Smith-Magenis syndrome

March 22, 2017


Smith-Magenis syndrome

Natural Standard Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

Related Terms

  • 17p syndrome, autism, behavioral therapy, childhood intervention programs, chromosomal deletion, chromosome 17, circadian rhythm, cognitive disabilities, developmental disorder, FISH analysis, fluorescence in situ hybridization, genetic mutation, high-resolution chromosome analysis, intellectual disabilities, learning disabilities, RAI1 gene, RAI1 protein, retinoic acid-induced 1 gene, SMCR, Smith-Magenis chromosome region, speech-language therapy.


  • Smith-Magenis syndrome (SMS) is a genetic disorder that is characterized by varying degrees of intellectual disabilities (formerly called mental retardation), distinctive facial features, sleep disturbances, and behavioral problems. Symptoms are usually apparent shortly after birth. The disease is not considered progressive, but the distinct facial features are usually more noticeable once the patient reaches adolescence or adulthood.

  • SMS occurs when a person is born with a mutated retinoic acid-induced 1 (RAI1) gene or a missing region of chromosome 17. Most cases occur randomly during development and are not passed down among family members.

  • Researchers estimate that SMS affects at least one out of 25,000 people worldwide. However, many experts believe that the condition is often undiagnosed and misdiagnosed, because genetic tests for the disorder have only been available since the mid-1990s. Therefore, some believe that the prevalence may be closer to one out of 15,000 people. SMS affects males and females equally.

  • There is currently no cure for SMS. However, many treatments and therapies may help patients cope with the disorder. With proper therapy, some patients with intellectual disabilities are able to live independently once they become adults, while others may need lifelong support or residential care. Adults with profound intellectual disabilities usually require lifelong nursing care. However, it should be noted that most people with SMS have mild-to-moderate intellectual disabilities. Although there are limited data regarding the average life expectancy of someone with SMS, it has been reported that some people have lived to be older than 70 years of age.

Types of the Disease

  • The clinical presentation of Smith-Magenis syndrome (SMS) may vary according to the type of genetic change in chromosome 17. Dysfunction of the retinoic acid-induced 1 (RAI1) gene on chromosome 17 is related to the cardinal features (symptoms that lead to diagnosis) of SMS. Most cases of SMS are caused by a deletion in chromosome 17, though rare cases are related to a mutation in the RAI1 gene. People with SMS who have a genetic mutation in the RAI1 gene typically experience milder symptoms than people with a chromosomal deletion. People with genetic mutations are less likely to have hearing loss, heart defects, kidney abnormalities, and short stature.

Risk Factors

  • There are no known risk factors for developing Smith-Magenis syndrome.


  • General: Smith-Magenis syndrome (SMS) is a genetic disorder that is not typically inherited. Instead, specific genetic changes randomly occur during the development of the egg, sperm, or embryo.

  • Chromosomal deletion: SMS typically occurs when a person is born with a chromosomal deletion (a missing region) in chromosome 17. Although this missing region of chromosome 17 contains many genes, researchers believe that the loss of the retinoic acid-induced 1 (RAI1) gene in particular leads to SMS. Normally, the RAI1 gene provides the body with instructions on how to make a protein that is found in nerve cells in the brain. When this gene is absent, the nervous system does not function properly. As a result, behavioral and physical symptoms, as well as intellectual disabilities, develop.

  • The loss of additional genes normally attached to the missing region of chromosome 17 may explain why people with the disorder experience varying symptoms.

  • Genetic mutation: In very rare cases, SMS may occur if a person is born with an abnormal or mutated RAI1 gene. When this gene is mutated, it leads to the production of either low levels of the RAI1 protein or a dysfunctional RAI1 protein. Because this is considered an autosomal dominant condition, only one mutated copy of the RAI1 gene is needed for the disorder to occur.

Signs and Symptoms

  • General: In general, people with Smith-Magenis syndrome (SMS) typically experience behavioral problems, varying degrees of intellectual disabilities (formerly called mental retardation), distinct facial features, and sleep disturbances. Other symptoms, such as hearing loss, heart defects, kidney abnormalities, and short stature, are more likely to occur in people who have chromosomal deletions than in people who have mutations in the retinoic acid-induced 1 (RAI1) gene.

  • Behavioral problems: Behavioral problems associated with SMS typically include frequent temper tantrums, aggressive or impulsive behaviors, anxiety, hyperactivity, and difficulty concentrating. It is also common for people with SMS to intentionally hurt themselves. For example, people may bang their heads repetitively against objects or bite themselves. Most people with SMS repetitively hug themselves, much like the self-stimulatory behavior common in autism. People with SMS also tend to compulsively lick their fingers before flipping pages of books or magazines. This behavior is commonly called "lick and flip."

  • Facial features: Most people with SMS have many distinct facial characteristics, which typically include a broad, square-shaped face, deep-set eyes, a prominent lower jaw, full cheeks, a broad and flattened nasal bridge, and a mouth that is usually turned downward with a full upper lip. These facial abnormalities may be noticeable during early childhood, but they are usually more distinct once the person reaches adolescence or adulthood. In addition, people with SMS commonly have deep, hoarse voices.

