• 1 Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 2005; 5: 243251.

  • 2 Kemeny ME, Schedlowski M. Understanding the interaction between psychosocial stress and immune-related diseases: a step-wise progression. Brain Behav Immun 2007; 21: 10091018.

    • Search Google Scholar
    • Export Citation
  • 3 Dhabhar FS. Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Allergy Asthma Clin Immunol 2009; 16: 300317.

    • Search Google Scholar
    • Export Citation
  • 4 Broadbent E, Petrie KJ, Alley PG, et al. Psychological stress impairs early wound repair following surgery. Psychosom Med 2003; 65: 865869.

    • Search Google Scholar
    • Export Citation
  • 5 Detillion CE, Craft TK, Glasper ER, et al. Social facilitation of wound healing. Psychoneuroendocrinology 2004; 29: 10041011.

  • 6 Leib MS. Treatment of chronic idiopathic large-bowel diarrhea in dogs with a highly digestible diet and soluble fiber: a retrospective review of 37 cases. J Vet Intern Med 2000; 14: 2732.

    • Search Google Scholar
    • Export Citation
  • 7 Davis MS, Willard MD, Nelson SL, et al. Prevalence of gastric lesions in racing Alaskan sled dogs. J Vet Intern Med 2003; 17: 311314.

    • Search Google Scholar
    • Export Citation
  • 8 Moberg GP. Biological response to stress: implications for animal welfare. In: Moberg GP, Mench JA, eds. The biology of animal stress. Wallingford, Oxfordshire, England: CABI Publishing, 2000;122.

    • Search Google Scholar
    • Export Citation
  • 9 Garnier F, Benoit E, Virat M, et al. Adrenal cortical response in clinically normal dogs before and after adaptation to a housing environment. Lab Anim 1990; 24: 4043.

    • Search Google Scholar
    • Export Citation
  • 10 Hiby EF, Rooney NJ, Bradshaw JW. Behavioural and physiological responses of dogs entering re-homing kennels. Physiol Behav 2006; 89: 385391.

    • Search Google Scholar
    • Export Citation
  • 11 Hennessy MB, Davis HN, Williams MT, et al. Plasma cortisol levels of dogs at a county animal shelter. Physiol Behav 1997; 62: 485490.

    • Search Google Scholar
    • Export Citation
  • 12 Hennessy MB, Voith VL, Mazzei SJ, et al. Behavior and cortisol levels of dogs in a public animal shelter, and an exploration of the ability of these measures to predict problem behavior after adoption. Appl Anim Behav Sci 2001; 73: 217233.

    • Search Google Scholar
    • Export Citation
  • 13 Hennessy MB. Using Hypothalamic-pituitary-adrenal measures for assessing and reducing the stress of dogs in shelters: a review. Appl Anim Behav Sci 2013; 149: 112.

    • Search Google Scholar
    • Export Citation
  • 14 Haverbeke A, Diederich C, Depiereux E, et al. Cortisol and behavioral responses of working dogs to environmental challenges. Physiol Behav 2008; 93: 5967.

    • Search Google Scholar
    • Export Citation
  • 15 Hekman JP, Karas AZ, Dreschel NA. Salivary cortisol concentrations and behavior in a population of healthy dogs hospitalized for elective procedures. Appl Anim Behav Sci 2012; 141: 149157.

    • Search Google Scholar
    • Export Citation
  • 16 Hekman JP, Karas AZ, Sharp CR. Psychogenic stress in hospitalized dogs: cross species comparisons, implications for health care, and the challenges of evaluation. Animals (Basel) 2014; 4: 331347.

    • Search Google Scholar
    • Export Citation
  • 17 Väisänen MA, Valros AE, Hakaoja E, et al. Pre-operative stress in dogs—a preliminary investigation of behavior and heart rate variability in healthy hospitalized dogs. Vet Anaesth Analg 2005; 32: 158167.

    • Search Google Scholar
    • Export Citation
  • 18 Siracusa C, Manteca X, Cerón J, et al. Perioperative stress response in dogs undergoing elective surgery: variations in behavioural, neuroendocrine, immune and acute phase responses. Anim Welf 2008; 17: 259273.

