Premenstrual Dysphoric Disorder (PMDD)

Primer

Premenstrual Dysphoric Disorder (PMDD) is a mood disorder characterized by dysphoria, mood lability, irritability, and anxiety that occur repeatedly during the premenstrual phase of the cycle and resolve around the time of (or after) menses.

Epidemiology
  • The 12-month prevalence is between 1.8 to 5.8%.[1]
Prognosis
  • PMDD can occur at any point after the age of menarche.
  • As individuals approach menopause, they may report symptom worsening.
  • Symptoms of PMDD will cease after menopause.
Comorbidity
  • A previous history of a major depressive episode is the most common comorbidity.[2]
Risk Factors
  • Stress, interpersonal trauma, and seasonal changes are risk factors.
  • There is also a sociocultural contribution to the expression of symptoms of PMDD.[3]
    • The intensity, frequency, and expression of symptoms may be influenced by cultural factors.
  • The heritability of premenstrual symptoms is estimated to be between 30% and 80% (average 50%).[4]
  • Women who use oral contraceptives (OCPs) may have fewer premenstrual symptoms.

DSM-5 Diagnostic Criteria

Criterion A

In the majority of menstrual cycles, at least 5 symptoms 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.

Criterion B

At least 1 of the following symptoms must be present:

  1. Marked affective lability (e.g. - mood swings, feeling suddenly sad or tearful, or in creased sensitivity to rejection)
  2. Marked irritability or anger or increased interpersonal conflicts
  3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts
  4. Marked anxiety, tension, and/or feelings of being keyed up or on edge
Criterion C

At least 1 of the following symptoms must additionally be present, to reach a total of 5 symptoms when combined with symptoms from Criterion B above.

  1. Decreased interest in usual activities (e.g. - work, school, friends, hobbies).
  2. Subjective difficulty in concentration
  3. Lethargy, easy fatiguability, or marked lack of energy
  4. Marked change in appetite; overeating; or specific food cravings
  5. Hypersomnia or insomnia
  6. A sense of being overwhelmed or out of control
  7. 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 2 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).

Specifiers

Note: If symptoms have not been confirmed by daily ratings (e.g. - a diary or mood tracker) of at least 2 symptomatic menstrual cycles, “provisional” specifier should be added (i.e. - “premenstrual dysphoric disorder, provisional”).

Episode Specifier

  • Single episode
  • Recurrent episode

Severity Specifier

  • Mild: Few, if any, symptoms in excess of those required to make the diagnosis are present, the intensity of the symptoms is distressing but manageable, and the symptoms result in minor impairment in social or occupational functioning.
  • Moderate: The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for “mild” and “severe.”
  • Severe: The number of symptoms is substantially in excess of that required to make the diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning.

Remission Specifier

  • In partial remission: Symptoms of the immediately previous major depressive episode are present, but full criteria are not met, or there is a period lasting less than 2 months without any significant symptoms of a major depressive episode following the end of such an episode.
  • In full remission: During the past 2 months, no significant signs or symptoms of the disturbance were present.

With anxious distress

  • Anxious distress is defined as the presence of at least 2 of the following symptoms during the majority of days of a major depressive episode or persistent depressive disorder (dysthymia):
    • (1) Feeling keyed up or tense
    • (2) Feeling unusually restless
    • (3) Difficulty concentrating because of worry
    • (4) Fear that something awful may happen
    • (5) Feeling that the individual might lose control of himself or herself
  • Severity:
    • Mild: 2 symptoms
    • Moderate: 3 symptoms
    • Moderate-severe: 4 or 5 symptoms
    • Severe: 4 or 5 symptoms and with motor agitation
Note: Anxious distress has been noted as a prominent feature of both bipolar and major depressive disorder in both primary care and specialty mental health settings. High levels of anxiety have been associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment nonresponse. As a result, it is clinically useful to specify accurately the presence and severity levels of anxious distress for treatment planning and monitoring of response to treatment.