  • Intellectual disabilities: People with SMS experience varying degrees of intellectual disabilities (formerly called mental retardation), which can range from mild to profound. Most adults with SMS experience mild-to-moderate intellectual disabilities. Symptoms of intellectual disabilities are usually noticeable shortly after birth or during early childhood. Researchers typically use intelligence quotient (IQ) tests to measure the severity of a person's intellectual disabilities. Individuals who have IQs of 85-115 are considered to have average intelligence. People with SMS can have mild-to-severe intellectual disabilities, with IQ scores between 20 and 80. Individuals may also have learning disabilities, and the development of motor, speech, or language skills may be delayed.

  • Sleep disturbances: Beginning in early childhood, over 75% of people with SMS develop sleep disturbances. People may feel very tired during the day but have difficultly falling asleep and/or wake up several times during the night.

  • Other: Other symptoms of SMS may include a curved spine (called scoliosis), short stature, reduced sensitivity to pain and temperature, and ear abnormalities that may lead to hearing loss. Some people may have vision problems, such as nearsightedness. Less common symptoms may include heart and kidney defects.


  • General: A high-resolution chromosome analysis and FISH (fluorescence in situ hybridization) analysis may be performed to confirm a diagnosis of Smith-Magenis syndrome (SMS). However, if the results are inconclusive, a diagnosis may also be made in an older child based on clinical signs alone. These signs include varying degrees of intellectual disabilities (formerly called mental retardation), distinctive facial features, sleep disturbances, and behavioral problems. Prenatal testing is not generally performed to diagnose SMS, because the condition is unpredictable and does not run in families.

  • High-resolution chromosome analysis: If SMS is suspected based on physical signs and symptoms, a high-resolution chromosome analysis may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed for a deletion in part of chromosome 17. The chromosome analysis involves treating chromosomes with a chemical that makes the locations of specific genes visible under a microscope. This type of chromosome analysis shows smaller structural chromosome abnormalities that would not be seen in a low-resolution chromosome analysis or karyotype study. In some cases, very small deletions in chromosome 17 may not be detectable, because these specific locations may not always be clearly visible during the analysis.

  • FISH analysis: If a chromosome analysis is inconclusive, a FISH analysis may be performed. This technique can be used to test for specific gene sequences in chromosomal DNA. A FISH analysis is more accurate than a high-resolution chromosome analysis, because it uses DNA sequences similar to the possible missing sequence being tested. These sequences used in FISH analyses are called DNA probes, and they only bind to other sequences like themselves. FISH analyses use probes treated with chemicals to make them appear fluorescent. The specific chromosome containing the retinoic acid-induced 1 (RAI1) gene can be identified by observing the location of the fluorescence under the microscope. If the region is absent, a positive diagnosis may be made.


  • Back problems: Some patients with Smith-Magenis syndrome (SMS) have scoliosis, a condition that causes the spine to curve abnormally. If left untreated, scoliosis may lead to arthritis of the spine, which causes pain and inflammation. People who have had scoliosis as children have an increased risk of experiencing chronic (long-lasting) back pain during adulthood.

  • Ear infections: SMS patients may have middle ear abnormalities. As a result, they typically have an increased risk of developing frequent ear infections.

  • Hearing loss: Some people with SMS have ear abnormalities that may lead to permanent hearing loss or deafness.

  • Heart problems: Fewer than 25% of SMS patients are born with heart defects, which may be life-threatening or require surgery.

  • Kidney problems: Fewer than 25% of SMS patients have kidney abnormalities.

  • Mood problems: Sleep disturbances may lead to anxiousness, irritability, fatigue, poor concentration, difficulty focusing, impaired memory, decreased motor coordination, irritability, and impaired social interaction.

  • Retinal detachment: SMS patients have an increased risk of experiencing retinal detachment. The retina, located at the back of the eye, sends visual images to the brain, where they are perceived. Retinal detachment happens when the retina separates from the layer of blood vessels below it (called the choroid). The condition is considered a medical emergency, because it can lead to permanent vision loss if it is not treated promptly.


  • General: There is currently no cure for Smith-Magenis syndrome (SMS). However, many treatments and therapies may help patients manage symptoms and complications of the disorder. Treatment varies depending on the severity of specific symptoms. With proper therapy, some patients with intellectual disabilities are able to live independently once they become adults, while others may need lifelong support or residential care.

  • Childhoodintervention programs: Patients with SMS typically experience physical and intellectual developmental delays. For instance, it may take a child with SMS longer to learn how to crawl or walk than a child without SMS. Therefore, caregivers should ask the doctors of SMS patients about early intervention programs. These specialized programs expose disabled children to age-appropriate sensory, motor, and cognitive activities and typically involve special educators and therapists who help babies and young children develop their language, social, motor, and self-help skills. Although intellectual disabilities can range from mild to profound, most people with SMS experience mild-to-moderate intellectual disabilities.

  • Education: Patients with SMS who suffer from intellectual disabilities must have access to education that is tailored to their specific strengths and weaknesses. According to the Individuals with Disabilities Education Act, all children with disabilities must receive free and appropriate education. This law states that members of the patient's school must consult with the patient's parents or caregivers to design and write an individualized education plan based on the child's needs. The school faculty should document the child's progress in order to ensure that the child's needs are being met.

  • Educational programs vary among patients, depending on the child's specific learning disabilities. In general, most experts believe that children with disabilities should be educated alongside their nondisabled peers. The idea is that nondisabled students will help the patient learn appropriate behavioral, social, and language skills. Therefore, some SMS patients are educated in mainstream classrooms. Other patients attend public schools but take special education classes. Others attend specialized schools that are designed to teach children with disabilities.

