280. Olanzapine therapy for posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a relatively common condition, for which there is no standard of pharmacological treatment. Preclinical research with the learned helplessness animal model of posttraumatic stress disorder, and prior clinical research with nefazodone, suggests that serotonin 5-HT2 receptor antagonists may successfully treat PTSD, including the “core” or intrusive symptoms. Since the atypical neuroleptic olanzapine (Zyprexa) has antagonist properties at the 5-HT2 receptor, we undertook a multi-site open label study of olanzapine in veterans with combat induced PTSD. Patients are recruited from VA clinics in Dallas, Fort Worth, Waco, Austin, and San Antonio. All procedures have been approved by the relevant ethical review committees, and no procedure is performed without fully informed, signed, witnessed consent. After evaluation and washout, patients are titrated up to a maximum dose of 20 mg per day, as tolerated. Primary outcome measure is the Clinician Administered PTSD Scale (CAPS), and secondary measures are the Hamilton Rating Scales for Anxiety and for Depression (HRSA, HRSD). Patients are seen in clinic weekly. Target enrollment for this ongoing study is 60. We have performed an interim analysis on the first 14 patients who received an “adequate” trial, defined as 4 weeks of therapy. The most significant improvement over baseline was seen in the total CAPS score (F 5 14.1, p 5 0.0001) and in the Cluster B (core symptoms) subscale score (F 5 14.8, p 5 0.0001). Significant improvement was also seen on the other CAPS subcales and on the HRSA and HRSD. If these findings continue in the larger sample, larger scale, randomized, placebo controlled clinical trials should be considered. Also, the efficacy of olanzapine in civilian PTSD should be tested.