Objectives. The aim of this naturalistic study was to investigate whether treatment with clozapine and other atypical antipsychotics for at least 2 years was associated with a reduction in psychotic and depressive symptoms and an improvement in chronic schizophrenia patients' awareness of their illness. Methods. Twenty-three adult outpatients (15 men and 8 women) treated with clozapine and 23 patients (16 men and 7 women) treated with other atypical antipsychotics were included in the study. Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS), and insight was assessed with the Scale to Assess Unawareness of Mental Disorder (SUMD). Results. The sample as a whole had a significant reduction in positive, negative, and general symptoms, whereas the reduction in depression was significant only for patients with CDSS scores of 5 and higher at the baseline. At the follow-up, patients treated with other atypical antipsychotics reported a greater reduction in depression than patients treated with clozapine, but not when limiting the analyses to those with clinically relevant depression. Conclusions. Atypical antipsychotics may be effective in reducing psychotic and depressive symptoms and in improving insight in patients with chronic schizophrenia, with no differences in the profiles of efficacy between compounds.