OBJECTIVE:To assess the efficacy and tolerability of dihydroergotamine (DHE) nasal spray for headache treatment in patients refractory to triptans. RESEARCH DESIGN AND METHODS:In this single-center, retrospective study, charts were reviewed to identify patients who received their first prescription for 2.0 mg DHE nasal spray between 2000 and 2004. Patients who failed previous treatments with one or more triptan formulations were considered refractory to triptan treatment and were included in the study. Headache severity was assessed by the patient at the center using a visual analog scale (VAS) of 1 to 10 (10 being most severe) at baseline and 4 weeks after initiating DHE. The responses to DHE were evaluated and categorized as complete response (headache symptoms resolved), partial response (> or = 50% reduction in VAS), or unresponsive (< 50% reduction in VAS). Four weeks after DHE use, any adverse event (AE) that occurred during DHE use was reported by the patient at the center. MAIN OUTCOME MEASURES:The efficacy of DHE was determined by headache severity reductions. Tolerability was assessed in terms of AE frequency. RESULTS:A total of 97 patients met the study criteria; 13 patients were lost to follow-up. Thirty-three patients (34.0%) reported a complete response to DHE treatment, 13 (13.4%) experienced a partial response, and 38 (39.2%) were unresponsive. Seven of 97 patients (7.2%) reported AEs (e.g., nasal congestion, dysphoria) while using DHE. CONCLUSIONS:This retrospective chart review included patients who failed triptan therapy for treatment of headaches. We found that 47% of patients experienced partial to complete response to DHE treatment. Study limitations included the retrospective design, the small sample size, and the use of patient recollection to evaluate the efficacy and tolerability of DHE. Randomized, double-blind, controlled trials are warranted.