Beyond control of acute exacerbation: enhancing affective and cognitive outcomes

From the perspective of efficacy, the main advantages of the group of new antipsychotic drugs, including ziprasidone, clozapine, quetiapine, olanzapine, and risperidone, are their ability to improve cognitive function. Other advantages are more selective, eg, clozapine in treatment-resistant schizophrenia, while the advantages for positive and negative symptoms in neuroleptic responsive patients are modest and sometimes difficult to demonstrate. The advantage for cognitive function is important because of abundant evidence that cognitive function is a key predictor of work and social function acquisition. The drug-induced cognitive improvement can synergize with typical rehabilitation programs and more experimental cognitive retraining programs to optimize these areas of improvement. Improved cognition also has implications for better compliance and decreased caretaker burden. It is also important to consider the efficacy of antipsychotics to improve mood and negative symptoms and to provide a biological framework for their ability to achieve these advantages over typical neuroleptic drugs. This article will provide new data on efficacy of this class of drugs relative to each other and to typical neuroleptics. Current theories linking efficacy in cognition to unique effects on cortical dopaminergic and cholinergic function and improved patterns of connectivity in the brain during cognitive task performance will be discussed. Finally, pharmacologic strategies to augment affect and cognitive improvements due to the new antipsychotic drug therapies will be discussed.