The NIMH Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was a large clinical trial comparing the effectiveness of first generation and second generation antipsychotic medications to treat schizophrenia. Almost three quarters of patients switched from their first medication to a different medication due to side effects or failure to adequately control symptoms. Perphenazine (the older, first generation medication) was equally effective and as well tolerated as the newer, second generation medications. The study’s findings indicated that on average, newer medications have no substantial advantage over the older medications. However, it is possible that individual patients may respond differently to different medications. Among patents who did not respond to first-line medications, clozapine was substantially better than all the other atypical medications in achieving a treatment response. For questions and answers about the CATIE study, visit https://www.nimh.nih.gov/funding/clinical-research/practical/catie/phase1results.shtml.