Venlafaxine but not bupropion decreases cerebrospinal fluid 5-hydroxyindoleacetic acid in unipolar depression

Background: While the antidepressants venlafaxine and bupropion are known to have different neurochemical profiles in vitro, their effects on human cerebral metabolism in vivo have not been directly compared. Methods: Cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA), serotonin, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were examined in 14 never-hospitalized outpatients with unipolar depression and 10 age-similar healthy controls. Patients received a baseline lumbar puncture (LP), which was repeated after at least 6 weeks of randomized monotherapy with either venlafaxine or bupropion, while controls received only a baseline LP. Results: Patients (n = 9) receiving venlafaxine showed a significant decrease (42%) in their CSF 5-HIAA concentrations after treatment, but no change in other CSF measures. In contrast, patients receiving bupropion (n = 8) showed no change in CSF measures compared to pretreatment values. Conclusions: While the mechanism for this differential effect of venlafaxine remains to be determined, the current study provides confirmation of the different aminergic effects of venlafaxine and bupropion.