Luteal Phase Dosing and Sexual Side Effects in PMDD
Luteal phase dosing of fluoxetine for PMDD will likely reduce the risk of sexual side effects compared to continuous daily dosing, though the evidence specifically examining sexual dysfunction with intermittent versus continuous SSRI regimens in PMDD is limited.
Key Evidence on Dosing Strategies
Fluoxetine is effective for PMDD when administered either continuously (daily throughout the menstrual cycle) or intermittently during the luteal phase only, with both 20 mg daily luteal dosing and even weekly 90 mg luteal dosing demonstrating efficacy 1, 2. The critical finding is that continuous SSRI administration appears more effective for overall symptom reduction than luteal-phase-only dosing (continuous: SMD -0.69 vs luteal: SMD -0.39, p=0.03 for difference) 3.
Sexual Dysfunction Risk Profile
- SSRIs cause sexual dysfunction or decreased libido with an odds ratio of 2.32 compared to placebo in PMDD treatment 3
- Among SSRIs, paroxetine carries the highest risk of sexual dysfunction at 70.7% incidence, while fluoxetine has lower rates 4, 5
- The theoretical advantage of luteal-phase-only dosing is reduced cumulative SSRI exposure—approximately 50% less drug exposure per month—which should translate to fewer sexual side effects 1, 6
Paradoxical Findings in PMDD
One study found a counterintuitive result: fluoxetine treatment showed a trend toward improving luteal phase sexual drive and desire in women with PMDD (p=0.057), suggesting that when decreased libido is part of the PMDD symptom cluster itself, treating the underlying disorder may restore sexual function 7. This highlights that you must distinguish between PMDD-related sexual dysfunction (which improves with treatment) versus SSRI-induced sexual dysfunction (which worsens with treatment).
Clinical Decision Algorithm
For patients prioritizing sexual function:
- Start with luteal-phase-only fluoxetine 20 mg daily (14 days premenstrually) to minimize SSRI exposure while maintaining efficacy 1, 6
- Intermittent dosing shows 75% response rates with minimal side effects 6
- If inadequate response after 2-3 cycles, escalate to continuous daily dosing, accepting the trade-off of better symptom control against higher sexual dysfunction risk 3
For patients with severe PMDD symptoms:
- Continuous dosing provides superior efficacy and should be first-line despite higher sexual side effect risk 3
- If sexual dysfunction emerges, consider switching to bupropion (though evidence for bupropion in PMDD specifically is lacking) 5
Important Caveats
- Sexual dysfunction rates are vastly underreported in clinical trials, so actual incidence may exceed published figures 4, 5
- Discontinuation effects have not been reported with intermittent SSRI dosing regimens in PMDD, making luteal-phase dosing particularly attractive 1
- The most common adverse effects with SSRIs in PMDD are nausea (OR 3.30), asthenia (OR 3.28), and somnolence (OR 3.26), not just sexual dysfunction 3