SAMe supplement for relieving depression

Know all about the safe & effective depression fighting super supplement.

Story Highlights
  • FDA approved antidepressants are associated with potentially dangerous side effects and in many cases they don’t work at all.
  • A number of studies have indicated that SAMe supplement can improve conditions of depression and osteoarthritis. It works even for patients who have failed to respond to drugs.
  • SAMe supplement can improve depressive symptoms within just one week, whereas conventional antidepressants can take up to three weeks to work.
  • SAMe can do everything that a conventional antidepressant does but without any severe side effect.
  • SAMe is totally safe to be taken with antidepressants. Various studies have proven that SAMe can speed up the action of antidepressant.

SAMe (also called as S-Adenosyl-L-methionine, S-adenosyl methionine, or S-adenosylmethionine) is a molecule that is naturally produced by our body from methionine, an amino acid. It is known to regulate some key functions in such as formation, activation, and breakdown of hormones, proteins, and some drugs. A healthy body can produce this molecule in appropriate quantity. Abnormal level of SAMe therefore, indicates that you are probably suffering from certain forms of liver diseases and/or depression. 1 Aging or general sickness may also affect the production of SAMe.

There are no known food sources of SAMe. It can either be produced by our body or you may get it from dietary supplements. Such supplements usually consist of synthetically produced SAMe along with folate, trimethylglycine (TMG or betaine), Vitamin B6 and B12. SAMe has been sold in the United States as a dietary supplement since 1999 but in many other countries such as Germany, Spain, and Italy, it is sold as a prescription drug. Various studies have indicated that SAMe supplements can improve conditions of depression 2 and osteoarthritis. 3 Studies on the effect of SAMe have also been conducted for many other conditions such as fibromyalgia, migraine, schizophrenia, Alzheimer’s disease, and liver cancer but nothing conclusive has been found yet. 4

I think the saddest people always try their hardest to make people happy because they know what it’s like to feel absolutely worthless and they don’t want anyone else to feel like that.

~ Robin Williams

How can SAMe be beneficial in depression?

Depression has become a global health concern, affecting millions of people across all age groups. Although, FDA approved prescription drugs have been successful in controlling this depressive disease, they are often associated with potentially dangerous side effects. In 2004, FDA mandated that all antidepressant drugs must carry a ‘black-box’ warning on their labels, informing people that these drugs can trigger suicidal tendencies, especially among adults. 5 Antidepressants are also associated with many other side effects such as weight gain, dry mouth, and constipation. Such side effects may prompt the depressives to stop using them, which may further worsen their condition.

Another major issue associated with antidepressants is that in many cases they don’t work. 6 In some cases, they even make the depressive person feel worse. According to a study published in Journal of clinical psychiatry, majority of depressed patients will not experience remission when they are treated with only antidepressants. 7 Depressive patients therefore, need more than just drugs and that’s where SAMe comes in. It produces the same effect as the antidepressants do but unlike those drugs, it has very limited, minor side effects. SAMe is well-tolerated by people of all age groups.

Daily doses of SAMe supplements can significantly improve depressive symptoms. People who do not respond to conventional drug treatment will also see improvement in their condition. 8 SAMe is also highly beneficial for women who are experiencing postmenopausal depression. 9 A study conducted by Harvard Medical School and Massachusetts General Hospital concluded that patients, who had taken SAMe supplements, showed 105% higher response rate and 121% higher remission rate. 10 Drug-resistant patients too showed double response rate and remission rate within 6 weeks. There is no reason why SAMe shouldn’t be sold as a prescription drug in the Unites States.

How does SAMe work?

Depressed people often have a variety of biochemical imbalances in their body, the major one being imbalance in the synthesis of neurotransmitters. Some common neurotransmitters that get affected due to depression are serotonin and norepinephrine.

Serotonin is related to mood, sleep, appetite and learning. Norepinephrine is related to heart rate, blood pressure, and fight-or-flight response. These two neurotransmitters belong to a class of molecule called monoamines. The production of these monoamines is controlled by Folic acid, Vitamin 12, and SAMe. When monoamines are present in abnormal quantities in our body, our brain cannot be in a positive mood. The antidepressant drugs basically boost the level of these monoamines. However, these drugs have too many side effects, including provoking suicidal tendencies.

SAMe supplements are better than antidepressants because they do everything that a standard prescription drug does but without any side effects. These supplements have synthetic SAMe along with Folate, Trimethylglycine (TMG or betaine), Vitamin B6 and B12; all you need for proper synthesis of neurotransmitters such as norepinephrine and serotonin.

How long does SAMe takes to work?

Depressed people require immediate help and unfortunately, standard prescription drugs could take up to three weeks to produce results. This is where SAMe can help. Studies have proven that 400mg per day doses of SAMe supplement injections can reduce depressive symptoms within just seven days. Significant improvement can be seen in patients within 15 days. 11 Since SAMe supplements take much less time to produce results, they are gaining popularity among depressed people, who often discontinue medication assuming that the drugs are not helping them.

How long does SAMe stays in your system?

When taken orally, SAMe achieves its peak plasma concentration within 3 to 5 hours after ingestion and it gets eliminated from our body in about 10 hours. 12 The half-life of SAMe supplement is 100 minutes.

