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

Abstract

Rationale: Alterations in 5-HT_2A receptor binding are implicated in suicidality and depression. 5-HT_2A receptors may also be involved in the therapeutic effects of antidepressants. Objectives: The purpose of this study was to assess the effect of paroxetine and nefazodone on 5-HT_2A 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-HT_2A binding potentials (B_max/K_d) were determined in each subject using [¹⁸F]-setoperone PET. Results: Nefazodone induced a significant change in 5-HT_2A binding potential (−39 ± 17%, P = 0.003) while paroxetine showed no significant alteration of 5-HT_2A binding potential (+3 ± 13%, P = 0.73). Conclusions: The change in 5-HT_2A binding potential seen with nefazodone represents blockade of 5-HT_2A receptors by the drug. We do not find evidence for acute downregulation of 5-HT_2A receptors with paroxetine within 9 h.