How should I manage a woman with premenstrual dysphoric disorder who is already taking sertraline 100 mg daily?

Management of PMDD in a Patient Already on Sertraline 100mg

If the patient is not adequately responding to sertraline 100mg daily, increase the dose to 150mg daily (or up to 200mg if needed), as the FDA-approved dosing range for PMDD is 50-150mg/day for continuous dosing and 50-100mg/day for luteal-phase dosing. 1

Assess Current Treatment Response

• Evaluate symptom control using validated tools like the Daily Record of Severity of Problems to determine if current therapy is providing adequate relief of emotional, behavioral, and physical symptoms 2
• Review dosing strategy: Confirm whether the patient is taking sertraline continuously throughout the menstrual cycle or only during the luteal phase, as both strategies are FDA-approved but may have different efficacy profiles 1
• Assess tolerability: Inquire specifically about sexual dysfunction (14% ejaculatory failure, 6% decreased libido), insomnia, and other side effects that may impact adherence 3

Dose Optimization Strategy

If Currently on Continuous Daily Dosing (100mg/day)

• Increase to 150mg daily if symptoms are inadequately controlled, as the FDA label supports doses up to 200mg/day for PMDD with dose increases at 50mg increments per menstrual cycle 1
• Maximum dose is 200mg/day for continuous dosing, with dose changes occurring no more frequently than once per week given sertraline's 24-hour elimination half-life 1

If Currently on Luteal-Phase Dosing (100mg/day)

• The maximum luteal-phase dose is 100mg/day per FDA labeling, which is already achieved 1
• Consider switching to continuous daily dosing starting at 100mg/day if luteal-phase dosing is insufficient, as continuous dosing may provide superior symptom control 4

Alternative Dosing Strategy: Switch to Luteal-Phase Dosing

If the patient is currently on continuous dosing and experiencing intolerable side effects (particularly sexual dysfunction), switch to intermittent luteal-phase dosing at 50-100mg/day starting 14 days before expected menses. 1, 2

• Luteal-phase dosing is equally effective as continuous dosing for PMDD symptoms, with 50% responder rates versus 26% for placebo by cycle 1 2
• Better tolerability profile: Only 8% discontinuation rate due to adverse events with luteal-phase sertraline versus higher rates with continuous dosing 2
• Initiation protocol: Start at 50mg/day during the luteal phase; if inadequate response, increase to 100mg/day in subsequent cycles 1
• Timing: Begin dosing 14 days before expected menses and continue through the first few days of menstruation 2, 5

Symptom-Onset Dosing Option

For patients who can reliably identify symptom onset, consider symptom-onset dosing at 25-50mg/day, which has demonstrated efficacy particularly at the 25mg dose. 6

• This strategy allows treatment initiation at the first sign of premenstrual symptoms rather than on a fixed calendar schedule 6
• Lower doses (25mg/day) may be effective for moderate-to-severe PMS, potentially reducing side effect burden 6

When Current Sertraline Therapy Fails

Dose Escalation First

• Increase to 150mg/day (or 200mg/day maximum) before considering medication switch, as higher doses may benefit non-responders to 100mg 1
• Allow adequate trial duration: Assess response over at least 2-3 menstrual cycles at the higher dose before declaring treatment failure 2

Consider Medication Switch

If sertraline at maximum tolerated dose (up to 200mg/day) fails after 2-3 cycles, switch to bupropion as first-line alternative, which has significantly lower sexual dysfunction rates (8-10%) and may be better tolerated. 3

• Bupropion is contraindicated in patients with seizure disorders or high agitation 3
• Alternative SSRIs: If bupropion is contraindicated, consider switching to another SSRI, though paroxetine should be avoided due to 70.7% sexual dysfunction rate 3
• Washout period: Allow 5-7 days (up to 2 weeks) washout when switching to an MAOI to prevent serotonin syndrome 7

Address Sexual Dysfunction if Present

Sexual dysfunction is the most common reason for SSRI discontinuation and must be directly assessed, as patients rarely volunteer this information. 3

Management Algorithm for Sexual Dysfunction

1. Reduce dose to minimum effective level (e.g., 50mg/day) if sexual dysfunction is problematic, as sexual side effects are strongly dose-related 3
2. Switch to luteal-phase dosing to reduce total drug exposure while maintaining efficacy 2, 5
3. If dysfunction persists, switch to bupropion (8-10% sexual dysfunction rate versus 14% with sertraline) 3
4. Adjunctive PDE5 inhibitors (sildenafil, tadalafil) can address erectile dysfunction if present, though they do not improve libido 3
5. Check testosterone levels (total morning testosterone >300 ng/dL) as low testosterone contributes to decreased libido independent of SSRI effects 3

Critical Safety Monitoring

• Avoid abrupt discontinuation of continuous daily sertraline to prevent SSRI withdrawal syndrome; taper gradually over 10-14 days if discontinuation is necessary 3, 7
• Monitor for serotonin syndrome if combining with other serotonergic agents, with symptoms including mental status changes, neuromuscular hyperactivity, and autonomic instability 8
• Screen for bipolar disorder history before continuing SSRI therapy, as SSRIs can precipitate mania in susceptible individuals 8
• Assess for suicidal ideation particularly in adolescents and patients with comorbid depression, though elevated suicide risk has not been found in non-depressed women treated for PMS 8

Maintenance Therapy Considerations

• Long-term efficacy beyond 3 menstrual cycles has not been systematically evaluated in controlled trials, though continued treatment is reasonable as symptoms typically worsen with age until menopause 1
• Periodic reassessment is required to determine ongoing need for treatment and to maintain patients on the lowest effective dose 1
• Dosage adjustments may include switching between continuous and luteal-phase regimens based on symptom control and tolerability 1