There is no shortage of medications that have been used to treat premenstrual symptoms -- some by prescription only and others over-the-counter. Many women have premenstrual symptoms that can be annoying but are usually rather mild. If these symptoms are more troublesome, they are called PMS or premenstrual syndrome. If they are quite severe and disabling and include depression, anxiety and/or irritability they may well be PMDD (premenstrual dysphoric disorder). Many medication studies have focused on PMS which, unfortunately, has often been vaguely defined.

More recently there have been large, well-designed research studies of PMDD. There are now four prescription drugs that have been approved by the U.S. Food and Drug Administration (FDA) for treating the condition. These FDA-approved medications are fluoxetine (Sarafem), paroxetine controlled-release (Paxil CR), and sertraline (Zoloft), together with drospirenone/ethinyl estradiol oral contraceptive (YAZ).

Antidepressants

The antidepressants most effective for treating PMDD are those with strong effects on serotonin, a chemical neurotransmitter. They are often referred to as SSRIs (selective serotonin reuptake inhibitors). There are 6 SSRIs marketed in the U.S., although only 3 have been approved thus far by the FDA for treating PMDD. The six SSRIs available in the U.S. are:

Sarafem and Prozac are the same chemical (different commercial names for fluoxetine). The manufacturer chose to use the name Sarafem when fluoxetine was approved for PMDD.

PMDD experts recommend an SSRI for PMDD when the main symptoms are depression, sudden mood shifts, anxiety, anger/irritability or fatigue with a preference in the direction of the FDA-approved drugs. If PMDD symptoms are quite severe or if PMDD is associated with another condition requiring an SSRI, treatment is usually continuous (medication is taken every day). For less severe symptoms, intermittent dosing may be all that is necessary. Intermittent dosing means taking an SSRI only during the second half of the cycle (the 2 weeks before menses). Fluoxetine (Sarafem), paroxetine controlled-release (Paxil CR), and sertraline (Zoloft) are FDA-approved for both continuous and intermittent use. Which approach is best varies from woman to woman and is best determined with your physician or nurse practitioner. Some other antidepressants (e.g., citalopram [Celexa], clomipramine [Anafranil], escitalopram [Lexapro], mirtazapine [Remeron], venlafaxine [Effexor]) show promise for treating PMDD, but they have not been as well studied as the SSRIs and none of them are FDA-approved for PMDD.

Anxiolytics (Antianxiety Drugs)

When anxiety symptoms are an outstanding feature of PMDD, antianxiety drugs are sometimes used. None are FDA-approved for PMDD. The best studied of these is alprazolam (Xanax and others), which led experts to recommend it first if an antianxiety drug is used. Both clonazepam (Klonopin and others) and lorazepam (Ativan and others) are similar drugs and can be used as alternatives. Drugs of this type tend to work quickly and may be used either as needed or regularly, but only for the second half of the cycle. Dependence and tolerance are occasional problems with these drugs.

A different type of antianxiety drug is buspirone (BuSpar and others), which is used at times for PMDD but is not high on the list of recommendations.

Analgesics (Pain Relievers)

There are many pain relievers that can be helpful if pain is a prominent feature of PMDD. However, they are not particularly useful as overall treatments for the disorder. You can find a wide selection in the over-the-counter section of your pharmacy and others are available by prescription. These drugs are used more commonly to treat cramps that occur during menses, a condition known as dysmenorrhea.

Hormones

There are two hormonal approaches to treating PMDD. One involves stopping ovulation either with a drug or surgically. Needless to say, surgery to remove the ovaries is considered only as a last resort in the most severe, disabling, and otherwise treatment resistant situations. Oral contraceptives (birth control pills) are used often to treat premenstrual symptoms, but somewhat surprisingly they have not been extensively studied and their effectiveness for PMDD is not well-established. An exception is drospirenone/ethinyl estradiol (YAZ), which was FDA-approved in 2006 for "the treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who choose to use an oral contraceptive as their method of contraception."

Danazol (Danocrine) is a synthetic steroid that suppresses ovulation and is FDA-approved for treating endometriosis. Its value in PMS is mostly for breast tenderness and it is not particularly well tolerated.

There is a class of drugs known as gonadotropin-releasing hormone (GnRH) agonists that prevent ovulation. These include leuprolide (Lupron), goserelin (Zoladex), and nafarelin (Synarel). These drugs are usually reserved for women who have severe PMDD that has not responded to better established and better tolerated treatments. Because these drugs cause a premature menopause, they are often used together with supplemental estrogen and progestin.

The second hormonal approach to PMS/PMDD is the use of progesterone or estrogen to directly relieve symptoms. There are literally thousands of websites with information about progesterone for PMS - natural progesterone, synthetic progesterone, progesterone-like compounds, oral progesterone, progesterone suppositories, progesterone creams, and even progesterone from wild yams. It has become progressively more difficult to separate progesterone science from progesterone hype. Remember that research studies have not found abnormal progesterone levels in women with PMS/PMDD. In addition, the best designed research studies in which progesterone was compared to placebo (a sugar pill) have not found it to be effective for severe PMS/PMDD. Nonetheless, progesterone continues to be widely prescribed by clinicians and widely used by patients, with both groups convinced that it is effective. This is an area where science and popular opinion continue to butt heads.

There has been some research to support the benefit of the estrogen patch for treating severe PMS symptoms. More study is needed to see just how this might fit into the treatment of PMDD. Estrogen is not considered a first-line treatment.

Diuretics

Diuretics (water pills) may be of some benefit for relieving water retention, bloating and body pain, but they are not particularly useful for the overall treatment of PMDD.

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