With mixed features

  • A. At least 3 of the following manic/hypomanic symptoms are present during the majority of days of a major depressive episode:
    • (1) Elevated, expansive mood
    • (2) Inflated self-esteem or grandiosity
    • (3) More talkative than usual or pressure to keep talking
    • (4) Flight of ideas or subjective experience that thoughts are racing.
    • (5) Increase in energy or goal-directed activity (either socially, at work or school, or sexually)
    • (6) Increased or excessive involvement in activities that have a high potential for painful consequences (e.g. - engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
    • (7) Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted with insomnia)
  • B. Mixed symptoms are observable by others and represent a change from the person’s usual behavior
  • C. For individuals whose symptoms meet full criteria for either mania or hypomania, the diagnosis should be bipolar I or bipolar II disorder.
  • D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication, other treatment)
Note: Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I or bipolar II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to treatment.

With melancholic features

  • A. 1 of the following is present during the most severe period of the current episode:
    • (1) Loss of pleasure in all, or almost all, activities
    • (2) Lack of reactivity to usually pleasurable stimuli (does not feel much better, even temporarily, when something good happens)
  • B. 3 or more of the following:
    • (1) A distinct quality of depressed mood characterized by profound despondency, despair, and/or moroseness or by so-called empty mood,
    • (2) Depression that is regularly worse in the morning
    • (3) Early-morning awakening (i.e. - at least 2 hours before usual awakening)
    • (4) Marked psychomotor agitation or retardation
    • (5) Significant anorexia or weight loss
    • (6) Excessive or inappropriate guilt

With atypical features

This specifier can be applied when these features predominate during the majority of days of the current or most recent major depressive episode or persistent depressive disorder.

  • A. Mood reactivity (i.e. - mood brightens in response to actual or potential positive events)
  • B. 2 or more of the following:
    • (1) Significant weight gain or increase in appetite
    • (2) Hypersomnia
    • (3) Leaden paralysis (i.e. - heavy, leaden feelings in arms or legs)
    • (4) A long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment
  • C. Criteria are not met for “with melancholic features” or “with catatonia” during the same episode

With psychotic features

Delusions and/or hallucinations are present.

  • With mood-congruent psychotic features:
    • The content of all delusions and hallucinations is consistent with the typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment
  • With mood-incongruent psychotic features:
    • The content of the delusions or hallucinations does not involve typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment, or the content is a mixture of mood-incongruent and mood-congruent themes

With catatonia

This specifier can apply to an episode of depression if catatonic features are present during most of the episode.

With peripartum onset

This specifier can be applied to the current or, if full criteria are not currently met for a major depressive episode, most recent episode of major depression if onset of mood symptoms occurs during pregnancy or in the 4 weeks following delivery.

With seasonal pattern

This specifier applies to recurrent major depressive disorder.

  • A. There has been a regular temporal relationship between the onset of major depressive episodes in major depressive disorder and a particular time of the year (e.g. - in the fall or winter). Do not include cases in which there is an obvious effect of seasonally related psychosocial stressors (e.g. - regularly being unemployed every winter).
  • B. Full remissions also occur at a characteristic time of the year (e.g. - depression disappears in the spring)
  • C. In the last 2 years, 2 major depressive episodes have occurred that demonstrate the temporal seasonal relationships defined above and no nonseasonal major depressive episodes have occurred during that same period.
  • D. Seasonal major depressive episodes (as described above) substantially outnumber the nonseasonal major depressive episodes that may have occurred over the individual’s lifetime.

Signs and Symptoms

  • Typically, symptoms peak at the time of the onset of menses. However, symptoms can linger into the first few days of menses, the individual must have a symptom-free period in the follicular phase after the menstrual period begins.
  • Having only physical and/or behavioural symptoms without mood and/or anxiety symptoms is not sufficient for a diagnosis of PMDD.[5]
  • Delusions and hallucinations have been reported in the late luteal phase of the menstrual cycle but is exceedingly rare. The premenstrual phase is considered to be a risk period for suicide.

Screening and Rating Scales

  • Daily Rating of Severity of Problems
  • Visual Analogue Scales for Premenstrual Mood Symptoms
  • Premenstrual Tension Syndrome Rating Scale

Pathophysiology

  • Like most psychiatric disorders, the cause of PMDD is complex and involves biological, psychological, and sociocultural factors.
    • There is however, a clear relationship between the presence of PMDD symptoms and the levels of sex steroids associated with ovulation.[6]
    • Changes in physiological levels of estrogen and progesterone, changes in serotonin, and genetic factors are all thought to play a role in PMDD.[7][8]

