List of investigational PMS/PMDD drugs
This is a list of investigational PMS/PMDD drugs, or drugs that are currently under development for clinical use for the treatment of premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) but are not yet approved.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action – Indication [Reference]".
This list was last comprehensively updated in March 2026. It is likely to become outdated with time.
Under development
Phase 2
- Pyridoxamine (RS-8001) – vitamin B6 and antioxidant – PMS [1][1][2]
- Refisolone (ORG-39479; PH-80; PH-80-M; PH80-PMD NS) – vomeropherine / "neurotransmitter receptor modulator" – PMDD [2]
- Sepranolone (isoallopregnanolone; UC-1010) – GABAA receptor negative allosteric modulator and excitatory neurosteroid – PMDD [3][3][4][5][6][7]
Not under development
No development reported
- Ethinylestradiol/drospirenone (dihydrospirorenone/ethinylestradiol; drospirenone/ethinylestradiol; Petibelle; SH-470; Yasmin; ZK-30595) – combination of ethinylestradiol (estrogen) and drospirenone (progestin) – PMS and PMDD [4]
- Progesterone intranasal (MetP Progesterone Nasal Gel; MPP 22; ProgestoMat) – progestogen (progesterone receptor agonist) and GABAA receptor positive allosteric modulator (via metabolites) – PMS [5]
- Progesterone vaginal – progestogen (progesterone receptor agonist) and GABAA receptor positive allosteric modulator (via metabolites) – PMS [6]
- Research programme: premenstrual syndrome therapeutic - Panacor Bioscience (PB301) – undefined mechanism of action – PMS [7]
Discontinued
- Ethinylestradiol/levonorgestrel continuous (EE/Levo continuous; EE/LNG continuous; Levo/EE continuous; Levonorgestrel/ethinlyestradiol continuous; Librel; LNG/EE continuous; Lybrel) – combination of ethinylestradiol (estrogen) and levonorgestrel (progestin) – PMS and PMDD [8]
- Progesterone transdermal (progesterone spray; Progesterone TDS®) – progestogen (progesterone receptor agonist) and GABAA receptor positive allosteric modulator (via metabolites) – PMS [9]
Clinically used drugs
Approved drugs
Hormonal agents
- Ethinylestradiol/drospirenone low-dose (BAY86-5300; BAY86-5300-YAZ-Flex; Drospirenone/ethinylestradiol; EE20/Drospirenone; EE20/DRSP; Ethinylestradiol-Drospirenone 24+4; Flexyess; SH-T-00186D; Yasmin® 20; Yasminelle; Yaz; Yaz 24+4; Yaz Extended Cycle; YAZ Extended Regimen; Yaz Flex; Yvidually) – combination of ethinylestradiol (estrogen) and drospirenone (progestin) – PMS and PMDD [10][8][9]
- Ethinylestradiol/drospirenone/levomefolic acid (BAY98-7071; Beyaz; EE20/DRSP/L-5MTHF; ethinylestradiol/drospirenone/methyltetrahydrofolate; Safyral; Yasmin Plus; Yaz Flex Plus; Yaz Plus) – combination of ethinylestradiol (estrogen), drospirenone (progestin), and levomefolic acid (vitamin B9) – PMDD [11][8]
- Progesterone gel (COL-1620; Crinone; Crinone 4%; Crinone 8%; Crinone8%; OneCrinone; Prochieve; Prochieve4%; Prochieve8%; progesterone vaginal gel 4%; progesterone vaginal gel 8%) – progestogen (progesterone receptor agonist) and GABAA receptor positive allosteric modulator (via metabolites) – PMS [12]
- Progesterone vaginal (Utrogestan) – progestogen (progesterone receptor agonist) and GABAA receptor positive allosteric modulator (via metabolites) – PMS [13]
Antidepressants
- Fluoxetine (LY-110140; Prozac; Prozac Weekly; Reneuron; Sarafem) – selective serotonin reuptake inhibitor (SSRI) – PMDD [14]
- Paroxetine (Aropax; BRL 29060; BRL 29060A; Deroxat; Divarius; FG 7051; Frosinor; Motivan; NNC 207051; Paxil; Paxil CR; Seroxat; SI 211103; Tagonis) – selective serotonin reuptake inhibitor (SSRI) – PMDD [15]
