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Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects.
Clin Pharmacol Ther 1998; 63(4):428-36CP

Abstract

OBJECTIVES

To assess whether acute 5-hydroxytryptamine-1A (5-HT1A)-receptor-mediated corticotropin, cortisol, and temperature responses are maintained after 3 weeks of treatment with controlled-release (CR) ipsapirone and fluoxetine compared with placebo and whether changes are reversible after cessation of treatment.

METHODS

This was a randomized parallel-group study. Ten healthy subjects received ipsapirone CR or fluoxetine, and eight received placebo in a double-blind manner. An ipsapirone challenge test with 20 mg ipsapirone immediate-release formulation (IR) was performed before treatment (day 0) and after 20 days of treatment with placebo, 80 mg/day ipsapirone CR, or 20 mg/day fluoxetine (day 21). From day 22 to day 34 all subjects received placebo in a simple-blind manner. A third ipsapirone challenge test was performed on day 35.

RESULTS

Before treatment, resting plasma corticotropin and cortisol concentrations and increases in plasma corticotropin and cortisol concentrations after challenge with 20 mg ipsapirone IR were similar for the three groups. After 20 days of treatment, plasma corticotropin and cortisol concentrations were similar before challenge, but ipsapirone IR-induced increases in plasma corticotropin and cortisol concentrations were significantly lower in both the ipsapirone CR group (corticotropin, 6.5 +/- 2 pg/ml; cortisol, 1.5 +/- 0.7 micrograms/dl) and fluoxetine group (corticotropin 4.4 +/- 2 pg/ml; cortisol 1.5 +/- 0.7 micrograms/dl) compared with placebo (corticotropin, 34 +/- 14 pg/ml; cortisol, 5.8 +/- 2 micrograms/dl, mean +/- SEM). After 2 weeks of placebo administration, plasma corticotropin and cortisol responses to ipsapirone IR again became identical in all three groups. Plasma ipsapirone concentrations were similar in all groups during each challenge. The hypothermic response to ipsapirone IR showed no difference before treatment, at the end of the treatment period, or 2 weeks after cessation of treatment. Long-term administration of antidepressants to the healthy subjects did not lead to any serious adverse effects.

CONCLUSIONS

Long-term administration of fluoxetine and ipsapirone did not influence resting plasma corticotropin and cortisol concentrations in the morning. Stimulation of corticotropin and cortisol release by a selective 5-HT1A-agonist is reduced with long-term administration of these serotoninergic antidepressants. This subsensitivity of postsynaptic 5-HT1A-receptors is reversible.

Authors+Show Affiliations

Department of Pharmacology, Pité-Salpêtière University Hospital, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9585797

Citation

Berlin, I, et al. "Blunted 5-HT1A-receptor Agonist-induced Corticotropin and Cortisol Responses After Long-term Ipsapirone and Fluoxetine Administration to Healthy Subjects." Clinical Pharmacology and Therapeutics, vol. 63, no. 4, 1998, pp. 428-36.
Berlin I, Warot D, Legout V, et al. Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects. Clin Pharmacol Ther. 1998;63(4):428-36.
Berlin, I., Warot, D., Legout, V., Guillemant, S., Schöllnhammer, G., & Puech, A. J. (1998). Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects. Clinical Pharmacology and Therapeutics, 63(4), pp. 428-36.
Berlin I, et al. Blunted 5-HT1A-receptor Agonist-induced Corticotropin and Cortisol Responses After Long-term Ipsapirone and Fluoxetine Administration to Healthy Subjects. Clin Pharmacol Ther. 1998;63(4):428-36. PubMed PMID: 9585797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects. AU - Berlin,I, AU - Warot,D, AU - Legout,V, AU - Guillemant,S, AU - Schöllnhammer,G, AU - Puech,A J, PY - 1998/5/20/pubmed PY - 1998/5/20/medline PY - 1998/5/20/entrez SP - 428 EP - 36 JF - Clinical pharmacology and therapeutics JO - Clin. Pharmacol. Ther. VL - 63 IS - 4 N2 - OBJECTIVES: To assess whether acute 5-hydroxytryptamine-1A (5-HT1A)-receptor-mediated corticotropin, cortisol, and temperature responses are maintained after 3 weeks of treatment with controlled-release (CR) ipsapirone and fluoxetine compared with placebo and whether changes are reversible after cessation of treatment. METHODS: This was a randomized parallel-group study. Ten healthy subjects received ipsapirone CR or fluoxetine, and eight received placebo in a double-blind manner. An ipsapirone challenge test with 20 mg ipsapirone immediate-release formulation (IR) was performed before treatment (day 0) and after 20 days of treatment with placebo, 80 mg/day ipsapirone CR, or 20 mg/day fluoxetine (day 21). From day 22 to day 34 all subjects received placebo in a simple-blind manner. A third ipsapirone challenge test was performed on day 35. RESULTS: Before treatment, resting plasma corticotropin and cortisol concentrations and increases in plasma corticotropin and cortisol concentrations after challenge with 20 mg ipsapirone IR were similar for the three groups. After 20 days of treatment, plasma corticotropin and cortisol concentrations were similar before challenge, but ipsapirone IR-induced increases in plasma corticotropin and cortisol concentrations were significantly lower in both the ipsapirone CR group (corticotropin, 6.5 +/- 2 pg/ml; cortisol, 1.5 +/- 0.7 micrograms/dl) and fluoxetine group (corticotropin 4.4 +/- 2 pg/ml; cortisol 1.5 +/- 0.7 micrograms/dl) compared with placebo (corticotropin, 34 +/- 14 pg/ml; cortisol, 5.8 +/- 2 micrograms/dl, mean +/- SEM). After 2 weeks of placebo administration, plasma corticotropin and cortisol responses to ipsapirone IR again became identical in all three groups. Plasma ipsapirone concentrations were similar in all groups during each challenge. The hypothermic response to ipsapirone IR showed no difference before treatment, at the end of the treatment period, or 2 weeks after cessation of treatment. Long-term administration of antidepressants to the healthy subjects did not lead to any serious adverse effects. CONCLUSIONS: Long-term administration of fluoxetine and ipsapirone did not influence resting plasma corticotropin and cortisol concentrations in the morning. Stimulation of corticotropin and cortisol release by a selective 5-HT1A-agonist is reduced with long-term administration of these serotoninergic antidepressants. This subsensitivity of postsynaptic 5-HT1A-receptors is reversible. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/9585797/Blunted_5_HT1A_receptor_agonist_induced_corticotropin_and_cortisol_responses_after_long_term_ipsapirone_and_fluoxetine_administration_to_healthy_subjects_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9236&date=1998&volume=63&issue=4&spage=428 DB - PRIME DP - Unbound Medicine ER -