Premenstrual Dysphoric Disorder; Symptoms, Test, Treatment

Premenstrual Dysphoric Disorder; Symptoms, Test, Treatment

Premenstrual dysphoric disorder (PMDD) is a condition in which a woman has severe depression symptoms, irritability, and tension before menstruation. The symptoms of PMDD are more severe than those seen with premenstrual syndrome (PMS).PMS refers to a wide range of physical or emotional symptoms that most often occur about 5 to 11 days before a woman starts her monthly menstrual cycle. In most cases, the symptoms stop when, or shortly after, her period begins.

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.

Causes of Premenstrual Dysphoric Disorder

The causes of PMS and PMDD have not been found.

  • Being very sensitive to changes in hormone levels – Recent research suggests that PMDD is associated with increased sensitivity to the normal hormonal changes that occur during your monthly menstrual cycle.
  • Genetics – Some research suggests that this increased sensitivity to changes in hormone levels may be caused by genetic variations.
Many women with this condition have

Symptoms of Premenstrual Dysphoric Disorder

Symptoms of PMDD include:

Diagnosis of Premenstrual Dysphoric Disorder

Authoritative diagnostic criteria for PMDD are provided by a number of expert medical guides, notably the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). 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.

  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)

Criterion B one (or more) of the following symptoms must be present

  1. Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased 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.
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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.

  1. Decreased interest in usual activities (e.g., work, school, friends, hobbies).
  2. Subjective difficulty in concentration.
  3. Lethargy, easy fatigability, 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.

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. 

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-5, 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.

Laboratory studies should include the following:

Treatments of Premenstrual Dysphoric Disorder

Several common treatments include

Antidepressants (SSRIs)  

Several members of the selective serotonin reuptake inhibitor (SSRI) class of medications are effective in the treatment of PMDD.SSRI antidepressants such as fluoxetine , sertraline , paroxetine  and citalopram These medications work by regulating the levels of the neurotransmitter serotonin in the brain. SSRIs that have shown to be effective in the treatment of PMDD includeUp to 75% of women report relief of symptoms when treated with SSRI medications. Side effects can occur in up to 15% of women and include nausea, anxiety, and headache. SSRI medications to treat PMDD may be prescribed to be taken continuously or only during the 14-day luteal phase (second half) of the menstrual cycle. Other types of antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors) and lithium (Lithobid) have not been shown to be effective in the treatment of PMDD.

AGENTS DOSAGE USE RECOMMENDATION COMMENTS

SSRIs

Citalopram

10 to 30 mgper day

Full cycle or luteal phase only

Benefits physical, cognitive, and emotional symptoms

Administration during luteal phase

Luteal-phase use is superior to continuous treatment

Not approved by FDA for this use

Fluoxetine

20 mg per day

Full cycle or luteal phase only

Significant reduction of all symptoms

Decreased libido or delayed orgasm is most common side effect in long-term, continuous use

Approved by FDA for this use

Paroxetine

10 to 30 mgper day

Full cycle

Benefits all symptoms

Transient GI and sexual side effects

Superior to maprotiline

Not approved by FDA for this use

Sertraline

50 to 150 mg per day

Full cycle or luteal phase only

Benefits all symptoms

Transient GI and sexual side effects

Approved by FDA for this use

Other serotoninergic antidepressants

Clomipramine

25 to 75 mgper day

Full cycle or luteal phase only

Benefits all symptoms

Anticholinergic and sexual side effects

Not approved by FDA for this use

Anxiolytics

Alprazolam

0.375 to 1.5 mg per day

Luteal phase

Interrupted use during the luteal phase can reduce the risk of drug dependence

Use only if SSRIs are ineffective

Not approved by FDA for this use

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SSRIs = selective serotonin reuptake inhibitors; FDA = U.S. Food and Drug Administration; GI = gastrointestinal.

Some over-the-counter pain relievers  

Such as aspirin, ibuprofen, and nonsteroidal anti-inflammatory drugs (NSAIDs) may help some symptoms such as headache, breast tenderness, backache, and cramping. Diuretics, also called “water pills,” can help with fluid retention and bloating.

Miscellaneous Pharmacologic Interventions for PMDD

AGENTS DOSAGE USE RECOMMENDATION COMMENTS

Diuretics

Spironolactone

100 mg per day

Luteal phase

Aldosterone antagonist

Potassium-sparing diuretic

Could improve physical and psychologic symptoms

Dopamine agonist

Bromocriptine

Up to 2.5 mg three times per day

Days 10 through 26 of menstrual cycle

May relieve cyclic mastalgia; evaluate hepatic and renal functions before initiation

NSAIDs

Ibuprofen

500 to 1,000 mg per day

Days 17 through 28 of menstrual cycle

Take with food May relieve mastalgia

PMDD = premenstrual dysphoric disorder; NSAIDs = nonsteroidal anti-inflammatory drugs.

Oral contraceptives and GnRH agonists 

Medications that interfere with ovulation and the production of ovarian hormones have also been used to treat PMDD. Oral contraceptive pills (OCPs, birth control pills) can be prescribed to suppress ovulation and regulate the menstrual cycle.

Gonadotropin-releasing hormone analogs

GnRH analogs or GnRH agonists have also been used to treat PMDD.These drugs suppress estrogen production by the ovaries by inhibiting the secretion of regulatory hormones from the pituitary gland. As a result, menstrual periods stop, mimicking menopause. Nasal and injection forms of GnRH agonists are available . Gonadotropin-releasing hormone analogs such as leuprolide , nafarelin  and goserelin

Birth control pills 

Taking birth control pills with no pill-free interval or with a shortened pill-free interval may reduce PMS and PMDD symptoms for some women.

