I think it unlikely, however, that antidepressants are helpful in the treatment of certain schizophrenic patients with depression simply because they might raise plasma antipsychotic concentrations by means of metabolic influences. Indeed, Kramer et al. (1) found slower resolution of active psychotic symptoms when an antidepressant was added to patients’ antipsychotic treatment under randomized, double-blind conditions. Overall, the best results involving adjunctive antidepressant therapy have occurred among schizophrenic patients who were persistently and syndromally depressed but not flagrantly psychotic at the time of their antidepressant trial (2, 3, my article). In this light, the lack of an observed antidepressant effect in the Buchanan et al. (1996) study of fluoxetine in addition to clozapine therapy is not surprising, because this was a study of positive and negative symptoms specifically, involving patients who were not selected for having depression at baseline.