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Evaluation of prescribing practices for gabapentin as an analgesic among veterinary professionals

  • Rebecca Reader
    Correspondence
    Correspondence: Rebecca C Reader, Department of Clinical Sciences, Cummings Veterinary Medical Center at Tufts University, 200 Westboro Road, North Grafton, MA 01536, USA.
    Affiliations
    Department of Clinical Sciences, Cummings Veterinary Medical Center at Tufts University, North Grafton, MA, USA
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  • Oladapo Olaitan
    Affiliations
    Department of Quantitative Health Sciences, University of Massachusetts Medical School, The Albert Sherman Center, Worcester, MA, USA
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  • Emily McCobb
    Affiliations
    Department of Clinical Sciences, Cummings Veterinary Medical Center at Tufts University, North Grafton, MA, USA
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      Abstract

      Objective

      To describe the prescribing practices for gabapentin as an analgesic within the veterinary community.

      Study design

      Anonymous online voluntary survey.

      Population

      A total of 718 veterinarians within the United States and Canada, including general practitioners and diplomates of the American Colleges of Veterinary Anesthesia and Analgesia, Emergency and Critical Care, Surgery and Internal Medicine.

      Methods

      An anonymous online survey was used to gather information about individual prescribing practices for gabapentin including frequency of use, reasons for prescribing and procedures for authorizing refill requests. Questions specific to gabapentin covered mechanisms of action, perceptions of efficacy and the potential for abuse in people. Dunn’s test for multiple comparisons and pairwise Mann–Whitney U test were used to evaluate relationships between veterinary specialty and survey responses.

      Results

      A total of 718 veterinarians responded to the survey, 528 (73.5%) answered all questions of the survey to completion. Frequency of prescribing was high with 365/529 (69.0%) of respondents prescribing gabapentin as an analgesic on a daily or weekly basis. Surgeons and general practitioners used gabapentin significantly more frequently than other groups, with surgeons more likely to prescribe gabapentin for postoperative pain. The most common reason [254/517 (49.1%)] survey respondents prescribed gabapentin as an analgesic was because administration of a non-steroidal anti-inflammatory medication was contraindicated for that animal. The majority of survey respondents [362/527 (68.7%)] considered the abuse potential of gabapentin to be low in people.

      Conclusions and clinical relevance

      Veterinary prescribing practices for gabapentin closely mirrored that of human physicians, with gabapentin being prescribed frequently and for uses largely unrelated to its labeled indication. The perception of the potential for abuse of gabapentin is low within the veterinary community.

