SAM-e for Depression

November 23, 2011 Written by JP    [Font too small?]

S-adenosylmethionine or SAM-e, a natural antidepressant, has been in the news lately thanks to Dr. Andrew Weil. In Dr. Weil’s new book, Spontaneous Happiness, he recommends SAM-e for prompt relief of low mood states that don’t respond to other dietary and lifestyle modifications. A review in the June 2011 issue of the journal Canadian Family Physician also presents a largely optimistic view of this nutritional supplement. In the summary, the primary criticism of SAM-e is how much it costs. In order to reach a therapeutic dosage, the author of the piece estimates a monthly expense of $80 – an amount that likely won’t be covered by most insurance plans. In reality, savvy online shoppers can find even lower prices in the $60/month neighborhood.

The first thing you need to know about SAM-e is that it can be administered in two ways: orally or parenterally (via injection). All of the research you’ll find below is based on human studies using oral SAM-e supplements. The most common dosage used as a stand-alone treatment for patients with major depression has been 1,600 mg/day. In one study, a four week trial comparing SAM-e to a conventional antidepressant (desipramine) resulted in a 62% response rate in the SAM-e users vs. 50% in the patients given desipramine. Other trials have examined the effects of combining SAM-e with pharmaceutical antidepressants in patients who didn’t respond to the medications alone. The findings of these trials have been quite impressive. SAM-e has consistently demonstrated an ability to improve treatment response rates and reduce remission rates. The most recent study also reported an improvement in cognitive performance in depressed patients taking SAM-e as an adjunct to standard care. Other health conditions that frequently involve mood disturbance, such as fibromyalgia and Parkinson’s disease, may likewise respond to SAM-e supplementation. But, it’s important to note that the dosages employed for these conditions vary from 800 mg/day for fibromyalgia to up to 3,200 mg/day for those living with Parkinson’s disease. In terms of safety and tolerability, SAM-e trumps conventional antidepressants according to preliminary research. However, a small number of users may experience transient anxiety, gastrointestinal upset or manic episodes.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

To learn more about the studies referenced in today’s column, please click on the following links:

Study 1 – Complementary and Alternative Medicine for the Treatment of (link)

Study 2 – S-Adenosylmethionine Blood Levels in Major Depression (link)

Study 3 – Double-Blind, Placebo-Controlled Study of S-Adenosyl-L-Methionine(link)

Study 4 – Oral S-Adenosylmethionine in Depression: A Randomized (link)

Study 5 – S-Adenosyl Methionine (SAMe) Augmentation of Serotonin Reuptake (link)

Study 6 – S-Adenosyl-L-Methionine (SAMe) as an Adjunct for Resistant Major (link)

Study 7 – Effects of S-Adenosylmethionine Augmentation of Serotonin-Reuptake (link)

Study 8 – Oral S-Adenosylmethionine in Primary Fibromyalgia. Double-Blind (link)

Study 9 – S-Adenosyl-Methionine Improves Depression in Patients w/ Parkinson’s (link)

Study 10 – Bioavailability and Lack of Toxicity of S-Adenosyl-L-Methionine (SAMe) (link)

SAM-e + Antidepressant Benefits Some “Non-Responders”

Source: Am J Psychiatry 2010;167:942-948. (link)

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Posted in Alternative Therapies, Mental Health, Nutritional Supplements

11 Comments & Updates to “SAM-e for Depression”

  1. Chris Lindsay Says:

    Hey JP, Good article.

    But I wonder if the descriptive “natural” is being used a bit loosely here? Setting aside the whole notion that skeptics have with the word “natural” (, in this particular case … what distinguishes this supplement from a pharmaceutical drug in terms of it being “natural?”

    I know that supplements aren’t required by the FDA to show efficacy (, so could it be that it’s cost is so low because it’s not had to go through the same trials that drugs go through (that cost hundreds of thousands of dollars to millions of dollars)?

  2. Iggy Dalrymple Says:

    I take SAMe because I take therapeutic doses of niacin and
    I read that niacin can boost your CRP. I read somewhere that SAMe reduces elevated CRP.

  3. JP Says:

    Thank you, Chris.

