Atypical antipsychotics: revolutionary or incremental advance?

The discovery of chlorpromazine half a century ago and the subsequent emergence of other first generation antipsychotics, heralded a new advance in the treatment of schizophrenia. However, these new medications were not always effective. Even when they reduced the positive symptoms of schizophrenia, they were not as helpful in the relief of other symptom domains of schizophrenia, such as negative symptoms, impaired cognition and persistent aggressivity. Clozapine was the first of the new second generation of antipsychotics. It was introduced in the USA specifically for the indication of treatment-refractory schizophrenia. However, clozapine's side effect burden has led to a search for its replacement. This quest has pointed out the limitations of our treatments for refractory patients, but has made available a variety of second generation antipsychotics that have raised our expectations. Furthermore, the atypical antipsychotics hold promise for the treatment of the nonpsychotic patient with mood dysregulation or acute agitation.