Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial

J Clin Psychopharmacol. 2024 Sep-Oct;44(5):472-480. doi: 10.1097/JCP.0000000000001888. Epub 2024 Jul 16.

Abstract

Background: Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST).

Methods: Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs.

Results: The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo.

Conclusions: Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetamides* / administration & dosage
  • Acetamides* / adverse effects
  • Acetamides* / pharmacology
  • Adult
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / drug therapy
  • Citalopram* / administration & dosage
  • Citalopram* / pharmacology
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Heart Rate / drug effects
  • Humans
  • Hydrocortisone / blood
  • Male
  • Naphthalenes
  • Prolactin / blood
  • Venlafaxine Hydrochloride* / administration & dosage
  • Venlafaxine Hydrochloride* / pharmacology
  • Young Adult

Substances

  • agomelatine
  • Acetamides
  • Citalopram
  • Venlafaxine Hydrochloride
  • Hydrocortisone
  • Anti-Anxiety Agents
  • Prolactin
  • Naphthalenes