What is S-Adenosylmethionine and how does it work in the body. How can SAMe potentially help with depression, osteoarthritis, and liver disease. What are the possible side effects and precautions when taking SAMe supplements.

Understanding S-Adenosylmethionine: A Vital Compound in the Human Body

S-Adenosylmethionine, commonly known as SAMe, is a naturally occurring compound found in nearly every tissue and fluid within the human body. This versatile molecule plays a crucial role in numerous physiological processes, making it an subject of interest for researchers and health professionals alike.

SAMe’s importance stems from its involvement in several key bodily functions:

• Immune system regulation
• Maintenance of cell membranes
• Production and breakdown of neurotransmitters (serotonin, melatonin, and dopamine)
• Collaboration with vitamin B12 and folate (vitamin B9)

Interestingly, a deficiency in either vitamin B12 or folate may lead to reduced levels of SAMe in the body, highlighting the interconnected nature of these compounds in maintaining optimal health.

The Potential of SAMe in Treating Depression

Research into SAMe’s efficacy in treating depression has yielded promising results. Studies suggest that SAMe may be more effective than placebo in alleviating symptoms of mild-to-moderate depression, potentially rivaling the effectiveness of traditional antidepressant medications without their common side effects.

How does SAMe work to combat depression? While the exact mechanism remains unclear, researchers speculate that it might increase serotonin levels in the brain, similar to the action of some antidepressants. One notable advantage of SAMe is its potentially faster onset of action compared to conventional antidepressants, which typically take 6 to 8 weeks to show significant effects.

SAMe vs. Traditional Antidepressants

When comparing SAMe to traditional antidepressants, several key differences emerge:

1. Fewer side effects: SAMe appears to cause fewer adverse reactions such as headaches, sleeplessness, and sexual dysfunction.
2. Faster onset: SAMe may begin to work more quickly than conventional antidepressants.
3. Natural compound: As a naturally occurring substance in the body, SAMe may be appealing to those seeking alternative treatments.

Can SAMe replace traditional antidepressants? While the results are encouraging, it’s crucial to note that more research is needed to definitively establish SAMe’s efficacy in treating depression. Additionally, given the serious nature of depression, it’s essential to consult with a healthcare professional before starting any new treatment regimen, including SAMe supplements.

SAMe’s Role in Managing Osteoarthritis

Osteoarthritis, a common form of joint disease, has been another area of focus for SAMe research. Several well-designed studies have demonstrated SAMe’s potential in reducing pain and inflammation in the joints, with some researchers suggesting it may even promote cartilage repair.

How does SAMe compare to traditional osteoarthritis treatments? Short-term studies ranging from 4 to 12 weeks have shown that SAMe supplements can be as effective as nonsteroidal anti-inflammatory drugs (NSAIDs) in managing osteoarthritis symptoms. These benefits include:

• Reduced morning stiffness
• Decreased pain and swelling
• Improved range of motion
• Increased walking pace

Are there advantages to using SAMe over NSAIDs for osteoarthritis? Some studies suggest that SAMe may have fewer side effects compared to NSAIDs, potentially making it a more tolerable option for long-term use. Additionally, a study comparing SAMe to celecoxib (Celebrex), a COX-2 inhibitor NSAID, found that over time, SAMe was equally effective in relieving pain.

Exploring SAMe’s Potential in Fibromyalgia Treatment

Fibromyalgia, a chronic condition characterized by widespread pain and fatigue, has also been a subject of SAMe research. Studies have shown that SAMe can be effective in reducing various fibromyalgia symptoms, including:

• Pain
• Fatigue
• Morning stiffness
• Depressed mood

However, it’s important to note that most of these studies used injectable forms of SAMe. Research on oral SAMe supplements for fibromyalgia has produced mixed results, with some studies showing benefits while others found no significant improvements.

Oral vs. Injectable SAMe for Fibromyalgia

Why might there be a difference between oral and injectable SAMe in treating fibromyalgia? Several factors could contribute to this discrepancy:

1. Bioavailability: Injectable forms may have higher bioavailability, allowing for more efficient absorption and utilization by the body.
2. Dosage: Injectable SAMe may deliver higher concentrations to target tissues compared to oral supplements.
3. Study design: Differences in study protocols, duration, and participant characteristics could influence outcomes.

