SSRIs like fluoxetine, sertraline can be used to treat severe PMS. Women with PMS may be able to take medication only on the days when symptoms are expected to occur. Although intermittent therapy might be more acceptable to some women, this might be less effective than continuous regimens. Side effect such as nausea and weakness are however relatively common.

Tentative evidence supports vitamin B6 and chasteberry. Evidence does not support the use of St. John's wort, soy, vitamin E, and saffron. Evening primrose oil may be useful.

Medication may be used for people with severe and debilitating symptoms. Selective serotonin reuptake inhibitors (SSRIs) are the first-line medication. The U.S. Food and Drug Administration (FDA) has approved four SSRIs for the treatment of PMDD: Fluoxetine (available as generic or as Prozac or Sarafem), sertraline (Zoloft), paroxetine (Paxil), and escitalopram oxalate (Lexapro). Unlike treatments for depressive disorders, SSRIs do not need to be taken daily but instead can be taken only in the luteal phase or during PMDD symptoms. This is because those who respond to SSRIs usually experience symptoms relief within 1–2 days. Studies in rats suggest this rapid response to SSRIs is due to the elevation of the neuroactive progesterone metabolite allopregnanolone in the brain, rather than serotonin. Luteal phase dosing can be started 14 days before menses and subsequently discontinued after start of menstrual flow. People taking SSRIs to ease PMDD generally report >50% alleviation in symptoms, which was significant improvement compared to placebo.

Although less studied, SNRIs have also shown benefit in PMDD. In a randomized, controlled clinical trial of people with PMDD, 60% of the people taking venlafaxine improved versus 35% on placebo. Improvement was noticed during the first treatment cycle with 80% symptom reduction.

Another FDA approved treatment for PMDD is the oral contraceptive with ethinylestradiol and drospirenone, a novel progestin. It has been shown that hormonal birth control containing drospirenone and low levels of estrogen helps relieve severe PMDD symptoms, for at least the first three months it is used. The idea behind using oral contraceptives is to suppress ovulation by controlling sex hormone fluctuations during the luteal phase.

Cognitive behavioral therapy (CBT) has been shown to be effective in PMS and is suggested as a successful adjunct to SSRI treatment. CBT is an evidence-based treatment approach for treating depression and focuses on the link between mood, thoughts, and actions to help patients address current issues and symptoms. When CBT was compared to SSRI alone or in combination with SSRI, groups receiving CBT had significant improvement of PMS symptoms. Through the practice of CBT, patients are better able to recognize and modify recurrent issues as well as thought and behavior patterns that interfere with functioning well or that make depressive symptoms worse.

Danazol, an estrogen biosynthesis inhibitor, tamoxifen, an antagonistic modulator of the estrogen receptor, and bromocriptine, a prolactin-lowering D receptor agonist, are the main drugs used in the treatment of mastodynia and are effective.

Other medications and supplements have been found to be of benefit. Spironolactone (Aldactone), low dose oral contraceptives, low-dose estrogen have helped to relieve pain. Topical anti-inflammatory medications can be used for localized pain. For anti hormonal treatment, danazol (Danocrine) can be helpful. Tamoxifen citrate is used in some cases of severe breast pain. Vitamin E is not effective in relieving pain nor is Evening primrose oil. Vitamin B and Vitamin A have not been consistently found to be beneficial. Flaxseed has shown some activity in the treatment of cyclic mastalgia.

Pain may be relieved by the use of nonsteroidal anti-inflammatory drugs or, for more severe localized pain, by local anaesthetic. Pain may be relieved psychologically by reassurance that it does not signal a serious underlying problem, and an active life style can also effect an improvement.

Information regarding how the pain is real but not necessarily caused by disease can help to understand the problem. Learning breast self-examination helps to orient the woman to normal and expected texture and structure of the breast and nipple. Yearly breast exams may be suggested. Counseling can also be to describe changes that vary during the monthly cycle. Women on hormone replacement therapy may benefit from a dose adjustment. Another non-pharmacological measure to help relieve symptoms of pain may be to use good bra support. Breasts change during adolescence and menopause and refitting may be beneficial. Applying heat and/or ice can bring relief. Dietary changes may also help with the pain. Methylxanthines can be eliminated from the diet to see if a sensitivity is present. Some clinicians recommending a reduction in salt, though no evidence supports this practice.

