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DOI : 10.1017/S1461145704004134
Ann M. Mortimer
Department of Psychiatry, The University of Hull, East Riding Campus, Beverley Road, Willerby, Hull HU10 6NS, UK
Abstract
Clinician choice of an atypical antipsychotic may depend on a number of factors such as perceived
ecacy, tolerability and cost. It is also important that the choice of treatment takes into consideration
the previous response to treatment, experience of side-eects and personal clinical characteristics. The
receptor-anity proles of the atypical antipsychotics dier ; with the exception of amisulpride, a selective
D2/D3 antagonist, all the atypical antipsychotics exhibit a greater anity for the serotonin-2A receptors
than dopamine receptors. However, there is no evidence that the variation in receptor anities is relevant
to ecacy. Indeed, the crucial factor may be fast dissociation from/low anity for the D2 receptor.
Tolerability also varies between the atypical antipsychotics and the side-eect prole may be related to
the receptor-anity prole of the individual drugs. Extrapyramidal side-eects are generally less of a
problem with most atypical drugs than with conventional drugs, but weight gain, loss of glycaemic
control, sedation and hyperprolactinaemia remain problematic in some patients. Amisulpride is eective
for the treatment of both positive and negative symptoms, and is well tolerated with regard to weight gain,
glucose tolerance and sedation. In two clinical trials, the AMIRIS and SOLIANOL studies, amisulpride dem-
onstrated clear advantages over some other atypical antipsychotics with respect to negative symptoms,
depressive symptoms and weight gain.
Received 27 July 2003 ; Reviewed 17 September 2003 ; Revised 25 October 2003 ; Accepted 29 October 2003
Responders 6 months
Maintenance >day 56
ziprasidone is any better than conventional antipsy- 70 77
60 72
chotics for relieving negative symptoms, and current 65
58
65
50
concerns exist regarding cardiac side-eects. 52
40
30
20
Amisulpride 10
0
Amisulpride is eective in treating both positive and PANSS* BPRS* CGI-2**
negative symptoms of schizophrenia, and is, in fact,
Figure 1. Ecacy of amisulpride vs. risperidone after 6
the most thoroughly evaluated atypical antipsychotic
months of treatment. Responders were dened as :
for the treatment of negative symptoms. At low doses (*) patients who had greater than 50 % improvement from
(f300 mg), amisulpride produces placebo-level EPS. baseline in their symptoms or (**) patients who were
The safety prole of amisulpride is favourable with considered much or very much improved on CGI-I score.
respect to weight gain, glucose tolerance and sedation, %, Amisulpride (n=121) ; &, risperidone (n=123).
and amisulpride does not compromise cognitive (Adapted from Sechter et al., 2002.)
functions in healthy volunteers, unlike conventional
treatment (Peretti et al., 1997). Disadvantages of
p = 0.033
amisulpride include anxiety, agitation, insomnia and
49% ns
hyperprolactinaemia. p 0.10
38%
35% 33%
31%
Direct comparative trials with amisulpride 23%
p = 0.015 40%
Increase 7%
(baseline to end-point)
33%
30% *p < 0.05
Completers
93%
80% 83%
20% 18%
70%
12%
10%
6%
0%
2 months 6 months
and negative symptoms of schizophrenia. Moreover, antipsychotics ? : a new hypothesis. American Journal of
amisulpride demonstrates clear advantages over some Psychiatry 158, 360369.
other atypical antipsychotics with respect to negative Loo H, Poirier-Littre MF, Theron M, Rein W, Fleurot O (1997).
symptoms, depressive symptoms and weight gain. Amisulpride versus placebo in the medium-term
treatment of the negative symptoms of schizophrenia.
British Journal of Psychiatry 170, 1822.
Martin S, Ljo H, Peuskens J, Thirumalai S, Giudicelli A,
Acknowledgements
Fleurot O, Rein W, SOLIANOL Study Group (2002).
Professor Mortimer has received unrestricted edu- A double-blind, randomised comparative trial of
cational and research grants from Sano-Synthelabo, amisulpride versus olanzapine in the treatment of
Novartis, Astra Zeneca, Eli Lilly and Janssen-Cilag. schizophrenia : short-term results at two months.
Current Medical Research and Opinion 18, 355362.
Munro J, O Sullivan D, Andrews C, Arana A, Mortimer A,
Kerwin R (1999). Active monitoring of 12,760 clozapine
Statement of Interest
recipients in the UK and Ireland. Beyond pharma-
Professor Mortimer received an honorarium from covigilance. British Journal of Psychiatry 175, 576580.
Sano-Synthelabo for presentation at the Symposium. National Institute for Clinical Excellence (NICE) (2002).
No honorarium was provided for the writing of this Guidance on the use of newer (atypical) antipsychotic
paper. drugs for the treatment of schizophrenia. Technology
Appraisal Guidance No. 43.
Paillere-Martinot ML, Lecrubier Y, Martinot JL, Aubin F
(1995). Improvement of some schizophrenic decit
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