Comparative Efficacy and Safety of First - and Second-Generation Antipsychotics in the Treatment of Schizophrenia: Facts and Fiction

Abstract

The introduction of chlorpromazine into clinical practice a half-century ago revolutionized the pharmacological treatment of schizophrenia (Nasrallah and Tandon, 2009). Fifty typical or first-generation antipsychotics (FGAs) have since become available around the world (Table 1). These agents are extremely effective in reducing the positive symptoms of schizophrenia (delusions, hallucinations, disorganized thinking, and paranoia) and allowed deinstitutionalization of persons with schizophrenia. These agents are found to be minimally effective, however, against negative and cognitive symptoms that contribute to much of the disability associated with schizophrenic illness. Additionally, they do not substantially diminish the suicidality and social dysfunction associated with the illness. Furthermore, these medications cause a range of adverse effects including acute extrapyramidal symptoms and tardive dyskinesia. To a considerable extent because of their poor tolerability, patients often do not take these medications as prescribed and this, in turn, leads to psychotic relapses and poor outcome.