Efficacy of treatment with trazodone in combination with pindolol or fluoxetine in major depression

Abstract

Fluoxetine, a selective serotonin (5-HT) reuptake inhibitor (SSRI), and trazodone, a heterocyclic antidepressant, are effective in the treatment of major depression and treatment resistant depression (TRD). Chronic treatment with both drugs causes increases in extracellular 5-HT through 5-HT reuptake inhibition and desensitization of inhibitory 5-HT 1A autoreceptors. It has been shown that pindolol, a serotonin (5-HT) 1A-receptor antagonist, may shorten the latency of onset of SSRIs in depression. The aim of the present study was to examine whether pindolol may increase the efficacy of a subtherapeutical dosage of trazodone in the treatment of major depression and TRD, defined according to the Thase and Rush criteria (1995). Thirty-three major depressed inpatients of whom 26 with TRD participated in this study. Ten days after hospitalization, treatment with trazodone 100 mg/day was started. After 1 week trazodone treatment, patients were randomized — using a double blind placebo controlled design — to receive trazodone 100 mg/day + placebo; trazodone 100 mg/day + pindolol 7.5 mg/day; or trazodone 100 mg/day + fluoxetine 20 mg/day and treated during 4 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) was used as outcome measure. It was found that trazodone + pindolol was as effective as trazodone + fluoxetine in the treatment of major depression and TRD and significantly more effective than trazodone + placebo. Using an outcome measure of 50% reduction in the HDRS, we found that 72.5% of the depressed patients treated with trazodone + pindolol and 75% of depressed patients treated with trazodone + fluoxetine showed a clinically significant response compared with 20.0% of trazodone + placebo-treated patients.