Over-the-Counter Antidepressants

When you are suffering from more severe depression and need reliable relief from symptoms, prescription antidepressants are your best option. However, if you have mild to moderate depression without suicidal thoughts and urges, certain over-the-counter preparations may be worth a try.

St. John's Wort

St John's Wort flowers
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St. John's wort has a long history of usage, going back to ancient times. In the modern world, it has become a popular depression remedy as well, backed by increasing support in the medical literature, based on a review published in 2019.

Always talk to your doctor before you begin taking St. John's wort, since medication interactions and side effects can occur and may sometimes be severe. 

Its reported side effects are uncommon and rare, including dry mouth, dizziness, constipation, gastrointestinal symptoms, and confusion. Experts also recommend the usage of sunscreen with this herb due to the potential for creating sun sensitivity.

There are also potential interactions with other medications that can have serious and sometimes fatal consequences. For instance, St. John's wort with HIV medications can cause the body to clear HIV medications at a much higher rate, making it possible for a resurgence of HIV viral counts in a previously stable person. If combined with an SSRI, there is a risk for serotonin syndrome, which can be fatal. 

Dosages used in studies have been quite variable and are dependent upon the formulation of the herb or its extracts. You should follow the package directions for your particular brand of product.

Omega-3 Fatty Acids

Oil capsules spilling out of a bottle
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Omega-3 fatty acids are very important for health; but, since our bodies can't make them from scratch, they must be obtained from the foods that we eat. Unfortunately, we tend to not eat enough of these in order to maintain a proper balance in our bodies, which is believed to contribute to depression and other health issues. However, a review published in 2017 says that while promising, the research results on omega-3 fatty acids for depression are mixed.

While omega-3 fatty acid supplements, generally derived from fish oil, are considered to be quite safe, some people may experience stomach upset and fishy burps with higher doses. In addition, doctors warn that they may increase the effects of blood-thinning medications.

No particular dosage is recommended at this time for depression. The FDA recommends not going over 3 g per day without your doctor's permission due to a potentially increased risk for bleeding.

For those who opt to eat fish rather than take a supplement, the American Heart Association recommends two servings of fish per week for general health, which could be taken as good minimum consumption level.


Chemical model
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5-HTP, or 5-hydroxytryptophan, is an amino acid that our body makes from a dietary amino acid called l-tryptophan. Since it can be made into serotonin, a neurotransmitter that is believed to be involved in mood-regulation, it is thought that it can be supplemented in pill form in order to help depression.

While better-quality studies are needed to firmly establish its effectiveness as an antidepressant, a 2019 review says there is some evidence that 5-HTP supplementation, along with creatine, may improve the effectiveness of SSRI medications in some cases. However, it's essential that you speak with your doctor before adding this or any other supplement to your treatment program.

It is generally safe and well-tolerated, although side effects can occur and there are concerns that it could lead to a dangerous build-up of high serotonin levels if it is used in conjunction with other medicines that impact serotonin.


Chemical formula
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SAMe (S-adenosylmethionine) is produced in our bodies from the essential amino acid methionine and the energy-producing compound adenosine triphosphate (ATP). It can also be taken as a dietary supplement.

SAMe plays a role in methylation, a process involved in the regulation of neurotransmitters like serotonin so it could possibly play a role in depression.

Studies indicate that it may relieve depression as well as an older type of antidepressants called tricyclic antidepressants.

SAMe may be beneficial for depression as well as other psychiatric disorders.

Potential side effects include problems sleeping, loss of appetite, gastrointestinal symptoms, dizziness and elevated levels of homocysteine (a protein that has been linked to cardiovascular problems). Follow the package directions or consult with your physician for an appropriate dose for you. It also carries a risk for precipitating mania or hypomania in bipolar disorder.

Rhodiola Rosea

Rhodiola Rosea plant
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Although not much English-language research is currently available on Rhodiola rosea, it has been used traditionally as a tonic in Norway, Sweden, Iceland and Russia as an herbal antidepressant and stress-reliever. In addition, it has long been used by herbalists as an adaptogen, meaning that it is thought to be able to help people better cope with the effects of stress.

While American and European research is still in its early stages, this herb does appear to have some action as an antidepressant and it has a good safety record.

According to a review published in 2016, there were very few clinical trials examining Rhodiola rosesa and its effect on depression. They were quite limited in their design and ability to determine outcomes, however it appears to be well-tolerated, at least in short term use.

Vitamins and Minerals

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A wide variety of vitamins and minerals have been investigated for their potential role in depression. Some of the nutritional treatments which have been researched include vitamin B12, chromium,​ and inositol. It is not possible within the scope of this article to give full details about all of the nutritional factors involved in depression. In general, however, an adequate, well-balanced diet will provide all of the vitamins and minerals needed by the individual for good health and emotional balance. Alternatively, vitamin and mineral supplements may be used. Please see your doctor if you have particular concerns about a vitamin or mineral deficiency.

If you or a loved one are struggling with depression, contact the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357 for information on support and treatment facilities in your area.

For more mental health resources, see our National Helpline Database.

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