Cyclical breast pain (cyclical mastalgia) is often associated with fibrocystic breast changes or duct ectasia and thought to be caused by changes of prolactin response to thyrotropin. Some degree of cyclical breast tenderness is normal in the menstrual cycle, and is usually associated with menstruation and/or premenstrual syndrome (PMS).

Noncyclical breast pain has various causes and is harder to diagnose. Noncyclical pain has frequently its root cause outside the breast. Some degree of non-cyclical breast tenderness can normally be present due to hormonal changes in puberty (both in girls and boys), in menopause and during pregnancy. After pregnancy, breast pain can be caused by breastfeeding. Other causes of non-cyclical breast pain include alcoholism with liver damage (likely due to abnormal steroid metabolism), mastitis and medications such as digitalis, methyldopa (an antihypertensive), spironolactone, certain diuretics, oxymetholone (an anabolic steroid), and chlorpromazine (a typical antipsychotic). Also, shingles can cause a painful blistering rash on the skin of the breasts.

Hypothyroidism caused by Hashimoto's thyroiditis is treated with thyroid hormone replacement agents such as levothyroxine, triiodothyronine or desiccated thyroid extract. A tablet taken once a day generally keeps the thyroid hormone levels normal. In most cases, the treatment needs to be taken for the rest of the person's life. In the event that hypothyroidism is caused by Hashimoto's thyroiditis, it may be recommended that the TSH levels be kept under 3.0 mIU/L.

Wilson's (temperature) syndrome, also called Wilson's thyroid syndrome or WTS, is an alternative medicine concept which is not recognized as a medical condition by evidence-based medicine. Its supporters describe Wilson's syndrome as a mix of various common and non-specific symptoms which they attribute to low body temperature and impaired conversion of thyroxine (T4) to triiodothyronine (T3), despite normal thyroid function tests. E. Denis Wilson, a physician who named the syndrome after himself, advocates treating these symptoms with sustained-release triiodothyronine.

The American Thyroid Association (ATA) describes Wilson's syndrome as at odds with established knowledge of thyroid function. The ATA described the diagnostic criteria for Wilson's syndrome as imprecise and non-specific, and found a lack of any scientific evidence supporting Wilson's claims. The ATA further raised concern that the proposed treatments were potentially harmful. Florida State Medical Board members described Wilson's syndrome as a "phony syndrome" and a scam during disciplinary action against Wilson.

The term "Wilson’s syndrome" was coined in 1990 by E. Denis Wilson, a physician practicing in Longwood, Florida. Wilson said that the syndrome's manifestations included fatigue, headaches, PMS, hair loss, irritability, fluid retention, depression, decreased memory, low sex drive, unhealthy nails, easy weight gain, and about 60 other symptoms. Wilson wrote that the syndrome can manifest itself as "virtually every symptom known to man." He also says that it is "the most common of all chronic ailments and probably takes a greater toll on society than any other medical condition."

Wilson says that low thyroid symptoms and low temperatures in the presence of normal thyroid function tests are not due to hypothyroidism, and might be reversed with a few months of treatment. To distinguish this condition from hypothyroidism, he named it Wilson's (temperature) syndrome. He states that it is "especially brought on by stress" and can persist after the stress has passed. He says that the main diagnostic sign is a body temperature that averages below (oral), and that the diagnosis is confirmed if the patient responds to treatment with a "special thyroid hormone treatment". He says that certain herbs can also help support normal body temperatures.

