What Are the Effects of SAM-e for Depression?

What Are the Effects of SAM-e for Depression?

S-adenosyl-L-methionine (SAM-e) is a compound naturally found in the body that helps produce and regulate hormones and maintain cell membranes. In 1999, a synthetic version of SAM-e became available in the U.S. after being investigated in Spain, Italy, Russia, and Germany for arthritis and depression. But what is SAM-e, and what are the outcomes of its use in depression treatment? Mid City TMS can help you understand SAM-e, depression, and your various depression treatment options, such as transcranial magnetic stimulation (TMS).

What Is SAM-e?

SAM-e naturally occurs from methionine, a sulfur-containing amino acid, and the energy-producing compound adenosine triphosphate. SAM-e is a physiologically essential compound and is most concentrated in the brain in the liver. SAM-e is also crucial to transmethylation, which has shown a boost neurotransmitters serotonin, dopamine, and norepinephrine.

SAM-e and Depression

The deficiency of red blood cell folate and serum folate levels in the body are considered independent risk factors for Major Depressive Disorder (MDD). Folate deficiency is also associated with inadequate responses to medicinal depression treatment and more severe episodes of depression. L-methylfolate increases folate levels for patients with a lack of this vitamin, which positively impacts the body’s response to medicinal depression treatment.

The synthesis of the neurotransmitters by SAM-e requires B12 and folate. B12 plays an essential role in the production of your red blood cells and DNA in addition to the proper functioning of your nervous system.  Folate, a B-vitamin, is needed to make red and white blood cells in the bone marrow, convert carbohydrates into energy, and produce DNA and RNA.

SAM-e Forms for Depression

SAM-e has been used in many European countries over the decades to treat depression and osteoarthritis. The drug is available on a prescription basis in oral form, intramuscular injection, or intravenous use. The effectiveness of SAM-e degrades rapidly when exposed to air and has undergone significant manufacturing challenges regarding oral preparations. Therefore, many studies have focused on the drug administered intramuscularly or intravenously.

However, in the United States, SAM-e is only available in oral form and can be purchased over-the-counter. The oral form is combined with other molecules to reduce oxidative degradation and extend its shelf life. The oral form’s standard regimen is between 800 and 1600 mg in two-to-four divided doses.

Research on SAM-e and Depression Treatment

While some preliminary research has found that SAM-e can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI non-responders with MDD, other studies do not see significant benefits.

Positive Outcomes of SAM-e Depression Treatment

A study conducted in 2010 for the American Journal of Psychiatry examined SAM-e augmentation of serotonin reuptake inhibitors (SRI) for antidepressant non-responders with MDD. The researchers aimed at discovering more effective treatments for a group of patients with MDD who continued to be symptomatic even with increases in antidepressants.

The study consisted of 73 SRI non-responders with MDD enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAM-e with a trial dose of 800 mg/twice daily. The patients continued to receive their SRI treatment at a stable dose throughout the study, and the primary outcome measure was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM-D).

  • One group of participants were assigned to receive 2 dummy (placebo) pills twice daily; the second group received two 400 mg SAMe pills daily (administered as one pill twice daily).
  • Study visits occurred weekly for a total of six postbaseline visits
  • All participants had their number of bills doubled on completion of 2 weeks of treatment.
  • After the 6 weeks, 36% of patients taking a combination of SAM-e and an antidepressant showed substantial improvement compared to 18% of those taking an antidepressant and a placebo.

Overall, the study found that the HAM-D response and remission rates were higher for patients treated with SAM-e than the adjunctive placebo leading to the conclusion that SAM-e can be useful, well-tolerated, and a safe adjunctive treatment strategy for SRI non-responders with MDD.

Inconclusive Outcomes of SAM-e in Depression Treatment

A 2014 study conducted by researchers at Massachusetts General Hospital examined the efficacy of SAM-e and escitalopram in a placebo-controlled, randomized, double-blind clinical trial. The study recruited 189 outpatients from April 2005 to December 2009 and randomized them for 12 weeks to 1,600-3,200 mg/day of SAMe, 10-20 mg/day of escitalopram, or placebo. The patient received escalated doses at 6 weeks in case of nonresponse.

  • The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS-17).
  • The Systemic Assessment assessed tolerability for Treatment of Emergent Events-Specific Inquiry (SAFTEE-SI).
  • All 3 treatments demonstrated significant improvement of about 5-6 points in HDRS-17 scores, and there were no significant differences found between the treatment types.
  • Response rates in the intent-to-treat sample were 36% for SAM-e, 34% for escitalopram, and 30% for placebo.
  • No comparisons between treatment groups attained significance.
  • SAM-e treatment had the highest side effect percentage for gastrointestinal pain, with 19% experiencing stomach discomfort, and 20% experiencing diarrhea.
  • The study found significant differences between treatment groups for dizziness, anorgasmia, diminished mental acuity, and hot flashes.

Overall, neither SAM-e nor escitalopram exhibited significant advantages over the placebo for the treatment of MDD.

Can SAM-e Help Me Treat MDD?

Currently, there is not enough research to definitively determine the effectiveness of SAM-e in treating your MDD. In addition, there is no clear understanding of how SAM-e might work to curb depression. The standard theory is that SAM-e facilitates neurotransmitters’ synthesis so that antidepressants can then act on boosting neurotransmitter release and availability to alleviate symptoms of depression. While some studies are producing promising results, there is still more that needs to be studied.

Find Depression Relief through Mid City TMS

Many patients experiencing depression wonder what options they have for relief. With over three decades of research and over a decade of clinical use, TMS therapy has shown consistently positive results amongst patients with depression. Contact Mid City TMS today to talk with one of our healthcare experts about TMS treatment benefits for depression.

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