    • Search Google Scholar
    • Export Citation
  • 19 Siracusa C, Manteca X, Cuenca R, et al. Effect of a synthetic appeasing pheromone on behavioral, neuroendocrine, immune, and acute-phase perioperative stress responses in dogs. J Am Vet Med Assoc 2010; 237: 673681.

    • Search Google Scholar
    • Export Citation
  • 20 van Vonderen IK, Kooistra HS, Rijnberk A. Influence of veterinary care on the urinary corticoid:creatinine ratio in dogs. J Vet Intern Med 1998; 12: 431435.

    • Search Google Scholar
    • Export Citation
  • 21 Kim YM, Lee JK, Abd El-aty AM, et al. Efficacy of dog-appeasing pheromone (DAP) for ameliorating separation-related behavioral signs in hospitalized dogs. Can Vet J 2010; 51: 380384.

    • Search Google Scholar
    • Export Citation
  • 22 Väisänen M, Raekallio M, Kuusela E, et al. Evaluation of the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication. Am J Vet Res 2002; 63: 969975.

    • Search Google Scholar
    • Export Citation
  • 23 Döring D, Roscher A, Scheipl F, et al. Fear-related behaviour of dogs in veterinary practice. Vet J 2009; 182: 3843.

  • 24 Beerda B, Schilder MBH, van Hooff JA, et al. Manifestations of chronic and acute stress in dogs. Appl Anim Behav Sci 1997; 52: 307319.

    • Search Google Scholar
    • Export Citation
  • 25 Beerda B, Schilder MB, van Hooff JA, et al. Behavioural, saliva, cortisol, and heart rate responses to different types of stimuli in dogs. Appl Anim Behav Sci 1998; 58: 365381.

    • Search Google Scholar
    • Export Citation
  • 26 Beerda B, Schilder MB, Bernadina W, et al. Chronic stress in dogs subjected to social and spatial restriction. II. Hormonal and immunological responses. Physiol Behav 1999; 66: 243254.

    • Search Google Scholar
    • Export Citation
  • 27 Beerda B, Schilder MB, Van Hooff JA, et al. Behavioural and hormonal indicators of enduring environmental stress in dogs. Anim Welf 2000; 9: 4962.

    • Search Google Scholar
    • Export Citation
  • 28 Kobelt AJ, Hemsworth PH, Barnett JL, et al. Sources of sampling variation in saliva cortisol in dogs. Res Vet Sci 2003; 75: 157161.

    • Search Google Scholar
    • Export Citation
  • 29 Kikkawa A, Uchida Y, Nakade T, et al. Salivary secretory IgA concentrations in Beagle dogs. J Vet Med Sci 2003; 65: 689693.

  • 30 Skandakumar S, Stodulski G, Hau J. Salivary IgA: a possible stress marker in dogs. Anim Welf 1995; 4: 339350.

  • 31 Palestrinia C, Previde EP, Spieziob C, et al. Heart rate and behavioural responses of dogs in the Ainsworth's strange situation: a pilot study. Appl Anim Behav Sci 2005; 94: 7588.

    • Search Google Scholar
    • Export Citation
  • 32 Gomart SB, Allerton FJ, Gommeren K. Accuracy of different temperature reading techniques and associated stress response in hospitalized dogs. J Vet Emerg Crit Care (San Antonio) 2014; 24: 279285.

    • Search Google Scholar
    • Export Citation
  • 33 Beerda B, Schilder MB, van Hooff JA, et al. Chronic stress in dogs subjected to social and spatial restriction. I. Behavioral responses. Physiol Behav 1999; 66: 233242.

    • Search Google Scholar
    • Export Citation
  • 34 Rushen J. Some issues in the interpretation of behavioural response to stress. In: Moberg GP, Mench JA, eds. The biology of animal stress. Wallingford, Oxfordshire, England: CABI Publishing, 2000;2341.

    • Search Google Scholar
    • Export Citation
  • 35 Plumb DC. Plumb's veterinary drug handbook. 8th ed. Ames, Iowa: John Wiley and Sons, 2015;26.

  • 36 Thompson SB. Pharmacologic treatment of phobias. In: Dodman NH, Shuster L, eds. Psychopharmacology of animal behavior disorders. Malden, Mass: Blackwell Science, 1998:141182.