Despite the mixed results, the potential of SAMe in managing fibromyalgia symptoms warrants further investigation. Larger, well-designed studies focusing on oral SAMe supplements could provide more definitive answers about its efficacy in treating this complex condition.

SAMe and Liver Health: A Promising Avenue for Research

The liver plays a crucial role in SAMe synthesis, and interestingly, people with liver disease often struggle to produce adequate amounts of this compound. This observation has led researchers to investigate the potential of SAMe supplementation in treating various liver conditions.

What evidence supports the use of SAMe in liver disease? Several preliminary studies have shown promising results:

• A study of 123 individuals with alcoholic liver cirrhosis found that SAMe treatment for 2 years improved survival rates and delayed the need for liver transplants compared to placebo.
• Other research suggests that SAMe may help normalize liver enzyme levels in people with liver disease.
• Studies in mice have demonstrated SAMe’s potential to both protect against and reverse liver damage.

Can SAMe be considered a viable treatment for liver disease? While these initial findings are encouraging, it’s important to note that most studies have been small in scale and of short duration. Larger, long-term studies are necessary to confirm these results and establish SAMe as a reliable treatment option for liver conditions.

Potential Mechanisms of SAMe in Liver Health

How might SAMe contribute to liver health? Researchers have proposed several potential mechanisms:

1. Antioxidant effects: SAMe may help protect liver cells from oxidative stress and damage.
2. Methylation support: As a methyl donor, SAMe could aid in critical liver functions that rely on methylation reactions.
3. Anti-inflammatory properties: SAMe might help reduce liver inflammation, a common feature of many liver diseases.
4. Cell membrane stabilization: SAMe’s role in maintaining cell membranes could be particularly beneficial for liver cells.

While these mechanisms are plausible, further research is needed to fully elucidate how SAMe exerts its potential liver-protective effects.

SAMe’s Potential in Cognitive Health and Dementia

As the global population ages, the search for effective treatments for cognitive decline and dementia intensifies. Preliminary evidence suggests that SAMe may have a role to play in this important area of research.

How might SAMe benefit cognitive function? Studies have indicated that SAMe supplementation could potentially improve various aspects of cognitive performance, including:

• Information recall
• Word memory
• Overall cognitive symptoms

What is the proposed mechanism behind SAMe’s cognitive benefits? Researchers hypothesize that SAMe may act on specific regions of the brain that regulate gene expression of amyloid proteins, which are closely associated with Alzheimer’s disease. By influencing these proteins, SAMe could potentially slow or prevent the progression of cognitive decline.

SAMe and Alzheimer’s Disease: A Promising Avenue for Research

While the research on SAMe and cognitive health is still in its early stages, the potential implications for Alzheimer’s disease treatment are significant. Here are some key areas of interest:

1. Neuroprotection: SAMe’s antioxidant properties may help protect brain cells from damage.
2. Neurotransmitter regulation: SAMe’s role in neurotransmitter production could influence cognitive function and mood.
3. Epigenetic modulation: As a methyl donor, SAMe might influence gene expression patterns relevant to cognitive health.
4. Anti-inflammatory effects: Reducing brain inflammation could potentially slow cognitive decline.

Despite these promising avenues, it’s crucial to emphasize that more extensive clinical trials are needed to fully understand SAMe’s potential in cognitive health and dementia prevention or treatment.

SAMe in Cancer Research: Emerging Insights and Potential

While SAMe is primarily known for its potential benefits in mood disorders, joint health, and liver function, recent studies have begun to explore its possible role in cancer research. This emerging field of investigation has yielded some intriguing preliminary results.

What evidence suggests SAMe might have anti-cancer properties? Several studies have indicated that SAMe can effectively inhibit cancer tumor cells. While these findings are still in the early stages, they open up exciting possibilities for future research and potential therapeutic applications.

