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 5-HT1A 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 (30 mg p.o.) were measured. After 8 weeks on citalopram, the delta max of hypothermic response elicited by buspirone was markedly decreased (p<0.001). Patients showed a decrease in responses to ACTH (delta max p=0.005; AUC p=0.028) and cortisol (delta max p=0.05). However, the prolactin response increased (delta 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.
Navinés
Ricard
R
Institut de Neurociències. Servei de Psiquiatria. Hospital Clínic, Barcelona, Spain. rnavines@hotmail.com
Martín-Santos
Rocío
R
Gómez-Gil
Esther
E
Martínez de Osaba
María J
MJ
Imaz
M Luisa
ML
Gastó
Cristóbal
C
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D002065:Buspirone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007035:Hypothermia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D058825:Serotonin 5-HT1 Receptor Agonists; D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D002065:Buspirone; D006854:Hydrocortisone