      Keywords

      Introduction

      Veterinary use of gabapentin has increased dramatically over the past several years, probably as an oral analgesic alternative to non-steroidal anti-inflammatory drugs (NSAIDs) and as a result of the lack of evidence for the analgesic effects of tramadol in some species, particularly dogs (
      • Davila D.
      • Keeshen T.P.
      • Evans R.B.
      • Conzemius M.G.
      Comparison of the analgesic efficacy of perioperative firocoxib and tramadol administration in dogs undergoing tibial plateau leveling osteotomy.
      ;
      • KuKanich B.
      Outpatient oral analgesics in dogs and cats beyond nonsteroidal anti-inflammatory drugs: an evidence-based approach.
      ;
      • Donati P.A.
      • Tarragona L.
      • Franco J.V.A.
      • et al.
      Efficacy of tramadol for postoperative pain management in dogs: systematic review and meta-analysis.
      ). However, there is little evidence that gabapentin is an effective analgesic for acute pain in animals. Existing evidence suggests that gabapentin may be effective as part of a multimodal analgesic treatment when combined with an opioid or an NSAID (
      • Wagner A.E.
      • Mich P.M.
      • Uhrig S.R.
      • Hellyer P.W.
      Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb.
      ;
      • Aghighi S.A.
      • Tipold A.
      • Piechotta M.
      • et al.
      Assessment of the effects of adjunctive gabapentin on postoperative pain after intervertebral disc surgery in dogs.
      ;
      • Crociolli G.C.
      • Cassu R.N.
      • Barbero R.C.
      • et al.
      Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy.
      ). However, this evidence is based largely on studies with small sample sizes, possibly ineffective dosing regimens based on previous pharmacokinetic studies (
      • KuKanich B.
      • Cohen R.L.
      Pharmacokinetics of oral gabapentin in greyhound dogs.
      ;
      • Siao K.T.
      • Pypendop B.H.
      • Ilkiw J.E.
      Pharmacokinetics of gabapentin in cats.
      ) and the presence of multiple baseline analgesics as confounding factors. Despite the lack of evidence to support its use, we have observed that veterinarians in our practice community are prescribing gabapentin for any type of pain, including use as the sole analgesic for acute pain.
      Similar trends in prescribing practices are present in human medicine. Gabapentinoids (gabapentin, pregabalin) were initially developed as anticonvulsants, and later labeled by the US Food and Drug Administration for treatment of postherpetic neuralgia, fibromyalgia and neuropathic pain associated with diabetes and spinal cord injuries (
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ). Over the past several years, gabapentin has become one of the top 10 most frequently prescribed medications in the United States (
      • Goodman C.W.
      • Brett A.S.
      A clinical overview of off-label use of gabapentinoid drugs.
      ). The number of human patients taking gabapentin tripled in 2002–2015, and greater than 80% of prescriptions for gabapentin are for extra-label use (
      • Smith R.V.
      • Havens J.R.
      • Walsh S.L.
      Gabapentin misuse, abuse and diversion: a systematic review.
      ). The increase in use may reflect a desire among human physicians for a nonopioid alternative for pain management, and lack of data on adverse effects in early publications (
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ). However, the extra-label use of gabapentin lacks supporting evidence for efficacy, and is associated with increased adverse effects and a growing potential for diversion and abuse (
      • Smith R.V.
      • Havens J.R.
      • Walsh S.L.
      Gabapentin misuse, abuse and diversion: a systematic review.
      ;
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ;
      • Verret M.
      • Lauzier F.
      • Zarychanski R.
      • et al.
      Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis.
      ).
      The purpose of this study was to describe the prescribing practices for gabapentin as an analgesic among veterinarians in multiple practice settings to determine if they mirror those described in human medicine. Our hypotheses were: 1) that the use of gabapentin would be widespread, prescribing practices would vary among different specialties and that veterinary surgeons, internists, criticalists and general practitioners would be more likely to use gabapentin as a first-line analgesic when compared with anesthesiologists; 2) that most clinicians would be unaware of the proposed mechanism of action of gabapentin and effects on the pain pathway; and 3) that few respondents would be aware that gabapentin has potential for diversion and abuse.

      Materials and methods

       Survey development

      An anonymous, online survey was developed using a commercial survey software platform (Qualtrics XM; UT, USA). The study protocol was exempt from review by the Institutional Review Board at Tufts University (MA, USA). Following informed consent, survey participants were asked to answer a total of 20 questions about gabapentin, individual prescribing practices and their demographic characteristics. Respondents were asked to describe their prescribing practice using frequency of use, reasons for prescribing and procedures for authorizing refill requests. Questions about gabapentin focused on mechanisms of action, perceptions of efficacy and its potential for abuse in humans. Demographic information included age, gender, type of practice/species seen and board certifications. Survey questions required respondents to select from a set of answers provided. Two questions allowed respondents to provide information by writing the answer in a text box; one regarding postgraduate qualifications and one asking for the year of graduation from veterinary school. The survey was conducted between July 15, 2020 and October 8, 2020. Results were automatically recorded into an online database and were transferred to SPSS Version 25.0 (IBM SPSS Statistics; NY, USA) for data management once the survey was closed. The full survey is available as supplementary material (Appendix SA).

       Survey recruitment

      Study participants included individuals located within the United States and Canada who possessed a veterinary degree or its equivalent. Individuals located outside of the United States and Canada were excluded from the study because of differences in online survey privacy requirements between the two geographic regions. Participants included general practitioners and veterinarians who had achieved diplomate status in the following specialty colleges: American College of Veterinary Anesthesia and Analgesia (ACVAA), American College of Veterinary Emergency and Critical Care (ACVECC), American College of Veterinary Surgeons (ACVS) and American College of Veterinary Internal Medicine (ACVIM).
      An e-mail request to voluntarily participate in an anonymous online survey was sent to the following professional list servs: ACVAA, ACVECC, ACVIM, Veterinary Orthopedic Society, Society of Veterinary Soft Tissue Surgery, Veterinary Oncologic Surgery Society and a musculoskeletal research forum (VA3). In addition, a request to participate was posted to the ACVS online message board, the newsletter of the Connecticut Veterinary Medical Association, and social media platforms (Facebook, Twitter) for the Massachusetts Veterinary Medical Association and Tufts University Veterinary Alumni Network.
      Upon completion of the survey, participants were automatically directed to a link where they were given the option to enter their e-mail address to be included in a drawing for a $100 gift card to an online retail store.

