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In a double-blind study lasting for 4 weeks, the authors compared the effectiveness of amoxapine, an antidepressant with potential antipsychotic properties, with a combination of amitriptyline plus perphenazine in the treatment of 38 patients who had the diagnosis of major depression with psychotic features (psychotic or delusional depression). Patients in each group showed similar improvement in depression and psychosis. There was a tendency for the patients treated with amitriptyline plus perphenazine to have higher global response rates. However, the patients given amoxapine had significantly fewer extrapyramidal side effects.

Psychotic patients who also have endogenous depressive symptoms often require treatment with several drugs (usually a neuroleptic-antidepressant combination) or electroconvulsive therapy. Loxapine is a neuroleptic of the dibenzoxazepine class; it is metabolized in vivo to desmethylloxapine (amoxapine) and 8-hydroxyamoxapine, two compounds with antidepressant activity. We traced the serum levels of total amoxapine (amoxapine plus 8-hydroxyamoxapine) in two treatment-resistant patients with psychotic-depression syndromes. One patient was treated with loxapine alone and the other with a loxapine-amoxapine combination. We also determined the total loxapine and amoxapine serum levels of ten patients treated at various dosages of loxapine alone. The results demonstrate that many patients treated with loxapine attain substantial serum levels of total amoxapine, some in concentrations thought to be therapeutic for nonpsychotic endogenous depression. We recommend further studies to determine the efficacy of loxapine in the management of treatment-resistant patients with psychotic-depression syndromes.