SAM-e & Anxiety: An Effective Treatment?

By Sarah Cocchimiglio

Updated February 13, 2020

Reviewer Aaron Horn


SAM-e is a natural supplement often used for treating depression and similar mental health conditions. It has a fairly good history of effectiveness at relieving symptoms of depression, and with positive results and relief that patients frequently begin to experience more quickly than with traditional prescription medication treatment options. SAM-e may also yield results similar to treatments with pharmaceuticals.

What Exactly is SAM-e?

S-adenosyl-methionine (SAM-e) is an over-the-counter(in America) natural supplement widely used as a complementary or alternative treatment for patients suffering from several mental health issues, such as depressed mood and anxiety. Found naturally occurring throughout the body, SAM-e is mostly concentrated in the brain and liver, and controls or enables a variety of metabolic reactions essential to brain function and cell growth. These reactions are called "methylations," in which the SAM-e molecule donates a methyl group to another molecule, playing a crucial role in these physiological processes in the body. Poor methylation may be linked to depression and related mental health conditions.

SAM-e is a molecule that is produced by the pineal gland in the brain, but it can also be synthesized artificially in a lab to create a dietary supplement. It aids in forming, activating, and breaking down chemicals in the body, such as hormones, proteins, phospholipids, and drugs. SAM-e is believed to help the body fight pain, depression, liver disease, and more. When your body doesn't produce enough SAM-e on its own, you may benefit from taking a SAM-e supplement to compensate.

SAM-e works in the brain by aiding in the production of the neurotransmitters serotonin, dopamine, and noradrenaline, which supports overall mental health. This is likely the reason for SAM-e's positive effects on combating depression, which may be caused by a chemical imbalance in the brain of those neurotransmitters. SAM-e deficiency can result in several health complications aside from depressed mood and anxiety, such as liver disease, amyotrophic lateral sclerosis (ALS), congenital heart disease, and increased viral susceptibility.

SAM-e does occur in some of the foods we eat, but SAM-e is so unstable by nature and oxidizes so rapidly, that food is not responsible for contributing any measurable SAM-e to our diets.

SAM-e has been researched and documented extensively and is one of the most-studied alternative treatments for depression. Most research indicates that SAM-e is considerably safe and effective. As a supplement, it can be taken orally or intravenously.

What Does SAM-e do?


SAM-e is used to treat a wide variety of conditions, even many outside the mental health spectrum, including:

  • Fibromyalgia
  • Depression
  • Anxiety
  • Tendonitis
  • Osteoarthritis
  • Multiple sclerosis
  • Chronic fatigue syndrome (CFS)
  • Chronic lower back pain
  • Liver disease
  • Parkinson's disease
  • Premenstrual dysphoric disorder (PMDD)

Should You Take SAM-e For Anxiety?

Millions of people suffer from anxiety, a chronic and debilitating mental condition, and one of the most commonly diagnosed in the U.S. Although prescription anti-anxiety medications have proven to be extremely effective, they also have potential side effects and may be habit-forming, encouraging people to seek out alternative natural or holistic remedies, such as SAM-e, to treat anxiety symptoms.


Although much of the research into SAM-e's safety and efficacy have focused on its effects on depression, patients who suffer from depression often also suffer from anxiety disorders as well (this is known as comorbidity). There is ample evidence that SAM-e is effective at relieving symptoms of depression and there is some evidence that SAM-e may help relax patients with anxiety or nervousness, but there have been few studies focusing directly on the effectiveness of SAM-e for specifically treating anxiety. Bottom line: if you suffer from depression and anxiety, you may find relief from taking SAM-e, whereas if you take SAM-e for anxiety, exclusive of depression, you may or may not experience relief from your symptoms.

In addition, one of the possible side effects of SAM-e is anxiety, so there is potential for creating or exacerbating the very condition you may be trying to treat.

