Summary
Several new antidepressants have been introduced over the past 10 years with ever-differing mechanisms of action. The latest entry into clinical practice is nefazodone, a new member of a novel class of antidepressants known as serotonin receptor modulators (SRMs). SRMs have a pharmacological mechanism of action which distinguishes them from all other antidepressants, namely a dual mechanism of modulating serotonin receptors. SRMs specifically act by powerful and selective blockade of serotonin 2A receptors coupled with a lesser but necessary degree of serotonin uptake inhibition. This differs from the selective serotonin reuptake inhibitors (SSRIs) which only inhibit serotonin reuptake, and from the tricyclic antidepressants which also have undesirable blocking actions at alpha adrenergic, histaminergic and cholinergic receptors. The novel pharmacological actions of the SRM nefazodone suggest that its side effect profile differs significantly from other antidepressants, and that it may prove to have unique therapeutic activity in serotonin-related psychiatric disorders as clinical experience with this agent increases.