Easing the burden of premenstrual dysphoric disorder

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Applied Evidence

Easing the burden of premenstrual dysphoric disorder

J Fam Pract. 2013 January;62(1):E1-E7

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References

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SSRIs are the only class of antidepressants approved by the US Food and Drug Administration (FDA) for treatment of PMDD and are considered first-line pharmacologic therapy, although they have only about a 60% response rate.^9,11,27,28 Within this class, fluoxetine, sertraline, and paroxetine are FDA-approved for PMDD.^6,11,21,27

SSRIs have proven effective at low doses and produce a faster response time in treating PMDD—within 1 or 2 days of onset—than depression (2-4 weeks).⁶ Continuous and intermittent treatment are both effective.^29,30 However, continuous dosing yields a higher response rate, with 85% to 90% of patients experiencing improvement.^22,31 The symptoms that respond best to continuous dosing are irritability, mood swings, and affect lability.²² Lack of response to an SSRI after 2 menstrual cycles constitutes treatment failure.⁸

Another antidepressant that has been found effective compared with placebo is venlafaxine, a serotonin and noradrenaline reuptake inhibitor with a quick response time.³² TABLE 3 lists antidepressants used to treat PMDD.^32-34

TABLE 3
SSRIs used to treat PMDD^32-34

Fluoxetine*	10-20 mg
Sertraline*	25-50 mg
Paroxetine CR*	12.5-25 mg
Escitalopram	20 mg
Venlafaxine	50-200 mg
PMDD, premenstrual dysphoric disorder; SSRI, selective serotonin reuptake inhibitor. *FDA-approved for premenstrual dysphoric disorder.

The anxiolytic alprazolam, a GABA agonist,³⁵ is also effective for PMDD but is considered second-line therapy because of its adverse effects (drowsiness and confusion) and potential for dependence.^2,26

Hormonal therapy. Low-dose progestin oral contraceptives provide some relief of PMDD, although definitive evidence is lacking to support using progesterone to manage the disorder.³⁶ A combination oral contraceptive pill (OCP) containing 3 mg of the progestin drospirenone and 20 mcg of ethinyl estradiol has proved beneficial in treating the bloating, food cravings, breast tenderness, and mood swings of PMDD because of drospirenone’s antimineralocorticoid and antiandrogenic activity.^36-38 The OCP is taken in a 24/4 regimen (24 days of active medication with a 4-day hormone-free interval). It provides adequate blood levels of estrogen and progesterone to suppress gonadotropins at the beginning of the active medication cycle while the shortened hormone-free interval helps reduce symptoms.^36-38

Gonadotropin-releasing hormone (GnRH) agonists such as leuprolide relieve symptoms of PMDD by decreasing secretion of both follicle-stimulating hormone and luteinizing hormone, inducing anovulation and amenorrhea.²⁷ GnRH agonists also induce menopausal symptoms such as hot flashes, fatigue, irritability, vaginal dryness, osteopenia, and cardiac problems and are not recommended for prolonged use.^27,38

Like GnRH, danazol, a derivative of the synthetic modified testosterone ethisterone (pregneninolone), relieves PMDD symptoms by suppressing the HPA axis and causing anovulation. Its adverse effects may include acne, increased facial hair, weight gain, and depression, however.³⁸ GnRH and danazol are usually used as a last resort because of their adverse effects and significant cost.

Consider complementary therapy, as well

Nutritional and herbal supplements have been shown to be useful for relieving PMDD, but more evidence is needed to support their benefit.³⁹ TABLE 4 describes nutritional and herbal supplements used to treat PMDD.²⁷, ^39-44

TABLE 4
How strong is the evidence for nutritional and herbal supplements for premenstrual dysphoric disorder?

Nutritional supplements	Daily dose	Symptom(s)	Efficacy (SOR)	Adverse effects
Calcium²⁷, ⁴¹	1200 mg	Pain, fatigue, depression, insomnia, bloating, food cravings	Yes (A)	Kidney stones with doses >2500 mg²⁰
Magnesium^40,42	200-400 mg	Bloating, mood changes, pain	Possibly yes (B)	Diarrhea
Vitamin B₆^40,43	50-100 mg	Depression, overall symptoms	Possibly yes (B)	Peripheral neuropathy >100 mg/d
Vitamin E⁴⁰	400 IU	Mastalgia	Possibly yes (B)	Bleeding (hemorrhagic stroke), nausea, fatigue
Herbal supplements
Chasteberry (Vitex agnus-castus)^39,40,44	20 mg	Overall symptoms	Possibly yes (B)	Mild skin rash, acne, headache, gastrointestinal symptoms²⁶
Ginkgo biloba^40,42	160 mg in 2 80-mg doses	Mastalgia, bloating, mood changes	Possibly yes (B)	Increased risk of bleeding
St. John’s wort^40,42	900 mg in 3 300-mg doses	Mood changes	Possibly yes (B)	Photosensitivity
Evening primrose oil⁴⁰	2-3 g	Overall symptoms	Possibly no (B)	None

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence

B Inconsistent or limited-quality patient-oriented evidence

C Consensus, usual practice, opinion, disease-oriented evidence, case series

Acupuncture, which is widely used in the United States according to the National Institutes of Health Consensus Conference,⁴⁵ also shows promise for alleviating PMDD symptoms. A review article discussing the use of acupuncture in a woman who met 8 of the 11 DMV-IV-TR diagnostic criteria for PMDD reported that during menstrual cycles in which the woman was treated with acupuncture the number of symptoms, as recorded by the patient on the Menstrual Distress Questionnaire, decreased from 8 to between 3 and 5.⁴⁶ When treatment was stopped, the number of symptoms returned to 8, then decreased to between 2 and 5 when acupuncture resumed.

FAST TRACK

Acupuncture shows promise for alleviating symptoms of premenstrual dysphoric disorder.

CASE A thorough history and physical examination suggest that Ms. J’s symptoms are caused by PMDD uncomplicated by psychiatric illness. You ask her to record her symptoms for 2 menstrual cycles. You also suggest that she walk or engage in other regular exercise and eat more carbohydrates, such as brown rice and pasta, and less meat and other protein because doing these things may help her feel better in the meantime. When these measures fail to provide significant relief, you prescribe fluoxetine, 10 mg per day. Ms. J reports feeling markedly better at her next menstrual period.