Liver cytochrome P450 (CYP450) enzymes play an important role in metabolizing antipsychotics (APs) and other drugs. Excessive use of drugs can impair liver function and even other organs, thus causing several adverse effects. In addition, metabolizer types of CYP450 enzymes may influence the therapeutic effects and drug reactions. In this case report, we introduce a 52-year-old female with a 23-year history of schizophrenia who took overdose of multiple kinds of APs and other herbal preparations together for nearly two years, and she presented with poor treatment effects and minor side effects of APs. This case adds clinical examples for those patients with poor efficacy and alarming drug tolerance.