Trazodone
Trazodone hydrochloride
Also known as: Desyrel · Oleptro · Molipaxin · AF-1161 · trazodona · sleepeasy · Trazodone hydrochloride · Trazodonum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive treatment of anxiety-related disorders (Daily medication only) | 1.9 mg/kg/day-16.2 mg/kg/day (mean = 7.3 mg/kg/day) | PO | daily | — | 🌎 NA |
| Adjunctive treatment of anxiety-related disorders (As needed only) | 2.2 mg/kg/day- 14 mg/kg/day (mean 7.7 mg/kg/day) | PO | PRN | — | 🌎 NA |
| Adjunctive treatment of anxiety-related disorders (Daily medication and as needed) | 1.7 mg/kg/day-19.5 mg/kg/day (mean 7.25 mg/kg/day) | PO | daily and PRN | — | 🌎 NA |
| Adjunctive treatment of anxiety-related disorders | 1 mg/kg PO q12h for 7 days, then up to 3 mg/kg PO q12h. | PO | q12h | 7 days initially | 🌎 NA |
| Adjunctive treatment of anxiety-related disorders | 1-4.8 mg/kg PO twice daily; (titrate to effect in 1 mg increments every 7 days). | PO | q12h | — | 🌎 NA |
| Adjunctive treatment of anxiety-related disorders (Situational) | typical starting dose between 2-5 mg/kg and adjusting upwards as necessary to get control (maximum dose 14 mg/kg/day). | PO | PRN | — | 🌎 NA |
- Adjunctive treatment of anxiety-related disorders (Daily medication only): Begin at half target dose for 3 days to build tolerance.
- Adjunctive treatment of anxiety-related disorders (Situational): 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.
Overview
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 of action
Trazodone exerts its anxiolytic and sedative effects through multiple neurochemical pathways:
- Serotonin Reuptake Inhibition: Blocks the serotonin transporter (SERT) → increases extracellular serotonin (5-HT) in the synaptic cleft.
- 5-HT2A Receptor Antagonism: Blocks 5-HT2A receptors → 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 → can cause mild vasodilation and hypotension.
- Histamine (H1) Antagonism: Weak blockade of H1 receptors contributes to its sedative properties.
Safety & warnings
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)
- Excitability
- Dry mouth
- Third eyelid protrusion (in cats)
Precautions
Cardiac & Organ Impairment: Use with caution in patients with severe cardiac disease or hepatic or renal impairment. Pregnancy: FDA Category C. Animal studies show adverse effects at very high doses (15-50X). Weigh potential risks versus benefits in pregnant or nursing animals. Serotonin Syndrome: Risk increases significantly when combined with other serotonergic drugs (e.g., SSRIs, MAOIs, TCAs).
Drug interactions
May increase reductions in blood pressure and cause hypotension
Increase risk for GI bleeding; monitor
May increase trazodone blood levels
Use with trazodone may cause additive CNS depressant effects
Trazodone may increase digoxin levels
May increase trazodone blood levels
Increased risk for serotonin syndrome
Increased risk for GI bleeding; monitor
May increase trazodone blood levels; cause additive CNS effects
Increased risk for serotonin syndrome. Commonly used together, but monitor closely.
Contraindicated; high risk of serotonin syndrome
Metabolized by CYP450 2D6; potential for altered metabolism and toxicity
Metabolized by CYP450 2D6; potential for altered metabolism and toxicity
Increased risk of serotonin syndrome, though adjunctive therapy is sometimes used cautiously
Inhibits the breakdown of trazodone, leading to increased blood levels
Increases the breakdown of trazodone, leading to decreased blood levels
May inhibit the breakdown of trazodone (theoretical risk based on ketoconazole similarity)
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
Pharmacokinetics
Absorption
In humans, oral bioavailability of immediate-release tablets is about 65%. Presence of food increases absorption (AUC), decreases Cmax, and delays Tmax.
Distribution
Approximately 90-95% bound to plasma proteins. Volume of distribution ranges from 0.47-0.84 L/kg (in humans).
Metabolism
Extensive hepatic metabolism. Oxidative cleavage via CYP3A4 forms the active metabolite m-chlorophenylpiperazine (mCCP), which is further metabolized to inactive compounds via CYP2D6.
Elimination
Mostly (70-75%) excreted via renal mechanisms (only 0.13% unchanged in urine). About 21% is excreted in feces.
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.
Available products
Formulations
- Oral tablets (immediate-release)
- Oral tablets (extended-release)
- 100 mg tablets
- 150 mg tablets
- 100 mg capsules
- 150 mg capsules
- 10 mg/ml oral liquid
Human-labeled
- Trazodone Oral Tablets: 50 mg, 100 mg, 150 mg, & 300 mg; generic; (Rx)
- Trazodone Extended-Release (24-hour) Oral Tablets: 150 mg & 300 mg; Oleptro® (Labopharm); (Rx)
- Desyrel
- Molipaxin
Regulatory status
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store between 20-25°C (68-77°F); excursions are permitted to 15-30°C (59-86°F). Keep in an airtight container and protect from light.
Client information
- Administration: Preferably give with food to minimize gastrointestinal upset (like vomiting or gagging).
- Timing: For situational anxiety (e.g., vet visits, fireworks), administer 1 to 2 hours before the anticipated stressful event.
- Observation: Monitor your pet for excessive sedation, lethargy, or uncoordinated walking (ataxia).
- Paradoxical Effects: Rarely, pets may exhibit increased excitement, anxiety, or changes in appetite.
- Important Warning: Do not combine with other medications or supplements (especially tick collars containing amitraz) without consulting your veterinarian, as this can lead to a rare but serious condition called serotonin syndrome.
- Communication: Report any unforeseen adverse effects to your veterinarian, as trazodone is still being studied for extensive use in dogs.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.