Premenstrual dysphoric disorder (PMDD) is a severe and disabling form of premenstrual syndrome affecting 3-8% of women who menstruate. The disorder consists of a "cluster of affective, behavioral and somatic symptoms" that recur monthly during the luteal phase of the menstrual cycle. PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders 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.
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Signs and symptoms
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. 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.
The symptoms in PMDD can be both physical and emotional with mood symptom being dominant. The most debilitating symptoms are emotional and include "irritability, depression, mood lability, anxiety, feelings of 'loss of control', difficulty concentrating and fatigue." The physical symptoms include "abdominal bloating, breast tenderness, headache and generalized aches."
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Causes
The etiology of PMDD is still an active area of research. While the timing of symptoms suggests hormonal fluctuations as the cause of PMDD, a demonstrable hormonal imbalance in people with PMDD has not been identified. In fact, levels of reproductive hormones in people with and without PMDD are indistinguishable. 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. These symptoms are more predominant in people who have a predisposition to the disorder.
While the etiology of the PMDs is still under investigation, it is apparent that these disorders are biologically driven and are not simply psychological or cultural phenomena. PMDD is found in people worldwide, indicating a biological basis. Most psychologists infer that this disorder is caused by both reaction to hormone influx and genetic components. There is evidence of heritability of premenstrual symptoms not accounted for by family environment suggesting a genetic component to PMDD; however, which genes are involved is a broader question that is still being investigated. Environmental stress can also be a large contributor to triggering PMDD. While there is likely a genetic component to PMDs, the environment must also be considered. Genetics do not operate in a vacuum, and environmental effects such as stress, hormonal fluctuation, and epigenetics likely play a role as well. History of traumatic stress has been associated with PMDD.
Diagnosis
Authoritative diagnostic criteria for PMDD are provided by a number of expert medical guides, notably the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V). The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), established seven criteria (A through G) for the diagnosis of PMDD.
Diagnostic Criteria:
Criterion A is that in most menstrual cycles during the past year, at least 5 of the following 11 symptoms (including at least 1 of the first 4 listed) must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week postmenses.
- Marked lability (e.g., mood swings)
- Marked irritability or anger
- Markedly depressed mood
- Marked anxiety and tension
- Decreased interest in usual activities
- Difficulty in concentration
- Lethargy and marked lack of energy
- Marked change in appetite (e.g., overeating or specific food cravings)
- Hypersomnia or insomnia
- Feeling overwhelmed or out of control
- Physical symptoms (e.g., breast tenderness or swelling, joint or muscle pain, a sensation of 'bloating' and weight gain)
Criterion B one (or more) of the following symptoms must be present:
- Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection).
- Marked irritability or anger or increased interpersonal conflicts.
- Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts.
- Marked anxiety, tension, and/or feelings of being keyed up or on edge.
Criterion C one (or more) of the following symptoms must be present additionally, to reach a total of five symptoms when combined with symptoms from Criterion B above.
- Decreased interest in usual activities (e.g., work, school, friends, hobbies).
- Subjective difficulty in concentration.
- Lethargy, easy fatigability, or marked lack of energy.
- Marked change in appetite; overeating; or specific food cravings.
- Hypersomnia or insomnia.
- A sense of being overwhelmed or out of control.
- Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of "bloating," or weight gain.
Note: The symptoms in Criteria A-C must have been met for most menstrual cycles that occurred in the preceding year.
Criterion D The symptoms are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).
Criterion E The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder (dysthymia), or a personality disorder (although it may co-occur with any of these disorders).
Criterion F Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation.)
Criterion G The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).
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.
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). 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 occurring during the luteal phase of the menstrual cycle, symptoms being absent after menstruation and before ovulation and causing significant impairment. The ISPMD diagnostic criteria for PMDD do not specify symptom characteristics or number of symptoms.
Diagnostic criteria for PMDD are also provided by the 2016 World Health Organization's International Classification of Diseases (ICD-10-CM):
Premenstrual tension syndrome ...
