SAMe adenosylmethionine for depression

One in five people — 20% — will experience depression at some point in their lifetime. Because antidepressants — the standard treatment for depression — is ineffective, or has adverse side effects, for so many individuals, many people search for a more natural, non-prescription solution. As backed up by several clinical studies, SAMe, or adenosylmethionine, has been shown to be a natural, effective, safe treatment for depression.

Depression a Major Concern for Americans

According to the Anxiety and Depression Association of America (ADAA), depression and anxiety are by far the most common mental health concerns in the United States — depression affects an estimated one in 15 adults in any given year. Anyone can get depressed, and depression can occur at any age, and in any type of people.

Symptoms of Depression

Symptoms of depression are wide and varied, and may include:

  • Anxiety
  • Extreme fatigue and lack of energy
  • Sleeping too much or too little (insomnia)
  • Loss of interest, especially in things that previously were pleasurable
  • Unexplained aches and pains throughout the body
  • Lack of motivation in work or play
  • Suicidal thoughts
  • Changes in appetite or weight

Antidepressant Adverse Side Effects

The U.S. Food and Drug Administration (FDA) has approved several medications for the treatment of depression. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed of these FDA-approved antidepressants. SSRIs include paroxetine (such as Paxil), fluoxetine (Prozac), and sertraline (Zoloft). Less common but still popular are serotonin and norepinephrine reuptake inhibitors (SNRIs), of which duloxetine (Cymbalta) is the best-known.

Prescription antidepressants do work for many people who are prescribed them, but a majority of people experience adverse effects. Often the side effects are severe enough that a patient will stop taking the medication, and often people experience multiple side effects — sometimes even experiencing three or four of the common adverse effects:

  • Nausea or vomiting
  • Diarrhea
  • Insomnia
  • Drowsiness
  • Nervousness or restlessness
  • Change in appetite resulting in weight loss or gain
  • Dizziness
  • Headache
  • Sexual problems such as erectile dysfunction
  • Dry mouth

If you’ve experienced depression and have tried antidepressants but they were ineffective, or you experienced adverse reactions too severe to continue taking the medication, you still have other options. Many natural, non-prescription remedies exist, with the most popular and effective being SAMe (adenosylmethionine).

depression woman in bed

SAMe (Adenosylmethionine) for Treatment of Depression

SAMe is a natural forming molecule in plants and animals (including humans). SAMe doesn’t exist in foods — it’s produced within the human body from the amino acid methionine and adenosine triphosphate (or ATP, the important compound that provides the energy that drives most of the processes in cells).

You might also see SAMe referred to as SAM, SAM-e, adenosylmethionine, S-adenosylmethionine, or ademetionine — they all refer to the same SAMe molecule. SAMe is a form of the amino acid methionine, which is why you see methionine within some of the alternate names SAMe goes by. For consistancy we’ll refer to this molecule as SAMe throughout this article.

SAMe was discovered in the early 1950s, and has been found to help regulate many of the key functions in cells. Once formed in the body, SAMe has been found to play a role in a number of important biochemical reactions, including the production of DNA, proteins, and neurotransmitters.

Benefits of SAMe

Over the years the number of uses for SAMe has grown amazingly large. SAMe has been used with positive results for all of the following ailments:

  • depression
  • anxiety
  • dementia
  • Alzheimer’s disease
  • Parkinson’s disease
  • multiple sclerosis
  • seizures
  • heart disease
  • fibromyalgia
  • attention deficit-hyperactivity disorder (ADHD)
  • improving mental performance
  • chronic fatigue syndrome (CFS)
  • tendonitis
  • bursitis
  • osteoarthritis
  • migraine headache
  • chronic lower back pain

SAMe is formed naturally in the body, and isn’t available naturally in foods. This means a person whose body isn’t producing adequate levels of SAMe wouldn’t have any good means of amping up their SAMe levels without the availability of a synthetic version of this compound. Because SAMe plays such an important role in a variety of key body processes, successful efforts went into developing just such a synthetic SAMe.

SAMe a Popular Supplement for Treating Depression

Of importance in this article is the role SAMe plays in treating depression (and anxiety, as anxiety often accompanies depression). And studies have shown that for many people SAMe has been beneficial in treating both moderate and severe depression. So much so that SAMe has been used for decades in Europe to treat depression, and is considered such a serious treatment that in many European countries, including Italy, Spain and Germany, SAMe is available only as a prescription drug. Fortunately for United States residents SAMe is categorized as a dietary supplement, and as such it is available over the counter (OTC) without need for a prescription.

