Effect
Pharmacodynamics
The mechanism of action of trazodone is not fully understood, but it is known to inhibit serotonin reuptake and block both histamine and alpha 1-adrenoreceptors. Although trazodone is often considered a selective inhibitor of serotonin reuptake, several reports have shown that other mechanisms, including antagonism at additional serotonin receptor subtypes, may occur. The antidepressant effect of trazodone results from inhibition of the "reuptake" of serotonin from the synaptic cleft back into the presynapse. This permanently increases the concentration of serotonin and counteracts the depressive disorder.
Pharmacokinetics
Trazodone is rapidly absorbed in the gastrointestinal tract after oral administration, with bioavailability ranging from 63-91%. Plasma protein binding of trazodone is 89-95% according to in vitro studies. Trazodone is highly metabolized and activated in the liver by the enzyme CYP3A4. Approximately 60-70% of the dose is excreted in the urine within 48 hours of administration. Approximately 9-29% over a period of 60 to 100 hours is excreted in the feces.
Interactions
Trazodone is metabolized by several liver enzymes, including CYP3A4, CYP2D6, and CYP1A2. In general, any drug that is metabolized by or induces the same enzymes should not be combined with trazodone.
Severe and possibly fatal side effects (e.g.: serotonin syndrome) can be triggered by drugs that have a similar effect on serotonin action in the CNS. Therefore, combination with other antidepressants, especially MAO inhibitors, should be avoided.