  • Behavioral therapy: Behavioral therapy may also be beneficial. Several different types of behavioral therapies are available to help SMS patients improve their communication and social skills, as well as their learning abilities and adaptive behaviors. Therapy may also help reduce negative behaviors, such as aggression, temper tantrums, and hyperactivity. For instance, dialectical behavior therapy may be used teach behavioral skills to help a person tolerate stress, regulate emotions, and improve relationships with others. Evidence suggests that behavioral therapy is most effective if it is started early in life.

  • Speech-language therapy: Some patients with SMS may benefit from speech-language therapy, because communication skills may be delayed. During speech-language therapy, a qualified speech-language professional (SLP) works with the patient on a one-to-one basis, in a small group, or directly in a classroom, to help the patient improve speech, language, and communication skills. Programs are tailored to the patient's individual needs.

  • Speech pathologists use a variety of exercises to improve the patient's communication skills. Exercises typically start off simple and become more complex as therapy continues. For instance, the therapist may ask the patient to name objects, tell stories, or explain the purpose of an object.

  • On average, patients receive five or more hours of therapy per week for three months to several years. Doctors typically recommend that treatment be started early to ensure the best possible prognosis for the child.

  • Hearing aids: SMS patients who experience hearing loss may benefit from hearing aids. These battery-operated devices are available in three basic styles: behind-the-ear aids, in-the-ear aids, and canal hearing aids. Patients should talk to their healthcare providers to determine the type of hearing aid that is best for them. A behind-the-ear device is used for mild-to-profound hearing loss. The device is worn behind the ear and is attached to a plastic ear mold inside the outer ear. In-the-ear hearing aids are worn inside the outer ear and are used for mild-to-severe hearing loss. Canal hearing aids are smaller hearing aids that fit inside the patient's hearing canal. They are used for mild-to-moderately severe hearing loss.

  • If hearing loss is severe, patients may benefit from cochlear implants. These electronic devices are surgically implanted inside of the ears. Unlike a hearing aid, which amplifies sound, a cochlear implant makes up for damaged parts of the inner ear.

  • Medications for behavioral problems: Certain medications may be prescribed to treat the behavioral problems associated with SMS. Anticonvulsants, such as carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®, or Tegretol XR®), may be used to treat seizures. Antipsychotic drugs may be prescribed to help treat aggressive and repetitive behaviors, as well as hyperactivity, in SMS patients. These include risperidone (Risperdal®), olanzapine (Zyprexa®), and quetiapine (Seroquel®). However, medications have been found to be minimally effective at improving behavior in patients with SMS.

  • Medications for sleep disturbances: There are many sedative-hypnotic medications available to help patients fall asleep and stay asleep throughout the night. Commonly prescribed medications for insomnia include temazepam (Restoril®), flurazepam (Dalmane®), estazolam (ProSom®), triazolam (Halcion®), zolpidem (Ambien®), zaleplon (Sonata®), and eszopiclone (Lunesta®).

  • However, the U.S. Food and Drug Administration (FDA) has issued warnings for all sedative-hypnotic drugs used for sleep, because they may cause serious side effects. A life-threatening allergic reaction, called anaphylaxis, and severe facial angioedema (swelling) may occur the first time a sleep product is taken. Complex sleep-related behaviors may include sleep-driving (driving while not fully awake and with no memory of driving), making phone calls, and preparing and eating food while asleep.

  • Over-the-counter (OTC) sleep aids may be used in the short term to treat insomnia. For instance, diphenhydramine (Benadryl®) is the most commonly used OTC antihistamine sleep aid. It can be purchased alone (Benadryl®, Nytol®, or Sominex®) or in combination with other OTC items such as acetaminophen (Tylenol PM®). OTC sleep aids are not intended for long-term use, because dependency can develop.

  • Melatonin agonists, such as ramelteon (Rozerem®), have also been used to treat insomnia. Ramelteon promotes the onset of sleep by increasing levels of the natural hormone melatonin, which helps normalize normal circadian rhythm and sleep/wake cycles. These drugs are less likely to cause morning drowsiness than sedative-hypnotics. Side effects are generally mild and may include daytime sleepiness, dizziness, and fatigue.

  • Sedating antidepressants, including trazodone (Desyrel®), amitriptyline (Elavil®), and doxepin (Sinequan®), have been used to treat insomnia. When used to promote sleep, these medicines are used in lower doses than when used to treat depression. Side effects may include dry mouth, blurred vision, a "hangover" in the morning, constipation, urinary retention, and nausea.

Integrative Therapies

  • Note: Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Smith-Magenis syndrome (SMS). The therapies listed below have been studied for related conditions, including cognitive enhancement and sleep disturbances.

  • Good scientific evidence:

  • Bacopa: Bacopa monnieri leaf extract is called brahmi in Ayurvedic medicine. A number of drugs, including bacopa, have been described as capable of enhancing the mind. Good scientific evidence supports the use of bacopa to enhance cognition.

  • Avoid if allergic to Bacopa monnieri, its constituents, or any members of the Scrophulariaceae (figwort) family. Use cautiously if taking thyroid drugs; calcium-blocking drugs; sedatives; or herbs, supplements, or drugs that are broken down by the liver. Avoid if pregnant or breastfeeding.

