Antipsychotics amisulpride

The atypical antipsychotics are divided into two major pharamacological groups, namely the multiple receptor antagonists, such as clozapine, olanzapine and quetiapine, and the more selective 5-HT2/D2 antagonists as exemplified by risperidone, sertindole, ziprasidone and zotepine. The benzamide antipsychotic amisulpride is the most selective antagonist for the D2/D3 receptors which presumably gives it the mesocortical selectivity of action with a minimal effect on the dopamine receptors in the basal ganglia. 

Unlike other atypical antipsychotics, amisulpride does not have potent actions at serotonin receptors... 

Antipsychotics Atypical antipsychotics Amisulpride, Aripiprarole, Clo pine, Olanzapine, Quetiapine, Risperidone, Sertindole, Ziprasidone, Zotepine... 

A search of Medline, EMBASE and PsycLIT was conducted in August 2000, using the following terms Amisulpride, clozapine, olanzapine, risperidone, sertindole, zotepine, ziprasidone, economics, healthcare, costs. All manufacturers of atypical antipsychotic drugs were contacted in April 2000 and asked to supply primary reference data on their product, and all companies had complied with this request by August 2000. A further manual search was conducted of files and journals kept in the National Centre for Information on Psychotropics at the Maudsley Hospital. Reference sections from all retrieved papers were scrutinized for further relevant references. 

Table 41.5 summarizes existing studies on the use of atypical antipsychotics in EOS. As the table demonstrates, most studies have been carried out with clozapine, only three with olanzapine and two with risperidone each, and only one study has assessed use of amisulpride and one quetiapine. 

Antipsychotic drugs with strong sedative clinical effects (e.g. chlorpromazine. clozapine, olanzapine) produce subjective and objective sedation and impair most areas of performance in healthy volunteers, usually at doses far below those typically used in patients. Antipsychotic drugs with little sedative clinical action (e.g. pimozide, sulpiride, amisulpride) produce few subjective and objective effects in healthy... 

Ramaekers, J.G., Louwerens, J.W., Munjewerff, N.D., et al. Psychomotor, cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic. J. Clin. Psychopharmacol. 19, 209-221, 1999. 

First choice - atypical antipsychotic (e.g. risperidone, olanzepine, quetiapine, amisulpride, clozapine)... 

Fig. 13.1 Chemical structure of clozapine, some of its structural analogues, typical (chlorpromazine, haloperidol) and atypical antipsychotics (risperidone, ziprasidone, sertindole and amisulpride) unrelated to clozapine.

The example of amisulpride (launched by Sanofi-Synthelabo in 1986) also supports the primary importance of dopamine D2 (as well as D3) but not 5-HT2A receptors in atypical antipsychotic action. This benzamide derivative displays high affinity only to D2 and D3 receptors (with some selectivity toward D3) [42], and in low doses (i.e., 50-100 mg day-1) it acts preferentially on negative [43] symptoms and at higher doses (400-800 mg day-1) on depressive symptoms [44] and cognitive impairment [45]. 

First-generation (typical) antipsychotics include amisulpride, chlorpromazine, fluphenazine, haloperidol, promethazine, promazine, trifluoperazine... 

Leucht S, Pitschel-Walz G, Engel RR, Kissling W. Amisulpride, an unusual atypical antipsychotic a metaanalysis of randomized controlled trials. Am J Psychiatry 2002 159(2) 180-90. 

Puech A, Fleurot O, Rein W. Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia a dose-ranging study vs. haloperidol. The Amisulpride Study Group. Acta Psychiatr Scand 1998 98(l) 65-72. 

Amisulpride is an atypical antipsychotic drug, a benza-mide derivative, which may have a low propensity to cause extrapyramidal symptoms (SEDA-22, 55). 

Lecrubier Y, Azorin M, Bottai T, Dalery J, Garreau G, Lemperiere T, Lisoprawski A, Petitjean F, Vanelle JM. Consensus on the practical use of amisulpride, an atypical antipsychotic, in the treatment of schizophrenia. Neuropsychobiology 2001 44(l) 41-6. 

Leucht S. Amisulpride - a selective dopamine antagonist and atypical antipsychotic results of a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol 2004 7 Suppl 1 S15-S20. 

ADENOSINE ANTIPSYCHOTICS Risk of ventricular arrhythmias, particularly torsades de pointes, with phenothiazines and pimozide. There is also a theoretical risk of Q-T prolongation with the atypical antipsychotics All of these drugs prolong the Q-T interval Avoid co-administration of phenothiazines, amisulpride, pimozide or sertindole with adenosine. Monitor the ECG closely when adenosine is co-administered with atypical antipsychotics... 

FLECAINIDE ANTIPSYCHOTICS -PHENOTHIAZINES, AMISULPRIDE, PIMOZIDE, SERTINDOLE Risk of arrhythmias Additive effect. Also, haloperidol and thioridazine inhibit CYP2D6-mediated metabolism of flecainide Avoid co-administration... 

Although risk of diabetes and dyslipidemia with amisulpride has not been systematically studied, monitoring as for all ofher atypical antipsychotics Is suggested... 

Atypical antipsychotics may increase the risk for diabetes and dyslipidemia, although the specific risks associated with amisulpride are unknown... 

Amisulpride may accumulate in patients with renal insufficiency, requiring lower dosing or switching to another antipsychotic to avoid QTc prolongation in these patients... 

Compared to other atypical antipsychotics with potent serotonin 2A antagonism, amisulpride may have more extrapyramidal symptoms and prolactin elevation, but may still be classified as an atypical antipsychotic, particularly at low doses... 

Consider trying one of the first-line atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, amisulpride)... 

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