       Statistical analysis

      All statistical analyses were performed with two commercially available software programs (SAS Institute Inc., NC, USA; R Core Team, Vienna, Austria). Summary descriptive statistics are presented when appropriate. Dunn’s test for multiple comparisons and pairwise Mann–Whitney U test were used to evaluate relationships between veterinary specialty and the following: frequency of gabapentin use, the most common reason for prescribing gabapentin, use of gabapentin as a sole analgesic and the perception of potential for human abuse of gabapentin. A chi-square test was used to compare knowledge of mechanism of action among specialty groups. Data were considered significant when p < 0.05.

      Results

       Study population characteristics

      A total of 718 veterinarians responded to the survey, with 528 (73.5%) answering all questions of the survey to completion (Table 1). The majority of respondents, 516/564 (91.5%), worked primarily with small animals (cats and dogs). The respondents indicated that 353/558 (63.3%) were board certified and 171/558 (30.6%) were general practitioners (Table 1). Respondents selecting ‘other’ for board certification indicated their certification by writing in a text box the following specialties: diplomates of the American College of Veterinary Sports Medicine and Rehabilitation (n = 4), the American Board of Veterinary Practitioners (n = 4), the American College of Veterinary Dermatology (n = 3), the American College of Veterinary Nutrition (n = 1), the American College of Laboratory Animal Medicine (n = 1), the European College of Veterinary Anesthesia and Analgesia (n = 1), the European College of Veterinary Surgeons (n = 1) or residency-trained, board-eligible veterinary anesthesiologists (n = 6). Answers from respondents with board certifications outside the targeted specialties were not included in group analysis.
      Table 1Demographic and practice characteristics reported by veterinarians from the United States and Canada in an online survey administered from July 15 to October 8, 2020, to gather data relating to prescribing practices for gabapentin as an analgesic among veterinarians in multiple practice settings
      DemographicsRespondents (n)Total respondents (%)
      Gender
      Male12323.4
      Female40176.2
      Non-binary00.0
      Self-describe20.4
      Total responses526
      Age, years
      25–4023845.1
      40–5519937.7
      >559117.3
      Total responses528
      Practice type
      Academic11520.6
      General practice17130.7
      After hours71.3
      Specialty and referral26547.5
      Total responses558
      Board certification
      DACVIM9928.1
      DACVECC10028.3
      DACVS6919.6
      DACVAA5315.0
      Other329.1
      Total responses353
      DACVAA, diplomate of the American College of Veterinary Anesthesia and Analgesia; DACVECC, diplomate of the American College of Veterinary Emergency and Critical Care; DACVIM, diplomate of the American College of Veterinary Internal Medicine; DACVS, diplomate of the American College of Veterinary Surgeons.

       Gabapentin prescribing practices

       Frequency of use

      Greater than 97% (516/529) of respondents indicated that they prescribe gabapentin, with 46.9% (248/529) indicating that they have been prescribing gabapentin for > 5 years. The overall frequency of prescribing was high, with 69.0% (365/529) using gabapentin as an analgesic on a daily to weekly basis. The frequency of prescribing gabapentin differed among the specialty groups (Table 2). Veterinary surgeons and general practitioners prescribed gabapentin as an analgesic significantly more frequently (p < 0.00005 and p < 0.0001, respectively) than other groups, with 88.7% (55/62) of surgeons and 66.9% (107/160) of general practitioners using gabapentin on a daily or weekly basis.
      Table 2Frequency of use of gabapentin as an analgesic by veterinarians from the United States and Canada, broken down by specialty group, who reported in an online survey administered from July 15 to October 8, 2020, that they prescribe gabapentin daily, a few times a week, a few times a month, or never. Data are reported as number (percentage of total respondents)
      Specialty groupDailyWeeklyMonthlyNeverTotal respondents
      General practitioners40 (25.0%)67 (41.9%)50 (31.3%)3 (1.9%)160
      Anesthesiologists12 (27.3%)12 (27.3%)11 (25.0%)9 (20.5%)44
      Criticalists53 (29.0%)69 (37.7%)58 (31.7%)3 (1.6%)183
      Surgeons40
      Surgeons (p < 0.00005) and †general practitioners (p < 0.0001) prescribed gabapentin significantly more frequently than other groups.
      (64.5%)
      15 (24.2%)5 (8.1%)2 (3.2%)62
      Internists6 (33.3%)6 (33.3%)6 (33.3%)4 (22.2%)18
      Surgeons (p < 0.00005) and general practitioners (p < 0.0001) prescribed gabapentin significantly more frequently than other groups.

