Effects of citalopram treatment on hypothermic and hormonal responses to the 5-HT1A receptor agonist buspirone in patients with major depression and therapeutic response

Serotonin (5-HT) 5-HT1A receptor seems to play an important role in the pathophysiology of major depression and in the mechanism of action of antidepressants. In vivo function of 5HT(1A) receptors can be monitored using specific pharmacological challenge tests. The present study aimed at exploring the adaptative 5-HT1A receptor changes in depressed patients before and after 8 week treatment with citalopram. The study population consisted of 30 consecutive outpatients of both sexes aged 18-45 years with major depressive disorders (DSM-IV). Basal. score in the Hamilton Rating Scale for Depression (HRSD) was higher than 17. Therapeutic response was defined as a 50% decrease in the HRSD score. The hypothermic and endocrine responses (ACTH, cortisol, and prolactin) induced by the 5-HT1A receptor agonist, buspirone (30mg PO) were measured. After 8 weeks on citalopram, the triangle max of hypothermic response elicited by buspirone was markedly decreased (p < 0.001). Patients showed a decrease in responses to ACTH (triangle max p = 0.005; AUC p = 0.028) and cortisol. (triangle max p = 0.05). However, the prolactin response increased (triangle max p = 0.02; AUC p = 0.005). There was a significant correlation between the therapeutic effect and reductions of ACTH (r = 0.883; p < 0.001) and cortisol. (r = 0.610; p = 0.001) responses. Changes induced by citalopram support an alteration of 5-HT1A receptors in major depression. A decrease in the overactivity of the HPA axis may be one factor associated with the response to citalopram. (C) 2007 Elsevier Ltd. All rights reserved.