  • Melatonin: Melatonin is a neurohormone produced in the brain. Levels of melatonin in the blood are highest before bedtime. Good evidence suggests that melatonin may help treat symptoms of delayed sleep phase syndrome (DSPS).

  • Several human studies report that melatonin taken by mouth before bedtime decreases sleep latency (the amount of time it takes to fall asleep) in elderly individuals with insomnia. However, most studies have not been high quality in their designs, and some research has found limited or no benefits. The majority of trials have been brief in duration (several days long), and long-term effects are not known.

  • There are multiple trials investigating melatonin use in children with various neuropsychiatric disorders, including mental retardation (intellectual disabilities), autism, psychiatric disorders, visual impairment, or epilepsy. Studies have demonstrated reduced sleep latency and increased sleep duration. Well-designed controlled trials in select patient populations are needed before a stronger or more specific recommendation can be made.

  • Multiple human studies have measured the effects of melatonin supplements on sleep in healthy individuals. A wide range of doses has been used, often taken by mouth 30-60 minutes before bedtime. Most trials have been small, brief in duration, and not rigorously designed or reported. However, the weight of scientific evidence does suggest that melatonin decreases the time it takes to fall asleep, increases the feeling of sleepiness, and may increase the duration of sleep. Better research is needed in this area.

  • There are rare reports of allergic skin reactions after taking melatonin by mouth. Avoid with bleeding disorders or if taking blood thinners. Use cautiously with seizure disorders, major depression, psychotic disorders, diabetes, low blood sugar levels, glaucoma, high cholesterol, or atherosclerosis, or if at risk for heart disease. Use cautiously if driving or operating heavy machinery.

  • Music therapy: During music therapy, music is used to influence physical, emotional, cognitive, and social well-being. It may involve listening to or performing music, with or without the presence of a music therapist. In older adults, music may result in significantly better sleep quality, as well as longer sleep duration, greater sleep efficiency, a shorter time needed to fall asleep, less sleep disturbance, and less daytime dysfunction. There is also evidence of benefit in elementary-aged children who use music during nap time and bedtime. Music therapy may also be as effective as chloral hydrate in inducing sleep or sedation in children undergoing electroencephalogram (EEG) testing.

  • Valerian: Valerian is an herb native to Europe and Asia. Today, the herb grows in most parts of the world. Several studies in adults suggest that valerian improves the quality of sleep and reduces sleep latency for up to 4-6 weeks. Ongoing nightly use may be more effective than single-dose use, with increasing effects over four weeks. Better effects have been found in poor sleepers. However, most studies have not used scientific ways of measuring sleep improvements, such as sleep pattern data in a sleep laboratory.

  • Use cautiously if allergic to valerian or other members of the Valerianaceaefamily. Use cautiously with liver disorders. Use cautiously before surgery. Avoid if driving or operating heavy machinery, as it may cause drowsiness. Avoid if pregnant or breastfeeding.

  • Unclear or conflicting scientific evidence:

  • 5-HTP: 5-HTP is the precursor for serotonin. Serotonin is the brain chemical associated with sleep, mood, movement, feeding, and nervousness. There is insufficient evidence regarding the use of 5-HTP for sleep disorders. Additional studies are needed before a conclusion can be drawn.

  • Avoid if allergic to 5-HTP. Avoid with eosinophilia, Down syndrome, or mitochondrial encephalomyopathy. Avoid if taking monoamine oxidase inhibitors (MAOIs). Use cautiously with gastrointestinal disorders. Use cautiously with kidney disorders. Use cautiously if taking antidepressants, carbidopa, phenobarbital, pindolol, reserpine, tramadol, or zolpidem. Avoid if pregnant or breastfeeding.

  • Acupressure, shiatsu: During acupressure, finger pressure is applied to specific acupoints on the body. Acupressure is used around the world for relaxation, wellness promotion, and the treatment of many health problems. Preliminary research supports the use of acupressure for improving sleep quality in elderly patients and possibly in healthy adults of all ages. Better-designed trials are needed to support these results.

  • With proper training, acupressure appears to be safe if self-administered or administered by an experienced therapist. No serious long-term complications have been reported, according to scientific data. Hand nerve injury and herpes zoster ("shingles") cases have been reported after shiatsu massage. Forceful acupressure may cause bruising.

  • Acupuncture: Acupuncture is commonly used throughout the world. According to Chinese medicine theory, the human body contains a network of energy pathways through which vital energy, called "qi" (or "chi"), circulates. These pathways contain specific points that function like gates, allowing qi to flow through the body. Needles are inserted into these points to regulate the flow of qi. Traditional Chinese medicine (TCM) commonly uses acupuncture to treat insomnia. A review of the available studies found reports of benefit, but major weaknesses in the design of the research make the evidence insufficient to recommend for or against acupuncture for insomnia.

  • There is insufficient available evidence to determine if acupuncture is an effective treatment for cognitive disorders.

  • Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, medical conditions of unknown origins, or infections. Acupuncture should not be applied to the chest in patients with lung diseases or to any area that may rely on muscle tone to provide stability. Avoid use in infants, young children, and patients with needle phobias. Use cautiously with bleeding disorders, neurological disorders, seizure disorders, or diabetes. Use cautiously in elderly or medically compromised patients. Use cautiously in patients who will drive or operate heavy machinery after acupuncture. Use cautiously if taking anticoagulants. Avoid if pregnant.