       Reasons for prescribing

      The most common reasons that survey respondents chose to prescribe gabapentin as an analgesic was because an NSAID was contraindicated in the animal, 49.1% (254/517), or because gabapentin was believed to be an effective analgesic in veterinary species, 31.9% (165/517). When analyzed by specialty, anesthesiologists expressed different reasons for prescribing gabapentin from surgeons and internists. Anesthesiologists indicated the most common reason they prescribed gabapentin was because the animal should not be treated with an NSAID, whereas veterinary surgeons and internists more frequently considered gabapentin to be an effective analgesic in veterinary species (p = 0.0045 and p = 0.0170, respectively).

       Intended use of gabapentin

      Anesthesiologists, criticalists, internists and general practitioners frequently prescribed gabapentin for chronic pain and sedation of anxious or fearful animals (Table 3). Surgeons prescribed gabapentin for acute (postoperative) pain significantly more frequently (p = 0.02). General practitioners (p = 0.0019), surgeons (p < 0.0096) and criticalists (p < 0.00005) prescribed gabapentin as the sole analgesic significantly more frequently than anesthesiologists (Fig. 1).
      Table 3Common uses of gabapentin by veterinarians from the United States and Canada, broken down by specialty group, who reported in an online survey administered from July 15 to October 8, 2020, that they prescribe gabapentin for acute pain, chronic pain, seizures, adjunct analgesia or sedation of anxious/fearful animals. Data are reported as number (percentage of total respondents). Survey respondents were allowed to select more than one option; category totals reflect the number of times that option was chosen by a member of the specialty group
      Specialty groupAcute painChronic painSeizuresAdjunct analgesiaSedationTotal responses
      General practitioners79 (16.8%)143 (30.4%)14 (3.0%)95 (20.2%)139 (29.6%)470
      Anesthesiologists17 (16.2%)31 (29.5%)4 (3.8%)17 (16.2%)36 (34.3%)105
      Criticalists99 (19.4%)158 (30.9%)12 (2.3%)84 (16.4%)158 (30.9%)511
      Surgeons51
      Surgeons prescribed gabapentin for acute (postoperative) pain significantly more frequently (p = 0.02).
      (29.5%)
      45 (26.0%)3 (1.7%)31 (17.9%)43 (24.9%)173
      Internists11 (23.4%)13 (27.7%)2 (4.3%)6 (12.8%)15 (31.9%)47
      Surgeons prescribed gabapentin for acute (postoperative) pain significantly more frequently (p = 0.02).
      Figure 1
      Figure 1Summary of the percentages of veterinarians in the United States and Canada, broken down by specialty group, who reported in an online survey administered from July 15 to October 8, 2020, that they prescribe gabapentin as the sole analgesic sometimes, frequently, almost always or never. The total number of respondents for each specialty group was anesthesiologists (n = 43), criticalists (183), surgeons (62), internists (22) and general practitioners (159). ∗General practitioners (p = 0.0019), surgeons (p < 0.0096) and criticalists (p < 0.00005) prescribed gabapentin as the sole analgesic significantly more frequently than anesthesiologists.

       Mechanism of action

      The survey identified that 44.3% (232/524) of respondents selected that the mechanism of action of gabapentin was on voltage-gated calcium channels. The remainder of respondents indicated that that they did not know the mechanism by which gabapentin is thought to provide analgesia, 20.8% (109/524), or attributed its action to the incorrect receptor, 34.9% (183/524). There was a significant difference (p < 0.00001) in knowledge of mechanism of action among groups. Anesthesiologists selected voltage-gated calcium channels as the correct mechanism of action significantly more often than criticalists, internists and general practitioners (p = 0.04, p = 0.04 and p < 0.00001, respectively).

