Am J Psychiatry 156:869-875, June 1999
© 1999 American Psychiatric Association
Suggested Minimal Effective Dose of Risperidone Based on PET-Measured D2 and 5-HT2A Receptor Occupancy in Schizophrenic Patients
Svante Nyberg, M.D., Ph.D.,
Bo Eriksson, B.Sc.,
Gabriella Oxenstierna, M.D.,
Christer Halldin, Ph.D., and
Lars Farde, M.D., Ph.D.
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, risperidone, 4 mg/day, should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients.
This article has been cited by other articles:
|
|
|
|
 
P. Vazquez-Borsetti, R. Cortes, and F. Artigas
Pyramidal Neurons in Rat Prefrontal Cortex Projecting to Ventral Tegmental Area and Dorsal Raphe Nucleus Express 5-HT2A Receptors
Cereb Cortex,
July 1, 2009;
19(7):
1678 - 1686.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Catafau, M. Penengo, G. Nucci, S. Bullich, I. Corripio, E. Parellada, C. Garcia-Ribera, R. Gomeni, E. Merlo-Pich, and Barcelona Clinical Imaging in Psychiatry Group
Pharmacokinetics and time-course of D2 receptor occupancy induced by atypical antipsychotics in stabilized schizophrenic patients
J Psychopharmacol,
November 1, 2008;
22(8):
882 - 894.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. Ezewuzie and D. Taylor
Establishing a dose-response relationship for oral risperidone in relapsed schizophrenia
J Psychopharmacol,
January 1, 2006;
20(1):
86 - 90.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. R. Pinninti and R. Mago
Use of Long-Acting Risperidone
Psychiatr Serv,
January 1, 2005;
56(1):
105 - 105.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Santana, A. Bortolozzi, J. Serrats, G. Mengod, and F. Artigas
Expression of Serotonin1A and Serotonin2A Receptors in Pyramidal and GABAergic Neurons of the Rat Prefrontal Cortex
Cereb Cortex,
October 1, 2004;
14(10):
1100 - 1109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Moresco, R. Cavallaro, C. Messa, D. Bravi, C. Gobbo, L. Galli, G. Lucignani, C. Colombo, G. Rizzo, I. Velona, et al.
Cerebral D2 and 5-HT2 Receptor occupancy in Schizophrenic Patients Treated with Olanzapine Or Clozapine
J Psychopharmacol,
September 1, 2004;
18(3):
355 - 365.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. Grunder, A. Carlsson, and D. F. Wong
Mechanism of New Antipsychotic Medications: Occupancy Is Not Just Antagonism
Arch Gen Psychiatry,
October 1, 2003;
60(10):
974 - 977.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. de HAAN and T. van AMELSVOORT
Comparable Dopamine 2 Receptor Occupancy
Am J Psychiatry,
December 1, 2002;
159(12):
2118 - 2118.
[Full Text]
|
|
|
|
|
|
|
G. J. E. Schmitt, E. M. Meisenzahl, S. Dresel, K. Tatsch, B. Rossmuller, T. Frodl, U. W. Preuss, K. Hahn, and H.-j. Moller
Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine
J Psychopharmacol,
May 1, 2002;
16(3):
200 - 206.
[Abstract]
[PDF]
|
|
|
|
|
|
|
X. XIBERAS, J. L. MARTINOT, L. MALLET, E. ARTIGES, C. LOC'H, B. MAZIERE, and M. L. PAILLERE-MARTINOT
Extrastriatal and striatal D2 dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia
The British Journal of Psychiatry,
December 1, 2001;
179(6):
503 - 508.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Metz, M. D. Cooper, T. F. Brown, L. H. Kinnunen, and D. J. Cooper
Neuroimaging in Drug Discovery and Development: Paradigms for Accelerating New Drug Availability
Journal of Pharmacy Practice,
October 1, 2001;
14(5):
407 - 415.
[Abstract]
[PDF]
|
|
|
|
|
|
|
N. P. L. G. Verhoeff and S. Kapur
The Role of Neuroimaging in Development of and Treatment With Antipsychotics
Journal of Pharmacy Practice,
August 1, 2001;
14(4):
332 - 340.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. J. Lang, L. C. Kopala, R. A. Vandorpe, Q. Rui, G. N. Smith, V. M. Goghari, and W. G. Honer
An MRI Study of Basal Ganglia Volumes in First-Episode Schizophrenia Patients Treated With Risperidone
Am J Psychiatry,
April 1, 2001;
158(4):
625 - 631.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. Windhaber, S. Urbanits, W. Grisold, M. F. Mazurek, and P. I. Rosebush
Neurologic side effects in neuroleptic-naive patients treated with haloperidol or risperidone
Neurology,
April 11, 2000;
54(7):
1542 - 1546.
[Full Text]
[PDF]
|
|
|
Get information about faster international access.
Privacy Policy
Copyright © 1999
American Psychiatric Association.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
