What is the relationship between histamine and Premenstrual Dysphoric Disorder (PMDD) and how is it treated?

The Relationship Between Histamine and Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMDD due to the disorder's connection to serotonergic dysfunction rather than histamine dysregulation. 1

Understanding PMDD

PMDD is a severe form of premenstrual syndrome characterized by specific symptoms that:

• Occur during the luteal phase of the menstrual cycle (two weeks before menstruation) 2, 3
• Resolve during menstruation or shortly after 3
• Substantially interfere with work, school, social activities, relationships, or cause significant distress 3

PMDD is officially recognized in both:

• DSM-5 (since 2013) as a depressive disorder 4
• ICD-11 (since 2019) as a distinct diagnostic entity 2, 4

Histamine and PMDD Connection

While the evidence provided doesn't specifically address a direct relationship between histamine and PMDD, the current understanding of PMDD pathophysiology focuses on:

• Serotonergic dysfunction rather than histamine dysregulation 5, 1
• Negative impact of natural hormonal fluctuations on certain neurotransmitters, particularly serotonin 4
• PMDD being a distinct diagnostic entity with irritability and affect lability as most characteristic features, rather than primarily a histamine-mediated disorder 5

Diagnosis of PMDD

Diagnosis requires:

• Consistent characteristic symptoms occurring in the luteal phase 3
• Symptoms resolving during menstruation or within the week following 3
• Documentation of symptoms for at least two cycles using:
  • Symptom-tracking diary or
  • Validated diagnostic instrument like the Daily Record of Severity of Problems 3

Treatment Approaches for PMDD

First-Line Treatment: SSRIs

SSRIs are the established first-line treatment for PMDD with:

• Rapid onset of improvement 3, 1
• Effectiveness in reducing overall premenstrual symptoms 1
• Options for continuous or luteal phase administration (with continuous administration showing greater effectiveness) 1

Specific SSRI options and dosages include:

• Sertraline (50-150 mg/day) 4
• Fluoxetine (10-20 mg/day) 4, 6
• Escitalopram (10-20 mg/day) 4
• Paroxetine (12.5-25 mg/day) 4

Other Treatment Options

• Hormonal treatments: Oral contraceptives containing drospirenone (3 mg with ethinyl estradiol 20 mg/day for 24 days, followed by 4 days inactive) 4
• Cognitive Behavioral Therapy (CBT): Shows positive results in reducing:
  • Functional impairment
  • Depressed mood and feelings of hopelessness
  • Anxiety, mood swings, and sensitivity
  • Irritability and insomnia
  • Conflict with others 4
• Complementary approaches:
  • Exercise
  • Acupuncture or acupressure
  • Vitex agnus castus (herb) 3

Common Side Effects of SSRI Treatment

SSRIs can cause several adverse effects that may limit their use:

• Nausea 1
• Insomnia 1
• Sexual dysfunction or decreased libido 1
• Fatigue or sedation 1
• Dizziness or vertigo 1
• Somnolence and decreased concentration 1

Clinical Considerations

• If symptoms are not controlled with medications or persist throughout the month, reassessment for another underlying cause should occur 3
• PMDD should be distinguished from premenstrual syndrome (PMS), which has different symptoms and severity 4
• PMDD is neither a variant of depression nor an anxiety disorder, but a distinct diagnostic entity 5

Treatment Algorithm

1. Confirm PMDD diagnosis through symptom tracking for at least two menstrual cycles 3
2. Start with an SSRI (sertraline, fluoxetine, escitalopram, or paroxetine) 4, 1
3. Consider continuous administration rather than luteal phase only for better efficacy 1
4. If SSRIs are not tolerated, consider:
   • Oral contraceptives containing drospirenone 4
   • CBT or other psychotherapeutic approaches 4
   • Complementary approaches (exercise, acupuncture) 3
5. Reassess if symptoms persist throughout the month or don't respond to treatment 3