       Abuse potential

      Almost half of survey respondents, 45.5% (254/558), indicated that there is a prescription monitoring system in place at their practice. Most respondents, 73.1% (380/520), indicated that they prescribe from 2 weeks to 1 month supply of gabapentin at a time, and 69.2% (362/523) of respondents do not require a recheck appointment or have additional restrictions in place prior to authorizing a refill of the medication. There were no differences in perception of potential for abuse among groups, and 68.7% (362/527) of respondents considered the abuse potential of gabapentin to be low in humans.

      Discussion

      The results of this online survey in the United States and Canada included responses from veterinarians in different working environments describing their usage of gabapentin as an analgesic in small animals. Survey responses indicated that the majority of practitioners prescribe gabapentin, and do so frequently.
      This study demonstrated that veterinary prescribing practices for gabapentin are similar to those described in human medicine. Two of the most frequently selected uses of gabapentin included the treatment of acute or chronic pain. Few veterinarians in the present survey indicated using gabapentin for its originally labeled use as an antiepileptic drug (
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ). This finding closely mirrors human medicine, where gabapentinoids are widely used extra-label to treat chronic pain conditions and are increasingly used for postoperative acute pain (
      • Smith R.V.
      • Havens J.R.
      • Walsh S.L.
      Gabapentin misuse, abuse and diversion: a systematic review.
      ). The motivation behind this extra-label use in humans is to avoid the adverse effects and addictive properties associated with opioids (
      • Verret M.
      • Lauzier F.
      • Zarychanski R.
      • et al.
      Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis.
      ). In a similar manner, the most common reason for the use of gabapentin among survey respondents was the avoidance of or inability to administer an NSAID. NSAIDs are effective analgesics in canine and feline patients but are often contraindicated because of concerns for gastrointestinal ulceration, hepatic or renal injury (
      • Epstein M.
      • Rodan I.
      • Griffenhagen G.
      • et al.
      2015 AAHA/AAFP pain management guidelines for dogs and cats.
      ).
      When compared with opioids and NSAIDs, gabapentinoids appear to be relatively safe alternatives. However, gabapentin administration is not without the risk of adverse effects. Sedation is a commonly accepted side effect of gabapentin in veterinary species (
      • Epstein M.
      • Rodan I.
      • Griffenhagen G.
      • et al.
      2015 AAHA/AAFP pain management guidelines for dogs and cats.
      ), and additional adverse effects can include ataxia, weakness and muscle tremors (
      • Guedes A.G.P.
      • Meadows J.M.
      • Pypendop B.H.
      • et al.
      Assessment of the effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life in osteoarthritic cats.
      ). Similarly, a recent systematic review and meta-analysis found that perioperative use of gabapentinoids were significantly associated with increased risk of sedation, dizziness and respiratory complications in humans (
      • Verret M.
      • Lauzier F.
      • Zarychanski R.
      • et al.
      Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis.
      ). There is a growing concern among physician anesthesiologists that the sedative effects of gabapentin may have a masking effect on pain (
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ). When the impact of gabapentin administration on postoperative pain in humans was compared with an active placebo (lorazepam), any evidence of benefit was eliminated (
      • Verret M.
      • Lauzier F.
      • Zarychanski R.
      • et al.
      Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis.
      ). A recent study in cats with osteoarthritis found that while owner perceptions of mobility were improved with gabapentin administration, there were significant decreases in mean daily activity levels and sedation was the most commonly noted side effect (
      • Guedes A.G.P.
      • Meadows J.M.
      • Pypendop B.H.
      • et al.
      Assessment of the effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life in osteoarthritic cats.
      ).
      Survey results confirmed our hypothesis that prescribing practices for gabapentin would be different for anesthesiologists compared with other veterinarians. Differences in prescribing practices between anesthesiologists and other veterinary specialties were noted across all survey questions, with the exception of awareness of the potential for abuse in the human population.
