). doi:10.1177/1098612X13476033
29. Vettorato E, Corletto F. Gabapentin as part of multi-modal analgesia in two cats suffering multiple injuries. Vet Anaesth Analg. 2011;38(5). doi:10.1111/J.1467-2995.2011.00638.X
30. Lorenz N, Comerford E, Iff I. Long-term use of gabapentin for musculoskeletal disease and trauma in three cats. J Feline Med Surg. 2013;15(6). doi:10.1177/1098612X12470828
31. Aghighi S, Tipold A, Piechotta M, Lewczuk P, Kästner S. Assessment of the effects of adjunctive gabapentin on postoperative pain after intervertebral disc surgery in dogs. Vet Anaesth Analg. 2012;39(6). doi:10.1111/J.1467-2995.2012.00769.X
32. Crociolli G, Cassu R, Barbero R, Rocha T, Gomes D, Nicácio G. Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy. J Vet Med Sci. 2015;77(8). doi:10.1292/JVMS.14-0602
33. Wagner A, Mich P, Uhrig S, Hellyer P. Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb. J Am Vet Med Assoc. 2010;236(7). doi:10.2460/JAVMA.236.7.751
34. Plessas I, Volk H, Rusbridge C, Vanhaesebrouck A, Jeffery N. Comparison of gabapentin versus topiramate on clinically affected dogs with Chiari-like malformation and syringomyelia. Vet Rec. 2015;177(11). doi:10.1136/VR.103234
35. Ruel H, Watanabe R, Evangelista M, et al. Pain burden, sensory profile and inflammatory cytokines of dogs with naturally-occurring neuropathic pain treated with gabapentin alone or with meloxicam. PLoS One. 2020;15(11). doi:10.1371/JOURNAL.PONE.0237121
36. Steagall P V, Benito J, Monteiro BP, Doodnaught GM, Beauchamp G, Evangelista MC. Analgesic effects of gabapentin and buprenorphine in cats undergoing ovariohysterectomy using two pain-scoring systems: a randomized clinical trial. J Feline Med Surg. 2018;20(8):741-748. doi:10.1177/1098612X17730173
37. Peck C. The adverse effect profile of gabapentin in dogs – a retrospective questionnaire study. 2017.
Please don’t tell me that Gabapentin is not helping to keep my old dog comfortable *sigh*
It’s rather expensive, plus all the eyedrops $$$ to try to keep her eye pressure (due to glaucoma) down in an attempt to avoid enucleation.
It appears to be helping her along with a little Trazodone. Appetite good, no signs or symptoms of discomfort observed.
I’m not say9ing it doesn’t help, only that the evidence is weak and some things we have used in the past based on similar evidence later turned out not to work. I think we don’t know if it is helpful, and we won’t until we have better studies. It is very safe, and it shouldn’t be that expensive since it is generic, so you might look for another source?
If you need a low dose , compounded, it runs about a dollar a pill, it adds up.
Thanks, for your response.
dog came in yesterday for a second opinion on gabapentin scheduled for the first of two 7000 thousand dollar cruciate surgeries. Suspect the surgeon did not want to use nsaids before surgery. Seems like we get forced into trying treatment even if RCT studies do not support.
Thanks for the post, informative as always, and which was timely in our case…
I’ll add to the anecdotal evidence.
Our cat gradually reached to a point where he couldn’t eat anything anymore, except for a type of soft crunchy treat.
He was given Meloxicam and I believe an opioid for over a couple weeks before and after extracting a few of his teeth (which were thought to be causing him problems). He kept doing his best “trying” to eat, but just ended up causing a mess and managing to eat extremely little.
The vets decided to try gabapentin, and it worked instantly. He’s been on it for several months now and doing well. We’ve tried to figure out how much of the stuff works. This has come down from 0.3 ml twice a day (every 12 hours) to 0.2 ml.
If we reduce or skip a couple doses it gets difficult for him to really eat (chew / swallow) soft food. Later it gets difficult to eat kibble.
It seems he’s got some kind of musculoskeletal jaw pain, or facial pain…
The problem was foreshadowed several months earlier when he could only suck the juice out of his favorite tuna wet food, and would barely touch any of the fish. Interestingly he continued to eat the rock-like kibble he used to eat on a daily basis until I guess the pain was just too much to bear…
Thanks again.
I myself take gabapentin for arthritis and have for almost 10 years. It’s useless as an analgesic (for me anyway) but works well as a sedative taken before bedtime. No side effects other than drowsiness.
I’ve had it prescribed for a dog and can’t say as it did anything.
As a human medicine, it’s cheap…at least if you are on Medicare or in many countries with national health plans. (In NZ I’m paying < 10¢ a day).
Is this another case where the drug raise the price for pet medicines?
If you need a low dose it has to be prepared by a “compounding” pharmacy (veterinary) hence the higher price.
It averages $1 a for a 25 mg pill for my dog, dog gets 2 pills per day.
It’s available as generic, and there is no approved animal version, so the price shouldn’t be different from human pharmacies, though online sources and individual veterinarians will have variable markups on drugs they stock and sell themselves.
