Rationale Treatment-resistant depression (TRD) is a common clinical problem, often complicated with suicidal ideations and greater lifetime functional impairment, and represents a considerable challenge to management and treatment. - - - - - Objective The aim of a prospective, open-label, noncomparative, flexible-dosed 20-week study was to evaluate the effects of quetiapine, as an add-on therapy, in patients with TRD who were refractory to previous treatments. - - - - - Method Eighteen patients with major depressive disorder (DSM-IV criteria) were treated for 20 weeks with quetiapine (mean dose 315 +/- 109 mg/day). Patients were evaluated at baseline, weekly from 1 to 9 weeks, and then after 12, 16, and 20 weeks of treatment, using Hamilton rating scale for depression-17 items (HAMD) scale. - - - - - Results Fourteen patients with TRD completed the 20-week open trial with quetiapine. The augmentation with quetiapine significantly reduced total scores and scores listed in the anxiety subscale on the HAMD, and these effects were observed after the fourth week of treatment, while the depressed mood scores were significantly reduced after the fifth week of treatment. Quetiapine add-on treatment significantly decreased the scores listed in the insomnia subscale on the HAMD subscale after the second week of treatment. - - - - - Conclusions Our preliminary data indicate that quetiapine add-on therapy appears to have beneficial effects in the treatment of patients with TRD.