Mechanisms of the development of trazodone withdrawal symptoms.

Three cases developed withdrawal symptoms of trazodone despite gradual discontinuation of therapeutic doses of the drug. This report suggests that effects of trazodone and its metabolite m-chlorophenylpiperazine on the serotonergic system, which may result in noradrenergic rebound after discontinuation, and short half-lives of these compounds are involved in the development of these symptoms. From a clinical point of view, we suggest that trazodone should be tapered off at a very slow rate.