Double-blind Comparison of Alprazolam, Diazepam, and Placebo for the Treatment of Negative Schizophrenic Symptoms

Fifty-five schizophrenic outpatients with negative symptoms were treated for up to six weeks by the addition of alprazolam (mean dose, 4.2 mg/d), diazepam (mean dose, 40.4 mg/d), or placebo to their ongoing neuroleptic treatment. A repeated-measures analysis of variance with baseline measurements entered as covariates indicated the presence of a significant time × drug interaction effect for the weekly Brief Psychiatric Rating Scale (BPRS) withdrawal/retardation subfactor scores. During the initial weeks of the study, the alprazolam-treated group had lower scores, while the diazepam-treated group had higher scores than the placebo-treated group. However, an end point analysis performed on the final BPRS withdrawal/retardation subfactor scores showed no significant differences among the three groups, nor were beneficial effects observed on any of the BPRS subfactor scores that assess positive symptoms. Plasma alprazolam levels were maintained throughout the study and ranged from 20 to 100 ng/mL. These results suggest that alprazolam had no sustained significant effect on negative schizophrenic symptoms.