Treatment of Premenstrual Dysphoric Disorder (PMDD)
Selective serotonin reuptake inhibitors (SSRIs) are the established first-line treatment for PMDD, with fluoxetine (10-20 mg/d), sertraline (50-150 mg/d), paroxetine (12.5-25 mg/d), or escitalopram (10-20 mg/d) as preferred agents. 1, 2, 3
First-Line Pharmacologic Treatment: SSRIs
SSRIs demonstrate superior efficacy for PMDD compared to placebo, reducing overall premenstrual symptoms with moderate-certainty evidence. 2
Dosing Strategies
Continuous daily dosing is more effective than luteal-phase-only administration (continuous: SMD -0.69 vs. luteal phase: SMD -0.39, P = 0.03 for subgroup difference). 2
Luteal-phase dosing (from ovulation to menstruation onset) remains an effective alternative for women who prefer intermittent treatment or experience intolerable side effects with continuous dosing. 1, 4
Symptom-onset dosing (starting medication only when symptoms appear) can also be effective, though continuous dosing shows stronger evidence. 1
Specific SSRI Options
Fluoxetine: FDA-approved for PMDD (marketed as Sarafem), dosed at 10-20 mg/d continuously or 20 mg/d during luteal phase. 5, 3
Sertraline: 50-150 mg/d, with robust evidence for efficacy. 1, 3
Paroxetine: 12.5-25 mg/d (controlled-release formulation preferred). 3
Escitalopram: 10-20 mg/d, effective with favorable tolerability profile. 3
Expected Adverse Effects
Patients should be counseled that 68% will experience at least one adverse effect, but these are generally manageable. 2
Common Side Effects (in order of frequency):
Nausea (OR 3.30): Most common, typically improves after 1-2 weeks. 2
Asthenia/decreased energy (OR 3.28). 2
Somnolence/decreased concentration (OR 3.26). 2
Dry mouth (OR 2.70). 2
Sexual dysfunction/decreased libido (OR 2.32): Important to discuss proactively given impact on quality of life. 2
Sweating (OR 2.17). 2
Diarrhea (OR 2.06). 2
Insomnia (OR 1.99). 2
Dizziness (OR 1.96). 2
Second-Line Pharmacologic Options
Other Antidepressants
Venlafaxine (SNRI): Effective alternative when SSRIs fail or are not tolerated. 1
Duloxetine (SNRI): Demonstrated efficacy in PMDD treatment. 1
Anxiolytics
Alprazolam: Can be used for severe anxiety symptoms, though carries risk of dependence. 1
Buspirone: Alternative anxiolytic with lower abuse potential. 1
Hormonal Treatments
Drospirenone-containing oral contraceptives (3 mg drospirenone + 20 mcg ethinyl estradiol, 24 days active/4 days inactive): Effective as first or second-line treatment, particularly for women desiring contraception. 3
Ovulation suppression with various hormonal preparations can be effective but limited by side effects and cost compared to SSRIs. 1, 6
Non-Pharmacologic Treatments
Cognitive Behavioral Therapy (CBT)
CBT reduces functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict with others in PMDD. 3
CBT should be considered as adjunctive therapy or as monotherapy for women who refuse or cannot tolerate medications. 3
Specific benefits include: reduction in feelings of hopelessness, sensitivity, insomnia, impact on daily life, and symptom handicap. 3
Supplements with Evidence
Calcium supplementation: Only supplement with consistent therapeutic benefit demonstrated. 1, 6
Chasteberry (Vitex agnus castus): May be useful adjunct but evidence less robust. 6
St. John's wort (Hypericum perforatum): Potential benefit but drug interactions limit use. 6
Treatment Algorithm
Step 1: Initial Treatment
Start with SSRI monotherapy using continuous daily dosing (fluoxetine 10-20 mg/d, sertraline 50-150 mg/d, paroxetine 12.5-25 mg/d, or escitalopram 10-20 mg/d). 1, 2, 3
Step 2: If Continuous Dosing Not Tolerated
Switch to luteal-phase dosing (starting at ovulation, approximately day 14 of cycle, through menstruation onset). 1, 4
Step 3: If First SSRI Fails After 2-3 Cycles
Switch to alternative SSRI before abandoning the class entirely. 1, 4
Step 4: If SSRIs Ineffective or Not Tolerated
Consider SNRI (venlafaxine or duloxetine) or drospirenone-containing oral contraceptive if contraception desired. 1, 3
Step 5: Adjunctive Therapy
Add CBT to ongoing pharmacotherapy for enhanced functional improvement. 3
Step 6: Refractory Cases
Consider anxiolytic augmentation (buspirone or alprazolam) or referral to specialist for consideration of GnRH agonists with add-back therapy. 1, 4
Critical Diagnostic Requirement
Diagnosis must be confirmed with prospective daily symptom charting for at least two consecutive menstrual cycles showing clear luteal-phase onset and follicular-phase remission. 1, 6, 4
Distinguish PMDD from premenstrual exacerbation of underlying mood/anxiety disorder: symptoms must be absent or minimal in follicular phase. 4
Differentiate from premenstrual syndrome (PMS): PMDD requires predominance of mood symptoms, marked functional impairment, and meeting specific DSM-5 criteria. 6, 4
Treatment Duration
Initial treatment trial should last at least 2-3 menstrual cycles to adequately assess response, as some women require this duration to achieve full benefit. 1, 4
For responders, continue treatment for at least 12 months before considering discontinuation, as PMDD is typically a chronic condition requiring long-term management. 6, 4