PREMENSTRUAL DYSPHORIC DISORDER (PMDD): CURRENT PHARMACOTHERAPY AND EMERGING TREATMENT APPROACHES

Authors

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6100

Keywords:

Premenstrual Dysphoric Disorder; Premenstrual Syndrome; Selective Serotonin Reuptake Inhibitors; Hormonal Therapy; Women's Mental Health

Abstract

Premenstrual dysphoric disorder (PMDD) is a cyclic mood disorder affecting a subset of women in the late luteal phase, marked by severe affective and physical symptoms that resolve with menses. It is distinguished from milder premenstrual syndrome (PMS) by symptom severity and functional impairment. PMDD causes substantial distress: women with PMDD have functional impairments comparable to other depressive disorders and increased work absences, and PMDD is associated with higher rates of suicidal ideation and attempts. First-line pharmacotherapy consists of selective serotonin reuptake inhibitors (SSRIs) and hormone-based treatments. SSRIs (e.g. sertraline, fluoxetine, paroxetine, escitalopram) are effective when dosed continuously or in the luteal phase, often producing rapid symptom relief at low doses. Hormonal therapies (e.g. combined oral contraceptives with drospirenone/ethinyl estradiol, GnRH agonists with add-back) can mitigate symptoms by suppressing cyclic ovarian hormone fluctuations. Emerging treatments target PMDD’s neuroendocrine underpinnings: for example, sepranolone (an allopregnanolone antagonist) has shown promising early results. Novel approaches under investigation include neurosteroid modulators, anti-inflammatory strategies, and personalized interventions (genetic or biomarker-driven therapy). This review summarizes current evidence-based pharmacotherapies for PMDD and discusses emerging treatment avenues based on advances in PMDD neurobiology and psychoneuroendocrinology.

References

Appleton, S. M. (2018). Premenstrual syndrome: Evidence-based evaluation and treatment. Clinical Obstetrics and Gynecology, 61(1), 52–61. https://doi.org/10.1097/GRF.0000000000000339

Bäckström, T., Ekberg, K., Hirschberg, A. L., Bixo, M., Epperson, C. N., Briggs, P., Panay, N., & O’Brien, S. (2021). A randomized, double-blind study on efficacy and safety of sepranolone in premenstrual dysphoric disorder. Psychoneuroendocrinology, 133, 105426. https://doi.org/10.1016/j.psyneuen.2021.105426

Behboudi-Gandevani, S., Hariri, F.-Z., & Moghaddam-Banaem, L. (2018). The effect of omega 3 fatty acid supplementation on premenstrual syndrome and health-related quality of life: A randomized clinical trial. Journal of Psychosomatic Obstetrics and Gynaecology, 39(4), 266–272. https://doi.org/10.1080/0167482X.2017.1348496

Berger, C. P., & Presser, B. (1994). Alprazolam in the treatment of two subsamples of patients with late luteal phase dysphoric disorder: A double-blind, placebo-controlled crossover study. Obstetrics and Gynecology, 84(3), 379–385.

Bertone-Johnson, E. R., Ronnenberg, A. G., Houghton, S. C., Nobles, C., Zagarins, S. E., Takashima-Uebelhoer, B. B., Faraj, J. L., & Whitcomb, B. W. (2014). Association of inflammation markers with menstrual symptom severity and premenstrual syndrome in young women. Human Reproduction, 29(9), 1987–1994. https://doi.org/10.1093/humrep/deu170

Bixo, M., Ekberg, K., Poromaa, I. S., Hirschberg, A. L., Jonasson, A. F., Andréen, L., Timby, E., Wulff, M., Ehrenborg, A., & Bäckström, T. (2017). Treatment of premenstrual dysphoric disorder with the GABA-A receptor modulating steroid antagonist sepranolone (UC1010)—A randomized controlled trial. Psychoneuroendocrinology, 80, 46–55. https://doi.org/10.1016/j.psyneuen.2017.02.031

Busse, J. W., Montori, V. M., Krasnik, C., Patelis-Siotis, I., & Guyatt, G. H. (2009). Psychological intervention for premenstrual syndrome: A meta-analysis of randomized controlled trials. Psychotherapy and Psychosomatics, 78(1), 6–15. https://doi.org/10.1159/000162296

