Guideline for the pharmacotherapy of treatment-resistant schizophrenia. Royal College of Psychiatrists of Thailand.

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.

Structural and functional neuroimaging findings in substance-related disorders.

Intoxication with alcohol results in depressed global glucose metabolism that continues into the stages of withdrawal and abstinence. The decrease in metabolism, however, is not equal across the brain, with certain regions more affected than others. Such a pattern of disturbance suggests that the effect of alcohol on the brain cannot simply be a nonspecific depressant effect secondary to decreased blood flow or glucose transport into the cells but may be related to the dysfunction of the various neurotransmitter systems. Different authors have suggested the dysfunction to be related to the GABAergic, cholinergic, and dopaminergic systems. Long-term alcoholism is associated with atrophy of several brain regions. The frontal lobes and limbic structures seem to be most vulnerable. The data are encouraging with regard to the normalization in brain metabolism and in size of vulnerable brain regions with continued abstinence. In addition to findings of improvement in cognitive functioning and many health parameters, these findings arm clinicians with further data on the benefits of abstinence in the struggle to aid patients in maintaining their sobriety. Several areas remain to be addressed. In particular, clinicians are in need of data, neuroimaging and otherwise, that serve as prognostic indicators, thus allowing patients at higher risk for relapse to be identified and provided with more intensive treatment. A similar need exists for indicators of diagnostic heterogeneity that would guide the development of more highly tailored treatment regimens for identified subgroups of patients. Currently, we have rudimentary knowledge of the gender differences of the effects of alcohol and cocaine on the brain.