- Sertraline (Aremis; Besitran; CP 51974; CP 51974 01; Gladem; J Zoloft; Lustral; Serad; Serlain; Tatig; Zoloft) – selective serotonin reuptake inhibitor (SSRI) – PMDD [16]
Off-label drugs
Hormonal agents
- 5α-Reductase inhibitors (e.g., dutasteride) (via neurosteroid synthesis inhibition)[4][5][10][11]
- Androgens (androgen receptor agonists) (e.g., danazol)[3][12]
- GnRH agonists (e.g., leuprorelin) and GnRH antagonists (e.g., elagolix, relugolix) (with or without add-back estrogen–progestogen therapy)[13][14][15]
- Neurosteroids acting as GABAA receptor positive allosteric modulators (e.g., brexanolone (allopregnanolone), zuranolone, ganaxolone)[10][5][16]
- Other contraceptive and non-contraceptive estrogen–progestogen therapies[3][9][17]
- Other progesterone formulations and progestogens[18][19]
- Selective progesterone receptor modulators (SPRMs) (e.g., ulipristal acetate)[20][5][3][21]
- Spironolactone (Aldactone) – antimineralocorticoid (mineralocorticoid receptor antagonist), other actions[12][22]
Psychiatric medications
- Anxiolytics (e.g., benzodiazepines (e.g., alprazolam), buspirone)[3][12][22]
- Other selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, escitalopram)[23][3][22]
- Other serotonergic antidepressants (e.g., venlafaxine, duloxetine, clomipramine)[12][22][3]
See also
- List of investigational drugs
- List of investigational sex-hormonal agents
- List of investigational antidepressants
References
- ^ Takeda T (February 2023). "Premenstrual disorders: Premenstrual syndrome and premenstrual dysphoric disorder". J Obstet Gynaecol Res. 49 (2): 510–518. doi:10.1111/jog.15484. PMID 36317488.
- ^ Robinson J, Ferreira A, Iacovou M, Kellow NJ (February 2025). "Effect of nutritional interventions on the psychological symptoms of premenstrual syndrome in women of reproductive age: a systematic review of randomized controlled trials". Nutr Rev. 83 (2): 280–306. doi:10.1093/nutrit/nuae043. PMC 11723155. PMID 38684926.
- ^ a b c d e f g Carlini SV, Lanza di Scalea T, McNally ST, Lester J, Deligiannidis KM (January 2024). "Management of Premenstrual Dysphoric Disorder: A Scoping Review". Focus (Am Psychiatr Publ). 22 (1): 81–96. doi:10.1176/appi.focus.23021035. PMC 11058916. PMID 38694162.
- ^ a b Sikes-Keilp C, Rubinow DR (August 2023). "GABA-ergic Modulators: New Therapeutic Approaches to Premenstrual Dysphoric Disorder". CNS Drugs. 37 (8): 679–693. doi:10.1007/s40263-023-01030-7. PMID 37542704.
- ^ a b c d Tiranini L, Nappi RE (2022). "Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome". Fac Rev. 11: 11. doi:10.12703/r/11-11. PMC 9066446. PMID 35574174.
- ^ Bäckström T, Ekberg K, Hirschberg AL, Bixo M, Epperson CN, Briggs P, Panay N, O'Brien S (November 2021). "A randomized, double-blind study on efficacy and safety of sepranolone in premenstrual dysphoric disorder". Psychoneuroendocrinology. 133 105426. doi:10.1016/j.psyneuen.2021.105426. PMID 34597899.
- ^ Bixo M, Ekberg K, Poromaa IS, Hirschberg AL, Jonasson AF, Andréen L, Timby E, Wulff M, Ehrenborg A, Bäckström T (June 2017). "Treatment of premenstrual dysphoric disorder with the GABAA receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial". Psychoneuroendocrinology. 80: 46–55. doi:10.1016/j.psyneuen.2017.02.031. PMID 28319848.
- ^ a b Ma S, Song SJ (June 2023). "Oral contraceptives containing drospirenone for premenstrual syndrome". Cochrane Database Syst Rev. 6 (6) CD006586. doi:10.1002/14651858.CD006586.pub5. PMC 10289136. PMID 37365881.
- ^ a b Berni LC, Nunes LR, Oliveira RC (March 2026). "Comparison of premenstrual dysphoric disorder treatment with antidepressants and combined oral contraceptives: a systematic review with network meta-analysis". J Psychiatr Res. 194: 99–115. doi:10.1016/j.jpsychires.2025.12.046. PMID 41468627.