Differential Diagnosis

  • Premenstrual syndrome (PMS)
    • PMS differs from PMDD in that a minimum of five symptoms is not required, and there is no requirement for mood and/or anxiety symptoms in PMS. PMS may be more common than premenstrual dysphoric disorder, although the estimated prevalence of PMS varies. It is also considered to be less severe than PMDD.
  • Dysmenorrhea
    • Dysmenorrhea is a syndrome of painful menses, but this is distinct from a syndrome characterized by mood and anxiety changes. Importantly, dysmenorrhea begin with the onset of menses, whereas symptoms of PMDD, by definition, begin before the onset of menses, even if they continue into the first few days of menses.
  • Bipolar disorder, major depressive disorder, and persistent depressive disorder (dysthymia)
    • Many individuals with bipolar or major depressive disorder or persistent depressive disorder may believe that they have PMDD. However, when symptoms are charted, it often does not follow a premenstrual pattern. This is why one of the requirements for diagnosis is that the symptoms are confirmed by daily prospective ratings.
  • Use of hormonal treatments (i.e. - substance/medication-induced depressive disorder)
    • Some women who present with moderate-severe premenstrual symptoms may be on hormonal treatments, such as hormonal contraceptives. If such PMDD symptoms develop after starting exogenous hormone use, the symptoms may be due to the hormones rather than to PMDD. If the woman stops hormones and the symptoms disappear, this is consistent with a substance/medication-induced depressive disorder.

Investigations

  • Other medical disorders can mimic symptoms of PMDD, including anemia, hypothyroidism, autoimmune disorders, diabetes, and other gynecologic conditions such as dysmenorrhea and endometriosis.[9]
  • Specific investigations for these conditions should be ordered as clinically indicated.

Physical Exam

  • As per above and as clinically indicated.

Treatment

Psychotherapy

Pharmacotherapy

  • Selective serotonin reuptake inhibitors (SSRIs) are the most studied pharmacological treatments, in particular fluoxetine, sertraline, and paroxetine.[11]
    • SSRIs have been shown to be effective even when only used in the luteal (premenstrual) phases of each cycle.
      • Intermittent dosing of fluoxetine 20 mg daily for 14 days premenstrually only (i.e. - 14 days before anticipated menses – during the luteal phase) may also be effective in treating the symptoms of PMDD.[12]
    • Serotonin norepinephrine reuptake inhibitors (SNRIs) have also been shown to be effective.
  • Hormonal contraceptives including drospirenone can also be effective for PMDD.[13]

Guidelines

Resources

For Patients
For Providers
Articles
Research

References

1) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
2) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
3) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
4) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
5) American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, VA.
6) De Berardis, D., Serroni, N., Salerno, R. M., & Ferro, F. M. (2007). Treatment of premenstrual dysphoric disorder (PMDD) with a novel formulation of drospirenone and ethinyl estradiol. Therapeutics and clinical risk management, 3(4), 585-590.
7) Hantsoo, L., & Epperson, C. N. (2015). Premenstrual dysphoric disorder: epidemiology and treatment. Current psychiatry reports, 17(11), 1-9.
8) Vigod, S. N., Frey, B. N., Soares, C. N., & Steiner, M. (2010). Approach to premenstrual dysphoria for the mental health practitioner. Psychiatric Clinics, 33(2), 257-272.
9) Vigod, S. N., Frey, B. N., Soares, C. N., & Steiner, M. (2010). Approach to premenstrual dysphoria for the mental health practitioner. Psychiatric Clinics, 33(2), 257-272.
10) Vigod, S. N., Frey, B. N., Soares, C. N., & Steiner, M. (2010). Approach to premenstrual dysphoria for the mental health practitioner. Psychiatric Clinics, 33(2), 257-272.
11) Vigod, S. N., Frey, B. N., Soares, C. N., & Steiner, M. (2010). Approach to premenstrual dysphoria for the mental health practitioner. Psychiatric Clinics, 33(2), 257-272.
12) Steiner, M., Korzekwa, M., Lamont, J., & Wilkins, A. (1997). Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria. Psychopharmacology bulletin, 33(4), 771.
13) De Berardis, D., Serroni, N., Salerno, R. M., & Ferro, F. M. (2007). Treatment of premenstrual dysphoric disorder (PMDD) with a novel formulation of drospirenone and ethinyl estradiol. Therapeutics and clinical risk management, 3(4), 585-590.