The publicly funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) did not support superiority hypotheses for second-generation antipsychotic drugs in schizophrenia. Instead, the study supported the view that first- and second-generation antipsychotics have similar therapeutic properties and diverse adverse effect profiles. This emphasizes the importance of designing pharmacotherapy for the individual in order to optimize the benefit-to-risk profile. First- and second-generation antipsychotic drugs are extensively similar in mechanism of action, efficacy for psychosis, and lack of efficacy for avolition and impaired cognition. However, adverse effect profiles vary between drugs. The authors review the clinical implications of these data, with an emphasis on individualizing pharmacotherapy in an effort to reduce risk. Rather than selecting drugs on the basis of unfounded expectations of superior efficacy, clinicians can focus on selecting drugs and optimizing dosages to minimize adverse effects without sacrificing efficacy. Tardive dyskinesia may be a good reason to avoid a high dosage of first-generation antipsychotics, although the evidence for differential risk is less compelling for a modest dosage of low-affinity first-generation antipsychotics. Similarly, the metabolic effects of some second-generation antipsychotics can be decisive in considering risks. In either case, the clinician should detect earliest signs and take action while dyskinetic or metabolic effects are most reversible.
Bottom line: the dichotomy between first- and second-generation antipsychotics was not supported by efficacy data (and now, is not supported effectiveness data). Only clozapine has documented superiority in treatment-resistant cases.