Potential Mechanisms of SAMe’s Anti-Cancer Effects

How might SAMe exert anti-cancer effects? Researchers have proposed several potential mechanisms:

1. Epigenetic regulation: SAMe’s role as a methyl donor could influence gene expression patterns in cancer cells.
2. Apoptosis induction: Some studies suggest SAMe might promote programmed cell death in cancer cells.
3. Antioxidant effects: By reducing oxidative stress, SAMe could potentially inhibit cancer cell growth.
4. Metabolic modulation: SAMe might influence cellular metabolism in ways that are unfavorable to cancer cell proliferation.

While these mechanisms are promising, it’s important to note that most of the current research has been conducted in laboratory settings or animal models. Extensive clinical trials will be necessary to determine whether SAMe could play a role in cancer prevention or treatment in humans.

SAMe and Parkinson’s Disease: A Complex Relationship

The relationship between SAMe and Parkinson’s disease is complex and not yet fully understood. Research in this area has produced some conflicting results, highlighting the need for further investigation.

How does SAMe interact with Parkinson’s disease treatment? Studies have revealed two potentially important interactions:

• Levodopa (L-dopa) treatment may lower SAMe levels in the body, potentially contributing to depression and increased side effects of L-dopa.
• Conversely, taking SAMe supplements might make L-dopa less effective in treating Parkinson’s symptoms.

These findings underscore the importance of careful consideration and professional medical advice when it comes to SAMe supplementation for individuals with Parkinson’s disease.

Balancing Potential Benefits and Risks

Given the complex interplay between SAMe and Parkinson’s disease treatment, what factors should be considered? Here are some key points to keep in mind:

1. Individual variation: The effects of SAMe may vary significantly between individuals with Parkinson’s disease.
2. Treatment goals: The potential benefits of SAMe for mood or other symptoms must be weighed against the risk of reducing L-dopa efficacy.
3. Monitoring: Close medical supervision is essential to track any changes in Parkinson’s symptoms or medication effectiveness.
4. Alternative approaches: Other strategies for managing depression or other symptoms in Parkinson’s disease may be preferable to SAMe supplementation.

Given these complexities, it is crucial for individuals with Parkinson’s disease to consult with their healthcare provider before considering SAMe supplementation. A personalized approach, taking into account the individual’s specific symptoms, treatment regimen, and overall health status, is essential for making informed decisions about SAMe use in the context of Parkinson’s disease.

S-adenosylmethionine Information | Mount Sinai

Ademetionine; SAMe

S-Adenosylmethionine (SAMe) is a naturally-occurring compound found in almost every tissue and fluid in the body. It is involved in many important processes. SAMe plays a role in the immune system, maintains cell membranes, and helps produce and break down brain chemicals, such as serotonin, melatonin, and dopamine. It works with vitamin B12 and folate (vitamin B9). Being deficient in either vitamin B12 or folate may reduce levels of SAMe in your body.

Several studies show that SAMe helps relieve the pain of osteoarthritis. Other studies suggest that SAMe may help treat depression. Researchers have also examined SAMe’s use in the treatment of fibromyalgia and liver disease with mixed results. Many of the early studies used SAMe given intravenously or as an injection. Only recently have researchers been able to look at the effects of SAMe taken by mouth.

Depression

Some research suggests that SAMe is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without the side effects (headaches, sleeplessness, and sexual dysfunction). In addition, antidepressants tend to take 6 to 8 weeks to begin working, while SAMe seems to begin more quickly. Researchers are not sure how SAMe works to relieve depression. But they speculate it might increase the amount of serotonin in the brain just as some antidepressants do.

Many studies have examined injectable forms of SAMe, not oral supplements. More research is needed to determine whether SAMe works for depression. Because serious depression is a dangerous illness, you should seek help from your doctor before taking SAMe or any supplement.

Osteoarthritis

A number of well-designed studies show that SAMe may reduce pain and inflammation in the joints, and researchers think it may promote cartilage repair. In several short-term studies (ranging from 4 to 12 weeks), SAMe supplements were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen and naproxen) in adults with knee, hip, or spine osteoarthritis, in lessening morning stiffness, reducing pain and swelling, improving range of motion, and increasing walking pace. Several studies also suggest that SAMe has fewer side effects than NSAIDs. Another study compared SAMe to celecoxib (Celebrex), a type of NSAID called a COX-2 inhibitor, and found that over time SAMe was as effective as celecoxib in relieving pain. Other studies show no differences in pain relief or tolerability between treatment with SAMe or habumetone over 8 weeks in people with knee osteoporosis.

