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Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandins, substances that dilate blood vessels and cause inflammation. NSAIDs are usually among the first drugs recommended for almost any kind of minor pain. The most common ones used for PMS are nonprescription ibuprofen (Advil, Motrin, Midol) and naproxen (Aleve) or prescription mefenamic acid (Postel). Studies indicate that NSAIDs are most helpful when started 7 days before menstruation and continued for 4 days into the cycle.
Long-term daily use of any NSAID can increase the risk for gastrointestinal bleeding and ulcers. Long-term NSAID use can also increase the risk for heart attack and stroke.
Acetaminophen (Tylenol) is a good alternative to NSAIDs, especially when stomach problems, ulcers, or allergic reactions prohibit their use. Products that combine acetaminophen with other drugs that reduce PMS symptoms may be helpful. Brands include Pamprin and Premsyn. Such drugs typically also include a diuretic to reduce fluid and an antihistamine. Little evidence exists to indicate whether they are more or less effective than NSAIDs or other mild pain relievers.
Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) are drugs that keep higher levels of serotonin available in the brain. They have become the most effective treatments for premenstrual dysphoric disorder (PMDD) and for severe PMS symptoms.
SSRIs currently approved by the FDA for the treatment of PMDD symptoms include:
SSRIs may help not only premenstrual dysphoric disorder but also premenstrual physical symptoms, irritability, and tension. SSRIs appear to work much faster for relieving PMS-related depression than when used in major depression. These drugs are typically prescribed with either continuous (daily) dosing throughout the month or an intermittent dosing regimen. With intermittent dosing, women take the antidepressant during the 14-day premenstrual period of their luteal phase. This approach is also associated with fewer adverse effects than the standard regimens for major depression.
General side effects of SSRIs may include nausea, drowsiness, headache, weight gain and sexual dysfunction. In May 2007, the FDA proposed that all antidepressant medications should carry a warning about increased risks for suicidal thinking and behavior in young adults ages 18 - 24. This risk for “suicidality” generally occurs during the first few months of treatment.
Other Antidepressants. Non-SSRI antidepressants sometimes prescribed for PMDD include the serotonin-noradrenaline reuptake inhibitor venlafaxine (Effexor) and the tricyclic antidepressant clomipramine (Anafranil). Patients should not take tricyclics with either SSRIs or other antidepressants known as monoamine oxidase inhibitors (MAOIs).
[For more information, see In-Depth Report #8: Depression.]
Antianxiety drugs (called anxiolytics) may be helpful for women with severe premenstrual anxiety that is not relieved by SSRIs or other treatments.
Benzodiazepines. The standard anxiolytics are the benzodiazepines, with alprazolam (Xanax) most often used for PMS. Doctors, however, generally do not recommend these drugs for PMS-related anxiety. Dependence is a risk and can occur after as short a time as 3 months of use. (Using Xanax for only a few days per month when symptoms are most severe reduces this risk.) Common side effects are daytime drowsiness and a hung-over feeling. Respiratory problems may be worsened. Benzodiazepines also increase appetite, particularly for fats, during the premenstrual cycle. Overdose is very serious, although rarely fatal. Benzodiazepines are potentially dangerous when used in combination with alcohol.
Buspirone.. Buspirone (BuSpar) is an anti-anxiety drug that may help reduce premenstrual irritability. Unlike benzodiazepines, buspirone is not addictive. Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. [For more information, see In-Depth Report #28: Anxiety.]
Hormone therapies are used to interrupt the hormonal cycle that triggers premenstrual syndrome symptoms. One method to accomplish this is through birth control pills.
Birth Control Pills. Oral contraceptives (OCs), commonly called "the Pill" collectively, contain combinations of an estrogen (usually estradiol) and a progestin (either a natural progesterone or the synthetic form called progestin). Some women may experience worsening of symptoms with oral contraceptives.
One birth control pill, Yaz, is approved specifically for treatment of premenstrual dysmorphic disorder (PMSS). Yaz is a low-dose birth control pill that combines the estrogen estradiol with a newer type of progestin called drospirenone. This type of progestin is related to spironolactone, a diuretic. Yaz uses a 24-day dosing regimen (24 days active pills, 4 days placebo pills).
Newer “continuous-dosing” (also called “continuous-use”) oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. These OCs contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills. Examples of these include:
Side effects of OCs include nausea, breakthrough bleeding, breast tenderness, headache, and weight gain. Women who smoke, or who are at risk for blood clots or stroke, should avoid oral contraceptives or use them with caution.
[For more information, see In-Depth Report #91: Birth control options for women.]
GnRH Agonists. Gonadotropin-releasing hormone (GnRH) agonists (also called analogs) are powerful hormonal drugs that suppress ovulation and, thereby, the hormonal fluctuations that produce PMS. They are sometimes used for very severe PMS symptoms and to improve breast tenderness, fatigue, and irritability. GnRH analogs, however, appear to have little effect on depression.
GnRH agonists include nafarelin (Synarel), goserelin (Zoladex), leuprolide (Lupron Depot), and histrelin (Supprelin).
Commonly reported side effects (which can be severe in some women) include menopausal-like symptoms that include hot flashes, night sweat, weight change, and depression. The side effects vary in intensity, depending on the particular GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.
The most important concern is possible osteoporosis from estrogen loss. Doctors recommend that women not take these drugs for more than 6 months.
Danazol. Danazol (Danocrine) is a synthetic substance that resembles male hormones and should be used only if other therapies fail. It suppresses estrogen and menstruation and is used in low doses for severe PMS and premenstrual migraines. Taking it only during the luteal phase relieves cyclical mastalgia (severe breast pain) and avoids major side effects, but this intermittent regimen has no effect on other PMS symptoms.
Side effects from continuous use of Danazol can be severe. They include masculinizing effects such as facial hair growth, deepening of the voice, and acne. Danazol also increases the risk for unhealthy cholesterol levels. A few cases of blood clots and strokes have been reported. Women who are trying to become pregnant should not take this drug, because it may cause birth defects.
Diuretics are drugs that increase urination and help eliminate water and salt from the body. They reduce bloating in women with PMS and may also have a beneficial effect on mood, breast tenderness, and food craving. Diuretics can have considerable side effects and should not be used for mild or moderate PMS symptoms.
Spironolactone (Aldactone) is most commonly used for PMS. Other common diuretics include hydrochlorothiazide (Esidrix, HydroDiuril) and furosemide (Lasix). Unless potassium is replaced, many diuretics deplete the body's supply of potassium, which can lead to heart rhythm disturbances. Spironolactone is a potassium-sparing drug and does not have this problem. (However, women should be sure not to take additional potassium if they are taking spironolactone, and patients with kidney disease should avoid this medication.)
Diuretics interact with a number of other drugs, including certain antidepressants. Women who are considering diuretics should let their doctors know of any other drugs or supplements that they are taking.
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