With the arrival of atypical antipsychotics, it was widely assumed that the new generation of drugs was superior to the old generation. Not only did the atypicals have a more benign side effect profile than the typicals, atypicals were assumed to be more effective in treating both the positive and negative symptoms of schizophrenia. (Positive symptoms refer to the active psychotic symptoms, and negative symptoms to the social withdrawal, reduced energy, and emotional flattening associated with schizophrenia.)

The CATIE study is a landmark study published in 2005 that challenged assumptions about the superiority of atypicals over typicals. This study showed no difference in efficacy between three atypical antipsychotic medications (quetiapine, risperidone, ziprasidone) and perphenizine (Trilafon), a mid-potency typical antipsychotic. While olanzapine (Zyprexa) proved superior to perphenizine, it also had the highest rates of metabolic side effects. Of note, this study was funded by the National Institute of Mental Health, a government institution. The study received no funding from pharmaceutical companies.