Major depressive disorder (MDD) is a leading cause of disability and mortality in adolescents. Empirical evidence suggests that many adolescents with MDD do not respond or respond only partially to commonly used interventions (antidepressants, psychotherapy, or a combination of antidepressants and psychotherapy). There is preliminary data in adults that adjunctive second-generation antipsychotics may be useful in treatment-resistant depression.The aim of this study was to obtain preliminary data regarding the safety, tolerability, and clinical usefulness of quetiapine as adjunctive therapy for adolescents (13-18 years of age) diagnosed with treatment-resistant MDD. Treatment-resistant MDD was defined as a failure to respond to an adequate dose for at least 8 weeks of a selective serotonin reuptake inhibitor (SSRI).The medical charts of 10 adolescents (13-18 years of age) diagnosed with treatment- resistant MDD, who were treated with adjunctive quetiapine, were evaluated. Doses of preexisting antidepressants remained unchanged during the period of evaluation. Response to treatment was defined as a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved).Seven adolescents (70%) qualified as responders to treatment with adjunctive quetiapine. The median dose of quetiapine was 200 mg (mean +/- SD = 275 +/- 190.4 mg, range; 150-800 mg). Side effects included sedation (40%) and weight gain (mean +/- SD = 4.5 +/- 7.24 pounds). There was no serious adverse event.This case series suggests that there may be a role for adjunctive quetiapine in treatment-resistant adolescent depression. Clinical safety and efficacy trials of quetiapine in this population appear to be warranted.