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Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study.
Am J Psychiatry. 2003 Feb; 160(2):303-9.AJ

Abstract

OBJECTIVE

The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol.

METHOD

Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography.

RESULTS

The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group.

CONCLUSIONS

A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.

Authors+Show Affiliations

Academic Medical Center, University of Amsterdam Department of Psychiatry, The Netherlands. l.dehaan@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12562577

Citation

de Haan, Lieuwe, et al. "Subjective Experience and D2 Receptor Occupancy in Patients With Recent-onset Schizophrenia Treated With Low-dose Olanzapine or Haloperidol: a Randomized, Double-blind Study." The American Journal of Psychiatry, vol. 160, no. 2, 2003, pp. 303-9.
de Haan L, van Bruggen M, Lavalaye J, et al. Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. Am J Psychiatry. 2003;160(2):303-9.
de Haan, L., van Bruggen, M., Lavalaye, J., Booij, J., Dingemans, P. M., & Linszen, D. (2003). Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. The American Journal of Psychiatry, 160(2), 303-9.
de Haan L, et al. Subjective Experience and D2 Receptor Occupancy in Patients With Recent-onset Schizophrenia Treated With Low-dose Olanzapine or Haloperidol: a Randomized, Double-blind Study. Am J Psychiatry. 2003;160(2):303-9. PubMed PMID: 12562577.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. AU - de Haan,Lieuwe, AU - van Bruggen,Marion, AU - Lavalaye,Jules, AU - Booij,Jan, AU - Dingemans,Peter M A J, AU - Linszen,Don, PY - 2003/2/4/pubmed PY - 2003/3/5/medline PY - 2003/2/4/entrez SP - 303 EP - 9 JF - The American journal of psychiatry JO - Am J Psychiatry VL - 160 IS - 2 N2 - OBJECTIVE: The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol. METHOD: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography. RESULTS: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group. CONCLUSIONS: A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy. SN - 0002-953X UR - https://www.unboundmedicine.com/medline/citation/12562577/Subjective_experience_and_D2_receptor_occupancy_in_patients_with_recent_onset_schizophrenia_treated_with_low_dose_olanzapine_or_haloperidol:_a_randomized_double_blind_study_ L2 - https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.160.2.303?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -