Fluoxetine was used to treat nine adolescents (ages 15 to 18) with a DSM-III-R diagnosis of major depression who had failed to respond to milieu or intensive individual psychotherapy. One patient developed a hypomanic episode after 8 weeks, and fluoxetine was discontinued. Seven of the eight patients who continued open-label treatment showed "very much" or "much" clinical improvement, as measured by the Clinical Global Impression Scale, by 24 weeks of treatment. A greater than 50% reduction in symptoms on the Beck Depression Inventory was reported by most patients following 4 to 12 weeks of treatment. Similar reductions were clinically observed (over 50% reduction on the Hamilton Depression Rating Scale) after 4 to 12 weeks. Self-reported depression ratings at weeks 12,16, and 24 were significantly lower than those at weeks 2 and 4. Patients whose depressive episode had lasted less than 6 months reported significantly fewer symptoms by week 8 of treatment than patients with a longer duration of illness, but extending the duration of treatment increased apparent treatment response in those patients with long illness duration. Self-report ratings of suicidal ideation decreased by more than 50% for most patients between weeks" 6 and 16 of treatment. No patient reported an increase in suicidal ideation during fluoxetine treatment. The most common side effects, behavioral activation (increased activity, silliness, disruptive behavior) and gastrointestinal complaints, were transient and well tolerated. These uncontrolled clinical data suggest that fluoxetine might have some value in treating adolescents with major depression, but controlled studies with larger samples are needed before claims about efficacy can be ventured or the use of fluoxetine can be recommended for treating adolescent depression. These preliminary data also suggest that extending a fluoxetine trial beyond 8 weeks might enhance clinical response, especially in adolescents whose major depressive episode has lasted more than 6 months. ¥