Carlini, S. V., & Deligiannidis, K. M. (2020). Evidence-based treatment of premenstrual dysphoric disorder: A concise review. The Journal of Clinical Psychiatry, 81(2), 19ac13071. https://doi.org/10.4088/JCP.19ac13071

Cary, E., & Simpson, P. (2024). Premenstrual disorders and PMDD—A review. Best Practice & Research Clinical Endocrinology & Metabolism, 38(1), 101858. https://doi.org/10.1016/j.beem.2023.101858

Cho, S.-E., & Na, K.-S. (2019). Questioning the beneficial effects of internet-based cognitive behavioral therapy on premenstrual dysphoric disorder. Psychotherapy and Psychosomatics, 88(4), 236. https://doi.org/10.1159/000499681

Cohen, L. S., Soares, C. N., Lyster, A., Cassano, P., Brandes, M., & Leblanc, G. A. (2004). Efficacy and tolerability of premenstrual use of venlafaxine (flexible dose) in the treatment of premenstrual dysphoric disorder. Journal of Clinical Psychopharmacology, 24(5), 540–543. https://doi.org/10.1097/01.jcp.0000138767.53976.10

Dehnavi, S. I., Mortazavi, S. S., Ramezani, M. A., Gharraee, B., & Ashouri, A. (2024). Emotion-focused therapy for women with premenstrual dysphoric disorder: A randomized clinical controlled trial. BMC Psychiatry, 24(1), 501. https://doi.org/10.1186/s12888-024-05681-8

Diagnostic and statistical manual of mental disorders | Psychiatry Online. (n.d.). DSM Library. Retrieved June 3, 2026, from https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890425787

Dimmock, P. W., Wyatt, K. M., Jones, P. W., & O’Brien, P. M. (2000). Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: A systematic review. The Lancet, 356(9236), 1131–1136. https://doi.org/10.1016/S0140-6736(00)02754-9

Dubey, N., Hoffman, J. F., Schuebel, K., Yuan, Q., Martinez, P. E., Nieman, L. K., Rubinow, D. R., Schmidt, P. J., & Goldman, D. (2017). The ESC/E(Z) complex, an effector of response to ovarian steroids, manifests an intrinsic difference in cells from women with premenstrual dysphoric disorder. Molecular Psychiatry, 22(8), 1172–1184. https://doi.org/10.1038/mp.2016.229

Eisenlohr-Moul, T. A., Girdler, S. S., Johnson, J. L., Schmidt, P. J., & Rubinow, D. R. (2017). Treatment of premenstrual dysphoria with continuous vs. intermittent dosing of oral contraceptives: Results of a three-arm randomized controlled trial. Depression and Anxiety, 34(10), 908–917. https://doi.org/10.1002/da.22673

Endicott, J., Nee, J., & Harrison, W. (2006). Daily Record of Severity of Problems (DRSP): Reliability and validity. Archives of Women’s Mental Health, 9(1), 41–49. https://doi.org/10.1007/s00737-005-0103-y

Freeman, E. W., Kroll, R., Rapkin, A., Pearlstein, T., Brown, C., Parsey, K., Zhang, P., Patel, H., Foegh, M., & PMS/PMDD Research Group. (2001). Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder. Journal of Women’s Health & Gender-Based Medicine, 10(6), 561–569. https://doi.org/10.1089/15246090152543148

Freeman, E. W., Rickels, K., Sondheimer, S. J., Polansky, M., & Xiao, S. (2004). Continuous or intermittent dosing with sertraline for patients with severe premenstrual syndrome or premenstrual dysphoric disorder. The American Journal of Psychiatry, 161(2), 343–351. https://doi.org/10.1176/appi.ajp.161.2.343

Freeman, E. W., Rickels, K., Yonkers, K. A., Kunz, N. R., McPherson, M., & Upton, G. V. (2001). Venlafaxine in the treatment of premenstrual dysphoric disorder. Obstetrics and Gynecology, 98(5 Pt 1), 737–744. https://doi.org/10.1016/S0029-7844(01)01530-7

Freeman, E. W., Sondheimer, S. J., & Rickels, K. (1997). Gonadotropin-releasing hormone agonist in the treatment of premenstrual symptoms with and without ongoing dysphoria: A controlled study. Psychopharmacology Bulletin, 33(2), 303–309.

