D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate

Am J Psychiatry. 1995 Feb;152(2):173-8. doi: 10.1176/ajp.152.2.173.


Objective: The aim of this study was to examine the relationships among clinical effects, central D2 dopamine receptor occupancy, and plasma concentrations of haloperidol in eight clinically stabilized schizophrenic outpatients who were responding to treatment with low doses of haloperidol decanoate.

Method: During a 4-week interval of haloperidol decanoate dosage (dose range = 30-50 mg), the patients' D2 receptor occupancy was determined with positron emission tomography on two occasions. Plasma concentrations of haloperidol were determined with a sensitive high-performance liquid chromatography method.

Results: One week after injection of haloperidol decanoate, the mean D2 receptor occupancy was 73% (range = 60%-82%), and the mean plasma concentration of haloperidol was 4.6 nmol/liter (range = 2.9-9.7). After 4 weeks, the mean D2 receptor occupancy had decreased to 52% (range = 20%-74%), and the mean haloperidol concentration to 2.3 nmol/liter (range = 1.0-4.4).

Conclusions: The D2 receptor occupancy 1 week after injection was high and comparable to that previously found in patients responding to acute treatment with classic neuroleptics. Prevention of relapse was maintained despite low D2 receptor occupancy during the latter part of the treatment interval. These observations indicate that continuously high D2 receptor occupancy may not be necessary to prevent schizophrenic relapses. The results emphasize the need for systematic clinical evaluation of intermittent low-dose treatment strategies.

Publication types

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

MeSH terms

  • Adult
  • Ambulatory Care
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Basal Ganglia / diagnostic imaging
  • Basal Ganglia / drug effects
  • Basal Ganglia / metabolism
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Haloperidol / analogs & derivatives*
  • Haloperidol / blood
  • Haloperidol / metabolism
  • Haloperidol / pharmacology
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Receptors, Dopamine D2 / chemistry
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism*
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Tomography, Emission-Computed


  • Antipsychotic Agents
  • Receptors, Dopamine D2
  • haloperidol decanoate
  • Haloperidol