An American study has used a ligand binding technique and brain imaging to visualise dopamine D2 receptor blockade and to determine the threshold window for antipsychotic medication (American Journal of Psychiatry 2000;157:514). According to the authors of the study, the data show that the therapeutic window for antipsychotics can be reached at doses much lower than those used previously.
In a double-blind study, 22 patients with first-episode schizophrenia were randomly assigned to 1 or 2.5mg/day of haloperidol, increased after two weeks to 5mg/day in patients who were unresponsive.
After four weeks of treatment, the study patients showed a wide range of D2 receptor occupancy (determined by positron emission tomography scanning) which correlated with the level of clinical improvement and extrapyramidal side effects. The researchers found that blocking 65 per cent of dopamine D2 receptors was sufficient for treatment while higher levels of blockade (over 80 per cent) were associated with side effects. Commenting on the study, Mr David Taylor (chief pharmacist, the South London and Maudsley NHS trust) said that studies using ligand binding to measure receptor occupancy should be interpreted with caution. He added that the levels of receptor occupancy depend on the relative affinities of the ligand and drug to the receptor and that there is some doubt whether such measurements reflect what happens in clinical situations.