Ethanol or CNS depressants should be used with caution in combination with trazodone because of additive CNS-depressant effects and possible respiratory depression or hypotension. Barbiturates and carbamazepine induce hepatic microsomal enzymes and increase the metabolism of trazodone. The most critical and well-studied pathway is 2D6. Trazodone's interaction has not been clearly elucidated at this time. Patients receiving an SSRI and trazodone should be monitored closely for excessive adverse effects from either agent.
Trazodone can lower the seizure threshold.
Patients may require increased concentrations of anticonvulsants to achieve equivalent effects if trazodone is added. Trazodone metabolism can be inhibited by cimetidine or ranitidine, resulting in increased plasma levels of trazodone that could lead to toxicity. Patients should be closely observed for toxic effects such as orthostatic hypotension or sedation. Trazodone may have an increased risk of causing toxicity if used with oral contraceptives, fluoxetine, erythromycin, or methylphenidate because of the inhibition of hepatic metabolism. Priapism occasionally results in permanent impairment of erectile function or impotence.