A more severe and disabling form of premenstrual syndrome in which mood symptoms are the primary characteristic. A term used to describe the psychological aspects of premenstrual syndrome, such as the "indescribable tension", depression, hostility, and increased seizure activity in people with seizure disorder.
Applicable To
Premenstrual dysphoric disorder ...
Thus today many well-recognized health organizations in many parts of the world provide guides for the diagnosis of PMDD. As a historical footnote, early drafts of the ICD failed to recognize PMDD as a separate condition. In 2003, before the current ICD 10 guidelines, 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. Reflecting an earlier approach by the ICD, the committee found in 2003 that PMDD was not a well-established disease entity across Europe, and noted "considerable concern that [people] with less severe pre-menstrual symptoms might erroneously receive a diagnosis of PMDD resulting in widespread inappropriate short and long-term use of fluoxetine."
In Australia, PMDD is recognized by the Therapeutic Goods Administration. However, SSRIs are not reimbursed for PMDD under the Pharmaceutical Benefits Scheme.
Treatment
Medication
Medication may be used for people with severe and debilitating symptoms. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication. 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). 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. This is because those who respond to SSRIs usually experience symptoms relief within 1-2 days. Studies in rats suggest this rapid response to SSRIs is due to the elevation of the neuroactive progesterone metabolite allopregnanolone in the brain, rather than serotonin. Luteal phase dosing in women can be started 14 days before menses and subsequently discontinued after start of menstrual flow. Women taking SSRIs to ease PMDD generally report >50% alleviation in symptoms, which was significant improvement compared to placebo.
Although less studied, SNRIs have also shown benefit in PMDD. In a randomized, controlled clinical trial of people with PMDD, 60% of the people taking venlafaxine improved versus 35% on placebo. Improvement was noticed during the first treatment cycle with 80% symptom reduction.
Another FDA approved treatment for PMDD is the oral contraceptive with ethinylestradiol and drospirenone, a novel progestin. 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. The idea behind using oral contraceptives is to suppress ovulation by controlling sex hormone fluctuations during the luteal phase.
Psychotherapy
Cognitive behavioral therapy (CBT) has been shown to be effective in PMS and is suggested as a successful adjunct to SSRI treatment. CBT is an evidence-based treatment approach for treating depression and focuses on the link between mood, thoughts, and actions to help patients address current issues and symptoms. When CBT was compared to SSRI alone or in combination with SSRI, groups receiving CBT had significant improvement of PMS symptoms. Through the practice of CBT, patients are better able to recognize and modify recurrent issues as well as thought and behavior patterns that interfere with functioning well or that make depressive symptoms worse.
Alternative medicine
There have been some nutritional supplements that have been shown to help alleviate the symptoms of PMDD. In 1998, a placebo-controlled, randomized trial of 720 people with PMDD found that calcium carbonate demonstrated up to a 50% reduction in symptoms, compared with a 30% reduction in the control group. Herbal treatments that have shown promise in PMDD include chasteberry (Vitex agnus castus), St. John's wort (Hypericum perforatum), and ginkgo (Ginkgo biloba). Studies have been conducted on the efficacy of chasteberry and gingko, but as of this writing, no randomized controlled trial has been conducted on the efficacy of St. John's wort in alleviating PMDD symptoms.
Epidemiology
20-30% of people who menstruate experience symptoms severe enough to meet PMS criteria and 3-8% of females who are of reproductive age meet the PMDD criteria.
Bipolar depression, anxiety disorders, and other Axis I disorders are more common in people with PMDD than in the general population. In people 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.
The symptoms in which coincide with mood disorders, such as major depressive disorder or bipolar disorder, may worsen during the premenstrual period and thus may mimic PMDD. This phenomenon is known as premenstrual exacerbation (PME) and refers to the worsening of mood disorder symptoms during the premenstrual phase. An estimated 40% of people who seek treatment for PMDD are found to not have PMDD, but rather a PME of an underlying mood disorder.
