Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients

Am J Psychiatry. 1999 Jun;156(6):869-75. doi: 10.1176/ajp.156.6.869.

Abstract

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.

Method: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Basal Ganglia Diseases / chemically induced
  • Basal Ganglia Diseases / epidemiology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Male
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Raclopride
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Serotonin / metabolism*
  • Risperidone / administration & dosage
  • Risperidone / therapeutic use*
  • Salicylamides
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Schizophrenic Psychology
  • Spiperone / analogs & derivatives
  • Tomography, Emission-Computed*
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Salicylamides
  • Raclopride
  • Spiperone
  • 3-N-methylspiperone
  • Risperidone