Premenstrual dysphoric disorder

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Premenstrual dysphoric disorder
Classification and external resources
Specialty Psychiatry
ICD-10 F38.8
ICD-9-CM 311,[1] 625.4[2]
MedlinePlus 007193
eMedicine article/293257

Premenstrual dysphoric disorder (PMDD) is a severe and disabling form of premenstrual syndrome affecting 3–8% of women.[3] The disorder consists of a "cluster of affective, behavioral and somatic symptoms" that recur monthly during the luteal phase of the menstrual cycle.[3] PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders V in 2013. The exact pathogenesis of the disorder is still unclear and is an active research topic. Treatment of PMDD relies largely on antidepressants that modulate serotonin levels in the brain via serotonin reuptake inhibitors as well as ovulation suppression using contraception.[4]


Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). Like PMS, premenstrual dysphoric disorder follows a predictable, cyclic pattern. Symptoms begin in the late luteal phase of the menstrual cycle (after ovulation) and end shortly after menstruation begins.[5] On average, the symptoms last six days but can start up to two weeks before menses. The most intense symptoms occur two days before the start of menstrual blood flow through the first day of menstrual blood flow. The symptoms should cease shortly after the start of the menstrual period.[4][6]

The symptoms in PMDD can be both physical and emotional with mood symptom being dominant.[5] The most debilitating symptoms are emotional and include "irritability, depression, mood lability, anxiety, feelings of ‘loss of control’, difficulty concentrating and fatigue."[4] The physical symptoms include " abdominal bloating, breast tenderness, headache and generalized aches."[4]


The etiology of PMDD is still an active area of research. While the timing of symptoms suggest a hormonal fluctuations as the cause of PMDD, a demonstrable hormonal imbalance in women with PMDD has not been identified. In fact, levels of reproductive hormones in women with and without PMDD are indistinguishable.[7] It is instead hypothesized that women with PMDD are more sensitive to normal levels of hormone fluctuations, predominantly estrogen and progesterone which produces biochemical events in the nervous system that cause the premenstrual symptoms.[7] These symptoms are more predominant in women who have a predisposition to the disorder.[5]


In 2013, PMDD became a disorder with official diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V). The DSM-V lists the following eleven signs as possible symptoms experienced by those with PMDD:[4][8]

  1. Marked lability (e.g., mood swings)
  2. Marked irritability or anger
  3. Markedly depressed mood
  4. Marked anxiety and tension
  5. Decreased interest in usual activities
  6. Difficulty in concentration
  7. Lethargy and marked lack of energy
  8. Marked change in appetite (e.g., overeating or specific food cravings)
  9. Hypersomnia or insomnia
  10. Feeling overwhelmed or out of control
  11. Physical symptoms (e.g., breast tenderness or swelling, joint or muscle pain, a sensation of ‘bloating’ and weight gain)[4][8]

According to the DSM-V, a diagnosis of PMDD requires the presence of at least five of these symptoms with one of the symptoms being number 1-4 (marked lability, irritability, depressed mood, anxiety and tension. These symptoms should occur during the week before menses and remit after initiation of menses. In order to meet criteria for the diagnosis, the symptoms should be charted prospectively for two consecutive ovulation cycles in order to confirm temporal and cyclical nature of symptoms. The symptoms should also be severe enough to affect normal work, school, or social activities or relationships with others.[8]

Other organizations that have published diagnostic criteria for PMDD include the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians and Gynecologists, and the International Society for the Study of Premenstrual Disorders (ISPMD).[9][10][11] The ISPMD was a consensus group established by an international multidisciplinary group of experts. The group's diagnostic criteria for PMDD focuses on the cyclic nature of the symptom occuring during the luteal phase of the menstrual cycle, symptoms being absent after menstruation and before ovulation and causing sigificant impairment. The ISPMD diagnostic criteria for PMDD do not specify symptom characteristics or number of symptoms. [11]

While there are many well-recognized health organizations that acknowledge PMDD as a medical disorder, in many parts of the world, PMDD is not recognized as a disease. PMDD is not listed as a separate disorder in the World Health Organization's International Classification of Diseases (ICD).[12]

