Amisulpride: efficacy in the management of chronic patients with predominant negative symptoms of schizophrenia

Abstract

Amisulpride is a dopamine D2/D3-selective antipsychotic drug with potent antipsychotic efficacy in acute exacerbations of schizophrenia. It also possesses substantial efficacy in chronic schizophrenic patients with enduring predominant negative symptoms. This unique property has been demonstrated in a series of short (6 weeks) and medium-/long-term (6-12 months) double-blind placebo-controlled studies. The patients in these studies were carefully selected and assessed to avoid confounding results with non-specific changes in other symptom domains. The results not only show effects on negative symptoms at the optimal dose of 100 mg/day, but also significant improvement in global functioning. The effect observed in short-term studies was maintained over longer treatment periods (6-12 months). Amisulpride was well tolerated with a safety profile similar to placebo. These results open a new therapeutic approach for negative symptoms, one of the most disabling aspects of schizophrenia.

Why Olanzapine Beats Risperidone, Risperidone Beats Quetiapine, and Quetiapine Beats Olanzapine: An Exploratory Analysis of Head-to-Head Comparison Studies of Second-Generation Antipsychotics

“…For the first time antipsychotic drugs with clearly defined dose ranges were made available, while the optimum dose, even of the standard conventional antipsychotic haloperidol, is still in doubt. Industry-organized trials also markedly improved our knowledge about general clinical questions such as medication switching strategies (72), the treatment of patients with refractory disorders (34), and the overall effectiveness of new and conventional antipsychotics for treatment of negative symptoms (73). However, if all studies by drug companies report positive outcomes, the findings may lose credibility.…”

“…The use of structured clinical interviews may help identify the proper study population. For example, a characterization of patients with predominantly negative symptoms has been proposed (73). Defining a valid study population is essential in studies of patients with treatment-resistant illness that focus on the efficacy of antipsychotics, and other aspects of previous treatment discontinuation, such as medication intolerance, should not be used as alternative inclusion criteria.…”

How Does the Benzamide Antipsychotic Amisulpride get into the Brain?—An In Vitro Approach Comparing Amisulpride with Clozapine

“…Furthermore, AMS preferentially antagonizes D 2 /D 3 receptors in the limbic system in comparison to striatal areas . The predominant action of AMS in extrastriatal areas became especially obvious at low concentrations (Möller, 2001;Xiberas et al, 2001). Although it was speculated that at these low dosages mainly D 3 autoreceptors in cortical areas were antagonized Pani and Gessa, 2002), the reason for the limbic selectivity of AMS remains unclear.…”

Correlations between negative symptoms and peripheral G protein levels in mononuclear leukocytes of deficit and nondeficit schizophrenics

“…Indeed, although post-mortem studies have failed to produce a consistent finding of abnormal D-1 receptor density in schizophrenic brains, recent PET investigations have found that, in the prefrontal cortex of schizophrenic subjects, the number of D-1 receptors was significantly reduced and correlated to both negative symptoms and cognitive impairments (Okubo et al 1997;Sedvall 1995). Analogously, blockade of 5-HT 2A receptors by novel antipsychotics has been proposed as a mechanism mediating their ability to improve negative symptoms, thus suggesting a possible role for 5-HT 2A hyperactivity in the genesis of negative symptomatology (Moller 1999(Moller , 2001; Abi-Dargham and Krystal 2000). Thus, keeping in mind the possible interference of antipsychotic drug treatment on MNL G protein expression, our results seem to support the idea that a prevalent dysfunction of D-1 receptors could underlie negative symptoms in DS, whereas a prevalent dysfunction of 5-HT 2A receptors could be involved in the pathophysiology of negative symptoms of NDS.…”