Fibromyalgia

SAMe can be effective in reducing symptoms of fibromyalgia, including pain, fatigue, morning stiffness, and depressed mood. But most studies used an injectable form of SAMe. Among studies that examined doses of SAMe by mouth, some found it was effective at reducing these symptoms while others found no benefit.

Liver disease

People with liver disease often cannot synthesize SAMe in their bodies. Preliminary studies suggest that taking SAMe may help treat chronic liver disease caused by medications or alcoholism. A study of 123 men and women with alcoholic liver cirrhosis (liver failure) found that SAMe treatment for 2 years improved survival rates and delayed the need for liver transplants better than placebo. Other studies show that SAMe may help normalize levels of liver enzymes in people with liver disease. Studies in mice show that SAMe protects against and can also reverse liver damage. However, these studies have been small and of short duration. Larger and longer studies are needed to confirm these findings.

Dementia

Preliminary evidence suggests that SAMe may improve cognitive symptoms, such as the ability to recall information and remember words. Researchers suspect SAMe acts on regions of the brain that regulate gene expression of amyloid proteins, one of the hallmarks of Alzheimer disease.

Other

Some studies suggest SAMe can effectively inhibit cancer tumor cells. Other studies suggest that taking the drug levodopa (L-dopa) for Parkinson disease may lower the levels of SAMe in the body, which may contribute to depression and increase the side effects of L-dopa. However, researchers have also found evidence that taking SAMe may make L-dopa less effective. If you have Parkinson disease, do not take SAMe without talking to your doctor first.

Dietary Sources

SAMe is not found in food. It is produced by the body from the amino acid methionine and ATP which serves as the major energy source for cells throughout the body.

Available Forms

SAMe is available in tablets or capsules, which are more stable and may be more dependable in terms of the amount of SAMe in the pill. They should be stored in a cool, dry place, but not refrigerated. Tablets should be kept in the blister pack until you take them.

How to Take It

Starting with a low dose (for example, 200 mg per day) and increasing slowly helps avoid stomach upset.

It is important to note that many of the studies of SAMe have tested injectable, not oral, forms. It is not as clear whether taking SAMe orally is as reliable or effective. Small studies suggest that oral supplementation with SAMe is not well absorbed by the body. Clinicians recommend taking oral SAMe with vitamin B12, folic acid, methionine, and trimethylglycine to enhance absorption.

Pediatric

SAMe should never be given to a child without your doctor’s supervision.

Adult

Recommended doses of SAMe vary depending on the health condition being treated. The following list gives information on the dosages used in studies for each condition:

• Depression. 800 to 1,600 mg of SAMe per day, in 2 divided doses (morning and afternoon).
• Osteoarthritis. 600 to 1,200 mg per day in 2 to 3 divided doses.
• Fibromyalgia. A dosage of 400 mg, 2 times per day for 6 weeks.
• Alcoholic liver disease. 600 to 1,200 mg per day by mouth in divided doses for 6 months enhances liver function. For liver disease, a qualified health care provider should supervise administration of SAMe.

Precautions

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

Side effects may include dry mouth, nausea, gas, diarrhea, headache, anxiety, a feeling of elation, restlessness, and insomnia. Sweating, dizziness, and palpitations have also been reported. For this reason, you should not take SAMe at night.

Large doses of SAMe may cause mania (abnormally elevated mood). Start at a low dose and gradually increase it. DO NOT exceed recommended doses.

Pregnant and breastfeeding women should not take SAMe.

People with bipolar disorder (manic depression) should not take SAMe since it may worsen manic episodes.

SAMe should not be combined with other antidepressants without first consulting your doctor.

People taking SAMe may want to take a multivitamin that contains folic acid and vitamins B12 and B6.

Possible Interactions

If you are being treated with any of the following medications, you should not use SAMe without first talking to your health care provider.

