Introduction Pulse-loading treatment consists in a rapid titration of the pharmacological agent in the first days of treatment. A few studies suggested that this kind of titration with intravenous clomipramine could result in a greater and faster response than with a standard titration in obsessive-compulsive disorder (OCD) resistant patients. The aim of this open-label trial was to investigate the effectiveness and tolerability of a citalopram pulse-loading protocol in severe treatment-resistant OCD patients. Methods We enrolled 8 severe treatment-resistant OCD patients. Patients were treated with intravenous citalopram starting with 40 mg for 3 days and increasing the dose up to 80 mg from the fourth day. The patients continued the treatment with 80 mg of intravenous citalopram for 18 days (a total of 21 days of intravenous treatment), then they switched to oral treatment (80 mg of oral citalopram). Results During the pulse-loading treatment no patients showed significant adverse events. No patients showed clinical significant change of the QTc interval and/or of the sodium levels. Five out of eight patients had a partial or full response at the end-point (4 patients had a full response and 1 patient had a partial response) and two of these had remission. Pulse-loading treatment seemed to induce a faster improvement respect to a standard titration, since the responder patients showed a significant improvement already after 3 weeks. Three out of eight patients did not respond. Conclusion Taking into account the very limited sample size, this case series suggests that this treatment approach deserves further controlled studies