Trazodone is a human drug sometimes prescribed as an extra label use by Veterinarians to treat separation anxiety or anxiety in dogs. It is sold as individual tablets, in strengths of 50 mg or 100 mg.  
 
Trazodone is a prescription antidepressant medication that works by affecting chemical signals in the brain called neurotransmitters. It it used to treat and manage certain types of depression, anxiety, fear-based aggression and behavioral disorders in dogs. If your pet suffers from or has been diagnosed with a behavioral disorder, your veterinarian may prescribe an antidepressant type medication such as Trazodone. Consult with your veterinarian before administering this medication, and follow their specific recommendations for use.

Trazodone HCl

• (traz-oh-done)
• Desyrel®
• Serotonin 2a Antagonist/Reuptake Inhibitor

PRESCRIBER HIGHLIGHTS

• Antidepressant that may be useful for adjunctive treatment of behavioral disorders (esp. anxiety- or phobia-related) in dogs; not used in cats.
• Limited research or clinical experience available regarding appropriate veterinary use.
• Relatively inexpensive.

USES/INDICATIONS
Trazodone may be useful in treating behavioral disorders in small animals, particularly as an adjunctive treatment in patients that do not adequately respond to conventional therapies.
It is commonly used in dogs as an antianxiety agent, particularly in intensive care situations. In a retrospective study of 56 dogs evaluating trazodone as an adjunctive treatment for anxiety disorders, it was found to be well tolerated over a wide dose range and enhanced behavioral calming. The authors concluded that further controlled studies are needed to more fully evaluate the pharmacokinetics, safety profile, and efficacy of this drug in dogs (Gruen et al. 2008).
Anecdotally, it has been used to decrease the hyperesthetic effects associated with strychnine toxicity.
In humans, trazodone is used for treating depression, aggressive behavior, alcohol or cocaine withdrawal, migraine prevention, and insomnia. It has fewer anticholinergic effects than the tricyclic antidepressants and is among the antidepressants with the lowest seizure risk.
 
CONTRAINDICATIONS/PRECAUTIONS/WARNINGS
Trazodone is contraindicated in patients hypersensitive to it or those receiving MAO inhibitors (including amitraz and possibly, selegiline). It should be used with caution in patients with severe cardiac disease or hepatic or renal impairment.
Do not confuse traZODone with traMADol.

ADVERSE EFFECTS
The adverse effect profile for trazodone in dogs is not well documented. Potential adverse effects include sedation, lethargy, ataxia, priapism, cardiac conduction disturbances, increased anxiety, and aggression. In a retrospective study in 56 dogs (Gruen et al. 2008), trazodone adverse effects were generally mild, and only 3 dogs had to have the drug discontinued. Approximately 80% of the dogs in the study had no reported adverse effects. Adverse effects that were reported included: vomiting/gagging (2), behavioral changes (within hours of a dose) such as getting onto counters (1), or into trash (1), increased excitement (2), sedation (2), increased appetite (2) and colitis (1). Should trazodone be used more extensively in dogs, a more defined adverse effect profile may be discerned.
Trazodone alone is unlikely to cause serotonin syndrome at clinically used dosages, but when used with other serotonergic drugs, it is possible. The most common clinical signs seen with serotonin syndrome in dogs include (in descending order): vomiting, diarrhea, seizures, hyperthermia, hyperesthesia, depression, mydriasis, vocalization, death, blindness, hypersalivation, dyspnea, ataxia/paresis, disorientation, hyperreflexia, and coma (Wismer 2006).
In humans, the most common adverse effects include blurred vision; confusion, dizziness, dry mouth, orthostatic hypotension, sweating, lethargy or somnolence. QT prolongation can occur, but is much less common in humans with trazodone than with the tricyclic antidepressants. Priapism has been reported rarely in men taking trazodone.

REPRODUCTIVE/NURSING SAFETY
Trazodone appears to be relatively safe to use during pregnancy. At very high dosages (15-50X) in rats and rabbits, some increase in fetal death/resorption rates and congenital abnormalities were noted. For humans, the FDA categorizes trazodone as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.) Trazodone[x] is excreted into milk at very low levels and clinical effects in offspring seem unlikely. However, weigh the potential risks of using this medication versus the benefits in pregnant or nursing animals.

