Intermittent escitalopram treatment and reactive aggression in women with premenstrual irritability and anger: A crossover study

J Affect Disord. 2025 Jan 15:369:599-607. doi: 10.1016/j.jad.2024.10.020. Epub 2024 Oct 10.

Abstract

Background: Selective serotonin reuptake inhibitors (SSRI) are the primary treatment for premenstrual mood symptoms and particularly effective in reducing reactive aggression in the forms of irritability and anger. The present study examined whether behavioral responses in laboratory measures of reactive aggression are influenced by medication with the SSRI escitalopram in women reporting high levels of premenstrual irritability/anger.

Methods: Participants (N = 34) rated the cardinal mood symptoms of premenstrual dysphoric disorder over three menstrual cycles. During the second and third cycles, participants received escitalopram (20 mg) or placebo in a single-blind, cross-over design. In the luteal phase of the intervention cycles, participants completed two aggression tasks: The Anger-Infused Ultimatum Game (AI-UG) and the Point Subtraction Aggression Paradigm (PSAP). Additionally, they rated expression and control of anger using the State-Trait Anger Expression Inventory-2 (STAXI-2) once in the luteal phase and once in the follicular phase.

Results: While irritability/anger was reduced in the treatment (vs. placebo) cycle, no effect of escitalopram was detected in the PSAP. Escitalopram decreased reactive aggressive behavior in the AI-UG but only for a subset of participants who experienced a sharp premenstrual rise in outwardly expressed anger and/or did not experience a premenstrual rise in inwardly expressed anger.

Limitations: The participants' symptoms were based on the severity of only premenstrual irritability/anger, limiting the generalizability to the broader group of PMDD patients.

Conclusion: The results suggest that the behavioral consequences of severe premenstrual irritability/anger are not easily captured by traditional measures of reactive aggression and underline the importance of considering individual differences in symptom expression.

Keywords: Escitalopram; PMDD; Point Subtraction Aggression Paradigm; Premenstrual irritability; Selective serotonin uptake inhibitors; The Anger-Infused Ultimatum Game.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aggression* / drug effects
  • Anger* / drug effects
  • Citalopram / administration & dosage
  • Citalopram / therapeutic use
  • Cross-Over Studies*
  • Escitalopram* / administration & dosage
  • Female
  • Follicular Phase / drug effects
  • Humans
  • Irritable Mood* / drug effects
  • Luteal Phase / drug effects
  • Premenstrual Dysphoric Disorder / drug therapy
  • Premenstrual Dysphoric Disorder / psychology
  • Premenstrual Syndrome / drug therapy
  • Premenstrual Syndrome / psychology
  • Selective Serotonin Reuptake Inhibitors* / administration & dosage
  • Single-Blind Method
  • Young Adult

Substances

  • Selective Serotonin Reuptake Inhibitors
  • Escitalopram
  • Citalopram