EFFICACY OF TREATMENT WITH TRAZODONE IN COMBINATION WITH PINDOLOL OR FLUOXETINE IN MAJOR DEPRESSION

Fluoxetine, a selective serotonin (5-HT) reuptake inhibitor (SSRI), an d trazodone, a heterocyclic antidepressant, an effective in the treatm ent of major depression and treatment resistant depression (TRD). Chro nic treatment with both drugs causes increases in extracellular 5-HT t hrough 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 pindol ol may increase the efficacy of a subtherapeutical dosage of trazodone in the treatment of major depression and TRD, defined according to th e Thase and Rush criteria(1995). Thirty-three major depressed inpatien ts of whom 26 with TRD participated in this study. Ten days after hosp italization, treatment with trazodone 100 mg/day was started. After 1 week trazodone treatment, patients were randomized - using a double bl ind placebo controlled design - to receive trazodone 100 mg/day + plac ebo; trazodone 100 mg/day + pindolol 7.5 mg/day; or trazodone 100 mg/d ay + fluoxetine 20 mg/day and treated during 4 weeks. The 17-item Hami lton Depression Rating Scale (HDRS) was used as outcome measure. It wa s found that trazodone + pindolol was as effective as trazodone + fluo xetine in the treatment of major depression and TRD and significantly more effective than trazodone + placebo. Using an outcome measure of 5 0% reduction in the HDRS, we found that 72.5% of the depressed patient s treated with trazodone + pindolol and 75% of depressed patients trea ted with trazodone + fluoxetine showed a clinically significant respon se compared with 20.0% of trazodone + placebo-treated patients.