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Need for a New Framework to Understand the Mechanism of All Antipsychotics

J Clin Psychiatry 2000;61:387-388 [letter]

Letter to the Editor

Sir: The advent of atypical neuroleptics has transformed the pharmacologic treatment of schizophrenia. The advent of single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroreceptor imaging makes it possible to link biochemical events in the human brain to their clinical consequences. Remington and Kapur (supplement 10, 1999) have proposed an interesting model based on studies using PET that takes in account the serotonin-2/dopamine-2 (5-HT2/D2) occupancy threshold: conventional antipsychotics have low 5-HT2/high D2 ratios, olanzapine and risperidone have high 5-HT2/high D2 ratios, clozapine has a high 5-HT2/low D2 ratio, and quetiapine has a low 5-HT2/low D2 ratio. Beyond 80% of D2 blockade, extrapyramidal symptoms appear. To attain optimal blockade, 2 to 4 mg/day of a conventional neuroleptic such as haloperidol is sufficient.