Griffin, L. D., & Mellon, S. H. (1999). Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proceedings of the National Academy of Sciences of the United States of America, 96(23), 13512–13517. https://doi.org/10.1073/pnas.96.23.13512

Halbreich, U., Borenstein, J., Pearlstein, T., & Kahn, L. S. (2003). The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology, 28(Suppl. 3), 1–23. https://doi.org/10.1016/S0306-4530(03)00098-2

Halbreich, U., Freeman, E. W., Rapkin, A. J., Cohen, L. S., Grubb, G. S., Bergeron, R., Smith, L., Mirkin, S., & Constantine, G. D. (2012). Continuous oral levonorgestrel/ethinyl estradiol for treating premenstrual dysphoric disorder. Contraception, 85(1), 19–27. https://doi.org/10.1016/j.contraception.2011.05.008

Hantsoo, L., & Epperson, C. N. (2015). Premenstrual dysphoric disorder: Epidemiology and treatment. Current Psychiatry Reports, 17(11), 87. https://doi.org/10.1007/s11920-015-0628-3

Hantsoo, L., & Epperson, C. N. (2020). Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle. Neurobiology of Stress, 12, 100213. https://doi.org/10.1016/j.ynstr.2020.100213

Hoppe, J. M., Weise, C., Kleinstaeuber, M., Skalkidou, A., Vegelius, J., Comasco, E., Gröndal, M., Kaltsouni, E., Sundström, F., Sampaio, F., Andersson, G., & Buhrman, M. (2025). Emotion regulation-based internet-delivered cognitive behavioural therapy for premenstrual dysphoric disorder: Study protocol for a randomised controlled trial in Sweden. BMJ Open, 15(1), e091649. https://doi.org/10.1136/bmjopen-2024-091649

Hsiao, M.-C., & Liu, C.-Y. (2003). Effective open-label treatment of premenstrual dysphoric disorder with venlafaxine. Psychiatry and Clinical Neurosciences, 57(3), 317–321. https://doi.org/10.1046/j.1440-1819.2003.01123.x

Hunter, M. S., Ussher, J. M., Browne, S. J., Cariss, M., Jelley, R., & Katz, M. (2002). A randomized comparison of psychological (cognitive behavior therapy), medical (fluoxetine) and combined treatment for women with premenstrual dysphoric disorder. Journal of Psychosomatic Obstetrics and Gynaecology, 23(3), 193–199. https://doi.org/10.3109/01674820209074672

Jackson, C., Pearson, B., Girdler, S., Johnson, J., Hamer, R. M., Killenberg, S., & Meltzer-Brody, S. (2015). Double-blind, placebo-controlled pilot study of adjunctive quetiapine SR in the treatment of PMS/PMDD. Human Psychopharmacology, 30(6), 425–434. https://doi.org/10.1002/hup.2494

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), CD001396. https://doi.org/10.1002/14651858.CD001396.pub4

Kleinstäuber, M., Witthöft, M., & Hiller, W. (2012). Cognitive-behavioral and pharmacological interventions for premenstrual syndrome or premenstrual dysphoric disorder: A meta-analysis. Journal of Clinical Psychology in Medical Settings, 19(3), 308–319. https://doi.org/10.1007/s10880-012-9299-y

Lanza di Scalea, T., & Pearlstein, T. (2019). Premenstrual dysphoric disorder. The Medical Clinics of North America, 103(4), 613–628. https://doi.org/10.1016/j.mcna.2019.02.007

Loukzadeh, Z., Eslamy, N., Dehghan, M., & Houshang Mehrparvar, A. (2024). The impact of premenstrual disorders on work disruptions among working women: A cross-sectional study. International Journal of Reproductive Biomedicine, 22(2), 149–156. https://doi.org/10.18502/ijrm.v22i2.15712

Ma, S., & Song, S. J. (2023). Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database of Systematic Reviews, 2023(6), CD006586. https://doi.org/10.1002/14651858.CD006586.pub5