  • Aromatherapy: Aromatherapy refers to many different therapies that use essential oils. The oils are sprayed in the air, inhaled, or applied to the skin. Essential oils are usually mixed with a carrier oil (usually a vegetable oil) or alcohol. Based on human use, lavender and chamomile aromatherapy are thought to be effective sleep aids. Although preliminary small studies suggest some hypnotic effects, there have been no well-designed human trials. Further research is needed before any recommendation can be made. There is early research on lavender essential oil inhalation as a sedative for patients following intubation (placement of a breathing tube). Evidence in this area is preliminary, and a firm conclusion cannot be drawn.

  • Essential oils should be administered in a carrier oil to avoid toxicity. Avoid with a history of allergic dermatitis. Use cautiously if driving or operating heavy machinery. Avoid consuming essential oils. Avoid direct contact of undiluted oils with mucous membranes. Use cautiously if pregnant. Sage, rosemary, and juniper oils should be avoided if pregnant or breastfeeding.

  • Astragalus: In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. According to one human study, astragalus may help improve mental performance of children with low intelligence quotients (IQs). This study, however, used astragalus as part of a combination therapy and it is difficult to ascribe the effects to any one constituent. Further well-designed clinical trials are required before recommendations can be made.

  • Avoid if allergic to astragalus, peas, or any other related plants. Avoid with a history of Quillaja bark-induced asthma. Avoid if taking anticoagulants (such as warfarin or aspirin) or herbs or supplements with similar effects. Avoid with inflammation, fever, stroke, organ transplantation, or autoimmune diseases. Stop use two weeks before and immediately after surgery or dental or diagnostic procedures that have bleeding risks. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously if taking blood thinners, blood sugar drugs, diuretics, or herbs or supplements with similar effects. Avoid if pregnant or breastfeeding.

  • Ayurveda: Ayurveda is a form of natural medicine that originated in ancient India more than 5,000 years ago. Ayurveda is an integrated system of techniques that uses diet, herbs, exercise, meditation, yoga, and massage or bodywork to achieve optimal health on all levels. There is evidence from one well-designed study that a traditional Ayurvedic formula (Blissful Sleep, Maharishi Ayurvedic Products International), containing valerian (Valeriana wallichii), rose petals (Rosa centifolia), muskroot (Nardostachys jatamansi), heart-leaved moonseed (Tinospora cordifolia), winter cherry (Withania somnifera), pepper (Piper nigrum), ginger (Zingiber officinalis), aloeweed (Convolvulus pluricaulis), and licorice root (Glycyrrhiza glabra), may decrease sleep latency (the time needed to get to sleep) in people with sleep-onset insomnia, with no side effects. Further research is needed to confirm these results.

  • There is evidence from well-designed studies that the herb brahmi (Bacopa monnieri) may improve memory and cognitive functioning in adults.

  • Ayurvedic herbs should be used cautiously, because they are potent, and some constituents may be toxic if taken in large amounts or for a long time. Some herbs imported from India have been reported to contain high levels of toxic metals. Ayurvedic herbs may interact with other herbs, foods, or drugs. A qualified healthcare professional should be consulted before taking.

  • Chamomile: Chamomile is an herb that has an apple-like smell and taste. It is commonly taken as a tea. Traditionally, chamomile preparations, such as tea and essential oil aromatherapy, have been used to treat insomnia. Better research is needed to determine if chamomile is an effective sedative.

  • Avoid if allergic to chamomile or any related plants, such as aster, chrysanthemum, mugwort, ragweed, or ragwort. Avoid with heart disease, breathing disorders, hormone-sensitive conditions, or central nervous system disorders. Avoid if taking cardiac depressive agents, central nervous system depressants, respiratory depressive agents, or anticoagulants. Use cautiously if taking benzodiazepine, antiarrhythmic medications, calcium channel blockers, alcohol, sedative agents, anxiolytic medications, spasmolytic drugs, oral medications, or agents that are broken down by the liver. Use cautiously if driving or operating machinery. Avoid if pregnant or breastfeeding.

  • Ginseng: For more than 2,000 years, the roots of this slow-growing plant have been valued in Chinese medicine. Several studies suggest some improvement of mental performance in patients who take ginseng supplements. However, several trials used ginseng in combination with other herbs (e.g., Ginkgo biloba) or multivitamins. Future research should focus on determining whether such effects might be specific to clearly defined patient subgroups and whether longer treatment duration adds benefit.

  • Avoid ginseng with a known allergy to plants in the Araliaceae family. There has been a report of a life-threatening skin reaction, possibly caused by contaminants in the ginseng formulation.

  • Green tea: Green tea is made from the dried leaves of Camellia sinensis, an evergreen shrub. Green tea, black tea, and oolong tea are all made from the same plant. Green tea is a source of caffeine. Limited, low-quality research reports that the use of green tea may improve cognition and the sense of alertness. Green tea contains caffeine, which is a stimulant.

  • Avoid if allergic or hypersensitive to caffeine or tannin. Use cautiously with diabetes or liver disease.

  • Guarana: Guarana is a native species of South America. It has stimulating properties when taken by mouth. Guarana has the same stimulatory effect as caffeine, and it is often used to increase energy and weight loss. Guarana has not been shown to alter cognitive function or arousal in preliminary studies. Caffeine found in guarana may improve simple reaction time but may not improve immediate memory. Additional research is needed in this area.

