Using clonidine and trazodone for anxiety-based behavior disorders in dogs


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.
Mar 31, 2014

The use of psychoactive pharmaceuticals in veterinary behavior medicine has proved invaluable in managing anxiety-based disorders. Without the appropriate and judicious use of these medications, many dogs would be much less likely to respond to behavior modification therapy. Medications such as fluoxetine and sertraline (selective serotonin reuptake inhibitors [SSRIs]) and clomipramine (a tricyclic antidepressant [TCA]) can allow successful therapy for many animals experiencing conditions such as separation anxiety, thunderstorm phobia, and fear-based aggression.

In some cases, however, use of a single pharmaceutical agent does not provide sufficient anti-anxiety effects to achieve a suitable outcome. When a patient fails to respond to monotherapy with an SSRI or a TCA, clinicians have three options:

1. Increase the dose of the medication if the typical maximum dose has not been reached or if the patient has not shown undesirable side effects.

2. Switch to a different drug.

3. Augment the first drug with a second drug.1

If the first two steps prove ineffective in managing the case, combination drug therapy is a viable alternative. Numerous possible combinations of agents can be used to manage particular cases. In this article, we review the use of clonidine and trazodone in dogs, two medications that are being used more frequently in behavior specialty practices to manage a variety of anxiety-based behavior problems.


Clonidine is classified primarily as an alpha-2 agonist. (An example of another alpha-2 agonist used in veterinary medicine is the injectable sedative dexmedetomidine.) Alpha-2 agonists increase alpha-2 adrenoreceptor activity. The increase in alpha-2 adrenoreceptor functioning results in a decrease in norepinephrine release from the locus ceruleus. Through its activation of the hypothalamic-pituitary-adrenal axis, norepinephrine is associated with fear-based responses such as increased vigilance and arousal.2 This can impair a patient's ability to relax in stressful situations, especially when triggering stimuli cannot be avoided or controlled. Common examples of this include meeting unfamiliar people or dogs while on walks or when unfamiliar guests enter a home.

Clonidine is also used as an antihypertensive agent. It has a short half-life (7.7 hours in people2), with its effect reducing over four to six hours. Pharmacokinetic data are lacking for dogs.

Indications and dosage

In veterinary behavior medicine, clonidine is most often used as an add-on agent, combined with an SSRI such as fluoxetine or a TCA such as clomipramine. It is usually dosed on an as-needed basis but can be given up to every eight hours. It needs to be administered one or two hours before exposure to an anticipated stressor.

Clonidine is commonly used to treat noise phobias (including thunderstorms and generalized noise responses), separation anxiety, and fear-based aggression with identifiable triggers. Generally, it is an effective agent when increased arousal or reactivity is a concern. Clonidine has a wide dosing range (0.01 to 0.05 mg/kg). It is available in 0.1-, 0.2-, and 0.3-mg tablets.

Keep in mind that no data support the dose recommendations (e.g. oral bioavailability, half-life); the recommendations are anecdotal as well as extrapolated from human data. Thus, close client communication is vital in determining an effective dose without excessive side effects.

Potential side effects

Side effects from clonidine can include dry mouth, ataxia, constipation, and sedation. Exercise caution when using clonidine in patients with existing cardiac disease.3 Starting at the lower end of the dose range and gradually tapering upward can help minimize the severity of side effects.

Clonidine is metabolized by the liver and excreted by the kidneys, so exercise caution in patients with compromised hepatic or renal function. Also exercise caution when using clonidine in patients with preexisting heart disease as it decreases cardiac output.

Clonidine can produce a dose-dependent biphasic response in blood pressure, with lower doses producing central mediated hypotension, but higher doses producing peripheral mediated vasoconstriction and hypertension (alpha-2-mediated). Use of clonidine in patients also receiving agents that affect atrioventricular node function (e.g. digoxin, calcium channel blockers, or beta blockers) may result in bradycardia or atrioventricular nodal block.4

If clonidine has been used daily for an extended period, consider slow withdrawal to diminish the chance of rebound hypertension.