Purpose: To prospectively assess the efficacy of the selective serotonin inhibitor escitalopram on painful bone metastases, in combination with external beam irradiation. Methods: Forty-three patients with cancer metastatic to bone and suffering from depression were treated with 3 Dimensional Conformal Radiotherapy (3DCRT) (30 Gy; 3 Gy/fraction, 5 days/week) combined with escitalopram (20 mg/day). Pain relief was evaluated with Wong/Baker Faces Pain Scale. The patients reported outcome using a RTOG-EORTC quality-of-life self-questionnaire (QLQ-C30 v3.0) and the status of depression according to Hamilton Scale (HAM-17). The assessment was performed at baseline and 6-8 weeks afterradiotherapy. Results: Patients treated with radiotherapy and escitalopram tended to show a good response to pain and improvement of their quality of life. Conclusions: Though our data concerned a rather small number of patients, addition of escitalopram to 3DCRT accomplished a high clinical benefit rate on neuropathic pain from bone metastasis.