Taking SAMe at the same time as these drugs may increase the risk of serotonin syndrome (a potentially dangerous condition caused by having too much serotonin in your body):

• Dextromethorphan (Robitussin DM, other cough syrups)
• Meperidine (Demerol)
• Pentazocine (Talwin)
• Tramadol (Ultram)

Antidepressant medications

SAMe may interact with antidepressant medications, increasing the potential for side effects including headache, irregular or accelerated heart rate, anxiety, and restlessness, as well as the potential fatal condition called Serotonin Syndrome, mentioned above. Some experts theorize that taking SAMe increases the levels of serotonin in the brain, and many antidepressants do the same. The concern is that combining the two may increase serotonin to dangerous levels. Talk to your doctor before using SAMe if you are taking any medications for depression or anxiety.

Levodopa (L-dopa)

SAMe may reduce the effectiveness of this medication for Parkinson disease.

Medications for diabetes

SAMe may reduce levels of blood sugar and may strengthen the effect of diabetes medications, which increases the risk of hypoglycemia (low blood sugar).

Supporting Research

Alpert J E, Papakostas G, Mischoulon D, Worthington J J, Petersen T, Mahal Y, et al. S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol. 2004;24(6):661-4.

Bottiglieri T. Folate, Vitamin B12, and S-Adenosylmethionine. Psychiatric Clinics of North America. W.B. Saunders Company. 2013:36(1).

Chavez M. SAMe: S-Adenosylmethionine. Am J Health Syst Pharm. 2000;57(2):119-23.

Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L- methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002;76(5):1172S-6S.

Dey A, Caro AA, Cederbaum AL. S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G91-103.

Fetrow CW, Avila JR. Efficacy of the dietary supplement S-adenosyl-L-methionine. Ann Pharmacother. 2001;35(11):1414-25.

Kim J, Lee EY, Koh EM, et al. Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis; an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients. Clin Ther. 2009;31(12):2860-72.

Li T, Yu G, Guo T, et al. The plasma S-adenosylmethionine level is associated with the severity of hepatitis B-related liver disease. Medicine. 2015;94(4):e489.

Lieber CS. Hepatic, metabolic, and nutritional disorders of alcoholism: from pathogenesis to therapy. Crit Rev Clin Lab Sci. 2000;37(6):551-84.

Luo J, Li YN, Wang F, Zhang WM, Geng X. S-adenosylmethionine inhibits the growth of cancer cells by reversing the hypomethylation status of c-myc and H-ras in human gastric cancer and colon cancer. Int J Biol Sci. 2010;6(7):784-95.

Mato JM, Lu SC. Role of S-adenosyl-L-methionine in liver health and injury. Hepatology. 2007;45(5):1306-12.

Mischoulon D, Alpert J, Arning E, et al. Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder. J Clin Psychiatry. 2012;73(6):843-8.

Morelli V, Zoorob RJ. Alternative therapies: Part 1. Depression, diabetes, obesity. Am Fam Phys. 2000;62(5):1051-60.

Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. BMC Musculoskelet Disord. 2004 February 26;5:6.

Rakel, D. Rakel Integrative Medicine. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012.

Ringdahl E, Pandit S. Treatment of knee osteoarthritis. Am Fam Physician. 2011;83(11):1287-92.

Stern. Massachusetts General Hospital Comprehensive Clinical Psychiatry. 1st ed. Philadelphia, PA: Elsevier Mosby; 2008.

Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews

Overview

SAMe is a molecule that is made naturally in the body from homocysteine and folate. It can also be made in a lab and taken in supplements.

SAMe is involved in the formation, activation, and breakdown of other chemicals in the body, including hormones, proteins, and certain drugs. The body uses it to make certain chemicals that play a role in pain, depression, liver disease, and other conditions.

People most commonly take SAMe for depression and osteoarthritis. It is also used for anxiety, liver disease, fibromyalgia, schizophrenia, and many other conditions, but there is no good scientific evidence to support these uses.

SAMe has been available as a dietary supplement in the US since 1999, but it has been used as a prescription drug in Italy, Spain, and Germany for many decades.

Uses & Effectiveness ?

Likely Effective for

• Osteoarthritis. Taking SAMe by mouth seems to work about as well as ibuprofen and other similar drugs for reducing symptoms of osteoarthritis. But most people need to take SAMe for about a month before they feel better.