In 2003, the Committee for Proprietary Medicinal Products required the manufacturer of Prozac (fluoxetine) to remove PMDD from the list of indications for fluoxetine sold in Europe.[13] Reflecting the approach of the ICD-10, the committee found that

...PMDD is not a well-established disease entity across Europe... There was considerable concern that women with less severe pre-menstrual symptoms might erroneously receive a diagnosis of PMDD resulting in widespread inappropriate short and long-term use of fluoxetine.[14]

In Australia, PMDD is recognized by the Therapeutic Goods Administration. However, SSRIs are not reimbursed for PMDD under the Pharmaceutical Benefits Scheme.[15]


Pharmacologic treatment[edit]

Pharmacologic treatment of PMDD is indicated for women with severe and debilitating symptoms. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication.[5] The U.S. Food and Drug Administration (FDA) has approved four SSRIs for the treatment of PMDD: Fluoxetine (available as generic or as Prozac or Sarafem), sertraline (Zoloft), paroxetine (Paxil), and escitalopram oxalate (Lexapro).[16] Unlike treatments for depressive disorders, SSRIs do not need to be taken daily but instead can be taken only in the luteal phase or during PMDD symptoms.[3] This is because those who respond to SSRIs usually experience symptoms relief within 1-2 days.[17] Luteal phase dosing can be started 14 days before menses and subsequently discontinued after start of menstrual flow.[16] Women respond to SSRIs generally report >50% alleviation in symptoms, which was significant improvement compared to placebo.[17] Although less studied, SNRIs have also shown benefit in PMDD. In a randomized, controlled clinical trial, 60% of women taking venlafaxine improved versus 35% on placebo. Improvement was noticed during the first treatment cycle with 80% symptom reduction.[18]

Another FDA approved treatment for PMDD is the oral contraceptive with ethinyl estradiol and drospirenon, a novel progestin.[16] It has been shown that hormonal birth control containing drospirenone and low levels of estrogen helps relieve severe PMDD symptoms, for at least the first three months it is used.[19] The idea behind using oral contraceptives is to suppress ovulation by controlling sex hormone fluctuations during the luteal phase.

Nonpharmacologic treatment[edit]

Of the dietary supplements, calcium is one that seems to help for PMS. The thought is that by maintaining levels of calcium during menses, calcium supplementation help avoid hypocalcemia, which can cause some of the mood symptoms of PMDD. The use of calcium, however, has not been formally studied in PMD.[3] There is some evidence that vitamin B6 can alleviate symptoms, but studies are of poor quality.[20] Herbal treatments that have shown promise in PMDD include agnus castus (chasteberry) and hypericum perforatum (St John’s wort).[3]


Cognitive Behavioral Therapy (CBT) has been shown to be effective in PMS and is suggested as a successful adjunct to SSRI treatment. When CBT was compared to SSRI alone or in combination with SSRI, groups receiving CBT had significant improvement of PMS symptoms. There is a lack of rigorous studies looking into CBT in women with PMDD.[3]


20-30% of women experience symptoms severe enough to meet PMS criteria and 3-8% of women of reproductive age meet the PMDD criteria.[3]

Bipolar depression, anxiety disorders, and other Axis I disorders are more common in women with PMDD than in women without PMDD.[21] In women with PMDD, there is a 50-78% lifetime incidence of various psychiatric disorders such as generalized anxiety disorder, seasonal affective disorder and major depressive disorder.[3]


