Better indicators of prognosis are needed to personalise post-traumatic stress disorder (PTSD) treatments.

We aimed to evaluate early symptom reduction as a predictor of better outcome and examine predictors of early response.

Patients with PTSD (N = 134) received sertraline or prolonged exposure in a randomised trial. Early response was defined as 20% PTSD symptom reduction by session two and good end-state functioning defined as non-clinical levels of PTSD, depression and anxiety.

Early response rates were similar in prolonged exposure and sertraline (40 and 42%), but in sertraline only, early responders were four times more likely to achieve good end-state functioning at post-treatment (Number Needed to Treat = 1.8, 95% CI 1.28–3.00) and final follow-up (Number Needed to Treat = 3.1, 95% CI 1.68–16.71). Better outcome expectations of sertraline also predicted higher likelihood of early response.

Higher expectancy of sertraline coupled with early response may produce a cascade-like effect for optimal conditions for long-term symptom reduction. Therefore, assessing expectations and providing clear treatment rationales may optimise sertraline effects.

None.