Effect of penbutolol on neuroendocrine responses to buspirone and mood in SSRI-refractory patients: A preliminary study

The beta-adrenoceptor antagonist, penbutolol, is an effective serotonin(1A) (5-HT1A) receptor antagonist in the rat and through this action enhances t he ability of selective serotonin re-uptake inhibitors (SSRIs) to increase levels of serotonin in terminal fields. In healthy volunteers. penbutolol ( 40 mg orally), produced a modest attenuation of the prolactin response to t he 5-HT1A receptor antagonist, buspirone (30 mg orally), but did not antago nise the hypothermic response. Furthermore, penbutolol addition (40 mg dail y for 3 weeks) failed to improve the symptomatology of 10 depressed patient s who had shown an inadequate clinical response to serotonergic antidepress ants. These preliminary data suggest that at the typical dose used to treat hypertension, penbutolol does not antagonise 5-HT1A autoreceptors in human s and does not augment the effect of serotonergic antidepressants in treatm ent non-responders. (C) 1999 John Wiley & Sons, Ltd.