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.

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.

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:

• Thyroid function tests
• Complete blood count (CBC)
• Follicle-stimulating hormone (FSH) level

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

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

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.

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.

• Changes in diet
• Regular exercise
• Stress management
• Vitamin supplements
• Anti-inflammatory medicines
• Oral contraceptives
• Chasteberry extract

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

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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

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• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890701/
• https://www.ncbi.nlm.nih.gov/books/NBK279045/
• https://www.ncbi.nlm.nih.gov/pubmed/26377947
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC353031/

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