Treatment of Premenstrual Dysphoric Disorder (PMDD)
Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for PMDD, with sertraline 50-150 mg/day being the gold standard based on FDA approval and extensive evidence. 1, 2, 3
First-Line Pharmacologic Treatment: SSRIs
SSRIs demonstrate superior efficacy over non-serotonergic antidepressants for PMDD and work rapidly, often within the first treatment cycle. 4, 5
FDA-Approved Dosing for Sertraline in PMDD:
- Start at 50 mg/day, either continuously throughout the menstrual cycle or limited to the luteal phase only 1
- For patients not responding to 50 mg/day, increase by 50 mg increments up to 150 mg/day for continuous dosing or 100 mg/day for luteal-phase dosing 1
- If using 100 mg/day luteal-phase dosing, use a 50 mg/day titration step for 3 days at the beginning of each luteal phase 1
- Dose changes should not occur at intervals less than 1 week due to sertraline's 24-hour elimination half-life 1
Alternative SSRI Options:
- Fluoxetine 10-20 mg/day 2
- Escitalopram 10-20 mg/day 2
- Paroxetine 12.5-25 mg/day 2
- All SSRIs can be dosed continuously or during luteal phase only, with both regimens showing efficacy 4, 5
Critical Safety Consideration:
Monitor for treatment-emergent suicidality, particularly in adolescents and young adults, as SSRIs carry black box warnings for this population. 6
Second-Line Pharmacologic Options
Combined Hormonal Contraceptives:
Drospirenone 3 mg with ethinyl estradiol 20 mcg in a 24/4 extended cycle regimen (24 days active, 4 days inactive) is the only hormonal contraceptive with proven efficacy for PMDD. 2, 7
Other Psychiatric Medications:
- Venlafaxine and duloxetine (serotonin-norepinephrine reuptake inhibitors) have demonstrated efficacy 3
- Alprazolam (benzodiazepine) can be used cautiously due to dependence risk 6, 3
- Buspirone may be beneficial 3
Non-Pharmacologic Interventions
Cognitive Behavioral Therapy (CBT):
CBT reduces functional impairment, depressed mood, anxiety, mood swings, irritability, and symptom severity in PMDD. 2
Exercise:
Regular aerobic exercise is recommended as a first-line treatment option for mild-to-moderate PMDD symptoms. 6
Supplements with Evidence:
Calcium supplementation is the only supplement with consistent therapeutic benefit demonstrated across studies. 3, 5
Symptomatic Management
NSAIDs are recommended for physical pain symptoms associated with PMDD. 6
Contraceptive Counseling Considerations
Avoid in PMDD:
Progestin-only methods (progestin-only pills, levonorgestrel IUD, etonorgestrel implant, depot medroxyprogesterone acetate) have the potential to worsen mood symptoms and should be avoided or used with extreme caution and close follow-up. 7
Safe Options:
Copper IUDs are recommended for patients with PMDD who prefer non-hormonal contraception. 7
Treatment Algorithm
- Begin with SSRI monotherapy (sertraline 50 mg/day, either continuous or luteal-phase dosing) 1, 2
- If inadequate response after 1-2 cycles, increase SSRI dose as outlined above 1
- If SSRIs fail or are not tolerated, consider drospirenone-containing combined hormonal contraceptive 2, 7
- Add CBT as adjunctive therapy at any stage 2
- Recommend aerobic exercise and calcium supplementation as baseline interventions 6, 3
- Use NSAIDs for physical symptoms as needed 6
- Reserve alprazolam, venlafaxine, or duloxetine for refractory cases 6, 3
Common Pitfalls
Do not confuse premenstrual syndrome (PMS) with PMDD—PMDD requires significant functional impairment and specific DSM-5 criteria including at least 5 symptoms with at least one being affective. 2, 5
Avoid prescribing progestin-only contraceptives to patients with PMDD, as progesterone exposure at ovulation triggers the disorder and continuous progestin exposure may worsen symptoms. 7
SSRIs work rapidly in PMDD (often within days to weeks), unlike their delayed onset in depression, suggesting a different mechanism of action likely involving neurosteroid modulation. 4, 5