Nutritional supplements

Consuming 1,200 milligrams of dietary and supplemental calcium daily may possibly reduce symptoms of PMS and PMDD in some women. Vitamin B-6, magnesium and L-tryptophan also may help, but talk with your doctor for advice before taking any supplements.

Danazol (Danocrine) 

Danazol (Danocrine) is a synthetic drug that creates a high androgen (male type hormone) and low estrogen hormonal environment by interfering with ovulation and ovarian production of estrogen.

Herbal remedies

Some research suggests that chasteberry (Vitex agnus-castus) may possibly reduce irritability, mood swings, breast tenderness, swelling, cramps and food cravings associated with PMDD, but more research is needed. The Food and Drug Administration doesn’t regulate herbal supplements, so talk with your doctor before trying one.

Lifestyle changes

Regular exercise often reduces premenstrual symptoms. Cutting back caffeine, avoiding alcohol and stopping smoking may ease symptoms, too. Decreasing intake of sugar, salt, caffeine and alcohol and increasing protein and carbohydrate intake

Getting enough sleep 

Using relaxation techniques, such as mindfulness, meditation and yoga, also may help. Avoid stressful and emotional triggers, such as arguments over financial issues or relationship problems, whenever possible.

Dietary supplementation 

With calcium, vitamin B6, magnesium and vitamin E

Estrogen

Another option is to inhibit ovulation with estrogen, which can be delivered via a skin patch or via a subcutaneous implant. Doses of estrogen tend to be higher than those prescribed for hormone therapy during menopause, but lower than those used for contraception in childbearing years. If estrogen is prescribed, it should be taken along with a progestogen to reduce risk of uterine cancer — except for women who have had a hysterectomy.

GnRH agonists

Gonadotropin-releasing hormone (GnRH) agonists, which are usually prescribed for endometriosis and infertility, suppress the hormonal cycle — and may be helpful for women whose PMDD symptoms have not responded to other drugs.

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Councelling

Talking to a therapist may also help you deal with coping strategies. And relaxation therapy, meditation, reflexology, and yoga might provide you relief, but these haven’t been widely studied.

Acupuncture

In a systematic review of 10 trials with methodologic limitations comparing acupuncture versus sham acupuncture, medication, or no treatment for premenstrual syndrome, acupuncture was associated with improved symptoms compared with any control in an analysis of 8 trials with 429 patients.

Cognitive-behavioral therapy

Cognitive therapy is based on the view that behavioral disorders are influenced by negative or extreme thought patterns, which are so habitual that they become automatic and are unnoticed by the individual.

Light therapy

The light emitted by conventional fluorescent lamps is deficient in many of the colors and wavelengths of natural sunlight. The basis of light therapy is replacing such lamps with full-spectrum fluorescent lamps whose light (referred to as bright light) is more similar to sunlight.

Sleep deprivation

Most patients with major depressive disorder respond to a night of total sleep deprivation. Because of the relation of this disorder to PMDD, treatments for major depressive disorder may also be effective for PMDD.

Relaxation techniques

The relaxation response is a physiologic response that results in decreased metabolism, a lower heart rate, reduced blood pressure, a lower rate of breathing, and slower brain waves. The repetition of a word, sound, prayer, phrase, or muscular activity is required to elicit the relaxation response.

Efficacy Rating of Current Treatments for PMS/PMDD

RECOMMENDED TREATMENT EFFICACY IN PMS/PMDD EFFICACY RATING* COMMENTS/EVIDENCE

Lifestyle change

PMS or PMDD

G

Health benefits without risks

Vitamin B6

PMS or PMDD

B

Dosage > 100 mg per day may cause peripheral neuropathy

Vitamin E

PMS or PMDD

E

Antioxidant without significant risk

Calcium carbonate

PMS or PMDD

B

Placebo-controlled study supports benefits in moderate to severe PMS

Tryptophan

PMS or PMDD

B

Supported by a placebo-controlled study

Cognitive-behavioral therapy

PMS

A

Benefits documented; not many studies

PMDD

B

Herbal therapies

PMS or PMDD

E

Safety in pregnancy and lactation not documented; not FDA-approved

Selective serotonin reuptake inhibitors

Nonresponsive PMS or PMDD

A

Well-designed, randomized, placebo-controlled studies and metaanalyses

Clomipramine

PMDD

B

Anticholinergic side effects

Alprazolam

PMDD

B

Low-dose, luteal phase treatment; long-term use may cause tolerance

GnRH agonists or danazol

PMDD

C

Menopausal syndrome/masculinization/cost limit its use

Spironolactone, bromocriptine, or ibuprofen

PMS or PMDD

D

Symptom-focused efficacy; spironolactone efficacy supported by double-blind study

Oral contraceptives or progesterone

PMDD

E

Anecdotal efficacy or not consistently effective

Surgical or radiation oophorectomy

PMDD

F

Not recommended


PMS = premenstrual syndrome; PMDD = premenstrual dysphoric disorder; FDA = U.S. Food and Drug Administration; GnRH = gonadotropin-releasing hormone.

Herbal formulations often used by women in self-treatment of PMS symptoms include the following:

  • Cayenne
  • Dong quai
  • Siberian ginseng
  • Pulsatilla
  • Raspberry leaves
  • St. John’s wort
  • Sepia
  • Blessed thistle
  • American valerian
  • Wild yam

References

Premenstrual Dysphoric Disorder

 

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