Previous studies found that depressive symptoms and low functional self-efficacy are associated with the occurrence of disabling musculoskeletal pain, and diminished quality of life in elderly people. The target of this study was to consider the change in instrumental activities of daily living (IADL) disability and health related quality of life after integrative psychotherapeutic treatment program of depressive symptoms in senior female patients with musculoskeletal pain. In an 8-week outpatient-based, random, prospective, controlled trial, 36 female patients between 70 and 79 with a history of clinically evident musculoskeletal pain and afflicted with depressive symptoms, but who were able to bathe, walk, dress, and transferring inside the house were evaluated. The study was performed using the Center for Epidemiological Studies Depression Scale (CES-D), IADL, and the Health Survey (SF-36). In comparison with the untreated group, according to the intent-to-treat principle, significant changes on the CES-D (P < 0.01), IADL (P < 0.01), and all scales of SF-36 were observed after eight weeks in the treated subjects. The treatment of moderate depression with integrative psychotherapy may be efficacious in improving of IADL disability and health related quality of life in affected senior female patients with musculoskeletal pain.