SAMe Helps Release Neurotransmitters

Methylation is a term that’s become popular in the health industry. In short, methylation is a biochemical process that’s involved in the vast majority of a body’s functions. More scientifically, methylation is the addition of a methyl group — one carbon atom and three hydrogen atoms — to a molecule. This small act of adding a methyl group to a molecule serves a big purpose — it acts as a switch that turns something on or off in the body. That something can be a lot of different things. Among the functions methyl groups control are:

  • Neurotransmitters, and therefore the balancing of brain chemistry
  • Inflammation response
  • Production of the body’s master antioxidant, glutathione
  • Energy production
  • Fight-or-flight response (reaction to stress)
  • Repair of DNA
  • Immune response and fighting viruses and infections
  • Repair of free radical damaged cells

SAMe is an important methyl donor. So important that it is considered the master methyl donor. In terms of treating depression, it’s the first item in the above list that’s of most importance. Acting as a methyl donor is a crucial step in the synthesis of several neurotransmitters from amino acids in the diet. Included in these neurotransmitters are serotonin, dopamine, and norepinephrine. All three of these neurotransmitters (which also act as hormones) contribute to an antidepressant effect.

Dopamine and serotonin are referred to as the happy hormones — they play huge roles in regulating emotion and mood. Dopamine plays a key role in the reward system: the group of brain processes that control desire, cravings and motivation. A person’s dopamine level influences alertness, mood, learning and sleep. Serotonin inhibits impulsive behavior, and helps to regulate mood and anxiety. Norepinephrine levels affect attentiveness and energy, and contribute to the brain mobilizing for action (fight or flight). Add this all up and it’s easy to see why SAMe is popular and proven to be of great benefit to many people suffering from depression.

sam-e supplements

Advantages of SAMe Over Prescription Antidepressants

A 2017 paper by the National Center for Health Statistics reported that 12.7% of the U.S. population over age 12 took antidepressant medication in the past month. It turns out that antidepressants are among the most widely prescribed drugs. Most antidepressants can cause adverse effects that are bothersome enough that an estimated 30% to 60% of patients do not take their prescribed antidepressants on a regular basis, even knowing that failing to do so will have negative effects on their mental health.

SAMe Has Fewer Adverse Side Effects Than Antidepressants

It’s known that about 85% of patients prescribed an antidepressant experience at least one adverse effect, and a large number experience three or more adverse effects. The most common side effects are drowsiness and sexual dysfunction, followed by nausea, weight gain, insomnia, and irritability. Unsurprisingly, for about 20% of patients the benefits of prescription antidepressants do not outweigh the adverse effects. Interestingly (and sadly), physicians who prescribe antidepressants tend to significantly underestimate their patients’ occurrence — and bothersomeness — of adverse effects.

When it comes to side effects, the contrast between prescription antidepressants and SAMe could not be more dramatic. Very few people experience adverse effects from taking SAMe, and of those that do, the side effects are usually mild — much more mild than those experienced by people taking antidepressants. In one large study including over 20,000 patients, only about 4% discontinued SAMe due to side effects, with the majority of those patients citing nausea as the reason. This was the same percentage of dropouts who were given a placebo. Most of the patients who experienced side effects where on high doses of SAMe, and stated that the effects were mild and temporary — any adverse effects subsided within the first month.

SAMe Is Fast-Acting

One other advantage SAMe has over antidepressants is in onset of action. Most antidepressants have a delayed onset of action — consistent improvement in mood becomes noticeable only after one month to six weeks of daily use. In contrast, SAMe has a much more rapid onset of action — mood improvement is noticeable usually within one week.

Finally, patients who take SAMe for depression often see improvement in memory and other cognitive problems — issues that often accompany depression, but aren’t addressed by prescription antidepressants.

SAMe Dosage for Treating Depression

The typical SAMe dosage for treating depression is 800 mg per day, taken in two daily doses of 400 mg each. A typical strategy is to begin treatment with SAMe at one dose of 400 mg, once a day, monitoring for adverse effects and therapeutic response (positive mood-elevating results). After about one week, if there are no negative side effects, and only a minimal improvement in mood, then increase the dose of 400 mg from once daily to twice daily. Note that absorption of SAMe is improved greatly when taken on an empty stomach, so it is most beneficial to take any dose at least an hour before, rather than during or after, a meal.

SAMe and Vitamin B12 and Folate

It is well-known that in order for SAMe to be effective in synthesizing the above neurotransmitters, the body must have adequate levels of vitamin B12 and folate. Many depressed people are found to be deficient in B vitamins, thus individuals taking SAMe for the purpose of combating depression will invariably benefit from taking vitamin B12 and folate (folic acid) along with SAMe.

If you plan on taking SAMe, and are not already taking a vitamin B12 and folate supplements, you should consider also adding those two nutrients to your supplement regimen. If you take a multivitamin, though, you most likely are already getting B12 and folate — most multivitamins include these two very common nutrients.

If you plan on taking SAMe, and are already taking vitamin B12 and folate supplements, then a quality SAMe supplement such as Now SAMe from A1 Supplements will work perfect for you.


SAMe, or adenosylmethionine, doesn’t exist in foods — it’s produced within the body from the amino acid methionine and ATP. To increase your SAMe levels you’ll need to take SAMe supplements. SAMe has been used with positive results for a host of ailments and conditions, including depression.

The downside of SAMe is that compared to many supplements, it’s more expensive. The upside to SAMe is that it is well-established as a very effective, side effect free, non-prescription treatment for depression.