Trazodone for Dogs & Cats

Updated November 2025 by Blake R. Gibson, DVM, and Lore I. Haug, DVM, MS, DACVB, CABC; Texas Veterinary Behavior Services/VCA Lexington Boulevard Animal Hospital

Trazodone can reliably and safely induce sedation and anxiolysis in dogs and cats, making it a useful pharmacologic agent for treatment of acute fear, stress, and anxiety.

Indications

Trazodone has been used clinically in dogs, cats, and horses, as well as in a variety of exotic and zoo animals; however, use has been more extensively researched in dogs.

Indications include

• Situational anxiety related to

  • Separation-related distress¹

  • Noise phobias (eg, fireworks, thunderstorms)¹

  • Visits to the clinic^2,3

  • Hospitalizationand boarding^4,5

  • Travel^3,6

• Postoperative confinement⁴

• Adjunct therapy in combination with other psychopharmaceutic agents to treat anxiety-related behavioral problems (eg, fearful behavior toward humans or other animals)¹

Pharmacology & Clinical Applications

• Trazodone is an atypical antidepressant and anxiolytic that acts as a serotonin antagonist and weak reuptake inhibitor. Effects on other neurotransmitter systems contribute to sedative/hypnotic effects.^7,8

• Trazodone is most often administered for situational use during exposure to acute stressors or to achieve sedation as part of hospitalization or postoperative confinement, including as an adjunct to daily behavior medication (eg, selective serotonin reuptake inhibitor [SSRI], serotonin norepinephrine reuptake inhibitor [SNRI], tricyclic antidepressant [TCA]). See Cautions for recommendations on usage and monitoring.

• Trazodone is less suitable for use as a long-term daily maintenance therapeutic because of its mechanism of action and greater adverse effect profile as compared with many other behavior medications.

• Trazodone has variable effects at low versus high doses (see Recommended Starting Dose) due to differences in affinity between neurotransmitter receptors.^7,8 These trends are generalized to companion animal species because most pharmacologic studies on trazodone have used rodents. The updating authors therefore recommend trazodone be titrated up from a low dose to desired effect.

  • At lower doses, trazodone antagonizes postsynaptic serotonin 2A (5-HT_2A), histamine 1, and alpha-1-adrenergic receptors. These actions are responsible for the drug’s sedative/hypnotic effect.^7,8

    • Sedation may be achieved at lower doses as compared with doses needed for treatment of anxiolysis (see Recommended Starting Dose).^7,8

    • These effects may be useful for postsurgical confinement.⁴

  • At higher doses, trazodone inhibits serotonin reuptake via the serotonin transporter (SERT); antagonizes serotonin 1D (5-HT_1D), 2C (5-HT_2C), and 7 (5-HT₇) receptors; antagonizes alpha-2-adrenergic receptors; and acts as an agonist at the serotonin 1A (5-HT_1A) receptor.⁷ These receptors have a lower affinity for trazodone; their effects are thus graduated, with an increasing dose after higher-affinity receptors are occupied. In humans, these actions are believed to contribute to the anxiolytic and antidepressant effects of trazodone.⁷

    • The serotonin 1D receptor is theorized to function as a presynaptic autoreceptor that provides a negative feedback mechanism for serotonin release. Antagonism would therefore allow increased synaptic serotonin concentrations beyond SERT inhibition alone.⁷

    • Similarly, a function of the 1A receptor is presynaptic autoreception on serotonergic projection neurons. Activation of these 1A receptors slows transmission through the neuron and reduces synaptic serotonin release. A partial-agonist effect therefore reduces this system’s activity compared to basal levels.⁷

    • Antagonism of the serotonin 7 receptor inhibits a gamma-aminobutyric acid (GABA) receptor-mediated negative feedback mechanism on serotonin release.⁷

  • Antagonism of the serotonin 2A and 2C receptors inhibits glutamate release, thereby stimulating dopamine and norepinephrine release in the prefrontal cortex.

