Ulipristal Acetate for PMDD Treatment
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Close to 70-90 % of reproductive age women are known to have at least one or more signs of physical discomfort or emotional symptoms during the premenstrual period (luteal phase of the menstrual cycle). 20-40 % of women have these symptoms in mild to moderate severity and meet the criteria for premenstrual syndrome (PMS). A smaller number (~ 8 %) experience more severe symptoms in moderate-severe severity causing functional impairment and are referred to as premenstrual dysphoric disorder (PMDD).
Lifestyle, Dietary & Nutritional modification is the first-line treatment, followed by the use of serotonergic medications. A certain subset of patients do not respond to these first-line treatments and can benefit from other approaches.
On Dec 10, 2020, Erika Comasco et al recently published this proof-of-concept randomized controlled trial in the American Journal of Psychiatry investigating the role of continuous treatment with Ulipristal Acetate (UPA), as a potential treatment for PMDD. This post will be summarized in the following sections:
- AJP Study Findings: design & results.
- UPA Mechanism of Action
- Current FDA Indication
- Most Common Adverse Reactions
- Drug Interactions
- Multicenter, double-blind, randomized, parallel-group clinical trial.
- N= 95 (women with PMDD).
- UPA dose: 5 mg/day.
- Duration: UPA 5 mg/day or placebo during three 28-day treatment cycles.
- Scale used: Daily Record of Severity of Problems (DRSP).
(A) DRSP Score Improvement Over 3 Months (mean):
- UPA (41%) vs Placebo (22%)
(B) DRSP Depressive Symptoms Subscale:
- UPA (42%) vs Placebo (22%)
(C) DRSP Anger/Irritability Subscale:
- UPA (47%) vs Placebo (23%)
(D) DRSP physical symptom subscale:
- Treatment effects not noted.
- 20 in UPA (50 %) and 8 in placebo (21.1%) (statistically significant difference).
Ulipristal Acetate (UPA) Mechanism of Action:
- Selective progesterone receptor modulator with antagonistic and partial agonistic effects (a progesterone agonist/antagonist) at the progesterone receptor.
- When taken immediately before ovulation –> UPA postpones follicular rupture –> thereby inhibition or delay of ovulation.
Current FDA Indication:
- Emergency contraceptive indicated for the prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure.
- not intended for routine use as a contraceptive.
Most Common Adverse Reactions:
- Headache (18%)
- Abdominal pain (12%)
- Nausea (12%)
- Dysmenorrhea (9%)
- Fatigue (6%) and
- Dizziness (5%)
- In post-marketting expereince: Acne was noted.
Note that these adverse reactions were seen at 30 mg/day dose (but the above study used 5 mg/day dose).
- Known or suspected pregnancy (Contraindication)
- Not for repeated use: only for occasional use.
UPA is metabolized by CYP3A4.
MEDICATIONS (3A4 INDUCERS) DECREASING UPA CONCENTRATION:
- St. John’s Wort
MEDICATIONS (3A4 INHIBITORS) INCREASING UPA CONCENTRATION:
- Grapefruit juice
- Comasco E, Kopp Kallner H, Bixo M, Hirschberg AL, Nyback S, de Grauw H, Epperson CN, Sundström-Poromaa I. Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder: A Proof-of-Concept Randomized Controlled Trial. Am J Psychiatry. 2020 Dec 10:appiajp202020030286. doi: 10.1176/appi.ajp.2020.20030286. Epub ahead of print. PMID: 33297719. (pubmed)
- ella (ulipristal acetate) package insert (pdf)
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Premenstrual Dysphoric Disorder (PMDD):
This chapter will be summarized in the following nine sections:
- Diagnosing PMDD.
- PMS vs PMDD.
- Evaluating PMDD with Scales.
- Treatment Options: Lifestyle modifications and Medications.
- What medications are FDA approved for PMDD?
- What dose of medication is found effective for physical and mood symptoms in PMDD?
- How long it takes for PMDD symptoms to improve with antidepressants?
- Are intermittent dosing different than daily dosing (in terms of efficacy)?
- What if lifestyle modifications and antidepressants are not effective?
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