Maharaj, S., & Trevino, K. (2015). A comprehensive review of treatment options for premenstrual syndrome and premenstrual dysphoric disorder. Journal of Psychiatric Practice, 21(5), 334–350. https://doi.org/10.1097/PRA.0000000000000099

Management of premenstrual disorders. (2023). https://www.acog.org/clinical/clinical-guidance/clinical-practice-guideline/articles/2023/12/management-of-premenstrual-disorders

Marais-Thomas, H., Chapelle, F., de Vaux-Boitouzet, V., & Bouvet, C. (2024). [Premenstrual dysphoric disorder (PMDD): Drug and psychotherapeutique management, a literature review]. L’Encephale, 50(2), 211–232. https://doi.org/10.1016/j.encep.2023.08.007

Marjoribanks, J., Proctor, M., Farquhar, C., & Derks, R. S. (2010). Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database of Systematic Reviews, 2010(1), CD001751. https://doi.org/10.1002/14651858.CD001751.pub2

Mazza, M., Harnic, D., Catalano, V., Janiri, L., & Bria, P. (2008). Duloxetine for premenstrual dysphoric disorder: A pilot study. Expert Opinion on Pharmacotherapy, 9(4), 517–521. https://doi.org/10.1517/14656566.9.4.517

Mohammadi, M. M., Dehghan Nayeri, N., Mashhadi, M., & Varaei, S. (2022). Effect of omega-3 fatty acids on premenstrual syndrome: A systematic review and meta-analysis. The Journal of Obstetrics and Gynaecology Research, 48(6), 1293–1305. https://doi.org/10.1111/jog.15217

Naheed, B., Kuiper, J. H., O’Mahony, F., & O’Brien, P. M. (2025). Gonadotropin-releasing hormone (GnRH) analogues for premenstrual syndrome (PMS). Cochrane Database of Systematic Reviews, 2025(6), CD011330. https://doi.org/10.1002/14651858.CD011330.pub2

Nazari, H., Yari, F., Jariani, M., Marzban, A., & Birgandy, M. (2013). Premenstrual syndrome: A single-blind study of treatment with buspirone versus fluoxetine. Archives of Gynecology and Obstetrics, 287(3), 469–472. https://doi.org/10.1007/s00404-012-2594-x

Nguyen, A. T. (2024). U.S. medical eligibility criteria for contraceptive use, 2024. MMWR Recommendations and Reports, 73. https://doi.org/10.15585/mmwr.rr7304a1

Nguyen, T. V., Reuter, J. M., Gaikwad, N. W., Rotroff, D. M., Kucera, H. R., Motsinger-Reif, A., Smith, C. P., Nieman, L. K., Rubinow, D. R., Kaddurah-Daouk, R., & Schmidt, P. J. (2017). The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: Effects of estradiol and progesterone addback. Translational Psychiatry, 7(8), e1193. https://doi.org/10.1038/tp.2017.146

Pearlstein, T., & Steiner, M. (2008). Premenstrual dysphoric disorder: Burden of illness and treatment update. Journal of Psychiatry & Neuroscience, 33(4), 291–301.

Pinna, G., Costa, E., & Guidotti, A. (2006). Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake. Psychopharmacology, 186(3), 362–372. https://doi.org/10.1007/s00213-005-0213-2

Prasad, D., Wollenhaupt-Aguiar, B., Kidd, K. N., de Azevedo Cardoso, T., & Frey, B. N. (2021). Suicidal risk in women with premenstrual syndrome and premenstrual dysphoric disorder: A systematic review and meta-analysis. Journal of Women’s Health, 30(12), 1693–1707. https://doi.org/10.1089/jwh.2021.0185

Ramos, M. G., Hara, C., & Rocha, F. L. (2009). Duloxetine treatment for women with premenstrual dysphoric disorder: A single-blind trial. The International Journal of Neuropsychopharmacology, 12(8), 1081–1088. https://doi.org/10.1017/S1461145709000066

Reilly, T. J., Patel, S., Unachukwu, I. C., Knox, C.-L., Wilson, C. A., Craig, M. C., Schmalenberger, K. M., Eisenlohr-Moul, T. A., & Cullen, A. E. (2024). The prevalence of premenstrual dysphoric disorder: Systematic review and meta-analysis. Journal of Affective Disorders, 349, 534–540. https://doi.org/10.1016/j.jad.2024.01.066

