A significant number of patients with unipolar depression fail to achieve remission after one or a series of antidepressants. We present the results of a retrospective chart review of the efficacy and tolerability of lamotrigine as an augmentation drug in treatment-resistant unipolar depression. A previous absence of a response was defined as the clinically significant presence of depressive symptomatology after 6 weeks of treatment with an antidepressant, with at least 3 weeks at the maximum dose tolerated by the patient. The patients were rated retrospectively using the Clinical Global Impression rating scale. Seventy-six percent of the patients improved. Gender, age, basal severity of the episode and degree of previous non response were not statistically significantly associated with response to lamotrigine augmentation. Comorbidity showed a tendency to be negatively related with response to lamotrigine. Three patients abandoned the treatment with lamotrigine due to side-effects. Complaints were excessive somnolence, headache, dizziness, nausea and malaise. Data suggest that lamotrigine is a promising drug for treatment-refractory unipolar depression. Double-blind studies are necessary to confirm its use as an augmentation agent.