+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia

Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia

American Journal of Psychiatry 156(2): 286-293

Objective: Dopamine D2 receptor occupancy measurements provide a valid predictor of antipsychotic response, extrapyramidal side effects, and elevation of prolactin levels. The new antipsychotics clozapine, risperidone, and olanzapine obtain antipsychotic response with few extrapyramidal side effects and little prolactin elevation. The purpose of this study was to compare the D2 and serotonin 5-HT2 receptor occupancies of these drugs in patients receiving multiple-dose, steady-state regimens. Method: Forty-four patients with schizophrenia (16 taking risperidone, 2-12 mg/day; 17 taking olanzapine, 5-60 mg/day; and 11 taking clozapine, 75-900 mg/day) had their D2 and 5-HT2 occupancies determined with the use of (11C)raclopride and (18F)setoperone, respectively, and positron emission tomography imaging. Results: Clozapine showed a much lower D2 occupancy (16%-68%) than risperidone (63%-89%) and olanzapine (43%-89%). Risperidone and olanzapine gave equal D2 occupancies at doses of 5 and 20 mg/day, respectively. All three drugs showed greater 5-HT2 than D2 occupancy at all doses, although the difference was greatest for clozapine. Conclusions: Clozapine, at doses known to be effective in routine clinical settings, showed a D2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antipsychotics. The results also suggest that some previous clinical comparisons of antipsychotics may have been confounded by different levels of D2 occupancy. Clinical comparisons of these drugs, matching for D2 occupancy, may provide a better measure of their true "atypicality" and will help in understanding the contribution of non-D2 receptors to antipsychotic effects.

(PDF emailed within 0-6 h: $19.90)

Accession: 010328796

Download citation: RISBibTeXText

PMID: 9989565

DOI: 10.1176/ajp.156.2.286

Related references

Occupancy of dopamine D2 receptors by the atypical antipsychotic drugs risperidone and olanzapine: theoretical implications. Psychopharmacology 175(4): 473-480, 2004

Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia. Psychiatry Research 92(1): 33-44, 2000

Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia. Psychiatry Research 92(1): 33-44, Nov 8, 1999

Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia: a cross-sectional study. Progress in Neuro-Psychopharmacology & Biological Psychiatry 37(1): 182-187, 2012

Subjective experience and striatal dopamine D(2) receptor occupancy in patients with schizophrenia stabilized by olanzapine or risperidone. American Journal of Psychiatry 157(6): 1019-1020, 2000

D2 dopamine receptor occupancy during treatment with flupentixol decanoate in comparison to risperidone, olanzapine, clozapine, haloperidol and haloperidol decanoate A 123I-IBZM SPECT study D2-receptor occupancy under flupentixol decanoate. Pharmacopsychiatry 36(5): 259-260, September, 2003

D2 receptor occupancy during risperidone and clozapine treatment in chronic schizophrenia Relationship to blood level, efficacy and EPS. Society for Neuroscience Abstracts 22(1-3): 265, 1996

A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: implications for dopamine D2 receptor occupancy during maintenance treatment in schizophrenia. Journal of Clinical Psychiatry 73(8): 1147-1152, 2012

Improving symptoms and side effects in older patients with schizophrenia with decreasing dopamine D2/3 receptor occupancy following risperidone and olanzapine dose reduction. Evidence-Based Mental Health 18(4): 117-117, 2016

Dose reduction of risperidone and olanzapine and estimated dopamine Dâ‚‚ receptor occupancy in stable patients with schizophrenia: findings from an open-label, randomized, controlled study. Journal of Clinical Psychiatry 75(11): 1209-1214, 2015

An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo, haloperidol, risperidone, or clozapine. Journal of Clinical Psychiatry 64(8): 898-906, 2003

The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophrenia Bulletin 25(2): 233-255, 1999

Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatric Services 52(11): 1510-1514, 2001

Differences in craving for cannabis between schizophrenia patients using risperidone, olanzapine or clozapine. Journal of Psychopharmacology 26(1): 189-195, 2012

Efficacy of risperidone, olanzapine and clozapine in the treatment of therapy resistant schizophrenia. Acta Neuropsychiatrica 12(4): 183-192, 2000