    • Search Google Scholar
    • Export Citation
  • 37 Simon BT, Scallan EM, Siracusa C, et al. Effects of acepromazine or methadone on midazolam-induced behavioral reactions in dogs. Can Vet J 2014; 55: 875885.

    • Search Google Scholar
    • Export Citation
  • 38 Fagiolini A, Comandini A, Catena Dell'Osso M, et al. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs 2012; 26: 10331049.

    • Search Google Scholar
    • Export Citation
  • 39 Zhang L, Xie WW, Li LH, et al. Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial. Pharmacology 2014; 94: 199206.

    • Search Google Scholar
    • Export Citation
  • 40 Bossini L, Coluccia A, Casolaro I, et al. Off-label trazodone prescription: evidence, benefits and risks. Curr Pharm Des 2015; 21: 33433351.

    • Search Google Scholar
    • Export Citation
  • 41 Rickels K, Downing R, Schweizer E, et al. Antidepressants for the treatment of generalized anxiety disorder—a placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry 1993; 50: 884895.

    • Search Google Scholar
    • Export Citation
  • 42 Stahl SM. Antidepressants. In: Stahl SM. Stahl's essential psychopharmacology: neuroscientific basis and practical applications. 4th ed. Cambridge, England: Cambridge University Press, 2013:284369.

    • Search Google Scholar
    • Export Citation
  • 43 Gruen ME, Sherman BL. Use of trazodone as an adjunctive agent in the treatment of canine anxiety disorders: 56 cases (1995–2007). J Am Vet Med Assoc 2008; 233: 19021907.

    • Search Google Scholar
    • Export Citation
  • 44 Gruen ME, Roe SC, Griffith E, et al. Use of trazodone to facilitate postsurgical confinement in dogs. J Am Vet Med Assoc 2014; 245: 296301.

    • Search Google Scholar
    • Export Citation
  • 45 Herron ME, Shreyer T. The pet-friendly veterinary practice: a guide for practitioners. Vet Clin North Am Small Anim Pract 2014; 44: 451481.

    • Search Google Scholar
    • Export Citation
  • 46 Landsberg GM, Hunthausen W, Ackerman L. Pharmacologic intervention in behavioral therapy. In: Behavior problems of the dog and cat. 3rd ed. Edinburgh: Saunders, 2013:113138, 377–422.

    • Search Google Scholar
    • Export Citation
  • 47 Jay AR, Krotscheck U, Parsley E, et al. Pharmacokinetics, bioavailability, and hemodynamic effects of trazodone after intravenous and oral administration of a single dose to dogs. Am J Vet Res 2013; 74: 14501456.

    • Search Google Scholar
    • Export Citation
  • 48 de Lahunta A, Glass EN, Kent M. Lower motor neuron: general visceral efferent system. In: de Lahunta A, Glass EN, Kent M. Veterinary neuroanatomy and clinical neurology. 4th ed. St Louis: Saunders-Elsevier, 2014:197221.

    • Search Google Scholar
    • Export Citation
  • 49 Aloff B. Canine body language. A photographic guide. Wenatchee, Wash: Dogwise, 2005;41, 51, 9296, 161, 187.

  • 50 Handleman B. Canine behavior. A photo illustrated handbook. Wenatchee, Wash: Dogwise, 2008;175, 251.

  • 51 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159174.

  • 52 Crowell-Davis SL, Poggiagliolmi S. Understanding behavior: serotonin syndrome. Compend Contin Educ Vet 2008 30: 490493.

  • 53 Alusik S, Kalatova D, Paluch Z. Serotonin syndrome. Neuro Endocrinol Lett 2014; 35: 265273.

  • 54 Park SH, Wackernah RC, Stimmel GL. Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants? J Pharm Pract 2014; 27: 7178.

    • Search Google Scholar
    • Export Citation
  • 55 Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: a review. Pain Physician 2015; 18: 395400.

    • Search Google Scholar
    • Export Citation
  • 56 Rascati K. Drug utilization review of concomitant use of specific serotonin reuptake inhibitors or clomipramine with antianxiety sleep medications. Clin Ther 1995; 17: 786790.

