Psychiatric Centre Prague, Ústavní 91, 181 03 Praha 8Bohnice, Czech Republic
Xiberas et al (2001) measured D2 receptor occupancy in striatum, thalamus and temporal cortex in patients treated with haloperidol, risperidone, amisulpride, clozapine and olanzapine. On the basis of their findings, they conclude that in the striatum and in the thalamus atypical antipsychotics induce a significantly lower D2 binding index than haloperidol does. Their results are consistent with previous studies showing only small differences between striatal and temporal cortex blockade by traditional compounds and relatively selective D2 blockade in temporal cortex caused by atypical antipsychotics (Pilowsky et al, 1997; Bigliani et al, 2000).
Looking at the data from Xiberas et al (2001), we came to different conclusions. Using equipotent doses of antipsychotics (doses which lead to the same occupation of D2 receptors in the striatum), no differences in thalamo-striatal and temporostriatal indices between typical and atypical antipsychotics could be shown (Table 1). We suggest that atypical antipsychotics do not exert special temporal lobe or limbic selectivity. The selectivity depends more on the dose than on the type of antipsychotic (typical v. atypical). This is in agreement with Nyberg & Farde (2000) and Geddes et al (2000), who argue that non-equipotent doses can partly explain differences between classical and novel antipsychotics.
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REFERENCES
Bigliani, V., Mulligan, R. S., Acton, P. D., et al (2000) Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [1231]epidepride single photon emission tomography (SPET) study. Psychopharmacology, 150, 132-140.[CrossRef][Medline]
Geddes, J., Freemantle, N., Harrison, P., et al
(2000) Atypical antipsychotics in the treatment of
schizophrenia: systematic overview and meta-regression analysis.
BMJ, 321,
1371-1376.
Nyberg, S. & Farde, L. (2000) Non-equipotent doses partly explain differences among antipsychotics implications of PET studies. Psychopharmacology, 148, 22-23.[CrossRef][Medline]
Pilowsky, L. S., Mulligan, R. S., Acton, P. D., et al (1997) Limbic selectivity of clozapine. Lancet, 350, 490-491.[CrossRef][Medline]
Xiberas, X., Martinot, J. L., Mallet, L., et al
(2001) Extrastriatal and striatal D2 dopamine
receptor blockade with haloperidol or new antipsychotic drugs in patients with
schizophrenia. British Journal of Psychiatry,
179,
503-508.
INSERM U334 and Commissariat à l'Energie Atomique, Service Hospitalier Frédéric Joliot, 4 Place Gl. Leclerc, 91401 Orsay, France
Our team is funded by a donation from the INSERM. Also X.X. was partly funded by grants from the Fondation pour la Recherche Médicale and the Commissariat à l'Energie Atomique.
We thank Dr Kopeek et al for their interest in our paper
(Xiberas et al,
2001b). They conclude that atypical antipsychotics do not
exert special temporal or limbic selectivity, which depends instead on drug
dosages. First, we believe that generalisations drawn from data obtained from
five patients, each one treated with a different antipsychotic drug, are not
sound, because of intersubject variability. For instance, should Dr
Kope
ek et al have considered plasma drug concentrations and
patient H2 of our article, their conclusion would have been modified. In our
article, we drew conclusions from the statistical comparisons of
[76Br]-FLB457 measures obtained with positron emission tomography
(PET) in subgroups of patients, receiving the usual dosage recommended by the
pharmaceutical firms for each antipsychotic drug, for treating psychotic
episodes.
Second, we have already reported the importance of dosage when interpreting
neuroimaging measures of regional D2 dopamine receptor blockade by
antipsychotic drugs (Xiberas et
al, 2001a). Inspection of the table that
Kopeek et al draw from our article suggests that for a
striatal D2 receptor binding index approaching 65-70%, the atypical
antipsychotics induce extrastriatal/striatal indices comparable with that
induced by the lowest oral dosage of haloperidol reported. This is consistent
with our previous publication (Xiberas
et al, 2001a) where we specifically highlighted
the dose-dependence of extrastriatal/striatal D2 blockade, from a
study in a larger sample of patients treated with an atypical antipsychotic.
We demonstrated that plasma concentrations were more accurately related than
daily oral doses to the different regional binding profiles determined with
PET. Clearly, two binding profiles could be distinguished depending on the
plasma concentration of the drug: low striatal binding associated with marked
extrastriatal binding for low plasma concentrations, or marked binding in both
striatal and extrastriatal regions for higher plasma concentrations. This may
be applicable to both atypical and typical compounds, if very low doses of
typical neuroleptics (i.e. below the recommended therapeutic dose range) are
considered, but this is a speculation. Therefore, having previously
highlighted the effect of dosage (Xiberas
et al, 2001a), we chose to highlight in our
second article (Xiberas et al,
2001b) that, at plasma concentrations obtained in actual
clinical practice, and compared with haloperidol, various atypical
antipsychotic drugs have a regional binding profile that is higher in
mesocorticolimbic regions than in striatum.
REFERENCES
Xiberas, X., Martinot, J. L., Mallet L., et al (2001a) In vivo extrastriatal and striatal D2 dopamine receptor blockade by amisulpride in schizophrenia. Journal of Clinical Psychopharmacology, 21, 207-214.[CrossRef][Medline]
Xiberas, X., Martinot, J. L., Mallet L., et al
(2001b) Extrastriatal and striatal D2
dopamine receptor blockade with haloperidol or new antipsychotic drugs in
patients with schizophrenia. British Journal of
Psychiatry, 179,
503-508.
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