The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18(F)]-setoperone PET

Rationale: Alterations in 5-HT2A receptor binding are implicated in suicida lity and depression. 5-HT2A receptors may also be involved in the therapeut ic effects of antidepressants. Objectives: The purpose of this study was to assess the effect of paroxetine and nefazodone on 5-HT2A receptors after a single dose. Methods. Seven subjects received a single dose of nefazodone 200 mg and five subjects received a single dose of paroxetine 20 mg. Before and after the dose, 5-HT2A binding potentials (B-max/K-d) were determined in each subject using [F-18]-setoperone PET. Results: Nefazodone induced a significant change in 5-HT2A binding potential(-39 +/- 17%, P = 0.003) whil e paroxetine showed no significant alteration of 5-HT2A binding potential ( +3 +/- 13%, P = 0.73). Conclusions: The change in 5-HT2A binding potential seen with nefazodone represents blockade of 5-HT2A receptors by the drug. W e do not find evidence for acute downregulation of 5-HT2A receptors with pa roxetine within 9 h.