Comparative effectiveness of antipsychotic drugs in schizophrenia

Chlorpromazine, which was discovered in 1952, has an exhaustively characterized efficacy/safety profile comprising serious limitations: effectiveness in the field failing to match efficacy in trials, residual symptoms in 50% of patients, a 20% relapse rate in compliant patients, and worrisome extrapyramidal side effects, including tardive dyskinesia in 5% per year. Second-generation "atypical" antipsychotics bypass these effects by having less affinity for the dopamine D(2) receptor and affinities for other neuroreceptors. Clozapine, the lead atypical antipsychotic, was followed in the mid 1990s by risperidone, olanzapine, and quetiapine, which now account for over half of new antipsychotic prescriptions in North America, The debate over their relative efficacy involves the potential well-being of millions of schizophrenics and billions of dollars. Atypical antipsychotics are considerably more expensive; evidence for their superiority is highly variable and often inadequate, largely confined to short-term regulatory studies. Their effects on long-term outcome (particularly negative symptoms), relapse prevention, social and vocational functioning, suicide prevention and quality of life, and family and caregiver burden are largely unknown. The National institute of Mental Health's Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project is a combined efficacy-effectiveness trial that aims to answer these questions in a broad range of patients with schizophrenia and Alzheimer's disease.