      Anesthesiologists were less likely to use gabapentin as a first-line analgesic when compared with other veterinary specialties. Instead, anesthesiologists indicated that they use gabapentin most often to treat chronic pain and to induce sedation in anxious or fearful animals. Anesthesiologists were also significantly less likely to use gabapentin as the sole analgesic. These differences in prescribing practices may be related to the knowledge of the mechanism of action of gabapentin and its impact on the transmission of pain signals. The majority of anesthesiologists participating in the survey identified the gabapentin mechanism of action to be associated with voltage-gated calcium channels. Gabapentin is believed to provide analgesia by blocking the alpha (2)delta subunit of voltage-gated calcium channels in the spinal cord and periphery (
      • Sills G.J.
      The mechanism of action of gabapentin and pregabalin.
      ;
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ). This results in the modulation of pain signaling and prevention of hyperalgesia and central sensitization (
      • Sills G.J.
      The mechanism of action of gabapentin and pregabalin.
      ;
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ).
      Approximately 50% of surgeons and criticalists also identified the gabapentin mechanism of action to be associated with voltage-gated calcium channels. However, members of both specialties were significantly more likely to use gabapentin as the only analgesic, with surgeons more likely to use it for acute pain. This may result from differences among specialties in the awareness of the distribution and effect that voltage-gated calcium channels have on the pain pathway. Traditional first-line analgesics influence pain signaling at multiple levels of the pain pathway. Opioids, considered one of the most effective analgesics in both human and veterinary medicine, inhibit the conversion of noxious stimuli into pain signals in the periphery, modulate pain signals and decrease perception of pain signals in the cerebral cortex (
      • Lamont L.A.
      Multimodal pain management in veterinary medicine: the physiologic basis of pharmacologic therapies.
      ). Gabapentin acts only at the modulatory level of the pain pathway by decreasing the release of neurotransmitters involved in pain signaling (
      • Sills G.J.
      The mechanism of action of gabapentin and pregabalin.
      ;
      • Kharasch E.D.
      • Clark J.D.
      • Kheterpal S.
      Perioperative gabapentinoids: deflating the bubble.
      ).
      In the present study, the most common reason survey respondents prescribed gabapentin was to avoid administration of an NSAID. NSAIDs provide analgesia by inhibiting the chemical mediators that influence peripheral pain signals and by modulating pain signals within the central nervous system (
      • Lamont L.A.
      Multimodal pain management in veterinary medicine: the physiologic basis of pharmacologic therapies.
      ). Most clinical pain syndromes are complex and involve more than one type of pain. However, inflammatory pain is a significant component of pain in canine and feline patients, particularly acute pain. By inhibiting cyclooxygenase and lipoxygenase enzyme activity, NSAIDs prevent the release of chemical mediators directly responsible for inflammation at the site of injury (
      • Lamont L.A.
      Multimodal pain management in veterinary medicine: the physiologic basis of pharmacologic therapies.
      ). Considering the type of pain present and the different effects of the two drugs on the pain pathway, gabapentin is not interchangeable for an NSAID. Gabapentin, possessing only modulatory effects on the pain pathway, is best used as an adjunct analgesic to treat breakthrough pain in combination with other modalities (
      • Epstein M.
      • Rodan I.
      • Griffenhagen G.
      • et al.
      2015 AAHA/AAFP pain management guidelines for dogs and cats.
      ).
      Finally, the present survey showed that the perception of the potential for abuse of gabapentin was low across all veterinary specialties. This result has been described in human medicine, with many prescribers considering gabapentinoids to have little or no potential for abuse (
      • Evoy K.E.
      • Morrison M.D.
      • Saklad S.R.
      Abuse and misuse of pregabalin and gabapentin.
      ). However, there is growing evidence that some human patients misuse, abuse or divert gabapentin to recreational drug users (
      • Goodman C.W.
      • Brett A.S.
      A clinical overview of off-label use of gabapentinoid drugs.
      ). Supraclinical doses of gabapentin are reported to result in a wide variety of effects similar to opioids (euphoria, uninhibited behavior, improved sociability), benzodiazepines (relaxation, sedation) and psychedelics (dissociation, hallucinations) (
      • Smith R.V.
      • Havens J.R.
      • Walsh S.L.
      Gabapentin misuse, abuse and diversion: a systematic review.
      ;
      • Evoy K.E.
      • Morrison M.D.
      • Saklad S.R.
