Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients.
OBJECTIVE
Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy.


METHODS
Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy.


RESULTS
Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82% (range = 79%-85%), 5-HT2A receptor occupancy was 95% (range = 86%-109%), and six patients had developed extrapyramidal side effects. After dose reduction to 3 mg/day, D2 receptor occupancy was 72% (range = 53%-78%), and 5-HT2A receptor occupancy was 83% (range = 65%-112%). Three patients had extrapyramidal side effects at this time.


CONCLUSIONS
Treatment with risperidone, 6 mg/day, is likely to induce unnecessarily high D2 receptor occupancy, with a consequent risk of extrapyramidal side effects. High 5-HT2A receptor occupancy did not prevent extrapyramidal side effects completely. The authors previously suggested an optimal interval for D2 receptor occupancy of 70%-80%. To achieve this, resperidone, 4 mg/day, should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients.
Nyberg
S
S
Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden. svante.nyberg@neuro.ks.se
Eriksson
B
B
Oxenstierna
G
G
Halldin
C
C
Farde
L
L
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000453:epidemiology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D020891:Raclopride; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D012457:Salicylamides; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D012565:Schizophrenic Psychology; D013134:Spiperone / Q000031:analogs & derivatives; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012457:Salicylamides; D020891:Raclopride; D013134:Spiperone; C039167:3-N-methylspiperone; D018967:Risperidone