OVERDOSAGE/ACUTE TOXICITY
No specific information was located regarding trazodone overdoses in veterinary patients. In humans, incidence of serious toxicity from trazodone overdose (alone) was low compared with tricyclic antidepressant overdoses. However, in the event of substantial overdose of trazodone, it is recommended to contact an animal poison control center for further guidance.
There were 417 single agent exposures to trazodone reported to the ASPCA Animal Poison Control Center (APCC) during 2009-2013.[†] Of the 379 dogs, 104 were symptomatic with 43% sedated/lethargic, 16% ataxic and 14% vomiting. Of the 38 cats, 14 were symptomatic with lethargy (43%) and ataxia (36%) the most common.

DRUG INTERACTIONS
The following drug interactions have either been reported or are theoretical in humans or animals receiving trazodone and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.

• Antihypertensive Drugs: Trazodone may increase reductions in blood pressure and cause hypotension.
• Aspirin: Increase risk for GI bleeding; monitor.
• Azole Antifungals (e.g., ketoconazole, fluconazole): May increase trazodone blood levels.
• CNS Depressants: Use with trazodone may cause additive CNS depressant effects.
• Digoxin: Trazodone may increase digoxin levels.
• Macrolide Antibiotics: (e.g., erythromycin, clarithromycin): May increase trazodone blood levels.
• Metoclopramide: Increased risk for serotonin syndrome.
• NSAIDs: Increased risk for GI bleeding; monitor.
• Phenothiazines: May increase trazodone blood levels; cause additive CNS effects.
• SSRI Antidepressants (e.g., fluoxetine): Increased risk for serotonin syndrome. Trazodone is commonly used together with SSRI’s, but be alert for signs associated with serotonin syndrome (see adverse effects above).
   

LABORATORY CONSIDERATIONS
None noted.

DOSES
Dogs:
Note: All dosages are for regular tablets (not extended-release) unless otherwise noted.
As an adjunctive treatment of anxiety-related disorders (extra-label):
a)  From a retrospective study of 56 dogs. To allow dogs to become tolerant to the drug and avoid potential gastrointestinal adverse effects, trazodone was begun at an initial dose that was half of the target dose and administered for 3 days. Then the target dose was established as the lowest effective dose needed for behavioral calming. Additional dose increments were made empirically over time.
Weight (kg)    Initial Dosage (total; NOT mg/kg) Range    Target Dosage (total; NOT mg/kg) Range
<10 kg    ≤ 25 mg q8-24h    ≤ 50 mg q8-24h
≥10-20 kg    50 mg q12-24h    100 mg q8-24h
≥20-40 kg    100 mg q12-24h    200 mg q8-24h
>40 kg    100 mg q12-24h    200 – 300 mg q8-24h
In the study, the following minimum, maximum and mean daily dosages and dosing frequencies were used:
Daily medication only: 1.9 mg/kg/day to 16.2 mg/kg/day (mean = 7.3 mg/kg/day);
As needed only: 2.2 mg/kg/day to 14 mg/kg/day (mean 7.7 mg/kg/day);
Daily medication and as needed: 1.7 mg/kg/day to 19.5 mg/kg/day (mean 7.25 mg/kg/day). (Gruen et al.2008)

CLIENT INFORMATION

• Used in dogs for anxiety-related conditions, including thunderstorm or fireworks phobias, activity restrictions (cage rest) after surgery, etc. It is commonly used in combination with other drugs to help reduce anxiety.
• May give with food or on an empty stomach. If your animal vomits or acts sick after getting it on an empty stomach, try giving with food or small treat and see if this helps. If vomiting continues, contact your veterinarian.
• May take up to 2 weeks to achieve its calming effect, especially when used alone.
• Most common side effects are sleepiness and decreased activity. Use with caution in working/service dogs as they may be unable to perform their duties while on this medication.

CHEMISTRY/SYNONYMS
Trazodone is a triazolopyridine antidepressant agent. It occurs as a white to off-white crystalline powder and is sparingly soluble in water, alcohol, or chloroform.
Trazodone may also be known as AF-1161, trazodona, trazodon, or “sleepeasy”. A common trade name isDesyrel®.

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.

COMPATIBILITY/COMPOUNDING CONSIDERATIONS
No specific information noted.

DOSAGE FORMS/REGULATORY STATUS
Veterinary-Labeled Products: None.
Human-Labeled Products:
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®; (Rx)