Abstract
Guideline for the pharmacotheraphy of treatment-resistant schizophreniaObjectives: Treatment-resistant schizophrenia is a common problem in patients with schizophrenia that creates a huge economic burden for society. Since there has not been a guideline for the treatment of TRS, the PTRS Guideline Working Group, therefore, proposed to develop an evidence-based clinical practice guideline for the drug treatment of TRS. Method: The PTRS Guideline Working Group comprised eleven psychiatrists, a psychologist, and a pharmacologist. A MEDLINE search was performed to identify the relevant articles published between 1966-1998. The evidence presented in 163 articles was extracted and graded by the use of a system modified from that of the Agency for Health Care Policy and Research (AHCPR). The strength of recommendations was categorized into A, B, and C. Results: 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). A schizophrenic patient who does not respond to at least two adequate trials of classical antipsychotics should be classified as a TRS patient. For a TRS patient who is taking classical antipsychotic in high doses (at least 50 mg/day of haloperidol or its equivalence), a dose reduction strategy may be applied at this stage (B). In a TRS patient who is taking a usual dose of classical antipsychotic, clozapine should be considered as a first-line treatment (A). If a TRS patient does not respond to clozapine, physicians should add a classical antipsychotic to the ongoing clozapine, especially sulpiride (A) and loxapine (B). Risperidone should be considered in a TRS patient who refuses to have regular blood monitoring or have a contraindication for clozapine (A). Although there is no evidence supporting the use of olanzapine (or other atypical antipsychotics that will be available in the future) in a schizophrenic patient who resists both classical antipsychotics and risperidone, giving olanzapine (or other atypical antipsychotics that will be available in the future) may be worth a trial if the TRS patient refuses to take clozapine (C). Discussion: Physicians should regard the PTRS Guideline as a tool for assisting their practice but not for replacing their clinical judgments. Optimal management for a TRS patient requires the integration of medical treatment with psychosocial interventions. Electroconvulsive therapy may be a treatment option for schizophrenic patients who fail to show adequate improvement with classical antipsychotics. The definition of or the set of criteria for TRS still cannot reach a conclusion. In using this guideline, physicians should be aware of its limitations, e.g., the search, the patients' ethnicity, the study cites. Whether this guideline will affect treatment practice remains to be seen.
