Trazodone is classified as a serotonin receptor antagonist and reuptake inhibitor (SARI). It inhibits activity at the serotonin 5-HT2A postsynaptic receptor and acts as a weak presynaptic serotonin reuptake inhibitor. It is used as an adjunctive agent with TCAs and SSRIs to help manage anxiety-related disorders and facilitate sleep.
Trazodone can also be an alpha-1 antagonist, resulting in hypotension. It is metabolized by the hepatic cytochrome P450 system and reaches its peak plasma concentration at 445 ± 271 minutes; its half-life is 169 ± 53 minutes after a single oral dose.5
Indications and dosage
Trazodone can be administered as needed, daily as often as every eight hours, or by using a combination of the two schedules. Because of the wide range in reaching peak plasma concentration and in its half-life, it is important to recognize that dosing should be adjusted to account for this individual variability. Regular daily dosing is more common with generalized anxiety disorders in which it is difficult to identify a specific trigger, and as-needed dosing is used when those stimuli can be predictably recognized. Therefore, trazodone is used in situations in which there is an identifiable stimulus, such as thunderstorms, or before an owner's departure in separation anxiety cases.6
Trazodone is dosed at 1.7 to 9.5 mg/kg orally every eight to 24 hours. It is recommended to begin dosing at 2 to 3 mg/kg orally every 24 hours and then gradually taper up to effect. Dosing at the lower end of the range should be sufficient when trazodone is used along with a primary agent such as a TCA or an SSRI. Trazodone can also be used as a single agent. Trazodone is available in 50-, 100-, 150-, and 300-mg tablets.
Potential side effects
Side effects commonly include gastrointestinal effects (vomiting and diarrhea), sedation, ataxia, hypotension, excitement or agitation, and panting. Priapism is a rare side effect in people, so exercise caution when using trazodone in breeding male dogs.
When combined with an SSRI or a TCA, trazodone may increase the risk of seizures due to an unknown etiology, but consider that it could be a consequence of serotonin syndrome (see the sidebar "Serotonin syndrome: Be on the lookout"). SSRIs and TCAs may also increase plasma concentrations of trazodone. In addition, plasma concentrations of digoxin may be increased with trazodone administration.4,7
Serotonin syndrome: Be on the lookout
Most side effects diminish with time, so often waiting is the best response to the appearance of mild to moderate side effects. It is best to begin at the lower end of the dosage range to limit side effects. Administer a dose at the lower levels for three days and then gradually taper up as needed.8