Trazodone
Trazodone is a **Serotonin 2A Antagonist/Reuptake Inhibitor (SARI)** widely used in veterinary medicine as an anxiolytic and mild sedative. - **Clinical Utility**: Highly effective for situational anxiety (e.g., thunderstorms, fireworks, veterinary visits, travel) and to facilitate post-operative confinement or cage rest in dogs. - **Adjunctive Therapy**: Often combined with SSRIs (like fluoxetine) or gabapentin for refractory behavioral disorders. - **Safety Profile**: Generally well-tolerated with a wide margin of safety. It possesses fewer anticholinergic effects and a lower seizure risk compared to tricyclic antidepressants (TCAs). - **Human Uses**: Used for treating depression, aggressive behavior, alcohol/cocaine withdrawal, migraine prevention, and insomnia.
Mechanism: Trazodone exerts its anxiolytic and sedative effects through multiple neurochemical pathways: - **Serotonin Reuptake Inhibition**: Blocks the serotonin transporter (SERT) โ increases extracellular serotonin (5-HT) in the synaptic cleft. - **5-HT2A Receptor Antagonism**: Blocks 5-HT2A receptors โ prevents overstimulation by serotonin, contributing to its anxiolytic and antidepressant efficacy. Downregulation of these receptors can augment the efficacy of concurrent SSRIs. - **Active Metabolite**: Hepatic metabolism produces **m-chlorophenylpiperazine (mCPP)**, which acts as a direct, non-selective serotonin receptor agonist. - **Alpha-1 Adrenergic Antagonism**: Blocks peripheral alpha-1 receptors โ can cause mild vasodilation and hypotension. - **Histamine (H1) Antagonism**: Weak blockade of H1 receptors contributes to its sedative properties.
Dosing by species
- Adjunctive treatment of anxiety-related disorders (Daily medication only) ยท 1.9 mg/kg/day-16.2 mg/kg/day (mean = 7.3 mg/kg/day) ยท PO ยท daily ยท Begin at half target dose for 3 days to build tolerance.
- Adjunctive treatment of anxiety-related disorders (As needed only) ยท 2.2 mg/kg/day- 14 mg/kg/day (mean 7.7 mg/kg/day) ยท PO ยท PRN
- Adjunctive treatment of anxiety-related disorders (Daily medication and as needed) ยท 1.7 mg/kg/day-19.5 mg/kg/day (mean 7.25 mg/kg/day) ยท PO ยท daily and PRN
- Adjunctive treatment of anxiety-related disorders ยท 1 mg/kg PO q12h for 7 days, then up to 3 mg/kg PO q12h. ยท PO ยท q12h ยท 7 days initially
- Adjunctive treatment of anxiety-related disorders ยท 1-4.8 mg/kg PO twice daily; (titrate to effect in 1 mg increments every 7 days). ยท PO ยท q12h
- Adjunctive treatment of anxiety-related disorders (Situational) ยท typical starting dose between 2-5 mg/kg and adjusting upwards as necessary to get control (maximum dose 14 mg/kg/day). ยท PO ยท PRN ยท Given about an hour prior to the onset of anxiety.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Hypersensitivity to trazodone
- Concurrent use of MAO inhibitors (e.g., amitraz, selegiline)
- Glaucoma
- History of seizures
- Urinary retention
- Severe liver disease
Adverse effects
- Sedation
- Lethargy
- Ataxia
- Cardiac conduction disturbances
- Increased anxiety (paradoxical)
- Aggression (paradoxical)
- Vomiting/gagging
- Increased excitement
- Increased appetite
- Colitis
- Serotonin syndrome (rare, usually with concurrent serotonergic drugs)
- Vomiting
- Excitability
- Dry mouth
- Third eyelid protrusion (in cats)
Drug interactions
- Antihypertensive drugs ยท May increase reductions in blood pressure and cause hypotension
- Aspirin ยท Increase risk for GI bleeding; monitor
- Azole antifungals (e.g., ketoconazole, fluconazole) ยท May increase trazodone blood levels
- CNS depressants ยท Use with trazodone may cause additive CNS depressant effects
- Digoxin ยท Trazodone may increase digoxin levels
- Macrolide antibiotics (e.g., erythromycin, clarithromycin) ยท May increase trazodone blood levels
- Metoclopramide ยท Increased risk for serotonin syndrome
- NSAIDs ยท Increased risk for GI bleeding; monitor
- Phenothiazines ยท May increase trazodone blood levels; cause additive CNS effects
- SSRI antidepressants (e.g., fluoxetine) ยท Increased risk for serotonin syndrome. Commonly used together, but monitor closely.
- Monoamine oxidase inhibitors (MAOIs) ยท Contraindicated; high risk of serotonin syndrome ยท major
- Chlorphenamine ยท Metabolized by CYP450 2D6; potential for altered metabolism and toxicity ยท moderate
- Cimetidine ยท Metabolized by CYP450 2D6; potential for altered metabolism and toxicity ยท moderate
Monitoring
- Clinical efficacy (behavioral calming)
- Adverse effects (sedation, GI upset, paradoxical excitement)
- Signs of serotonin syndrome (vomiting, diarrhea, seizures, hyperthermia, hyperesthesia, mydriasis)
- Renal function (in patients with pre-existing renal disease)
- Signs of serotonin syndrome (tremors, agitation, hyperthermia)
- Efficacy of anxiety reduction
Overdose
No specific information is available regarding trazodone overdoses in veterinary patients. In humans, the incidence of serious toxicity from trazodone overdose alone is low compared with tricyclic antidepressant overdoses. In the event of a substantial overdose, contact an animal poison control center for guidance. Monitor for profound sedation, ataxia, hypotension, and signs of serotonin syndrome.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.