  • Avoid if allergic or hypersensitive to guarana (Paullinia cupana), caffeine, tannins, or related species of the Sapindaceae family. Avoid with high blood pressure, psychological or psychiatric disorders, liver disorders, or arrhythmia (irregular heartbeat). Avoid if taking other stimulatory agents (such as coffee or tea). Use cautiously with breast disease, impaired kidney function, diabetes, preexisting mitral valve prolapse, iron deficiency, gastric or duodenal ulcers, bleeding disorders, or glaucoma, or if at risk for osteoporosis. Use cautiously if undergoing electroconvulsive therapy (ECT). Avoid if pregnant or breastfeeding.

  • Guided imagery: Guided imagery may involve a number of techniques, including metaphor, storytelling, fantasy, game playing, dream interpretation, drawing, visualization, active imagination, or direct suggestion. Early research supports the value of combined pharmacotherapy and relaxation training in the treatment of insomnia. Further research is necessary in order to make a firm recommendation.

  • Guided imagery is usually intended to supplement medical care, not to replace it. Guided imagery should not be relied on as the sole therapy for a medical problem. Contact a qualified healthcare provider if mental or physical health is unstable or fragile. Never use guided imagery techniques while driving or doing any other activity that requires strict attention. Use cautiously with physical symptoms that can be brought about by stress, anxiety, or emotional upset, because imagery may trigger these symptoms. Individuals who have a history of trauma or abuse or those who feel unusually anxious while practicing guided imagery should speak with their qualified healthcare providers before practicing this therapy.

  • Hops: The hop is a climbing plant native to Europe, Asia, and North America. The cone-like, fruiting bodies of the plant are most commonly used as a flavoring agent in beer. Animal studies report that hops may have sedative and hypnotic (sleep-enhancing) effects. However, little human research has evaluated the effects of hops on sleep quality. Further research is needed in this area before a recommendation can be made.

  • Avoid if allergic to hops, pollen, peanut, chestnut, or banana. Use cautiously with a history of breast cancer, uterine cancer, cervical cancer, prostate cancer, or endometriosis. Use cautiously while driving or operating heavy machinery. Use cautiously with a history of diabetes, stomach ulcers, seizures, or asthma. Hops may affect hormone levels, including estrogen levels. Dust from hops may contain harmful bacteria. Avoid if pregnant or breastfeeding.

  • Hypnotherapy, hypnosis: Hypnosis is a trance-like state in which a person becomes more aware and focused and is more open to suggestion. Hypnotherapy has been used to treat health conditions and to change behaviors. Several early studies report that hypnosis may decrease the amount of time it takes to fall asleep, increase the duration of sleep, and improve sleep quality. However, this research is not well designed or reported and cannot be considered definitive.

  • It remains unclear whether hypnotherapy can enhance cognitive function and improve academic performance. Further research is warranted in this area.

  • Use cautiously with mental illnesses (e.g., psychosis or schizophrenia, manic depression, multiple personality disorder, or dissociative disorders) or seizure disorders.

  • Iodine: Iodine is required for the production of thyroid hormones, which are necessary for normal brain development and cognition. One study showed that oral iodized oil significantly improved performance on cognitive tests in 10-12 year-old schoolchildren. Further research is needed to confirm these results.

  • There have been reports of severe and even fatal reactions to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for more than 14 days. Avoid Lugol's solution and saturated solution of potassium iodide (SSKI, PIMA) with hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin, because it may irritate or burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

  • Khat: Khat is believed to have come from Ethiopia. It is a flowering evergreen plant found in tropical East Africa. Khat has been evaluated for its cognitive effects. However, the results are mixed, with some studies showing benefit and others showing negative effects. Additional research is needed in this area to clarify these findings.

  • It remains unknown if khat is physically addictive when taken by mouth. However, it is linked to psychological dependence, and it is illegal in the United States. Avoid if allergic to the Celastraceae (staff vine) family. Avoid with glaucoma or mental illness. Avoid driving or operating heavy machinery after using khat. Avoid holding khat in the cheek for a long time. Use cautiously if taking amoxicillin, ampicillin, or stimulants. Use cautiously with a history of high blood pressure, tachycardia (fast heartbeat), depression, or Tourette's syndrome (motor tics). Avoid if pregnant or breastfeeding.

  • Kundalini yoga: Kundalini yoga is one of many traditions of yoga that share common roots in ancient Indian philosophy. Kundalini yoga incorporates multiple modalities, including physical postures, chanting, mediation, breathing exercises, and visualization. One small study suggests improved sleep quality with the help of Kundalini yoga practices. However, there is insufficient evidence on which to base recommendations for or against this intervention with regard to insomnia.

  • There is some evidence from studies with healthy volunteers that certain breathing techniques used during Kundalini yoga may improve different aspects of cognitive functioning. More studies are needed to determine if these techniques can reliably be used to improve cognitive performance and possibly aid in treating cognitive and nervous system disorders.

  • Avoid exercises that involve stoppage of breath with heart or lung problems, insomnia, poor memory, or concentration. Avoid certain inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis, or if at risk for blood clots. Use cautiously with mental disorders. Kundalini yoga is considered safe and beneficial for use during pregnancy and breastfeeding when practiced under the guidance of expert instruction. Teachers of yoga are generally not medically qualified and should not be regarded as sources of medical advice for the management of clinical conditions.

