Using clonidine and trazodone for anxiety-based behavior disorders in dogs - Veterinary Medicine
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Using clonidine and trazodone for anxiety-based behavior disorders in dogs
For some behavior patients, the anti-anxiety effects of a single drug might not be enough. In cases in which monotherapy is insufficient, consider adding one of these drugs to your treatment plan.



The side effects mentioned previously and in this section are typically transient and mild. In some cases, however, these effects can be more prolonged and serious. Be sure to educate clients about the possible side effects and tell them to contact you or another veterinarian immediately with any concerns.

If you encounter adverse effects, you can decrease the dose (50% reduction is common) or, in more severe cases, discontinue the medication completely. Compounds with longer half-lives, such as SSRIs, can be discontinued abruptly, if necessary. But with shorter-acting compounds, such as TCAs, the dose should be gradually tapered to minimize withdrawal signs. Likewise, trazodone and clonidine should be slowly withdrawn if they have been administered two or three times daily for a prolonged period. Gradual withdrawal is helpful in all cases when there is a need to determine the lowest effective dose.

Dose adjustments for SSRIs should be made in four- to six-week increments, while shorter-acting compounds can be adjusted every one or two weeks. There is no need to withdraw these medications before anesthesia, but consider reducing premedication sedation to minimize interactions.

Other factors to consider when administering psychoactive pharmaceuticals include the following:

  • Serotonergic agents (SSRIs, TCAs, and SARIs) may decrease triiodothyronine and thyroxine concentrations.
  • Serotonergic medications such as SSRIs, TCAs, and SARIs should not be combined with monoamine oxidase inhibitors (MAOIs). MAOIs commonly used in veterinary medicine include selegiline and amitraz. These medications may precipitate a condition called serotonin syndrome when used in combination (see the sidebar "Serotonin syndrome: Be on the lookout"). Combining serotonergic agents with tramadol may have similar effects.
  • Perform baseline premedication database testing including a complete blood count, serum chemistry profile, and urinalysis. Repeat this testing within one or two months after starting medication and then again every six to 12 months.
  • For patients with a history of heart disease, consider performing a baseline electrocardiogram when prescribing serotonergic medications such as SSRIs, TCAs, and SARIs, particularly if a combination therapy is being used.
  • Consider giving clients a handout outlining the possible effects of clonidine and trazodone to educate them about when they should contact their veterinarian.9 (Download a client handout at
  • Any serotonergic medication (TCAs, SSRIs, and SARIs such as trazodone) may aggravate seizures in patients with a history of epileptic seizures and should also not be used in pregnant or breeding animals.10
  • Because of their propensity to inhibit cytochrome P450 hepatic enzyme activity, SSRIs and TCAs should be used cautiously with drugs that rely on the same metabolic system. These include narcotics, tramadol, benzodiazepines, ketoconazole, and carbamazepine.3
  • Phenobarbital may lower plasma concentrations of SSRIs and TCAs because of its induction effect on the cytochrome P450 system, thus increasing hepatic metabolism of medications in these two classifications.9 Similarly, because SSRIs and TCAs can suppress cytochrome P450 activity, there is a potential for these compounds to result in increased concentrations of phenobarbital and other medications that depend on the cytochrome P450 system for their metabolism.


Adjunctive therapy for anxiety-based behavioral disorders in veterinary medicine can greatly increase the likelihood of a beneficial outcome. Clonidine and trazodone are two agents that are being used more frequently in veterinary behavior medicine and can be used in combination with more traditional serotonergic medications to help implement a behavior modification plan. Care in dosing and diligent client communication can minimize side effects and increase client satisfaction when these drugs are prescribed for their dogs.

John J. Ciribassi, DVM, DACVB, and Kelly Ballantyne, DVM, Chicagoland Veterinary Behavior Consultants, 1042 Mountain Glen Way, Carol Stream, IL 60188.

Editors' note: Dr. Ciribassi is a coauthor of the recently available Decoding Your Dog: The Ultimate Experts Explain Common Dog Behaviors and Reveal How to Prevent or Change Unwanted Ones (Houghton Mifflin Harcourt), the first behavior book for pet owners from the American College of Veterinary Behaviorists.

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