Trazodone Drug Combinations for TPLO
Taly Reyes, BS, LVMT, VTS (Anesthesia & Analgesia) , University of Tennessee
Carrie Davis, DVM, DACVAA, University of Tennessee
Karen M. Tobias, DVM, MS, DACVS, University of Tennessee
Sirius, a 9-year-old neutered male Labrador retriever, is presented for surgical management of a right cranial cruciate ligament rupture. He has had previously identified episodes of anorexia, nausea, and anxiety. In addition, he has been treated with oral acepromazine for storm phobia intermittently for the past 2 years and currently receives oral amitriptyline for separation anxiety. He also has a history of atopic dermatitis, for which he receives hydroxyzine. He is currently on monthly heartworm and flea prevention. Physical examination is within normal limits except for right stifle swelling and pain. Thoracic radiography, CBC, serum chemistry profile, and urinalysis findings are within normal limits. Sirius will undergo anesthetic induction for tibial plateau-leveling osteotomy. The surgeon has prescribed trazodone during the procedure, and drug administration will be continued at home to facilitate exercise restriction and decrease anxiety.
MECHANISM OF ACTION
Trazodone, an antidepressant used to treat anxiety in dogs, antagonizes 5-HT2A receptors2 and inhibits serotonin reuptake.1,10 The drug also antagonizes α1-adrenergic receptors, causing some vasodilatory effects, as well as histamine 1 receptors and T-type calcium channels, which could potentially result in adverse cardiovascular effects.10 The anxiolytic properties of trazodone seem to be related to the receptor site activities, which alter serotonin concentrations.1 The neurotransmitter serotonin is primarily found in the GI tract, platelets, and CNS.3
Plasma concentrations of trazodone may increase when the drug is administered in combination with drugs that are selective serotonin reuptake inhibitors and tricyclic antidepressants; if concentrations subsequently increase excessively in the CNS, serotonin syndrome may develop.7 Signs of serotonin syndrome include confusion, agitation, hyperthermia, tachycardia, seizures, ataxia, tremors, myoclonus, coma, diarrhea, vomiting, inappetence, and hyper- or hypotension.3,8,11
5-HT = 5-hydroxytryptamine, CYP3A = cytochrome P450 3A, GABA = γ-aminobutyric acid, MAOI = monoamine oxidase inhibitor
Editor's note: This article was originally published in June 2018 as "Which Drugs Can Be Used Concurrently with Trazodone During & After Tibial Plateau-Leveling Osteotomy?"