Risperidone, quetiapine, and fluphenazine in the treatment of patients with therapy-refractory schizophrenia.

This 12-week, double-blind study evaluated the effectiveness of risperidone (4 mg/day), quetiapine (400 mg/day), or fluphenazine (12.5 mg/day) in a stringently defined treatment-resistant population of people with schizophrenia. No differences were noted in total Brief Psychiatric Rating Scale (BPRS) or Clinical Global Impression scores among the drug groups (n = 38). More subjects tended to complete the study on risperidone (69%) or quetiapine (58%) than those treated with fluphenazine (31%; P value not significant). Eighty-nine percent of those who discontinued on fluphenazine (8 of 9) were due to lack of efficacy. Discontinuation due to adverse effects was low, with only 2 subjects (both on quetiapine) stopping due to side effects. Three of 13 risperidone-treated subjects (23%) and 3 of 12 quetiapine-treated subjects (25%) met response criteria (decrease of 20% of total BPRS score), whereas 2 of 13 subjects (15%) responded to fluphenazine. Side effect occurrence was similar among drug groups and EPS ratings on the Simpson Angus Scale improved in all drug groups (quetiapine, 1.64; risperidone, 1.30; fluphenazine, 0.69; P value not significant). Despite the newer class of second-generation antipsychotic medications, this treatment-resistant population remains difficult to treat. Many people have only minimal to modest improvements with antipsychotic treatment and most continue to have residual psychotic symptoms. Treatment with first- and second-generation antipsychotics may demonstrate similar efficacy; however, patients treated with second-generation antipsychotics may be more likely to adhere to treatment.