Dogs

In dogs, latency to onset is typically <2 hours following oral administration.^1,4

• Anxiety-provoking situations that may benefit from trazodone treatment include veterinary visits, travel/transport, separation anxiety, and noise phobias associated with fireworks or thunderstorms.

  • Oral trazodone may be administered to anxious hospitalized patients as long as there are no contraindications (eg, patients receiving or exposed to a monoamine oxidase inhibitor [MAOI], patients with known hypersensitivity or previous adverse reaction to trazodone, patients presented with suspected serotonin syndrome).

• Trazodone can be pre-emptively administered 1.5 to 2 hours before onset of anxiety to prevent emotional sensitization.

• Presence of food in the upper GI tract may delay absorption.¹²

• For dogs with situational anxiety, trazodone may be given as-needed daily every 8 to 12 hours or when a combination of daily and as-needed administration is required.^1,9,10

  • Duration of effect is variable.

    • Median duration of action when used to facilitate postsurgical calming was ≥4 hours in a study.⁴

Cats

The updating authors rarely use trazodone in cats due to anecdotal experience of poor efficacy and find other event medications (eg, gabapentin, pregabalin, lorazepam) to be more effective for situational use in this species.

In one study, trazodone was well-tolerated in cats and caused sedation at doses of 50, 75, and 100 mg/cat.² Cats achieved peak sedation 2 to 2.5 hours after oral administration.² Another study using a dose of 50 mg/cat demonstrated improvement in signs of anxiety during transport and ease of handling during examination.³

• Trazodone may be a good alternative anxiolytic in cats that experience adverse effects with other event medications.

• Trazodone may be used in clinical situations similar to that of dogs.

• The recommended starting dose in adult cats is 25 mg/cat and can be titrated to effect up to 100 mg.¹³ Trazodone can be coadministered with other event medications (eg, gabapentin) but should be anticipated to produce additive sedative effects.

Adverse Effects & Withdrawal

Adverse effects associated with oral administration of trazodone in dogs and cats are typically mild and well tolerated.

• Potential effects include^1,2,3,5,6

  • Sedation

  • Ataxia

  • GI effects (eg, vomiting, diarrhea)

  • Increased or decreased appetite

  • Agitation

  • Tachycardia

  • Increased fearfulness or signs of paranoia

Tolerance, withdrawal effects, and dependence have not been reliably demonstrated in veterinary patients.

Cautions

Serotonin syndrome is a potential adverse effect associated with serotonergic medications. Some patients experience idiosyncratic reactions even at low doses; caution should therefore be exercised when combining multiple serotonergic medications. Trazodone’s primary effect, however, is antagonism of serotonin receptors; use with SSRIs, SNRIs, and TCAs is thus generally safe when these medications are used at appropriate doses. Patient response to an individual drug or combination of behavior medications should be closely monitored.

Concurrent use of drugs with the same cytochrome P450 pathway (eg, ketoconazole) also increases the risk for adverse effects, including serotonin syndrome.^9,10 Trazodone is contraindicated in patients receiving an MAOI (eg, selegiline/L-deprenyl, amitraz) or in patients in which an MAOI has been recently (<4 weeks) discontinued.^9,10

Signs of serotonin syndrome include

• Cardiovascular effects (eg, tachycardia, bradycardia, hypertension, arrhythmias)

• Tachypnea

• Hyperthermia

• Nervous system effects (eg, disorientation, weakness, hyperexcitability, agitation, hyperreflexia, hyperesthesia, tremors, seizures, coma)

• GI effects (eg, vomiting, diarrhea, hypersalivation)

• Death

When writing prescriptions or discharge instructions for trazodone, it is important not to mistake trazodone for tramadol.

• On the prescription label, FOR ANXIETY should be specified as the treatment indication.

• To minimize prescription errors, exaggerated lettering (ie, tall man lettering) should be used to distinguish look-alike medications (eg, traZODone vs traMADol).¹⁴

• Owners should be educated about the difference between trazodone and tramadol, particularly if both medications are being given.