Correlates of Nonimprovement to Pharmacotherapy for Chronic, Antidepressant-Resistant, Military Service-Related Posttraumatic Stress Disorder: Insights From the Veterans Affairs Cooperative Study No. 504.

Background: Posttraumatic stress disorder (PTSD) is a chronic and often difficult-to-treat condition that is prevalent among military veterans. First-line pharmacotherapy for this population typically involves antidepressants; however, veterans who do not improve are sometimes prescribed antipsychotics such as risperidone. A 2011 randomized controlled trial of adjunctive risperidone versus placebo for veterans with chronic, antidepressant-resistant, military service-related PTSD revealed no difference between groups. Hence, there is a need to examine predictors of nonimprovement for chronic, treatment-resistant PTSD.

Methods: We examined correlates of nonimprovement and delayed improvement (ie, ≥12 weeks) using data from 267 veterans with chronic, antidepressant-resistant PTSD who were prescribed adjunctive risperidone or a placebo. Veterans received 1 to 4 mg adjunctive risperidone (n = 133; mean dose, 2.74 mg) or a placebo daily (n = 134) in addition to their original treatment regimen over the 24-week trial.

Results: Greater severity of PTSD symptoms at baseline, specifically reexperiencing (ie, nightmares) and emotional numbing (ie, sense of foreshortened future), was independently associated with nonimprovement. Of the 194 veterans (72.7%) who did improve, 95 (49.0%) showed delayed improvement, taking 12 weeks or longer to demonstrate a 10-point reduction in Clinician-Administered PTSD Scale scores. Emotional difficulties affecting role functioning, as assessed using the Veterans RAND 36-item Health Survey, independently predicted nonimprovement.

Conclusions: While results are indicative of nonspecific pharmacotherapeutic effects, they suggest that specific PTSD symptom clusters and impairment are associated with variable improvement in veterans with antidepressant-resistant PTSD. They underscore the importance of developing more effective and targeted pharmacotherapies for specific symptom clusters in this population.