First-line pharmacologic treatments for PTSD act predominantly on the serotonergic and, to a lesser extent, the noradrenergic systems. Specifically, these agents include the selective serotonin reuptake inhibitors (SSRIs) and the serotonin norepinephrine reuptake inhibitors (SNRIs). In this chapter, the mechanisms of action of agents within these two pharmacologic classes are explained, and a brief overview of clinical characteristics of each agent is provided in turn.

Of the SNRIs, only venlafaxine has been studied in controlled trials in PTSD; however, they are all included here as a first-line option due to their mechanistic similarity to venlafaxine and SSRIs as well as their evidence of efficacy in other anxiety disorders.