Possibly Effective for

• Reduced or blocked flow of bile from the liver (cholestasis). Taking SAMe by mouth or by IV is about as effective as taking the prescription drug called ursodeoxycholic acid. IV products can only be given by a healthcare provider.
• Depression. Taking SAMe by mouth might reduce symptoms of major depression in some people. It might be helpful for people who don’t have a good response to prescription antidepressants. Sometimes it’s helpful when used together with prescription antidepressants.

There is interest in using SAMe for a number of other purposes, but there isn’t enough reliable information to say whether it might be helpful.

Side Effects

When taken by mouth: SAMe is likely safe. Side effects might include gas, diarrhea, constipation, dry mouth, headache, and nervousness, especially at higher doses.

Special Precautions and Warnings

When taken by mouth: SAMe is likely safe. Side effects might include gas, diarrhea, constipation, dry mouth, headache, and nervousness, especially at higher doses. Pregnancy and breast-feeding: There isn’t enough reliable information to know if SAMe is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.

Bipolar disorder: SAMe can cause people with bipolar disorder to enter a manic state. If you have bipolar disorder, don’t use SAMe.

Inherited disorder called Lesch-Nyhan syndrome: SAMe might make symptoms of Lesch-Nyhan syndrome worse.

Parkinson disease: There is some concern that SAMe might make symptoms of Parkinson disease worse.

Surgery: SAMe might affect the central nervous system. This could interfere with surgery. Stop taking SAMe at least 2 weeks before a scheduled surgery.

Interactions ?

Moderate Interaction

Be cautious with this combination

• Levodopa is used for Parkinson disease. SAMe can change levodopa in the body and decrease its effects. Taking SAMe along with levodopa might make Parkinson disease symptoms worse. Do not take SAMe if you are taking levodopa.

• SAMe might increase a brain chemical called serotonin. Some medications also have this effect. Taking SAMe along with these medications might increase serotonin too much. This might cause serious side effects including heart problems, seizures, and vomiting.

Dosing

SAMe has most often been used by adults in doses of 400-1600 mg by mouth daily for up to 12 weeks. Speak with a healthcare provider to find out what dose might be best for a specific condition.

View References

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CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.

This copyrighted material is provided by Natural Medicines Comprehensive Database Consumer Version. Information from this source is evidence-based and objective, and without commercial influence. For professional medical information on natural medicines, see Natural Medicines Comprehensive Database Professional Version.
© Therapeutic Research Faculty 2020.

S-adenosylmethionine for depression in adults

Description of disease

Depression is a common, recurrent mood disorder. Typically, people with depression experience symptoms such as depressed mood, loss of interest or pleasure. They also suffer from insomnia or increased sleepiness, fatigue, weight loss or gain, decreased or increased appetite. They are often tormented by excessive guilt, feelings of worthlessness, poor concentration, indecision, and recurring thoughts of death and suicide. The most commonly used medications to treat depression are antidepressants.

Description of medicine

S-adenosylmethionine (SAMe) is a naturally occurring compound in the body and there is evidence that it is effective as an antidepressant. Since the mid-1980s, it has already been marketed in some European countries for the treatment of depression and other conditions such as osteoarthritis (a disease that causes joint pain and stiffness), fibromyalgia (pain and stiffness of muscles throughout the body), liver disease, and migraines. However, in the UK S-Adenosylmethionine is not officially approved for the treatment of depression, and in the US it is classified as a dietary supplement.

Purpose of review

Given the prevalence of depression, the high incidence of chronicity, and the large number of people who do not respond to traditional treatments, there is a need to explore alternative medicines. In this review, we investigated the efficacy of S-Adenosylmethionine in the treatment of depression.

Results

We searched scientific databases to find all randomized controlled trials (clinical trials in which people are randomly assigned to one of two or more treatment groups) in adults diagnosed with major depression in which S-Adenosylmethionine were compared with placebo or another antidepressant (eg, imipramine or escitalopram) given up to February 2016.

We included eight studies with 934 participants in this review. There was insufficient evidence of a difference in efficacy between SAMe and imipramine or escitalopram when used alone. When used in combination with a selective serotonin reuptake inhibitor, they were superior to placebo (low-quality evidence). There were no significant differences in efficacy between SAMe and placebo alone (very low-quality evidence). The acceptability of SAMe did not differ from placebo and other antidepressants. The exception was that fewer people had side effects with SAMe than those who took imipramine. However, the quality of the evidence regarding the acceptability of SAMe was low.