Who can and cannot take SAMe?

  • SAMe is considerably safe for adults of all age groups, especially for short-term use. Long term safety of SAMe supplements is yet to be clinically proven, as most studies conducted till date are for short term use only.
  • SAMe supplement is not recommended for people with bipolar disorder, as it may worsen their condition. 13
  • Expecting and lactating mothers should avoid SAMe supplements, as its safety during those periods is yet to be established.
  • This dietary supplement is not suitable for people with Lesch-Nyhan syndrome and Parkinson’s disease.
  • SAMe is yet to be proven safe for kids.
  • If you are suffering from kidney or liver disease, you must speak to your doctor before starting SAMe supplements.

Can you take SAMe with antidepressants?

Some recent studies have concluded that in SAMe is safe to be taken along with antidepressants. However, some antidepressants increase the level of serotonin. Combining SAMe with them is not recommended. You must therefore, consult your primary healthcare provider before starting SAMe supplements.

SAMe can speed up the onset of action of standard antidepressants such as imipramine. 14 Standard drugs take three to four weeks to manifest their effects. This is a long period, especially for people who are suffering from depression and require immediate relief. Some of them may discontinue the treatment if they don’t see any result within a week. Combining SAMe along with the drugs can speed up the action of the antidepressants and can make the patients feel better even during the first week.

Are there any side effects of SAMe?

SAMe is relatively safe to be taken by mouth or through IV. It may however, in some cases, cause gas, vomiting, diarrhea, constipation, and nausea. 15 Further, SAMe may not go well with some drugs such as antidepressants, antipsychotics, amphetamines, cough suppressants, diabetes medication, levodopa (L-dopa), L-tryptophan and other medicines that increase the level of serotonin. Such combination can cause serotonin syndrome, a group of symptoms such as confusion, restlessness, headache, change in blood pressure, nausea, heavy sweating shivering, etc.

SAMe dosage for depression

SAMe supplements are available in 200 mg or 400 mg tablets. The typical dosage for depression is 400 mg-1600 mg daily. If you are starting with a higher dosage, you need to split the doses. The dosage can be reduced once the effect of SAMe starts, which is typically one week. If you are taking SAMe through injection, the dosage is 400 -800 mg. For shots, the dosage is 45-400 mg. These dosages can be taken with or without antidepressants.

How to take SAMe for depression?

SAMe supplements are available as tablets, injections, and as shots. It can be taken in any form but the dosage should be correct. The best time to take SAMe is during the morning in an empty stomach, preferably one hour before meal. If you missed having it in an empty stomach, you can take it two hours after meals. SAMe must not be taken late in the day, as it can cause insomnia.


SAMe is not only safe but a highly effective supplement for treating depression. However, you must consult your healthcare provider before opting it. Further, if you are already taking antidepressants, you must not discontinue them suddenly only to rely on SAMe. Let your healthcare provider evaluate your medication and decide if it is suitable for you at all.

Despite its impressive results, SAMe is still considered only as a dietary supplement in the United States. It’s high time that it should be officially considered as a prescription drug for depression and arthritis.

  1. S-Adenosyl-L-Methionine (SAMe): In Depth. NCCIH. 2017

  2. Knowlton L. Investigating SAM-e for Depression Psychiatric Times. 2017.

  3. Najm W, Reinsch S, Hoehler F, Tobis J, Harvey P. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskeletal Disorders. 2004;5(1). doi:10.1186/1471-2474-5-6.

  4. S-Adenosyl-L-Methionine (SAMe): In Depth. NCCIH. 2017

  5. Pompili M, Serafini G, Innamorati M et al. Antidepressants and Suicide Risk: A Comprehensive Overview. Pharmaceuticals. 2010;3(9):2861-2883. doi:10.3390/ph3092861.

  6. Perović B e. Getting the balance right: Established and emerging therapies for major depressive disorders. PubMed – NCBI 2017

  7. Fava M. Switching Treatments for Complicated Depression. The Journal of Clinical Psychiatry. 2010;71(02):e04. doi:10.4088/jcp.8001tx14c

  8. Rosenbaum JF e. The antidepressant potential of oral S-adenosyl-l-methionine. PubMed – NCBI 2017

  9. Salmaggi P e. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. PubMed – NCBI 2017

  10. Papakostas G, Mischoulon D, Shyu I, Alpert J, Fava M. S-Adenosyl Methionine (SAMe) Augmentation of Serotonin Reuptake Inhibitors for Antidepressant Nonresponders With Major Depressive Disorder: A Double-Blind, Randomized Clinical Trial. American Journal of Psychiatry. 2010;167(8):942-948. doi:10.1176/appi.ajp.2009.09081198.

  11. Fava M e. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. PubMed – NCBI 2017

  12. Najm W, Reinsch S, Hoehler F, Tobis J, Harvey P. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. [ISRCTN36233495]. BMC Musculoskeletal Disorders. 2004;5(1). doi:10.1186/1471-2474-5-6.

  13. S-Adenosyl-L-Methionine (SAMe): In Depth. NCCIH. 2017

  14. Berlanga C e. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. PubMed – NCBI2017

  15. S-Adenosyl-L-Methionine (SAMe): In Depth. NCCIH. 2017

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