I used Wedgewood Pharmacy as per my vet’s recommendation. Angell (Boston) prices were comparable.
Wow. Very interesting. We’ve had gabapentin prescribed for every type of pain you can imagine for the cats in our rescue. I have quite a bit stocked up. Post-FHO pain, post-bladder blockage pain, etc. I hope we will know more in the future… I would hate to think we’re dosing these animals without any benefit to them. Perhaps confusing their sedation with an absence or reduction in pain?
Our 10 year old Sheltie, has been on Gabapentin for the last month. He seems ‘better’, but as I’ve learnt from this blog, it’s hard to know without an objective measurement. When I asked our vet if Meloxicam could be tried, she mentioned that his ALT level was 112 (from what they explained slightly elevated).
Due that number on his bloodwork, she suggested Gabapentin, until his numbers come down.
Is there an objective test name I can ask my vet to perform? Or would it perhaps be more fruitful to reexamine Meloxicam?
Any thoughts are greatly appreciated.
Thanks,
Szandra
A mild ALT elevation is not a reason to avoid NSAIDs. If it is persistent or progressive, then an attempt should be made to figure out where it is coming from. If no cause is found, then I would not avoid good pain control like NSAIDs just because of this lab value, I would simply monitor it closely. Definitely a conversation worth having with your vet since it is unclear how helpful gabapentin is for arthritis pain.
Thank you for sharing your thoughts. I look forward to bringing this up to my vet in a few weeks.
Is there anything else to bring up to the vet or orthopedic to try instead of gabapentin? We’ve been giving our dog gabapentin and meloxicam along with some shot once every two weeks for his arthritis and deformed front paw. The medication works now, but sometimes he still looks like he’s in pain so if there’s anything else we could try that anyone could recommend mentioning to our vet I’d appreciate it. So far all they mention is gabapentin and meloxicam so…
Unfortunately, there is little reliable evidence for most oral analgesics other than NSAIDs in dogs. Codein is sometimes used, though it has poor absorption and can lose effectiveness over time; acetaminophen can be helpful but has a very narrow range of safe dosing and can be a problem with other anti-inflammatories, tramadol probably doesn’t work, most supplements are untested or probably don’t work, etc. Physical therapy is quite helpful fo humans and we suspect it will be for dogs, though there isn’t much research yet, so you might ask about a rehab/physical therapy program. Lots on the blog about massage, acupuncture, laser, etc.,m and none are very impressive. I would consider seeing a rehab specialists.
My cat is currently on transmucosal buprenorphine for his pain and it is such a hassle!
I was very surprised when my vet told me there were few take-home treatments for severe chronic pain in pets… My cat is good with pills but hates the oral syringe. Do most human pain medications not work in pets or is it just a lack of studies? Do you know if researchers are looking in to better treatments for chronic pain in cats?
Thanks!
That’s unusual, since this is typically one of the easiest and best-accepted medicines in cats.
oat companies don’t specifically test their drugs in pets because the potential profit isn’t enough to justify the expense. We routinely use human drugs off-label, but with too little evidence (which is why they sometimes turn out not to work, as with tramadol). Vet Med is a severe resource and evidence-poor field. 🙁
Yes my vet said that as well, most cats take it quite easily… but his claws come out and I’ve never seen him as angry as when he gets his medicine.
This is a bit off-topic, but do you think resources allocated to veterinary medicine are increasing as people are willing to spend more on their pets?
Considering Cytopoint for example, I think the idea of a commercial monoclonal antibody being easily and (relatively) cheaply available for dogs would have been unimaginable 10 years ago. Although this may speak more to improved manufacturing of biologics rather than larger investments in veterinary medicine.
(I’m a pharmaceutical chemist but am not in the loop at all with regards to veterinary therapeutics)
There is certainly growth in the animal Pharma industry. Unfortunately, there is excessive concentration on a few lucrative indications (e.g. parasite prevention, NSAIDs), so we have more drugs than we need for those and none for many other common or important indications. Overall, it’s a tiny market from a Pharma perspective, so we’re stuck with off-label human drugs most of the time.
Ugh. My 15 year old cat was prescribed gabapentin for her arthritis and even though I knew about this page and the lack of clinical evidence, I tried it. I wanted to trust the vet and the anecdotal reports I’ve heard online of people’s elderly arthritic cats becoming more mobile because of gabapentin.
Unfortunately even though she was supposed to be on a low dose, there were several times that she was sedated off it. I tried to trust that she would get used to it so I kept it going for a few weeks until one night where she was sedated even though I had given her a smaller dose than I was supposed to (1/6 of a tablet instead of 1/4). I was like nope, this is not worth it. She is not enjoying herself, it looks like she is drunk and wants it to stop. So I stopped giving it to her and she’s back to her perky, purry self. I have no idea if she is in pain from her arthritis, her mobility is certainly low, but I’d rather have her bright eyed and responsive. I hope it hasn’t done her any damage, she is fifteen and also has cancer so who knows.
Also, last night she played with her lazer pointer for the first time in forever! It’s hard to do nothing but sometimes nothing is better than over treatment.