Limitations of this review are that not all relevant data could be obtained despite efforts to contact study authors, and the quality of some included studies was low.

What to do next?

No definitive conclusions can be drawn from this review and the limited quality of the included evidence. The efficacy and acceptability of SAMe in the treatment of depression in adults needs to be investigated in larger and well-designed trials.

Translation notes:

Translation: Gumerova Elvina Elmerovna. Editing: Prokopov Dmitry Yurievich, Yudina Ekaterina Viktorovna. Project coordination for translation into Russian: Cochrane Russia – Cochrane Russia (branch of the Northern Cochrane Center on the basis of Kazan Federal University). For questions related to this translation, please contact us at: cochrane. [email protected]; [email protected]

S-ADENOSYLMETHIONINE, S-ADENOSYLMETHIONINE – instructions for use of the drug, reviews, description, price

Manufacturer: ORCHID CHEMICALS & PHARMACEUTICALS Ltd. (India)

powder substance: containers Reg. №: ЛС-001524

Clinical and pharmacological group:

Release form, composition and packaging

substance – powder.

plastic bags (1) – aluminum containers.

Description of the active ingredients of the drug «

Ademetionine »

Pharmacological action

Hepatoprotector, has antidepressant activity. It has a choleretic and cholekinetic effect. It has detoxifying, regenerating, antioxidant, antifibrosing and neuroprotective properties.

Replenishes the deficiency of ademetionine and stimulates its production in the body, primarily in the liver and brain. Participates in biological reactions of transmethylation (donator of the methyl group) – the molecule of S-adenosyl-L-methionine (ademetionine), is a donator of the methyl group in the reactions of methylation of phospholipids of cell membranes, proteins, hormones, neurotransmitters; participates in transsulfation reactions as a precursor of cysteine, taurine, glutathione (provides the redox mechanism of cellular detoxification), acetylation coenzyme. Increases the content of glutamine in the liver, cysteine ​​and taurine in plasma; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. In addition to decarboxylation, it participates in the processes of aminopropylation as a precursor of polyamines – putrescine (a stimulator of cell regeneration and hepatocyte proliferation), spermidine and spermine, which are part of the structure of ribosomes.

It has a choleretic effect due to an increase in the mobility and polarization of hepatocyte membranes due to stimulation of the synthesis of phosphatidylcholine in them. This improves the function of bile acid transport systems associated with hepatocyte membranes and promotes the passage of bile acids into the biliary system. It is effective in the intralobular variant of cholestasis (impaired synthesis and flow of bile). Promotes detoxification of bile acids, increases the content of conjugated and sulfated bile acids in hepatocytes. Conjugation with taurine increases the solubility of bile acids and their removal from the hepatocyte. The process of sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates passage through the membrane of the hepatocyte and excretion with bile. In addition, sulfated bile acids protect the membranes of liver cells from the toxic effects of non-sulfated bile acids (in high concentrations present in hepatocytes in intrahepatic cholestasis). In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, it reduces the severity of pruritus and changes in biochemical parameters, incl. level of direct bilirubin, activity of alkaline phosphatase, aminotransferases.

Indications

Chronic non-calculous cholecystitis, cholangitis, intrahepatic cholestasis, toxic liver damage of various etiologies (including alcoholic, viral, drug-induced), fatty degeneration of the liver, chronic hepatitis, liver cirrhosis, encephalopathy, incl. associated with liver failure (including alcohol).

Depression (including secondary), withdrawal syndrome (including alcohol).

Dosage regimen

Used orally, intramuscularly or intravenously by drip.

When taken orally, the daily dose is 800-1600 mg.

With intravenous drip (very slowly) or intramuscular injection, the daily dose is 400-800 mg.

The duration of treatment is determined individually.

Side effects

From the digestive system: gastralgia, dyspepsia, heartburn.

Other: allergic reactions.

Contraindications

I and II trimester of pregnancy, lactation (breastfeeding), children and adolescents under 18 years of age, hypersensitivity to ademetionine.