Abstract
Introduction: Amisulpride appears to be an effective atypical agent for treating schizophrenia in a dose-dependent manner.
Methods: 29 patients suffering from schizophrenia or schizoaffective disorder were treated with a broad dose range of amisulpride (50–1 200 mg/day, mean: 455.2±278.8 mg/day). After 2 weeks, brain single photon emission tomography (SPET) scans were performed two hours after intravenous injection of 185 MBq [123 I]IBZM. Clinical evaluations and ratings of extrapyramidal symptoms were performed at baseline and after steady state treatment of two weeks with amisulpride.
Results: In patients treated with amisulpride, specific binding of [123 I]IBZM to D2 receptors was significantly decreased (p<0.001) compared to healthy controls. D2 receptor blockade correlated well with administered doses and plasma concentrations of amisulpride. Extrapyramidal side effects, which had to be treated with biperiden, were observed in 31% of the patients. Clinical response was very good, without correlation between the response and striatal D2 occupancy.
Discussion: Within the first two weeks of treatment with the atypical antipsychotic amisulpride a significant occupancy of striatal postsynaptic dopamine D2 receptors was achieved. At the same time amisulpride shows an excellent tolerability with good efficacy.
References
1
Andreasen N, Carpenter WT, Kane JM, Lasser RA, Marder SR, Weinberger DR.
Remission in schizophrenia: Proposed Criteria and Rationale Consensus.
Am J Psychiat.
2005;
162
441-449
2
Bressan RA, Erlandsson K, Jones HM, Mulligan R, Flanagan RJ, Ell PJ. et al .
Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? An in vivo quantitative [123 I]epidepride SPET study of amisulpride-treated patients.
Am J Psychiat.
2003;
160
1413-1420
3
Erlandsson K, Bressan RA, Mulligan RS, Ell PJ, Cunningham VJ, Pilowsky LS.
Analysis of D2 dopamine receptor occupancy with quantitative SPET using the high-affinity ligand [123 I]epidepride: resolving conflicting findings.
Neuroimage.
2003;
19
1205-1214
4
Fougere C la, Meisenzahl E, Schmitt G, Stauss J, Frodl T, Tatsch K. et al .
D2 receptor occupancy during high- and low-dose therapy with the atypical antipsychotic amisulpride: a 123I-iodobenzamide SPECT study.
J Nucl Med.
2005;
46
1028-1033
5
Kapur S, Zipursky R, Jones C, Remington G, Houle S.
Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia.
Am J Psychiat.
2000;
157
((4))
514-520
6
Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P.
A positron emission study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy.
Arch Gen Psychiatry.
2000;
57
553-559
7
Leucht S, Pitschel-Walz G, Engel RR, Kissling W.
Amisulpride, an unusual “atypical” antipsychotic: a meta-analysis of randomized controlled trials.
Am J Psychiat.
2002;
159
180-190
8
Leucht S, Wahlbeck K, Hamann J, Kissling W.
New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis.
Lancet.
2003;
361
1581-1589
9
Martinot JL, Paillere-Martinot ML, Poirier MF, Dao-Castellana MH, Loc’h C, Maziere B.
In vivo characteristics of dopamine D2 receptor occupancy by amisulpride in schizophrenia.
Psychopharmacology.
1996;
124
154-158
10
Möller HJ.
State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics.
Wld J Biol Psychiat.
2000;
1
204-214
11
Möller HJ.
Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality.
Prog Neuro-Psychopharmacol Biol Psychiat.
2003;
27
1101-1111
12
Möller HJ.
Antipsychotic and antidepressive effects of second generation antipsychotics: two different pharmacological mechanisms?.
Eur Arch Psychiat Clin Neurosci.
2005;
255
190-201
13
Müller MJ, Wetzel H, Eich FX, Rein W, Puech A. Benkert O, Amisulpride Study Group .
Dose-related effects of amisulpride on five dimensions of psychopathology in patients with acute exacerbation of schizophrenia.
J Clin Psychopharmacol.
2002;
22
554-560
14
Nordstrom AL, Farde L, Wiesel FA, Forslund K, Pauli S, Halldin C. et al .
Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients.
Biol Psychiat.
1993;
33
227-235
15
Olsson H, Farde L.
Potentials and pitfalls using high affinity radioligands in PET and SPET determinations on regional drug induced D2 receptor occupancy – a simulation study based on experimental data.
Neuroimage.
2001;
14
936-945
16
Pilowsky LS, Costa DC, Ell PJ, Murray RM, Verhoeff NP, Kerwin RW.
Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study.
Psycholog Med.
1993;
23
791-797
17
Scatton B, Claustre Y, Cudennec A, Oblin A, Perrault G, Sanger DJ. et al .
Amisulpride: from animal pharmacology to therapeutic action.
Int Clin Psychopharmacol.
1997;
12
29-36
18
Seeman P.
Atypical antipsychotics: mechanism of action.
Can J Psychiat.
2002;
47
27-38
19
Stone JM, Bressan RA, Erlandsson K, Ell PJ, Pilowsky LS.
Non-uniform blockade of intrastriatal D2/D3 receptors by risperidone and amisulpride.
Psychopharmacology.
2005;
180
664-669
20
Vernaleken I, Siessmeier T, Buchholz HG, Hartter S, Hiemke C, Stoeter P. et al .
High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia.
Int J Neuropsychopharmacol.
2004;
7
421-430
21
Wetzel H, Gründer G, Hillert A, Philipp M, Gattaz WF, Sauer H. et al .
Amisulpride versus flupentixol in schizophrenia with predominantly positive symptomatology – a double-blind controlled study comparing a selective D2-like antagonist to a mixed D1-/D2-like antagonist. The Amisulpride Study Group.
Psychopharmacology.
1998;
137
223-232
22
Xiberas X, Martinot JL, Mallet L, Artiges E, Canal M, Loc'h C. et al .
In vivo extrastriatal and striatal D2 dopamine receptor blockade by amisulpride in schizophrenia.
J Clin Psychopharmacol.
2001;
21
207-214
23
Xiberas X, Martinot JL, Mallet L, Artiges E, Loc'H C, Maziere B. et al .
Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia.
Br J Psychiat.
2001;
179
503-508
24
Leuner K, Müller WE.
Dopamine in the prefrontal cortex and its different modulation by conventional and atypical antipsychotics.
Pharmacopsychiatry.
2007;
40
17-33
25
Pietro NC, Seamans JK.
Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanisms of action.
Pharmacopsychiatry.
2007;
40
27-33
26
Assion HJ, Reinbold H, Lemanski S, Basilowski M, Juckel G.
Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial.
Pharmacopsychiatry.
2008;
41
24-28
27
Meisenzahl EM, Scheuerecker J, Schmitt GJS, Möller HJ.
Dopamine, prefrontal cortex and working memory in schizophrenia.
Pharmacopsychiatry.
2007;
40
((Suppl))
62-72
28
Sokoloff P, Diaz J, Foll B Le, Guillin O, Leriche L, Bezard E, Gross C.
The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders.
CNS Neurolog Disord – Drug Targets.
2006;
5
25-43
Correspondence
E. M. MeisenzahlMD
Department of Psychiatry
Ludwig-Maximilians-University of Munich
Nussbaumstraße 7
80336 Munich
Germany
Phone: +49/89/5160 24 23
Fax: +49/89/5160 45 55
Email: Eva.Meisenzahl@med.uni-muenchen.de