  • Lavender: Oils from lavender flowers are used in aromatherapy, baked goods, candles, cosmetics, detergents, jellies, massage oils, perfumes, powders, shampoo, soaps, and teas. Lavender aromatherapy is often promoted as a sleep aid. Although early evidence suggests possible benefits, more research is needed before a firm conclusion can be drawn.

  • Although lavender is a sedative-type aroma, use during recess periods in a work environment after accumulation of fatigue seemed to prevent deterioration of cognitive performance in subsequent work sessions. Further well-designed research is needed to confirm these results.

  • Avoid if allergic or hypersensitive to lavender. Avoid with a history of seizures, bleeding disorders, eating disorders (such as anorexia or bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.

  • Lemon balm: Lemon balm (Melissa officinalis) is a lemon-scented herb that is native to southern Europe. High-quality clinical evidence supporting the use of lemon balm as a sedative or hypnotic is lacking. The available evidence is conflicting. Additional research is required to better support the use of lemon balm as a sedative or hypnotic.

  • Clinical data suggest that the use of standardized lemon balm extract has some effect on particular self-reported measures of mood and cognition through cholinergic activities. More rigorous studies need to be conducted using patient-relevant outcomes to better assess the validity of these results as they apply to patient care.

  • According to available research, lemon balm taken by mouth has been reported to be relatively well tolerated when taken for up to eight weeks. The evidence for the topical administration of a cream has suggested minimal side effects for up to 10 days of application. Avoid if allergic or hypersensitive to lemon balm. Avoid with Graves' disease. Avoid if taking thyroid hormone replacement therapy. Use cautiously with glaucoma. Use cautiously while driving or operating heavy machinery. Lemon balm preparations may contain trace amounts of lead. Avoid if pregnant or breastfeeding.

  • Macrobiotic diet: Macrobiotics is a popular approach to diet that stresses vegetarianism and consumption of whole, healthy foods. Proponents of macrobiotics advocate a flexible approach that allows supplementation with dairy, fish, or other supplements as needed on an individual basis. The evidence is mixed as to whether or not a macrobiotic diet helps, hinders, or has no effect on cognitive functioning in children.

  • There is a risk of nutritional deficiencies with a macrobiotic diet. However, this can be avoided with appropriate menu planning. Use cautiously with cancer or other medical conditions. A macrobiotic diet is not recommended in children or adolescents without professional guidance or appropriate supplementation, and it is not recommended in pregnant or lactating women, due to potential deficiencies, unless properly supplemented.

  • Melatonin: Melatonin is a neurohormone produced in the brain. Levels of melatonin in the blood are highest before bedtime. Studies and individual cases suggest that melatonin, administered in the evening, may correct circadian rhythm disorders in blind patients. Large, well-designed controlled trials are needed before a stronger recommendation can be made.

  • It is unclear if melatonin helps treat insomnia of unknown origin in the nonelderly. Study results have been inconsistent, with some studies reporting benefits on sleep latency and subjective sleep quality and other research finding no benefits. Most studies have been small and not rigorously designed or reported. Better research is needed before a firm conclusion can be drawn. Notably, several studies in elderly individuals with insomnia have provided preliminary evidence of benefits on sleep latency.

  • Limited case reports describe benefits in patients with REM sleep behavior disorder who receive melatonin. However, better research is needed before a clear conclusion can be drawn.

  • There are several studies of melatonin used for improving sleep quality in people who work irregular shifts, such as emergency room personnel. The results are mixed. Additional research is necessary before a clear conclusion can be drawn.

  • There are rare reports of allergic skin reactions after taking melatonin by mouth. Avoid with bleeding disorders or if taking blood thinners. Use cautiously with seizures disorders, major depression, psychotic disorders, diabetes, low blood sugar levels, glaucoma, high cholesterol, or atherosclerosis, or if at risk of heart disease. Use cautiously if driving or operating heavy machinery.

  • Omega-3 fatty acids: Omega-3 fatty acids are found in fish oil and certain plant and nut oils. Fish oil contains both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Well-designed clinical trials are needed before omega-3 fatty acids can be recommended for the prevention of cognitive impairment or dementia.

  • Avoid if allergic or hypersensitive to fish, omega-3 fatty acid products that come from fish, nuts, linolenic acid, or omega-3 fatty acid products that come from nuts. Avoid during active bleeding. Use cautiously with bleeding disorders, diabetes, low blood pressure, and drugs, herbs, and supplements that treat any such conditions. Use cautiously before surgery. Pregnant or breastfeeding women should not take doses higher than the recommended dietary allowance (RDA).

  • Policosanol: Policosanol is a natural mixture that lowers cholesterol. The effects of policosanol supplementation on reactivity and related brain activity have been examined. Although there is early compelling evidence, further research is necessary before a clear conclusion can be reached.

  • Research suggests that policosanol is safe and well tolerated. Avoid if allergic or hypersensitive to policosanol. Use cautiously with nitrates, aspirin, or drugs that lower cholesterol or blood pressure. Avoid if pregnant or breastfeeding.

  • Psychotherapy: Psychotherapy is an interactive process between a person and a qualified mental health professional. The patient explores thoughts, feelings, and behavior to help with problem solving. A type of psychotherapy, called child therapy may improve children's language proficiencies. Individual therapy may be more successful than group therapy. Further research in this area is needed.