That risk alone may be enough to outweigh any potential benefit for anxious patients. It may not be the best treatment option to take SAM-e for anxiety until more studies are conducted and more is known about how it works and how it might affect those suffering from anxiety.

Recommended dosage varies, depending on the patient's age and the condition it is intended to treat; for example, the same course of treatment recommended for depression and anxiety may differ significantly from the indications for treating chronic pain. SAM-e has a very short half-life (only about 100 minutes) and metabolizes quickly, so you may also have to play with dosage and treatment schedules to find out what works best for you as an individual.

Is SAM-e Safe? What Are The Side Effects Or Dangers?

Most experts agree that SAM-e is relatively safe when standard doses are taken as directed, even for children. There are several side effects to watch out for, however, as well as drug interactions to avoid. There is also limited evidence for the safety and effectiveness of taking extremely high doses of SAM-e or taking it over long periods. Therefore, it should be considered mainly for short-term treatment until further study is done on the long-term effects of taking SAM-e.

Side effects can include gas, vomiting, diarrhea, constipation, dry mouth, lack of appetite, headache, mild insomnia, anorexia, sweating, and dizziness. At higher doses, SAM-e may cause nervousness or make some depressed patients feel anxiety. Some evidence suggests that intravenous administration of SAM-e produces effective results at lower doses and causes fewer adverse reactions than taking SAM-e orally, although at this time it is mainly only available in oral form in the U.S.

Since SAM-e increases the brain's production of serotonin, it should not be taken along with certain medications for depression, such as Prozac, Paxil, Zoloft, Elavil, etc., that also increase serotonin levels. An overabundance of serotonin can cause serious side effects, including heart problems and anxiety. For the same reason, anyone taking monoamine oxidase inhibitor-class (MAOI) medications, like Nardil and Parnate, should avoid taking SAM-e. The potential for serotonin syndrome - an overload of serotonin - is also cause for avoiding taking SAM-e along with dextromethorphan (DXM) which is found in many over-the-counter cough medicines, and several other medications.

SAM-e might also cause serious manic issues for some people with bipolar disorder, and is therefore not recommended for use by bipolar patients.


There is insufficient information about the safety of using SAM-e when pregnant or nursing, so pregnant and breastfeeding women should avoid using it. It should also not be taken by anyone with a compromised immune system.

If you plan to have any type of surgical procedure, you should stop taking SAM-e at least two weeks before surgery, because of how SAM-e affects the central nervous system and can alter medications administered during and after surgery.

SAM-e has been known to cause restlessness and insomnia, so it's recommended that you take it in the morning, rather than afternoon or evening when it could disrupt your sleep cycle.

Brand Matters

Another thing to keep in mind is that since SAM-e is not regulated by the FDA, manufacturers, and ingredients are not subject to the same rigorous testing and quality control that the makers of prescription drugs are required to perform. Using only USP-verified supplements can help minimize the risk of serious adverse effects related to quality control.

Speaking of quality control, if you decide to take a SAM-e supplement for anxiety, know that not all brands are created equal. Lower cost often indicates lower quality, which can also mean lower potency or even less safe. Look for enteric-coated tablets, protected in individual blister packs, since stomach acids and exposure to air can degrade SAM-e and compromise its effectiveness. These packs should never be refrigerated due to the risk of oxidation or moisture inside the pack.

Always Consult Your Healthcare Team First

In addition to discussing your anxiety and possible treatment with your healthcare provider, you should always tell your doctor about any vitamins or supplements you're taking, or alternative health methods you're using. Giving your doctor a complete picture of your healthcare regimen is the safest way to avoid any kind of interactions and to ensure your best care.

If you're considering SAM-e for anxiety, depression or other mental health condition, the safest course of action is definitely to schedule an appointment with your doctor, to discuss and determine whether SAM-e is right for you, and to work out dosage and length of treatment, as well as to eliminate any potential contraindications or drug interactions. SAM-e may work best for you alone, or in conjunction with other treatments, such as prescription pharmaceuticals, therapy, diet, and other supplements.

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