Treatment-resistant depression, i.e. partial or non response to antidepressants in spite of various treatment attempts with optimized doses and combinations, is rather common. With residual symptoms such as tiredness, anhedonia and concentration disturbances, the treatment strategy has often been to use monoamino-oxidase inhibitors (MAOIs). Their use, however, is limited due to interaction problems. Modafinil is recently developed wake-promoting drug with only minor side-effects. Pilot studies indicate that it appears to have an augmentation effect in treatment-resistant depression. This open-label study performed in the private psychiatric practice setting is the first to make a comprehensive evaluation of the target patient profile based on patient-reported symptoms. Modafinil in doses of 100-400 mg was administered as augmentation to ongoing antidepressant therapy in patients with partial response and suffering from hypersomnia. The total number of patients was 21 and 43% of these were responders (i.e. had a score reduction of >50% on the Major Depression Inventory (MDI) as well as remitters, i.e. the remission rate was 43%. At endpoint, the responders had psychological distress scores on the Symptom Checklist (SCL-92) on the level of the general Danish population. Baseline characteristics for responders were lower scores on depression, hostility, anxiety, somatization, obsession and psychoticism. Modafinil thus appears to be an appropriate augmentation to antidepressant treatment, leading to a remission rate of 43%. However, the results from this open-label study need ot be confirmed in a placebo-controlled trial.