  • Psychotherapy cannot always fix mental or emotional conditions. Psychiatric drugs are sometimes needed. In some cases, symptoms may worsen if the proper medication is not taken. Not all therapists are qualified to work with all problems. Use cautiously with serious mental illness or some medical conditions (such as post-traumatic stress disorder or personality disorders), because some forms of psychotherapy may stir up strong emotional feelings and expression.

  • Relaxation therapy: Relaxation techniques include behavioral therapeutic approaches that differ widely in philosophy, methodology, and practice. The primary goal is usually nondirected relaxation. Several human trials suggest that relaxation techniques may be beneficial in people with insomnia, although effects appear to be short-lived. Research suggests that relaxation techniques may produce improvements in some aspects of sleep, such as sleep latency and time awake after sleep onset. Cognitive forms of relaxation, such as meditation, are reported as being slightly better than somatic forms of relaxation, such as progressive muscle relaxation (PMR). However, most studies in this area are not well designed or reported. Better research is necessary before a firm conclusion can be drawn.

  • Avoid with psychiatric disorders such as schizophrenia or psychosis. Jacobson relaxation (flexing specific muscles, holding that position, and then relaxing the muscles) should be used cautiously with illnesses such as heart disease, high blood pressure, or musculoskeletal injury. Relaxation therapy is not recommended as the sole treatment approach for potentially serious medical conditions, and it should not delay the time to diagnosis or treatment with more proven techniques.

  • Sage: Sage has long been suggested as a possible therapy for memory and cognitive improvement. Several trials provide evidence for the use of sage for this indication. Additional research is needed to confirm these findings and determine the best dose.

  • Avoid if allergic or hypersensitive to sage species, their constituents, or to members of the Lamiaceae (mint) family. Use cautiously with hypertension (high blood pressure). Use sage essential oil or tincture cautiously in patients with epilepsy. Avoid if pregnant or breastfeeding.

  • Yoga: Yoga is an ancient system of relaxation, exercise, and healing, with origins in Indian philosophy. Preliminary research reports that yoga may benefit sleep efficiency, total sleep time, number of awakenings, and quality of sleep. Well-designed research is necessary before a firm recommendation can be made.

  • There is limited research on yoga therapy in children with intellectual disabilities (formerly called mental retardation). Better trials are needed to confirm these results and to evaluate the effects of yoga in adults with intellectual disabilities.

  • Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis, or if at risk for blood clots. Certain yoga breathing techniques should be avoided with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction. However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

  • Zinc: Zinc may have beneficial effects on cognitive function. More well-designed trials are needed before a conclusion may be made.

  • Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride, as studies have not been done on its safety or effectiveness. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

  • Fair negative scientific evidence:

  • DHEA: DHEA (dehydroepiandrosterone) is a hormone that is produced by the adrenal glands. Studies of the effects of DHEA on cognition have produced complex and inconsistent results. Additional research is warranted in this area.

  • Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders. Use cautiously if taking anticoagulants or drugs, herbs, or supplements that treat diabetes, heart disease, seizure, or stroke. Stop use two weeks before and immediately after surgery or dental or diagnostic procedures with bleeding risks. Avoid if pregnant or breastfeeding.

  • Vitamin B12: Vitamin B12 is a water-soluble vitamin commonly found in many foods, including fish, shellfish, meats, and dairy products. According to available evidence, taking vitamin B12 orally, in methylcobalamin form, does not seem to be effective for treating delayed sleep phase syndrome. Supplemental methylcobalamin, with or without bright light therapy, does not seem to help people with primary circadian rhythm sleep disorders.

  • Vitamin B12 is generally considered safe when taken in amounts that do not exceed the recommended dietary allowance (RDA). Avoid vitamin B12 supplements if allergic to cobalamin, cobalt, or any other product ingredients. Avoid with coronary stents or Leber's disease. Use cautiously if undergoing angioplasty.


  • There is currently no known method of prevention for Smith-Magenis syndrome (SMS). The disorder typically occurs randomly and is not inherited.

  • Early diagnosis and prompt treatment is important to ensure that a person with SMS maximizes his or her intellectual potential.

Author Information

  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).


Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Edelman EA, Girirajan S, Finucane B, et al. Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta-analysis of 105 cases. Clin Genet. 2007 Jun;71(6):540-50. View Abstract

  2. Elsea SH, Girirajan S. Smith-Magenis syndrome. Eur J Hum Genet. 2008 Apr;16(4):412-21. Epub 2008 Jan 30. View Abstract

  3. Gropman AL, Duncan WC, Smith AC. Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2). Pediatr Neurol. 2006 May;34(5):337-50. View Abstract

  4. National Human Genome Research Institute (NHGRI). www.genome.gov.

  5. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

  6. Parents and Researchers Interested in Smith-Magenis Syndrome (PRISMS). www.prisms.org.

  7. Shelley BP, Robertson MM. The neuropsychiatry and multisystem features of the Smith-Magenis syndrome: a review. J Neuropsychiatry Clin Neurosci. 2005 Winter;17(1):91-7. View Abstract

  8. Smith AC, Magenis RE, Elsea SH. Overview of Smith-Magenis syndrome. J Assoc Genet Technol. 2005;31(4):163-7. View Abstract

  9. Smith-Magenis Syndrome Foundation. www.smith-magenis.co.uk.

Copyright © 2013 Natural Standard (www.naturalstandard.com)

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.


March 22, 2017