  1. ^ Halbreich U (December 2004). "The diagnosis of premenstrual syndromes and premenstrual dysphoric disorder--clinical procedures and research perspectives". Gynecol. Endocrinol. 19 (6): 320–34. doi:10.1080/0951590400018215. PMID 15724807. 
  2. ^ Endicott J, McLaughlin TP, Grudzinski AN (December 2003). "Comparison of managed care charges among patients treated with selective serotonin reuptake inhibitors for premenstrual dysphoric disorder". J Clin Psychiatry 64 (12): 1511–6. doi:10.4088/JCP.v64n1216. PMID 14728114. 
  3. ^ a b c d e f g h Rapkin, AJ; Lewis, EI (November 2013). "Treatment of premenstrual dysphoric disorder". Womens Health (Lond Engl) 9 (6): 537–56. doi:10.2217/whe.13.62. PMID 24161307. 
  4. ^ a b c d e f Rapkin, Andrea J.; Lewis, Erin I. (2013-11-01). "Treatment of premenstrual dysphoric disorder". Women's Health (London, England) 9 (6): 537–556. doi:10.2217/whe.13.62. ISSN 1745-5065. PMID 24161307. 
  5. ^ a b c d Steiner, M; Pearlstein, T; Cohen, LS (2006). "Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs". J Womens Health (Larchmt) 15 (1): 57–69. doi:10.1089/jwh.2006.15.57. PMID 16417420. 
  6. ^ Biggs WS, Demuth RH (October 2011). "Premenstrual syndrome and premenstrual dysphoric disorder". Am Fam Physician 84 (8): 918–24. PMID 22010771. 
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  8. ^ a b c Diagnostic and Statistical Manual of Mental Disorders (5th Edition). Washington, DC, USA: American Psychiatric Association. 2013. ISBN 978-0-89042-554-1. 
  9. ^ "ACOG Practice Bulletin: No 15: Premenstrual syndrome". Obstetrics and Gynecology 95 (4): suppl 1–9. 2000-04-01. ISSN 0029-7844. PMID 24829972. 
  10. ^ "Premenstrual Syndrome, Management (Green-top Guideline No. 48)". Royal College of Obstetricians & Gynaecologists. Retrieved 2015-11-05. 
  11. ^ a b O'Brien, Patrick Michael Shaughn; Bäckström, Torbjorn; Brown, Candace; Dennerstein, Lorraine; Endicott, Jean; Epperson, C. Neill; Eriksson, Elias; Freeman, Ellen; Halbreich, Uriel (2011-02-01). "Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders: the ISPMD Montreal consensus". Archives of Women's Mental Health 14 (1): 13–21. doi:10.1007/s00737-010-0201-3. ISSN 1435-1102. PMC 4134928. PMID 21225438. 
  12. ^ Worcester, Nancy; Whatley, eds, Mariamne H. (2004). Women's health: Readings on social, economic, and political issues. Sage Publications. 
  13. ^ Ray Moynihan (2004-02-14). "Controversial disease dropped from Prozac product information". BMJ 328 (7436): 7436. doi:10.1136/bmj.328.7436.365. PMC 341379. PMID 14962861. 
  14. ^ European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products (2003-06-13). "Summary Information...for Prozac and associated names" (PDF). 
  15. ^ Sertraline (Zoloft), fluoxetine (Lovan, Prozac) for premenstrual dysphoric disorder (PMDD) National Prescribing Service Limited. (Australia)
  16. ^ a b c Ward, Susan (2016). Maternal-Child Nursing Care. Philadelphia, PA, USA: F.A. Davis Company. ISBN 9780803636651. 
  17. ^ a b Rapkin, Andrea J.; Winer, Sharon A. (2008-02-01). "The pharmacologic management of premenstrual dysphoric disorder". Expert Opinion on Pharmacotherapy 9 (3): 429–445. doi:10.1517/14656566.9.3.429. ISSN 1744-7666. PMID 18220493. 
  18. ^ Freeman, E. W.; Rickels, K.; Yonkers, K. A.; Kunz, N. R.; McPherson, M.; Upton, G. V. (2001-11-01). "Venlafaxine in the treatment of premenstrual dysphoric disorder". Obstetrics and Gynecology 98 (5 Pt 1): 737–744. ISSN 0029-7844. PMID 11704162. 
  19. ^ Lopez, LM.; Kaptein, AA.; Helmerhorst, FM. (2012). "Oral contraceptives containing drospirenone for premenstrual syndrome.". Cochrane Database Syst Rev 2: CD006586. doi:10.1002/14651858.CD006586.pub4. PMID 22336820. 
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