What is the next treatment step for a patient with premenstrual dysphoric disorder (PMDD) who has tried citalopram (Celexa), hydroxyzine, trazodone, and bupropion (Wellbutrin) without success, along with estrogen and progesterone?

Next Treatment Step for Treatment-Resistant PMDD

Switch to sertraline 50-150 mg/day as the next treatment step, as SSRIs are the established first-line pharmacologic treatment for PMDD and this patient has not yet tried an SSRI. 1, 2, 3

Why SSRIs Are the Appropriate Next Step

• SSRIs are the only FDA-approved and guideline-recommended first-line treatment for PMDD, with sertraline specifically having an FDA indication for this disorder 1, 2, 3
• The patient has tried citalopram (Celexa), but this was likely prescribed for comorbid depression rather than PMDD specifically, as the dosing and timing matter significantly for PMDD treatment 1
• Sertraline can be dosed either continuously (50-150 mg/day throughout the cycle) or intermittently (luteal phase only, starting 14 days before expected menses), with both approaches showing efficacy 1, 4, 5

Specific Dosing Algorithm for PMDD

Initial Dosing Strategy:

• Start sertraline 50 mg/day either continuously or limited to the luteal phase 1
• For luteal phase dosing: begin 14 days before expected menses and continue through the first few days of menstruation 4, 5
• Intermittent (luteal phase) dosing is preferred initially as it minimizes medication exposure, reduces side effects, and is equally effective as continuous dosing 4, 5

Dose Titration:

• If inadequate response at 50 mg/day, increase by 50 mg increments at the onset of each new menstrual cycle 1
• Maximum dose: 150 mg/day for continuous dosing or 100 mg/day for luteal phase dosing 1
• If initiating 100 mg/day luteal phase dosing, use a 50 mg/day titration step for 3 days at the beginning of each luteal phase 1

Alternative SSRI Options if Sertraline Fails

If sertraline is ineffective or not tolerated after 2-3 cycles:

• Fluoxetine 10-20 mg/day (can be dosed continuously or luteal phase only) 2, 3
• Escitalopram 10-20 mg/day 2
• Paroxetine 12.5-25 mg/day 2

Second-Line Options After SSRI Failure

SNRI Alternative:

• Venlafaxine has demonstrated efficacy for PMDD when SSRIs fail 3

Hormonal Option:

• Drospirenone-containing oral contraceptive (3 mg drospirenone + 20 mcg ethinyl estradiol, 24 days active/4 days inactive) is FDA-approved for PMDD and can be considered as first or second-line treatment 2, 4
• This is particularly appropriate if the patient desires contraception or if SSRIs are contraindicated 2, 6

Cognitive Behavioral Therapy Consideration

• CBT should be offered concurrently with pharmacotherapy or as monotherapy if the patient prefers non-pharmacologic treatment 2, 6
• CBT has shown effectiveness in reducing functional impairment, depressed mood, anxiety, mood swings, irritability, and conflict associated with PMDD 2

Critical Implementation Points

• Assess response after 2-3 menstrual cycles rather than the typical 4-6 weeks used for depression, as PMDD symptoms are cyclical 1
• SSRIs work rapidly in PMDD (often within days), unlike their delayed onset in depression, due to different mechanisms of action 4, 5
• The patient's previous trials of trazodone, hydroxyzine, and bupropion are not evidence-based treatments for PMDD and their failure should not discourage SSRI trial 2, 3
• Sexual dysfunction is a common SSRI side effect that should be monitored, though intermittent dosing may reduce this risk 5

Common Pitfall to Avoid

Do not assume that failure of citalopram for depression means SSRIs won't work for PMDD. The pathophysiology, dosing strategy (intermittent vs. continuous), and treatment duration differ significantly between major depressive disorder and PMDD 4, 5. Sertraline has the strongest evidence base and FDA approval specifically for PMDD 1, 2.