    • Search Google Scholar
    • Export Citation
  • 57 George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry 1996; 39: 384385.

  • 58 Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosomatics 1995; 36: 159160.

  • 59 Nisijima K, Shimizu M, Abe T, et al. A case of serotonin syndrome induced by concomitant treatment with low-dose trazodone and amitriptyline and lithium. Int Clin Psychopharmacol 1996; 11: 289290.

    • Search Google Scholar
    • Export Citation
  • 60 Frank D, Gauthier A, Bergeron R. Placebo-controlled double-blind clomipramine trial for the treatment of anxiety or fear in Beagles during ground transport. Can Vet J 2006; 47: 11021108.

    • Search Google Scholar
    • Export Citation

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Effects of trazodone on behavioral signs of stress in hospitalized dogs

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  • 1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 2 Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 3 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 4 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Abstract

OBJECTIVE To determine the effects of trazodone treatment on behavioral signs of stress in hospitalized dogs.

DESIGN Prospective observational study.

ANIMALS 120 client-owned dogs.

PROCEDURES Hospitalized dogs administered trazodone (n = 60) were observed for stress-related signs or behaviors ≤ 45 minutes after the drug was administered (time 1) and approximately 90 minutes later (time 2). Dogs that did not receive trazodone (n = 60) were selected to serve as controls for environmental stimuli that could affect behavior and were observed at the same times. Signs or behaviors (scored as present or absent) were assessed individually and grouped into behavioral summation categories (frenetic [lip licking, pacing, panting, spinning, trembling, wet dog shake, whining, and yawning], freeze [averting gaze, pinning back ears, and whale eye sign], or fractious [growling, lunging, showing teeth, and snapping], with lifting of a forelimb and pupil dilation included in all categories). Results were compared between groups and within groups over time. Logistic regression was performed to assess associations between reduction in stress-related signs or behaviors and trazodone administration while controlling for environmental influences.

RESULTS Lip licking, panting, and whining were reduced (defined as present at time 1 and absent at time 2) in trazodone-treated but not environmentally matched dogs. The median number of stress-related behaviors and of frenetic and freeze behaviors was significantly lower at time 2, compared with time 1, in trazodone-treated dogs. Odds of reduced panting and reduced frenetic behaviors at time 2 for trazodone-treated dogs were > 2 times those for environmentally matched dogs.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that trazodone administration reduced stress-related signs and behaviors in hospitalized dogs and may thereby improve patient welfare.

Abstract

OBJECTIVE To determine the effects of trazodone treatment on behavioral signs of stress in hospitalized dogs.

DESIGN Prospective observational study.

ANIMALS 120 client-owned dogs.

PROCEDURES Hospitalized dogs administered trazodone (n = 60) were observed for stress-related signs or behaviors ≤ 45 minutes after the drug was administered (time 1) and approximately 90 minutes later (time 2). Dogs that did not receive trazodone (n = 60) were selected to serve as controls for environmental stimuli that could affect behavior and were observed at the same times. Signs or behaviors (scored as present or absent) were assessed individually and grouped into behavioral summation categories (frenetic [lip licking, pacing, panting, spinning, trembling, wet dog shake, whining, and yawning], freeze [averting gaze, pinning back ears, and whale eye sign], or fractious [growling, lunging, showing teeth, and snapping], with lifting of a forelimb and pupil dilation included in all categories). Results were compared between groups and within groups over time. Logistic regression was performed to assess associations between reduction in stress-related signs or behaviors and trazodone administration while controlling for environmental influences.

RESULTS Lip licking, panting, and whining were reduced (defined as present at time 1 and absent at time 2) in trazodone-treated but not environmentally matched dogs. The median number of stress-related behaviors and of frenetic and freeze behaviors was significantly lower at time 2, compared with time 1, in trazodone-treated dogs. Odds of reduced panting and reduced frenetic behaviors at time 2 for trazodone-treated dogs were > 2 times those for environmentally matched dogs.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that trazodone administration reduced stress-related signs and behaviors in hospitalized dogs and may thereby improve patient welfare.

Contributor Notes

Address correspondence to Dr. Gilbert-Gregory (sgilbertgregory@gmail.com).