The effect of chronic fluvoxamine on hormonal and psychological responses to buspirone in normal volunteers

Abstract

We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT_1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D₂ receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT_1A receptor function is reduced by chronic fluvoxamine treatment.