Reilly, T. J., Wallman, P., Clark, I., Knox, C.-L., Craig, M. C., & Taylor, D. (2023). Intermittent selective serotonin reuptake inhibitors for premenstrual syndromes: A systematic review and meta-analysis of randomised trials. Journal of Psychopharmacology, 37(3), 261–267. https://doi.org/10.1177/02698811221099645

Sani, G., Kotzalidis, G. D., Panaccione, I., Simonetti, A., De Chiara, L., Del Casale, A., Ambrosi, E., Napoletano, F., Janiri, D., Danese, E., Girardi, N., Rapinesi, C., Serata, D., Manfredi, G., Koukopoulos, A. E., Angeletti, G., Nicoletti, F., & Girardi, P. (2014). Low-dose acetazolamide in the treatment of premenstrual dysphoric disorder: A case series. Psychiatry Investigation, 11(1), 95–101. https://doi.org/10.4306/pi.2014.11.1.95

Schmidt, P. J., Martinez, P. E., Nieman, L. K., Koziol, D. E., Thompson, K. D., Schenkel, L., Wakim, P. G., & Rubinow, D. R. (2017). Premenstrual dysphoric disorder symptoms following ovarian suppression: Triggered by change in ovarian steroid levels but not continuous stable levels. The American Journal of Psychiatry, 174(10), 980–989. https://doi.org/10.1176/appi.ajp.2017.16101113

Tiranini, L., & Nappi, R. E. (2022). Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome. Faculty Reviews, 11, 11. https://doi.org/10.12703/r/11-11

Weise, C., Kaiser, G., Janda, C., Kues, J. N., Andersson, G., Strahler, J., & Kleinstäuber, M. (2019). Internet-based cognitive-behavioural intervention for women with premenstrual dysphoric disorder: A randomized controlled trial. Psychotherapy and Psychosomatics, 88(1), 16–29. https://doi.org/10.1159/000496237

Wittchen, H.-U., Becker, E., Lieb, R., & Krause, P. (2002). Prevalence, incidence and stability of premenstrual dysphoric disorder in the community. Psychological Medicine, 32(1), 119–132. https://doi.org/10.1017/S0033291701004925

Yonkers, K. A., Brown, C., Pearlstein, T. B., Foegh, M., Sampson-Landers, C., & Rapkin, A. (2005). Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstetrics and Gynecology, 106(3), 492–501. https://doi.org/10.1097/01.AOG.0000175834.77215.2e

Yonkers, K. A., Kornstein, S. G., Gueorguieva, R., Merry, B., Van Steenburgh, K., & Altemus, M. (2015). Symptom-onset dosing of sertraline for the treatment of premenstrual dysphoric disorder: A randomized clinical trial. JAMA Psychiatry, 72(10), 1037–1044. https://doi.org/10.1001/jamapsychiatry.2015.1472

Yonkers, K. A., O’Brien, P. M. S., & Eriksson, E. (2008). Premenstrual syndrome. The Lancet, 371(9619), 1200–1210. https://doi.org/10.1016/S0140-6736(08)60527-9

Yonkers, K. A., Pearlstein, T., Fayyad, R., & Gillespie, J. A. (2005). Luteal phase treatment of premenstrual dysphoric disorder improves symptoms that continue into the postmenstrual phase. Journal of Affective Disorders, 85(3), 317–321. https://doi.org/10.1016/j.jad.2004.10.006

ZOLOFT (sertraline hydrochloride) label. (n.d.). Retrieved June 4, 2026, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019839s74s86s87_20990s35s44s45lbl.pdf

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2026-08-21

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Oziębło, J., Kijowska, M. ., Klusek, K., Batory, M., Jakubowski, J., Kraska, K., Krasucka, N., Zynkowska, A., Skrzyniarz, A. M., & Kiełbus, M. (2026). PREMENSTRUAL DYSPHORIC DISORDER (PMDD): CURRENT PHARMACOTHERAPY AND EMERGING TREATMENT APPROACHES. International Journal of Innovative Technologies in Social Science, 1(3(51). https://doi.org/10.31435/ijitss.3(51).2026.6100

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