Background. Sertraline has a proved efficacy in post-traumatic stress disorder (PTSD), but it is unknown which symptoms respond or in what sequence this occurs. Such information might be useful clinically and heuristically.

Method. The study examined the effects of sertraline on the individual symptoms of PTSD. It also examined whether early changes in anger explained drug-induced change in other symptoms over time. Mixed models analysis was applied to datasets from two 12-week placebo-controlled trials of sertraline. A validated self-rating scale (DTS) was used to assess treatment efficacy.

Results. Sertraline was superior to placebo on 15 of 17 symptoms, especially in the numbing and hyperarousal clusters. A strong effect was found on anger from week 1, which partly explained the subsequent effects of sertraline on other symptoms, some of which began to show significantly greater response to drug than to placebo at week 6 (emotional upset at reminders, anhedonia, detachment, numbness, hypervigilance) and week 10 (avoidance of activities, foreshortened future).

Conclusions. Sertraline exercises a broad spectrum effect in PTSD. Effects are more apparent on the psychological rather than somatic symptoms of PTSD, with an early modulation of anger and, perhaps, other affects, preceding improvement in other symptoms.