SAM-e: A Natural Antidepressant Supplement

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Antidepressant medications are one of the most common treatment options for those suffering from depression. Though typically effective, antidepressants can cause several negative side effects. 

There are several natural treatment options for depression, ranging from lifestyle changes to dietary supplements to ketamine infusions. SAM-e has earned recent attention as an effective alternative to traditional antidepressants.

Though it hit the U.S. market in 1999, SAM-e has been studied in Europe since the 1970’s. When researchers found abnormal levels of SAM-e in patients with liver disease and depression, they began clinical studies focused on SAM-e supplementation. 

Not only has SAM-e shown promise in aiding symptoms of depression, but it may also improve issues with liver function and osteoarthritis. 

At PrimeHealth, our team of providers specializes in treating depression at its root cause, naturally! If you are in Colorado and want a holistic approach to your mental health, we’d love to help create an individualized treatment plan with you.

Disclaimer: We may receive a small commission from products you purchase via links in this article.

What Is SAM-e?

SAM-e (S-adenosyl-L-methionine) is a compound produced naturally in the body. It also goes by the name adenoethionine. It is composed of the molecule adenosine triphosphate (ATP), and the amino acid methionine.

It is a methyl donor, meaning it contributes methyl groups to substances that need them. In this way, it helps to:

  • Maintain cell membranes
  • Synthesize proteins & enzymes
  • Build neurotransmitters like serotonin, dopamine, and adrenaline

SAM-e has been used to treat osteoarthritis, a condition in which the protective cartilage in the hands, knees, hips, and spine begins to wear down and cause pain and stiffness. 

One double-blind study found that it was as effective as a nonsteroidal anti-inflammatory drug (NSAID) for symptom management.

It has also been used to treat liver disease and stabilize liver health for years. One review found SAM-e effective in treating cholestasis (when the flow of bile becomes blocked) associated with hepatic diseases. SAM-e also shows promise for those suffering from alcoholic liver cirrhosis.

Other uses include enhancing cognitive function for those with Alzheimer’s disease and alleviating symptoms of fibromyalgia.

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Treating Depression With SAM-e

Our team of providers has been successfully recommending SAM-e to our patients for years as a safe and effective treatment for depression.

In the case of one of my patients, I found that they had a need for highly methylated vitamins that contribute to neurotransmitter production and function. Collaborating with their psychiatrist, we used SAM-e to successfully reduce the patient’s need for SSRIs to treat chronic depression.

Does SAM-e increase serotonin? Though researchers are not entirely certain of how, evidence implies that SAM-e raises serotonin levels.

It’s worth noting that many studies of SAM-e use injectable forms as opposed to oral SAM-e. The effects of oral SAM-e have been examined more recently. 

One study was conducted with postmenopausal women experiencing depression. Another study gave SAM-e to 15 patients with major depressive disorder. Both studies yielded positive results with increased levels of serotonin.

SAM-e vs. Antidepressants

The main difference between SAM-e and antidepressants like SSRIs (selective serotonin reuptake inhibitors) is that SAM-e is how they increase serotonin in the brain. 

SAM-e aids with the synthesis of serotonin, while SSRIs block the reabsorption of serotonin, leaving more available for signaling purposes. 

Other key differences between SAM-e and SSRIs include side effects, the timeframe to notice results, and drug interactions. 

Magnesium is another supplement that may be used complementary to SAM-e for natural mood interventions.

Side Effects

One of the reasons our providers love recommending SAM-e to our patients is that it doesn’t come with the side effects commonly associated with antidepressants — weight gain, sexual dysfunction, sedation, etc. 

While it is very safe with fewer side effects, some mild adverse effects of SAM-e supplementation may include:

  • Anxiety
  • Constipation
  • Diarrhea
  • Dizziness
  • Headaches
  • Nausea

Our medical advice is to discuss the use of SAM-e with your healthcare provider as an alternative medicine for the treatment of depression.

Read Next: Melatonin for Anxiety: Does it Work? 


Antidepressants tend to have a 4-6 week delay before mood improvement becomes noticeable. Meanwhile, SAM-e can prove effective in as little as a week.

How long does it take for SAM-e to start working? Patients taking SAM-e may start noticing relief from depressive symptoms in as little as 1-2 weeks.

Drug Interactions

Compared to other antidepressants, the list of drug interactions with SAM-e is extremely minimal. Some interactions include: 

  • Antidepressants (SSRIs), amphetamines, and antipsychotics: SAM-e should not be taken alongside any medications and supplements (such as St. John’s wort) that boost serotonin levels, as this may lead to serotonin syndrome (too much serotonin in the body). If you’re on these medications, talk to your prescriber before combining the two.
  • Dextromethorphan: The combination of SAMe with dextromethorphan (a cough suppressant) could also elevate the risk of serotonin syndrome, so it should be approached with caution.
  • Narcotics: If you’re taking meperidine (Demerol) or tramadol (Ultram, ConZip) as narcotics, be cautious about combining them with SAMe, as it could heighten the risk of serotonin syndrome.
  • Levodopa (Inbrija): SAMe may potentially reduce the effectiveness of levodopa (Inbrija), a medication commonly used for Parkinson’s disease treatment.

Those with health conditions such as bipolar disorder, Parkinson’s disease, or a weakened immune system should not take SAM-e unless directly advised by a physician. Also, be cautious of taking SAM-e if you’re pregnant or breastfeeding, as there isn’t much evidence yet as to how it may impact a developing fetus.

Because SAM-e can affect blood vessels, be sure to stop taking it at least 2 weeks before any surgery.

How to Take SAM-e

Though SAM-e has been prescribed in other forms in Europe for decades, it has not yet been approved by the Food and Drug Administration (FDA) for medicinal use. In the U.S., It is only available as a synthesized oral supplement. 

It is best taken on an empty stomach before meals. Look for enteric-coated tablets that allow it to pass through the stomach intact.

What’s the recommended dosage for SAM-e? Our team of healthcare providers at PrimeHealth recommended a SAM-e dosage between 400-800 mg, twice daily. 

SAM-e also works well alongside vitamin B12 and folate. Deficiency in vitamin B12 or folate can decrease levels of SAM-e. Be sure to eat plenty of meat (for vitamin B12) and leafy greens (for folate) to maintain your natural SAM-e. 

Can you get SAM-e from foods? Unfortunately, you cannot get it from food. You can, however, get the amino acid methionine from food, which helps the body produce SAM-e.

Discuss SAM-e With Your Healthcare Provider

SAM-e is a safe and promising option for anyone who either doesn’t respond to SSRIs or just doesn’t want to risk the side effects of traditional antidepressants. 

While SAM-e is a useful alternative to prescription drugs, it’s still important to discuss any changes in medication with your healthcare provider. 

If you’re in Colorado, PrimeHealth is here to help you explore holistic treatment options for any mental health conditions you’re concerned about.


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