Overt, symptomatic thyroid dysfunction is the most common complication, with about 5% of persons with subclinical hypothyroidism and chronic autoimmune thyroiditis progressing to thyroid failure every year. Transient periods of thyrotoxicosis (over-activity of the thyroid) sometimes occur, and rarely the illness may progress to full hyperthyroid Graves' disease with active orbitopathy (bulging, inflamed eyes). Rare cases of fibrous autoimmune thyroiditis present with severe dyspnea (shortness of breath) and dysphagia (difficulty swallowing), resembling aggressive thyroid tumors – but such symptoms always improve with surgery or corticosteroid therapy. Primary thyroid B cell lymphoma affects fewer than one in a thousand persons, and it is more likely to affect those with long-standing autoimmune thyroiditis.

1. Clinical Genetics and Genetic Testing

Genetic testing is necessary to confirm the diagnosis of PMS. A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small to detect with this method. Chromosomal microarray should be ordered in children with suspected developmental delays or ASD. Most cases will be identified by microarray; however, small variations in genes might be missed. The falling cost for whole exome sequencing may replace DNA microarray technology for candidate gene evaluation. Biological parents should be tested with fluorescence "in situ" hybridization (FISH) to rule out balanced translocations or inversions. Balanced translocation in a parent increases the risk for recurrence and heritability within families (figure 3).

Clinical genetic evaluations and dysmorphology exams should be done to evaluate growth, pubertal development, dysmorphic features (table 1) and screen for organ defects (table 2)

2. Cognitive and Behavioral Assessment

All patients should undergo comprehensive developmental, cognitive and behavioral assessments by clinicians with experience in developmental disorders. Cognitive evaluation should be tailored for individuals with significant language and developmental delays. All patients should be referred for specialized speech/language, occupational and physical therapy evaluations.

3. Neurological Management

Individuals with PMS should be followed by a pediatric neurologist regularly to monitor motor development, coordination and gait, as well as conditions that might be associated with hypotonia. Head circumference should be performed routinely up until 36 months. Given the high rate of seizure disorders (up to 41% of patients) reported in the literature in patients with PMS and its overall negative impact on development, an overnight video EEG should be considered early to rule out seizure activity. In addition, a baseline structural brain MRI should be considered to rule out the presence of structural abnormalities.

4. Nephrology

All patients should have a baseline renal and bladder ultrasonography and a voiding cystourethrogram should be considered to rule out structural and functional abnormalities. Renal abnormalities are reported in up to 38% of patients with PMS. Vesicouretral reflux, hydronephrosis, renal agenesis, dysplasic kidney, polycystic kidney and recurrent urinary tract infections have all been reported in patients with PMS.

5. Cardiology

Congenital heart defects (CHD) are reported in samples of children with PMS with varying frequency (up to 25%)(29,36). The most common CHD include tricuspid valve regurgitation, atrial septal defects and patent ductus arteriousus. Cardiac evaluation, including echocardiography and electrocardiogram, should be considered.

6. Gastroenterology

Gastrointestinal symptoms are common in individuals with PMS. Gastroesophageal reflux, constipation, diarrhea and cyclic vomiting are frequently described.

Table 3: Clinical Assessment Recommendations in Phelan McDermid Syndrome.

22q13 deletion syndrome (spoken as "twenty-two q one three", see Locus (genetics)) is a genetic disorder caused by deletions or rearrangements on the q terminal end (long arm) of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. 22q13 deletion syndrome is often called Phelan-McDermid syndrome (abbreviated PMS). There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by "SHANK3" mutations, a definition that appears to exclude terminal deletions. The requirement to include "SHANK3" in the definition is supported by many, but not by those who first described 22q13 deletion syndrome.

A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small. The availability of DNA microarray technology for revealing multiple genetic problems simultaneously has been the diagnostic tool of choice. The falling cost for whole exome sequencing and, eventually, whole genome sequencing, may replace DNA microarray technology for candidate evaluation. However, fluorescence in situ hybridization (FISH) tests remain valuable for diagnosing cases of mosaicism (mosaic genetics) and chromosomal rearrangements (e.g., ring chromosome, unbalanced chromosomal translocation). Although early researchers sought a monogenic (single gene genetic disorder) explanation, recent studies have not supported that hypothesis (see Etiology, below).