ABSTRACT
The authors proposed to develop an evidence-based guideline relevant to drug use for treatment-resistant schizophrenia (TRS), which will be called "Guideline for the Pharmacotherapy of Treatment-Resistant Schizophrenia or PTRS Guideline". The authors performed a MEDLINE search (between 1966 and December 1998) and classified the study designs of those trials by using the system proposed by the Agency for Health Care Policy and Research (AHCPR). The levels of evidence were graded and recommendations were made by the use of a system modified from that of the AHCPR. One hundred and sixty-three articles met the inclusion criteria for the review. For a schizophrenic patient who does not respond to a classical antipsychotic, physicians should switch from the first classical antipsychotic to the second one, which belongs to a different class. A schizophrenic patient who does not respond to at least two adequate trials of classical antipsychotics should be classified as a TRS patient. Clozapine should be considered as a first-line treatment for TRS. Risperidone should be considered in a TRS patient who refuses to have regular blood monitoring or has contraindication for clozapine. Physicians should use this guideline to accompany others that suggest the overview of treatment for schizophrenia. Appropriate application and the limitations of the guideline are also discussed.