Agatha was introduced in a prior PsychSnap as a 24-year old medical student with intermittent severe depressive symptoms that cause marked functional impairment. Her symptoms start 5 days before her period and fully resolve shortly after her period begins. 2 months ago, you gave Agatha a presumptive diagnosis of PMDD and asked her to prospectively track her symptoms. She filled out the DRSP daily for 2 months. Her depressed mood, feeling of overwhelm, fatigue, anxiety, and crying start in the week leading up to her period and abate by day 2-3 of her menses, confirming your presumptive diagnosis of PMDD. Agatha is interested in treatment.
How do you treat premenstrual dysphoric disorder (PMDD)?
There is moderate-quality evidence to support the use of SSRIs for the treatment of PMDD (Wakil 2012), and the American College of Obstetrics and Gynecology (ACOG) strongly recommends their use (ACOG 2023). The FDA has approved sertraline, paroxetine, and fluoxetine for the treatment of PMDD, and escitalopram and citalopram have also been shown to be effective (Marjoribanks 2013). For someone has never taken an SSRI, I would start with a very low to low-dose of sertraline, fluoxetine, or escitalopram, due to a higher risk of side effects from paroxetine and citalopram.
SSRIs reduce the core affective symptoms of PMDD with response rates of 60-70% (Yonkers 1997). These response rates are comparable to those observed in generalized anxiety disorder (GAD; approximately 50-60%) and higher than SSRI response rates in major depressive disorder (MDD; approximately 40-50%).
Notably, SSRIs improve PMDD symptoms faster than MDD or GAD symptoms, with rapid improvement in hours to days (versus weeks to months for MDD and GAD). The rapid response to SSRIs suggests a mechanism of action for PMDD other than serotonin reuptake inhibition. The leading model suggests that women with PMDD are abnormally sensitive to normal luteal-phase fluctuations in progesterone and its neuroactive metabolite allopregnanolone. Allopregnanolone is a potent positive allosteric modulator of the GABA-A receptor, like benzodiazepines and z-drugs, and cyclical changes in its concentration across the menstrual cycle may trigger mood symptoms in susceptible individuals (Gao 2023). The medication recently approved for post-partum depression (zuranolone) is a synthetic version of allopregnanolone.
The rapid response of PMDD symptoms to SSRIs opens the possibility of 3 dosing strategies:continuous, intermittent during the luteal phase, or intermittent during PMDD symptoms.
A patient who prefers intermittent dosing can start taking the SSRI on day 14 of her menses (luteal dosing) or when her PMDD symptoms are about to start (symptom-triggered dosing). She can stop the SSRI when PMDD symptoms abate.
Intermittent dosing strategies can make sense for women who respond to lower doses of SSRIs and who have predictable menses and PMDD symptoms. Intermittent dosing (compared with continuous dosing) may reduce the impact of some SSRI side effects, including weight gain and sexual side effects. Intermittent dosing may also be preferable for women who don’t like the idea of taking a pill every day, or who want to avoid the risk of SSRI withdrawal symptoms in the future.
Continuous dosing may be more effective than intermittent dosing for treating PMDD, however. A 2024 Cochrane review notes that SSRIs are “probably more effective” when taken continuously (SMD -0.69 (95% CI −0.88 to −0.51) rather than intermittently during the luteal phase (SMD −0.39 (95% CI −0.58 to −0.21), with P = 0.03 for subgroup difference (Jespersen 2024). Intermittent dosing of SSRIs may also carry a higher risk for early start-up SSRI side effects (agitation, insomnia, headache, nausea), particularly at moderate or high doses.
The first-line pharmacologic treatment for PMDD is either intermittent or continuous dosing with very-low or low-dose SSRIs. If luteal dosing of a low dose SSRI is not effective, switch to continuous dosing as the next step. If continuous dosing of a low dose SSRI is not effective, try a moderate dose of that SSRI. A 2013 Cochrane review of 31 randomized placebo-controlled trials for PMDD demonstrated that moderate dose SSRIs (OR 2.55; 95% CI 1.84 to 3.53) were significantly more effective than low-dose SSRIs (OR 1.76 95% CI 1.13 to 2.75), with both doses being more effective than placebo (Marjoribanks 2013). If continuous dosing of a moderate dose SSRI is ineffective, switch to another SSRI.
Evidence of antidepressant efficacy for PMDD is limited to SSRIs and venlafaxine (Wakil 2012). While bupropion can be very effective for MDD, bupropion should NOT be used for PMDD (or anxiety disorders, OCD or PTSD).
What are other treatment options for PMDD?
