Low-dose loxapine in the treatment of schizophrenia: is it more effective and more "atypical" than standard-dose loxapine?

Loxapine is chemically related to clozapine and shares with it and other atypical antipsychotic drugs relatively greater affinity for serotonin (5-HT)2A than for dopamine D2 receptors. However, as is the case for risperidone, the occupancy of 5-HT2A and D2 receptors can range from partial to full, depending upon the dose. It was, therefore, of interest to determine whether loxapine at low doses (< 50 mg/day) might be at least as or more effective and more tolerable than usual clinical doses (> or = 60 mg/day). We retrospectively examined data from 75 patients treated with loxapine and found psychopathology data from 10 and 12 patients treated with low-dose or standard-dose loxapine, respectively. No data were available on the other 53 patients, 28 of whom were initially treated with low-dose and 25 with standard-dose loxapine. For those treated for at least 6 weeks, there was evidence of equivalent efficacy for both low- and standard-dose loxapine with regard to improvement in Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale scores. There were 6 patients with a history of neuroleptic resistance among the 22 completers. Four of the low-dose group (40%) and 8 of the standard-dose group (67%) had at least a 20% decrease in BPRS total scores. Further study of the dose-response curve for loxapine and its usefulness in treating neuroleptic-resistant schizophrenia is indicated.