Objective: To assess the use of levetiracetam, a novel anticonvulsant agent, in the treatment of refractory posttraumatic stress disorder (PTSD). Method: Retrospective analysis was conducted of 23 patients with DSM-IV diagnosis of PTSD who, after being deemed partial or nonresponders to antidepressant therapy, received levetiracetam in a naturalistic fashion. The primary Outcome measure was the PTSD Checklist-Civilian Version (PCL-C). Secondary outcome measures included the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I). Results: Levetiracetam at a mean SD dose of 1967 +/- 650 mg/day for 9.7 +/- 3.7 weeks was generally well tolerated. Nineteen patients (83%) were taking at least I concomitant medication. Patients were severely ill with a mean baseline PCL-C score of 67.2 +/- 9.4. CGI-S score of 6.0 +/- 0.7, and HAM-A score of 26.8 +/- 4.9. Patients improved significantly on all measures (p < .001). Thirteen patients (56%) met responder criteria at endpoint (PCL-C mean change = 23.5, CGI-I score <= 2), and 6 (26%) met remission criteria (CGI-S score ! 2). Adverse events were generally mild. and no patients discontinued levetiracetam because of side effects. Conclusion: These preliminary data suggest that levetiracetam may be an effective treatment in combination with antidepressant therapy for patients with PTSD who remain symptomatic after initial intervention.