    I’m currently away on a business trip and have limited Internet access. So, I probably won’t be able to access the links you’ve posted until I return home. But, I did want to offer a brief reply to your thoughtful question.

    From my perspective, the short answer is as follows: SAM-e differs from any of the pharmaceutical antidepressants because it naturally occurs in the body. It’s not a foreign substance such as Effexor (Venlafaxine), Prozac (Fluoxetine) or Wellbutrin (Bupropion).

    As far as the cost goes, SAM-e is often more expensive than prescribed mood boosters (in the US and many other countries) because insurance plans rarely cover nutritional supplements.

    I wish you and yours a happy and healthy Thanksgiving!


  4. JP Says:

    Good day, Iggy.

    SAM-e probably doesn’t lower CRP levels. But, it may support liver health – a consideration for those using therapeutic levels of niacin (as you undoubtedly know).

    My best wishes to you and your family this Thanksgiving and beyond!


  5. Sue Says:

    SAM-e is involved in methylation so it will help in a number of conditions/symptoms.

  6. JP Says:

    Hi, Sue.

    Absolutely. SAM-e is an important methyl donor and has been applied successfully in various health conditions ranging from arthritis to liver disease.

    Be well!


  7. Ravi Says:

    Really great one, thanks for the tip.

  8. JP Says:

    Update 05/18/15:

    J Korean Acad Nurs. 2015 Apr;45(2):221-30.

    Effect and Path Analysis of Laughter Therapy on Serotonin, Depression and Quality of Life in Middle-aged Women.

    PURPOSE: This study was done to examine how laughter therapy impacts serotonin levels, QOL and depression in middle-aged women and to perform a path analysis for verification of the effects.

    METHODS: A quasi-experimental study employing a nonequivalent control group and pre-post design was conducted. Participants were 64 middle-aged women (control=14 and experimental=50 in 3 groups according to level of depression). The intervention was conducted five times a week for a period of 2 weeks and the data analysis was conducted using repeated measures ANOVA, ANCOVA and LISREL.

    RESULTS: Results showed that pre serotonin and QOL in women with severe depression were the lowest. Serotonin in the experimental groups increased after the 10th intervention (p=.006) and the rise was the highest in the group with severe depression (p=.001). Depression in all groups decreased after the 5th intervention (p=.022) and the biggest decline was observed in group with severe depression (p=.007). QOL of the moderate and severe groups increased after the 10th intervention (p=.049), and the increase rate was highest in group with severe depression (p<.006). Path analysis revealed that laughter therapy did not directly affect depression, but its effect was indirectly meditated through serotonin variation (p<.001). CONCLUSION: Results indicate that serotonin activation through laughter therapy can help middle-aged women by lessening depression and providing important grounds for depression control. Be well! JP

  9. JP Says:

    Updated 08/17/15:

    J Affect Disord. 2014 Aug;164:76-81.

    S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response.

    OBJECTIVE: To assess the antidepressant efficacy of S-adenosyl methionine (SAMe), a naturally occurring methyl donor, versus the selective serotonin reuptake inhibitor (SSRI) escitalopram and a placebo control; and to determine whether serum histamine or carnitine levels modified treatment response.

    METHODS: We examined a subsample (n=144) from one site of a two-site study of adults with diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09, who consented to the additional blood draw for serum histamine and carnitine levels. After washout, eligible subjects were randomized to SAMe (1600-3200mg/daily), escitalopram (10-20mg/daily), or matching placebo for 12 weeks of double-blind treatment (titration at week 6 in non-response).

    RESULTS: On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 (p=0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo (d=0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17≥50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D≤7) were 34% for SAMe (p=0.003), 23% for escitalopram (p=0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment.

    LIMITATIONS: While SAMe appears to be an effective antidepressant agent, the overall findings from the parent study (which showed no significant difference between groups due to site differences) must be taken into consideration.

    CONCLUSIONS: These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine serum level may not necessarily moderate response to SAMe.

    Be well!


  10. JP Says:

    Updated 08/17/15:

    Altern Ther Health Med. 2013 Sep-Oct;19(5):61-4.

