To the Editor: We applaud the efforts of Samuel G. Siris, M.D. (1), in summarizing the perplexing and heterogeneous literature regarding depressive symptoms in patients with schizophrenia. We add a discussion of drug interactions to Dr. Siris’s article, from the perspectives of both safety and efficacy. Regarding safety, many antidepressant medications have the potential of producing clinically important increases in antipsychotic plasma concentrations. One notable example is the addition of fluoxetine to clozapine therapy, which can increase clozapine plasma concentrations by more than 50% and has resulted in at least one reported fatality (2).