Nefazodone in the adjunctive therapy of schizophrenia: An open-label exploratory study

Compared to conventional antipsychotic medications, atypical antipsychotic medications demonstrate greater central serotonin (5HT(2)) receptor antagon ism than dopamine type 2 (D-2) receptor antagonism Nefazodone, an antidepre ssant medication, exhibits 5HT(2) receptor antagonism; we therefore wondere d if its addition to stable regimens of antipsychotic medication would incr ease antipsychotic efficacy, independently of a primary effect on mood, thr ough the mechanism of augmented 5HT(2) receptor antagonism. In a pilot inve stigation, we administered nefazodone (400 mg/d) for 6 weeks as an open-lab el adjunct to antipsychotic medication in 10 patients with chronic schizoph renia. The patients were moderately depressed at baseline but did not meet criteria for major depressive episode. The Brief Psychiatric Rating Scale ( BPRS) and Montgomery-Asberg Depression Rating Scale scores showed statistic ally significant and clinically robust improvements with nefazodone treatme nt, which were maintained at follow-up evaluation 2 weeks after the end of nefazodone treatment. There were no adverse events. These results suggest t hat nefazodone may be a safe and effective adjunct to antipsychotic medicat ions in schizophrenia and that augmentation of 5HT(2) antagonism may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treat ing depressive symptoms in schizophrenia.