    A pilot study of S-adenosylmethionine in treatment of functional abdominal pain in children.

    CONTEXT: Functional abdominal pain (FAP) is one of the most common functional gastrointestinal disorders (FGIDs) in children. Currently, medical practitioners widely use tricyclic antidepressants to treat FAP. Those antidepressants, however, have been associated with an increased risk of suicidal ideation, and the accompanying side effects often limit the benefits. S-adenosylmethionine (SAM-e) is a dietary supplement that has efficacy as an antidepressant and as a treatment for chronic pain.

    OBJECTIVE: The research team hypothesized that during SAM-e exposure (1) participants’ pain reports would significantly improve over time, (2) participants’ reported quality of life would significantly improve over time, and (3) toxicity measures (liver-function tests and mania and depression scales) would not change significantly.

    DESIGN: The research team performed an open-label, doseescalation trial of oral SAM-e among children with FAP. Participants came to the research facility for measurements at baseline and after 2 wk, 1 mo, and 2 mo. The research team monitored participants for potential toxicities (liver toxicity, mania, and depression) throughout the trial.

    SETTING: The trial was conducted at the University of California, San Diego.

    PARTICIPANTS: The research team recruited children and adolescents with FAP via advertisement at several community general pediatric clinics and at the research team’s subspecialty pediatric gastrointestinal clinic at a tertiary care center. The eight resulting participants were children with a median and mean age of 14 y.

    INTERVENTION: To treat persistent abdominal pain, all participants received SAM-e at an initial dose of 200 mg/d, with escalation to a maximum dose of 1400 mg/d over the period of 2 mo.

    OUTCOME MEASURES: The primary outcomes were the participants’ self-reports of pain and quality of life. The research team used the multidimensional measure for recurrent abdominal pain (MM-RAP), Wong-Baker FACES Pain Rating Scale, and the PedsQL for those measurements. The team used repeated measures analyses to analyze the data.

    RESULTS: Six participants completed the study. The research team demonstrated an improvement in self-pain reports over the 2-mo follow-up period (P = .004). The median dose of SAM-e that participants took at the 2-mo follow-up period was 1400 mg (interquartile range: 950-1400 mg) daily. Liver function tests and assessments for mania and depression did not change over the study period.

    CONCLUSIONS: Oral SAM-e demonstrates promise in reducing abdominal pain among children with FAP, with minimal toxicity. The research team needs to conduct larger, placebo-controlled trials to support its initial findings.

    Be well!


  11. JP Says:

    Updated 03/18/16:

    Eur Arch Psychiatry Clin Neurosci. 2016 Mar 16.

    Adjuvant thiamine improved standard treatment in patients with major depressive disorder: results from a randomized, double-blind, and placebo-controlled clinical trial.

    Given that antidepressants (ADs) work slowly, there is interest in means to accelerate their therapeutic effect and to reduce side effects. In this regard, thiamine (vitamin B1) is attracting growing interest. Thiamine is an essential nutrient, while thiamine deficiency leads to a broad variety of disorders including irritability and symptoms of depression. Here, we tested the hypothesis that adjuvant thiamine would reduce depression, compared to placebo. A total of 51 inpatients (mean age: 35.2 years; 53 % females) with MDD (Hamilton Depression Rating Scale score (HDRS) at baseline: >24) took part in the study. A standardized treatment with SSRI was introduced and kept at therapeutic levels throughout the study. Patients were randomly assigned either to the thiamine or the placebo condition. Experts rated (HDRS) symptoms of depression at baseline, and after 3, 6, and 12 weeks (end of the study). Between baseline and the end of the study, depression had reduced in both groups. Compared to placebo, adjuvant thiamine improved symptoms of depression after 6 week of treatment, and improvements remained fairly stable until the end of the study, though mean differences at week 12 were not statistically significant anymore. No adverse side effects were reported in either group. Results suggest that among younger patients with MDD adjuvant thiamine alleviated symptoms of depression faster compared to placebo. Importantly, improvements were observed within 6 weeks of initiation of treatment. Thus, thiamine might have the potential to counteract the time lag in the antidepressant effects of ADs.

    Be well!


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