Unmet needs in the treatment of schizophrenia: The role of aripiprazole [Bisogni irrisolti nel trattamento della schizofrenia: Ruolo di aripiprazolo]

Objective: Since the 1950s, psychiatrists have prescribed antipsychotic drugs to alleviate symptoms of schizophrenia. The first generation of antipsychotic medications (FGA) was considered to be a major advance; however, the cost of a number of untoward adverse events such as EPS and the lack of efficacy on cognitive dysfunction and negative symptoms led to the development of second-generation compounds (SGA). Despite expectations, even the latter proved to be unable to respond to substantial unmet needs in schizophrenia treatment, mainly due to their unsatisfactory tolerabilily profile. Aripiprazole, the most recently introduced antipsychotic, is considered to be a "third generation" compound, being a partial agonist at dopamine D2 and at serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors, with marginal effect on histaminic and muscarinic receptors. This mechanism predicts a wide range of effects, addressing the positive, negative and cognitive symptoms of schizophrenia, along with fair tolerability. This review focuses on a multidisciplinary discussion of results obtained with arip iprazole in clinical trials, with the aim to contextualize current issues in schizo-phrenia treatment, on the basis of available data and experience. Methods: A systematic search of scientific literature was performed to identify the main clinical trials of aripiprazole that were published (Table I). A multidisciplinary panel of 6 leading psychiatrists and endocrinologists was appointed to carry out a comprehensive review and analysis of results, based on personal expertise. All contributions were jointly discussed, leading to the present manuscript. Results: The following topics were considered: efficacy in the treatment of schizophrenia, extrapyramidal adverse events (Table II) and neuroleptic malignant syndrome, metabolic disturbances (diabetes, dyslipidaemia, overweight and obesity, and metabolic syndrome - Table III), cardiovascular adverse events, hyperprolactinaemia and sexual dysfunction (Table V), other adverse events (Tables VI, VII), functioning/quality of life/cognition. Aripiprazole confirmed its efficacy and safety profile, showing reduced incidence of several adverse events with negligible metabolic disturbances, including diabetes, obesity, dyslipidaemia, and metabolic syndrome. Insomnia and akathisia may be observed at the beginning of treatment with arip-iprazole and should be considered as manageable, dose-dependent adverse events. Conclusions: This comprehensive review confirms that SGA differ from FGA and may differ from each other, mainly as to their tolerability profile (Table IV). Adverse events impact on patient compliance, thus leading to exacerbations of psy-chotic symptoms and worsening of Quality-of-Life. The choice of medication should take into account the available tolerability and safety data.