Medical personnel can avoid misdiagnosis by having people seeking treatment for PMDD use a daily charting method to record their symptoms. Daily charting helps distinguish when mood disturbances are experienced and allows PMDD to be distinguished from other mood disorders. With PMDD, mood symptoms are present only during the luteal phase, or last two weeks, of the menstrual cycle. While PMDD mood symptoms are of a cyclical nature, other mood disorders are variable or constant over time. Although the medical community lacks a consensus on the most efficient instrument by which to confirm a PMDD diagnosis, several well-validated scales for recording premenstrual symptoms include the Calendar of Premenstrual Experiences (COPE), Daily Record of Severity of Problems (DRSP), and Prospective Record of the Severity of Menstruation (PRISM).
PMDD mood symptoms are only present in people who are menstruating. Thus, symptoms do not occur during pregnancy and after menopause. Other mood disorders typically persist across all reproductive life events and are independent of a person's menstrual cycle or lack thereof.
In addition to AXIS I disorders, several other medical illnesses such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome and migraine disorder may present symptoms similar or identical to those of PMDD. Clinicians must distinguish between PMDD and other medical and/or psychiatric conditions.
History
The diagnostic category was first made part of the DSM-IIIR in 1987, when it was named "Late Luteal Phase Dysphoric Disorder" and included in an appendix as a proposed diagnostic category needing further study. Preparations for the DSM-IV led to debate about whether to keep the category at all, keep it in the appendix, or remove it; the reviewers determined that the condition was still too poorly studied and defined, so it was kept in the appendix but elaborated with diagnostic criteria to aid further study.
As preparations were underway in 1998 for the DSM-IV-TR, the conversation changed, as Eli Lilly and Company had paid for a large clinical trial of fluoxetine as a potential treatment for the condition that had been conducted by Canadian academics and published in the New England Journal of Medicine in 1995, and other studies had been conducted as well that all found that about 60% of people with PMDD in the trials improved with the drug; representatives from Lilly and the FDA participated in the discussion.
Various strong stances were taken in the discussion. For example, Sally Severino, a psychiatrist, argued that because PMDD symptoms were more prevalent in the US, it was a culture-bound syndrome and not a biological condition, and also said it was "an unnecessary pathologizing of cyclical changes in women." Jean Endicott, another psychiatrist and chair of the committee, has argued that it is a valid condition from which people suffer and should be diagnosed and treated, and has said: "If men had PMDD, it would have been studied a long time ago." In the end the committee kept PMDD in the appendix.
The decision has been criticized as being driven by Lilly's financial interests, and possibly by financial interests of members of the committee who had received funding from Lilly. Paula Caplan, a psychologist who had served on the committee for the DSM-IV, noted at the time of the DSM-IV-TR decision that there was some evidence that calcium supplements could treat PMDD but the committee hardly looked at them; she also had claimed that the diagnostic category is harmful to people with PMDD, leading them to believe they are mentally ill, and potentially leading others to mistrust them in situations as important as job promotions or child custody cases. She has called PMDD "an invented disorder." Nada Stotland has expressed concern that people with PMDD may actually have a more serious condition like major depressive disorder or may be in difficult circumstances, like suffering domestic abuse, may have their true issues remain undiagnosed and managed, if their gynecologist diagnoses them with PMDD and gives them drugs to treat that condition.
The validity of PMDD was once more debated when it came to time to create the DSM-5 in 2008. In the end it was included as a formal category; a review in the Journal of Clinical Psychiatry published in 2014 examined the arguments against inclusion, which it summarized as: "(1) the PMDD label will harm women economically, politically, legally, and domestically; (2) there is no equivalent hormonally based medical label for males; (3) the research on PMDD is faulty; (4) PMDD is a culture-bound condition; (5) PMDD is due to situational, rather than biological, factors; and (6) PMDD was fabricated by pharmaceutical companies for financial gain" and addressed each and found no evidence of harm, that no hormonally-driven disorder has been identified in men despite research seeking it; that the research base has matured; that PMDD has been identified worldwide; that a small minority of people do suffer from the condition; and that while there has been financial conflict of interest it has not made the research unusable. It concluded by noting that women have historically been under-treated and told that problems are "all in their heads", and that the formal diagnostic criteria would spur more funding, research, diagnosis and treatment for people who suffer from PMDD.
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