The hormone fluctuations over the menstrual cycle and the cyclic fluctuations of PMDD symptoms make hormone-based treatments an intuitive option. Yaz (drospirenone/ethinyl estradiol with 4 placebo pills) is the only OCP that is FDA approved for the treatment of PMDD. In a multicenter, double-blind RCT of 450 people with moderate to severe PMDD, 48% of the treatment group experienced a response (50% reduction in symptoms) compared to 36% of the placebo group (Yonkers 2005). There have not been large studies comparing the effectiveness of Yaz to other combined OCPs. A meta-analysis of 9 low quality placebo-controlled RCTs demonstrated that combined OCPs improved PMS symptoms and functional impairment without helping mood or depressive symptoms (ACOG 2023).
In theory, continuous use of combined OCPs (with no placebo) or fewer placebo pill days (24-day with 4-days placebo vs 21-day with 1-week placebo) would limit a woman’s exposure to hormonal fluctuations. However, no specific dosing regimen has shown improved efficacy over another (de Wit 2021).
Patients with PMDD who want to start hormonal contraception could reasonably start the OCP first while continuing to track their PMDD symptoms. If their PMDD symptoms aren’t adequately controlled after 2 months on the OCP, an SSRI could be added.
For severe, refractory symptoms, GnRH agonists like leuprolide induce medical menopause and are highly effective. They must be combined with add-back therapy with continuous estrogen and progesterone (ACOG 2023). Consult with gynecology before initiating GnRH agonism.
Women who benefit from pharmacologic treatment of PMDD generally continue the treatment until menopause, except during pregnancy (women are symptom free when not menstruating) and, for OCPs, while trying to conceive. Women with PMDD have an elevated risk for post-partum depression and other mood disorders (Wakil 2012, Schleimann-Jensen 2025).
You express appreciation for the effort that Agatha put into symptom tracking and discuss evidence-based treatment options for PMDD, starting with an SSRI. Agatha has never taken an SSRI before and is concerned about the risk of weight gain. She thinks taking a pill daily will be easier for her than intermittent dosing. You recommend that she start taking fluoxetine 10mg daily this month, with a plan to increase to 20mg next month if her symptoms aren’t controlled. You recommend that she continue prospective symptom tracking until your follow up in 2 months.
Key Points
1) SSRIs are the first line treatment for patients with PMDD, with a response rate of 60-70%.
2) PMDD symptoms respond quickly to SSRIs, allowing SSRIs to be dosed continuously, intermittently during the luteal phase, or intermittently when symptomatic.
3) At a population level, continuous dosing of SSRIs for PMDD is more effective than intermittent dosing, and moderate doses of SSRIs are more effective than lower doses. However, intermittent dosing of low-dose SSRIs can be effective for some women.
4) Combined OCPs for PMDD should be considered after an inadequate response to 2 SSRIs or for a woman who wants to start them for birth control. Yaz is the only FDA approved OCP for PMDD.
Related PsychSnaps:”How do you diagnose premenstrual dysphoric disorder (PMDD)?” Zoë Kopp, January 2026.
References:
ACOG. (2023). Management of Premenstrual Disorders. Obstetrics and Gynecology. 142(6), 1516-1533.
de Wit AE, de Vries YA, de Boer MK, Scheper C, Fokkema A, Janssen CA, et al. (2021). Efficacy of combined oral contraceptives for depressive symptoms and overall symptomatology in pre- menstrual syndrome: pairwise and network meta-analysis of randomized trials. Am J Obstet Gynecol. 225, 624–33.
Gao, Q, et al. (2023). Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: toward precise targets for translational medicine and drug development. Frontiers in Psychiatry. 14, 1140796.
Jespersen, C., Lauritsen, M. P., Frokjaer, V. G., & Schroll, J. B. (2024). Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. Cochrane Database of Systematic Reviews, 2024(8).
Marjoribanks, J., Brown, J., O’Brien, P. M. S., & Wyatt, K. (2013). Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database of Systematic Reviews.
Schleimann-Jensen, E., Sundström-Poromaa, I., Meltzer-Brody, S., Eisenlohr-Moul, T. A., Papadopoulos, F. C., Skalkidou, A., & Comasco, E. (2025). Trajectories and dimensional phenotypes of depressive symptoms throughout pregnancy and postpartum in relation to prior premenstrual symptoms. The British Journal of Psychiatry, 226(6), 401–409.
Wakil, L., Meltzer-Brody, S., & Girdler, S. (2012). Premenstrual dysphoric disorder: How to alleviate her suffering. Current Psychiatry. 11(4), 22-37.
Yonkers KA, Brown C, Pearlstein TB, et al. (2005). Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol. 106(3), 492-501.
Yonkers KA, Clark RH, Trivedi MH. (1997). The psychopharmacological treatment of nonmajor mood disorders. Mod Probl Pharmacopsychiatry. 25, 146-166.