      Abuse and misuse of pregabalin and gabapentin.
      ). Of more concern, gabapentin has been identified in toxicology screens of individuals presenting to the emergency room following accidental drug overdose (
      • Millar J.
      • Sadasivan S.
      • Weatherup N.
      • Lutton S.
      Lyrica nights – recreational pregabalin abuse in an urban emergency department.
      ;
      • Evoy K.E.
      • Morrison M.D.
      • Saklad S.R.
      Abuse and misuse of pregabalin and gabapentin.
      ). Even worse, those who combine gabapentin with an opioid are more likely to suffer a fatal overdose or have life-threatening respiratory depression that requires mechanical ventilation (
      • Millar J.
      • Sadasivan S.
      • Weatherup N.
      • Lutton S.
      Lyrica nights – recreational pregabalin abuse in an urban emergency department.
      ;
      • Evoy K.E.
      • Morrison M.D.
      • Saklad S.R.
      Abuse and misuse of pregabalin and gabapentin.
      ;
      • Peckham A.M.
      • Fairman K.A.
      • Sclar D.A.
      All-cause and drug-related medical events associated with overuse of gabapentin and/or opioid medications: a retrospective cohort analysis of a commercially insured US population.
      ).
      The prevalence of abuse of gabapentin within the general population is low, approximately 1% (
      • Smith R.V.
      • Havens J.R.
      • Walsh S.L.
      Gabapentin misuse, abuse and diversion: a systematic review.
      ;
      • Evoy K.E.
      • Morrison M.D.
      • Saklad S.R.
      Abuse and misuse of pregabalin and gabapentin.
      ). For individuals with a history of opioid abuse, the prevalence is alarmingly greater, and for individuals possessing a prescription for gabapentin the prevalence of abuse increases to 40–65% (
      • Smith R.V.
      • Havens J.R.
      • Walsh S.L.
      Gabapentin misuse, abuse and diversion: a systematic review.
      ). The frequent, extra-label use of gabapentin in humans, combined with the low cost and ease of obtaining prescriptions for large quantities, are probably contributing factors in its appeal as a drug of abuse (
      • Evoy K.E.
      • Morrison M.D.
      • Saklad S.R.
      Abuse and misuse of pregabalin and gabapentin.
      ). As demonstrated by the present survey, many veterinarians are unaware of the potential for abuse. Despite prescription monitoring systems often in place, the majority of survey respondents authorize refill requests for significant quantities of gabapentin (1 month supply on average) without enhanced restrictions in place. While there is little concern that canine and feline patients will become addicted to gabapentin, such practices could potentially contribute to its diversion to recreational drug users, whether that is the client, family or friend.
      The current survey did not require respondents to specify the nature of the prescription monitoring systems in place at their hospitals. However, public health departments have started to include veterinarians in state-wide prescription monitoring programs. Under these regulations, veterinarians are subject to prescription tracking for narcotics. Several states are now including gabapentin in their prescription drug monitoring programs (
      Connecticut Department of Consumer Protection, Drug Control Division
      Memorandum. New medications to be added to the Connecticut Prescription Monitoring and Reporting System (CPMRS).
      ). As a result, even if the perception of potential for abuse remains low within the veterinary community, restrictions on gabapentin prescribing are likely to soon be mandated by state and local authorities.
      There were several potential limitations of this study. Because the survey was a convenience sample, it is possible that the results reflect the views of members of the list servs who are more inclined to respond to surveys rather than the membership of the specialty colleges as a whole. Additionally, there were differences in total number of respondents across specialty groups, which may have influenced comparisons among groups. Respondents may have received a solicitation to take the survey from one or more listservs or social media platforms, making it difficult to calculate a response rate among specialties. Surveys to general practitioners were distributed through two state veterinary medical associations and the alumni network of Tufts University School of Veterinary Medicine, which may not accurately represent North America in its entirety. Every effort was taken to make the survey short and easy to navigate; however, it is possible that some questions were ambiguous and led to responses different than intended, or the total number of questions posed reduced the response rate. Finally, survey logic requiring participants to answer a question before moving on was not used, which may have resulted in the collection of partial or incomplete data for some questions.

