Trazodone in Dogs & Cats

Trazodone can reliably and safely induce sedation and anxiolysis in dogs and cats, making it a useful pharmacologic agent beyond the treatment of behavior problems.

• Situational anxiety related to
  • Separation¹ 
  • Noise phobia (eg, fireworks, thunderstorms)¹
  • Veterinary visits² 
  • Hospitalization³
  • Travel
• Postoperative confinement³
• Adjunct therapy used in combination with other psychopharmaceutical agents to treat anxiety-related behavioral problems (eg, fearful behavior toward humans or other animals)¹

• Trazodone is most often prescribed as an augmenting agent to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). 
• It globally increases serotonin levels by blocking presynaptic reuptake in humans⁴ and presumably in dogs and cats.
  • Higher doses (see Recommended starting dose) are typically required to achieve reuptake inhibition.⁴
• The drug also readily antagonizes postsynaptic serotonin 2A and 2C receptors (5-HT_2A and 5-HT_2C, respectively), thereby inhibiting glutamate release and stimulating dopamine and norepinephrine release in the prefrontal cortex.⁴ 
• In addition to antagonizing serotonin receptors, trazodone antagonizes histamine 1 (H₁) and α₁-adrenergic receptors, resulting in a sedative-hypnotic effect.⁴
  • Sedation may be achieved at lower doses as compared with doses needed for treatment of anxiolysis (see Recommended starting dose).⁴
  • May be used to facilitate postsurgical confinement³ 
    • Could also promote calm behavior in other situations (eg, travel/transport, nighttime restlessness associated with cognitive dysfunction)

Recommended starting dose for dogs is 3-7 mg/kg PO once to twice a day.⁵ If the drug is used to treat situational anxieties, the same dose can be administered as needed 1 to 2 hours before the anticipated event; that dose may be further increased to effect.⁵ 

• When prescribing trazodone for the first time, instruct clients to administer a test dose at home in a quiet and calm environment to monitor for 
  • Time to onset of sedation or behavioral calming
  • Duration of effect
  • Adverse events and side effects 
• If behavioral calmness and/or anxiolysis are not achieved, the dose or administration frequency may be increased to effect.
• Studies have reported a large PO dose range of up to 14 mg/kg once a day (for as-needed administration only) and 19.5 mg/kg once a day (for both daily and as-needed administration).¹

• 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 also be administered by veterinary staff to anxious hospitalized patients as long as there are no contraindications.
• Preemptively administer trazodone 1 to 2 hours before onset of anxiety to prevent emotional sensitization.  
• Presence of food in the upper GI tract may delay absorption.⁶
• For dogs, trazodone may be used on an as-needed basis for situational anxieties, as daily medication administered every 8 to 10 hours, or when a combination of daily and as-needed administration is required.¹ 
  • Duration of effect is variable.  
    • Median duration of action when used to facilitate postsurgical calming was ≥4 hours.³ 

• Cats achieved peak sedation at 2 to 2.5 hours after oral administration.²
• Trazodone may be a good alternative fast-acting anxiolytic in cats that exhibited adverse events to benzodiazepines (eg, lorazepam).
• It may be used in similar situations as for dogs.
• Recommended starting dose in adult cats⁷ 
  • 25 mg/cat
  • Can be titrated to effect

• Potential effects include^1,2,6
  • Sedation
  • Ataxia
  • GI effects (eg, vomiting, diarrhea)
  • Increase or decrease in appetite
  • Agitation
  • Tachycardia
  • Behavioral disinhibition
• IV administration of trazodone has only been investigated in dogs and is not recommended, as doing so may trigger aggressive behavior in some dogs.⁶ 
  • An injectable form of trazodone is not commercially available. 

• As a precaution, patients may be tapered off medication to reduce the likelihood of withdrawal effects and to observe the patient for increased anxiety while trazodone is withdrawn.  

• Although trazodone is most often used to augment SSRIs and TCAs, caution must be taken when it is administered with these other agents. 
  • Signs of serotonin syndrome include
    • Cardiovascular changes (ie, tachycardia, bradycardia, hypertension, arrhythmias)
    • Tachypnea
    • Hyperthermia
    • Nervous system effects (ie, disorientation, weakness, hyperexcitability, agitation, hyperreflexia, hyperesthesia, tremors, seizures, coma)
    • GI changes (ie, vomiting, diarrhea, hypersalivation)
  • Signs can lead to death.
• Close patient monitoring via recheck appointments and/or client communication is recommended.

• On the prescription label, specify FOR ANXIETY as treatment indication.
• Educate clients about the difference between trazodone and tramadol, particularly if the pet receives both medications.  
• To minimize prescription errors, use exaggerated lettering, also known as Tall Man Lettering, to distinguish look-alike medications (eg, traZODone vs traMADol).⁸

5-HT_2A = serotonin 2A receptor, 5-HT_2C = serotonin 2C receptor, SARI = serotonin antagonist/reuptake inhibitor, SSRI = selective serotonin reuptake inhibitor, TCA = tricyclic antidepressant, MAOI= monoamine oxidase inhibitor