- ^ a b Bixo M, Stiernman L, Bäckström T (June 2025). "Neurosteroids and premenstrual dysphoric disorder". Br J Psychiatry: 1–9. doi:10.1192/bjp.2025.103. PMID 40518728.
In women with PMDD, premenstrual mood improves when serum levels of allopregnanolone are decreased, either by inhibition of ovarian progesterone/allopregnanolone production or hampering of progesterone metabolism to allopregnanolone using a 5α reductase inhibitor.83,84
- ^ Martinez PE, Rubinow DR, Nieman LK, Koziol DE, Morrow AL, Schiller CE, Cintron D, Thompson KD, Khine KK, Schmidt PJ (March 2016). "5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder". Neuropsychopharmacology. 41 (4): 1093–1102. doi:10.1038/npp.2015.246. PMC 4748434. PMID 26272051.
- ^ a b c d Maharaj S, Trevino K (September 2015). "A Comprehensive Review of Treatment Options for Premenstrual Syndrome and Premenstrual Dysphoric Disorder". J Psychiatr Pract. 21 (5): 334–350. doi:10.1097/PRA.0000000000000099. PMID 26352222.
- ^ Naheed B, Kuiper JH, O'Mahony F, O'Brien PM (June 2025). "Gonadotropin-releasing hormone (GnRH) analogues for premenstrual syndrome (PMS)". Cochrane Database Syst Rev. 6 (6) CD011330. doi:10.1002/14651858.CD011330.pub2. PMID 40492482.
- ^ Wyatt KM, Dimmock PW, Ismail KM, Jones PW, O'Brien PM (June 2004). "The effectiveness of GnRHa with and without 'add-back' therapy in treating premenstrual syndrome: a meta analysis". BJOG. 111 (6): 585–593. doi:10.1111/j.1471-0528.2004.00135.x. PMID 15198787.
- ^ Panay, Nick (2024). "Management of Severe Premenstrual Syndrome (PMS)/Premenstrual Dysphoric Disorder (PMDD)". Menstrual Bleeding and Pain Disorders from Adolescence to Menopause. Cham: Springer International Publishing. p. 95–104. doi:10.1007/978-3-031-55300-4_8. ISBN 978-3-031-55299-1. Retrieved 9 March 2026.
- ^ Marecki R, Kałuska J, Kolanek A, Hakało D, Waszkiewicz N (2023). "Zuranolone - synthetic neurosteroid in treatment of mental disorders: narrative review". Front Psychiatry. 14 1298359. doi:10.3389/fpsyt.2023.1298359. PMC 10729607. PMID 38116383.
- ^ Naheed B, Kuiper JH, Uthman OA, O'Mahony F, O'Brien PM (March 2017). "Non-contraceptive oestrogen-containing preparations for controlling symptoms of premenstrual syndrome". Cochrane Database Syst Rev. 3 (3) CD010503. doi:10.1002/14651858.CD010503.pub2. PMC 6464572. PMID 28257559.
- ^ Ford O, Lethaby A, Roberts H, Mol BW (March 2012). "Progesterone for premenstrual syndrome". Cochrane Database Syst Rev. 2012 (3) CD003415. doi:10.1002/14651858.CD003415.pub4. PMC 7154383. PMID 22419287.
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- ^ Sundström-Poromaa I, Comasco E (May 2023). "New Pharmacological Approaches to the Management of Premenstrual Dysphoric Disorder". CNS Drugs. 37 (5): 371–379. doi:10.1007/s40263-023-01004-9. PMC 10212816. PMID 37171547.
- ^ Comasco E, Kopp Kallner H, Bixo M, Hirschberg AL, Nyback S, de Grauw H, Epperson CN, Sundström-Poromaa I (March 2021). "Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder: A Proof-of-Concept Randomized Controlled Trial". Am J Psychiatry. 178 (3): 256–265. doi:10.1176/appi.ajp.2020.20030286. PMID 33297719.
- ^ a b c d Jarvis CI, Lynch AM, Morin AK (July 2008). "Management strategies for premenstrual syndrome/premenstrual dysphoric disorder". Ann Pharmacother. 42 (7): 967–978. doi:10.1345/aph.1K673. PMID 18559957.
- ^ Jespersen C, Lauritsen MP, Frokjaer VG, Schroll JB (August 2024). "Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder". Cochrane Database Syst Rev. 8 (8) CD001396. doi:10.1002/14651858.CD001396.pub4. PMC 11323276. PMID 39140320.