      Conclusion

      This study demonstrated that the prescribing practices for gabapentin among veterinarians closely mirrors those of human physicians, with gabapentin being prescribed frequently and for uses largely unrelated to its labeled indication. There is little evidence in both the human and veterinary literature to support its widespread use as an analgesic. Increasing evidence has documented adverse effects associated with gabapentin, including diversion and abuse. The veterinary community should reexamine the frequent and widespread use of gabapentin as an analgesic in canine and feline patients.

      Acknowledgements

      The authors thank Bruce A Barton, PhD (Department of Quantitative Health Sciences, University of Massachusetts Medical School, MA, USA) for assistance with statistical analysis. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

      Supporting Information

      The following is the Supplementary data to this article:

      Authors’ contributions

      RR: conception and study design, questionnaire design, survey distribution, data management, preparation of draft and final version of manuscript. OO: statistical analysis, critical review of manuscript. EM: supervision of study design, revision of questionnaire design, critical revision of manuscript. All authors read and approved the final version of the manuscript.

      Conflict of interest statement

      The authors declare no conflict of interest.

      References

        • Aghighi S.A.
        • Tipold A.
        • Piechotta M.
        • et al.
        Assessment of the effects of adjunctive gabapentin on postoperative pain after intervertebral disc surgery in dogs.
        Vet Anaesth Analg. 2012; 39: 636-646
        • Connecticut Department of Consumer Protection, Drug Control Division
        Memorandum. New medications to be added to the Connecticut Prescription Monitoring and Reporting System (CPMRS).
        2020 (Last accessed 11 January, 2021)
        • Crociolli G.C.
        • Cassu R.N.
        • Barbero R.C.
        • et al.
        Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy.
        J Vet Med Sci. 2015; 77: 1011-1015
        • Davila D.
        • Keeshen T.P.
        • Evans R.B.
        • Conzemius M.G.
        Comparison of the analgesic efficacy of perioperative firocoxib and tramadol administration in dogs undergoing tibial plateau leveling osteotomy.
        J Am Vet Med Assoc. 2013; 243: 225-231
        • Donati P.A.
        • Tarragona L.
        • Franco J.V.A.
        • et al.
        Efficacy of tramadol for postoperative pain management in dogs: systematic review and meta-analysis.
        Vet Anaesth Analg. 2021; 48: 283-296
        • Epstein M.
        • Rodan I.
        • Griffenhagen G.
        • et al.
        2015 AAHA/AAFP pain management guidelines for dogs and cats.
        J Am Anim Hosp Assoc. 2015; 51: 67-84
        • Evoy K.E.
        • Morrison M.D.
        • Saklad S.R.
        Abuse and misuse of pregabalin and gabapentin.
        Drugs. 2017; 77: 403-426
        • Goodman C.W.
        • Brett A.S.
        A clinical overview of off-label use of gabapentinoid drugs.
        JAMA Intern Med. 2019; 179: 695-701
        • Guedes A.G.P.
        • Meadows J.M.
        • Pypendop B.H.
        • et al.
        Assessment of the effects of gabapentin on activity levels and owner-perceived mobility impairment and quality of life in osteoarthritic cats.
        J Am Vet Med Assoc. 2018; 253: 579-585
        • Kharasch E.D.
        • Clark J.D.
        • Kheterpal S.
        Perioperative gabapentinoids: deflating the bubble.
        Anesthesiology. 2020; 133: 251-254
        • KuKanich B.
        Outpatient oral analgesics in dogs and cats beyond nonsteroidal anti-inflammatory drugs: an evidence-based approach.
        Vet Clin North Am Small Anim Pract. 2013; 43: 1109-1125
        • KuKanich B.
        • Cohen R.L.
        Pharmacokinetics of oral gabapentin in greyhound dogs.
        Vet J. 2009; 187: 133-135
        • Lamont L.A.
        Multimodal pain management in veterinary medicine: the physiologic basis of pharmacologic therapies.
        Vet Clin North Am Small Anim Pract. 2008; 38: 1173-1186
        • Millar J.
        • Sadasivan S.
        • Weatherup N.
        • Lutton S.
        Lyrica nights – recreational pregabalin abuse in an urban emergency department.
        Emerg Med J. 2013; 30: 874
        • Peckham A.M.
        • Fairman K.A.
        • Sclar D.A.
        All-cause and drug-related medical events associated with overuse of gabapentin and/or opioid medications: a retrospective cohort analysis of a commercially insured US population.
        Drug Saf. 2018; 41: 213-228
        • Siao K.T.
        • Pypendop B.H.
        • Ilkiw J.E.
        Pharmacokinetics of gabapentin in cats.
        Am J Vet Res. 2010; 71: 817-821
        • Sills G.J.
        The mechanism of action of gabapentin and pregabalin.
        Curr Opin Pharmacol. 2006; 6: 108-113
        • Smith R.V.
        • Havens J.R.
        • Walsh S.L.
        Gabapentin misuse, abuse and diversion: a systematic review.
        Addiction. 2016; 111: 1160-1174
        • Verret M.
        • Lauzier F.
        • Zarychanski R.
        • et al.
        Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis.
        Anesthesiology. 2020; 133: 265-279
        • Wagner A.E.
        • Mich P.M.
        • Uhrig S.R.
        • Hellyer P.W.
        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: 751-756