Over-the-Counter Antidepressants

When you have 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 (OTC) preparations may be worth a try.

OTC options may be most beneficial when they are utilized alongside other lifestyle modifications that have been shown to alleviate depression such as regular exercise, getting enough sleep, finding social support, and managing stress levels.

St. John's Wort

St John's Wort flowers

esemelwe / Getty Images

St. John's wort has a long history of use, 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.

The National Center for Complementary and Integrative Health notes, however, that St. John's wort does not offer consistent results for relieving depression. Because of this, it should not be used to postpone or replace seeing your doctor for depression treatment.

There are certain things you need to watch for when taking St. John's wort including:

  • Side effects: Always talk to your doctor before you begin taking St. John's wort since side effects can occur and can sometimes be severe. While its reported side effects are uncommon and rare, they include dry mouth, dizziness, constipation, gastrointestinal symptoms, and confusion.
  • Drug interactions: There are also potential medication interactions that can have serious and sometimes fatal consequences. For instance, taking 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.
  • Serotonin syndrome: If combined with a prescription selective-serotonin reuptake inhibitor (SSRI), MAOI's, or any other serotonergic medication there is a risk for serotonin syndrome, which can be fatal. 
  • Sun sensitivity: Experts recommend the usage of sunscreen with this herb due to the potential for creating sun sensitivity.

Dosages of St. John's wort used in studies have been quite variable and are dependent upon the formulation of the herb or its extracts. In addition to consulting your doctor before use, you should follow the manufacturer's directions for your chosen 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. They play a role in heart health and reducing inflammation, but some findings suggest that they may also influence mental health. More research is needed to explore the connection, but some evidence suggests that omega-3s may be helpful for preventing or possibly alleviating mild to moderate depression. 

There are three types of omega-3s:

  • Alpha-linolenic acid (ALA)
  • Eicosapentaenoic acid (EPA)
  • Docosahexaenoic acid (DHA)

EPA, which is found in fish and other seafood, seems to offer the greatest depression-fighting benefits.

While omega-3s offer promise, whether EPA or other omega-3s provide significant relief on their own remains unclear. Studies suggest omega-3 supplements used as an adjunct to standard antidepressant therapy resulted in the best outcomes.

A 2019 meta-analysis that looked at the results of 26 earlier studies found that omega-3 polyunsaturated fatty acids (PUFAs) had a beneficial effect on depression.

If you decide to try taking supplemental omega-3s, there are a few things to be aware of:

  • Stomach upset: 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.
  • Increased blood thinning: In addition, doctors warn that omega-3 supplements may increase the effects of blood-thinning medications.

How Much Do You Need?

According to the National Institutes of Health, most Americans get the amount of ALA they need from the food they eat, along with smaller amounts of EPA and DHA. You can get adequate omega-3s by eating a varied diet that includes fish and other seafood, nuts, seeds, plant oils, and fortified foods such as certain juices, yogurts, eggs, and milk.

No particular dosage is recommended at this time for depression. The FDA recommends not going over 3 grams per day without your doctor's permission due to a potential increase in the risk of bleeding.

How to Get More Omega-3s

Since our bodies can't make them from scratch, omega-3 fatty acids must be obtained from the foods that we eat or via supplementation.

Foods that are high in omega-3s include:

  • Fish (especially salmon, mackerel, tuna, sardines, and herring)
  • Nuts and seeds (including walnuts, chia seeds, and flax seeds)
  • Plant oils (including canola oil, soybean oil, and flaxseed oil)

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

Jynto / Wikimedia Commons / CC0

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 5-HTP can be supplemented in pill form in order to help depression.

5-HTP does not occur naturally in foods, so it must be obtained through supplementation. The supplement is derived from the seeds of Griffonia simplicifolia, a plant native to Central and Western Africa.

The body produces 5-HTP naturally as it converts L-tryptophan, but this ability is limited by the availability of an enzyme called tryptophan hydroxylase. Taking 5-HTP as a supplement bypasses this limitation, making it so there is more 5-HTP available for conversion to serotonin.

Is It Effective for Depression?

While better-quality studies are needed to firmly establish its effectiveness as an antidepressant, a 2019 review found that 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.

5-HTP is generally safe and well-tolerated, although side effects can occur. Some of the potential side effects include:

  • Diarrhea
  • Dizziness
  • Drowsiness
  • Feelings of anxiety
  • Muscular tenderness
  • Nausea
  • Sexual dysfunction

5-HTP can also lead to drug interactions when taken with some other medications including antidepressants like SSRIs and MAOIs, tramadol, and dextromethorphan (DXM).

There are also 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

NEUROtiker / Wikimedia Commons / Public Domain

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 antidepressant called tricyclic antidepressants.

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

Potential side effects include:

  • Dizziness
  • Elevated levels of homocysteine (a protein that has been linked to cardiovascular problems)
  • Gastrointestinal symptoms
  • Loss of appetite
  • Problems sleeping

Follow the package directions or consult with your physician for an appropriate dose for you. It is also important to note that SAMe may worsen symptoms of mania in people with bipolar disorder.

Rhodiola Rosea

Rhodiola Rosea plant

Daderot / Wikimedia Commons / Public Domain

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 rosea 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.

One 2018 study found that Rhodiola rosea extract helped improve symptoms of stress-related burnout including depression. 

Vitamins and Minerals

Mixed vitamins and supplements

Brian Hagiwara Photolibrary / Getty Images

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.

One meta-analysis suggested that the typical Western diet (which includes larger amounts of red/processed meats, refined sugars, and high-fat dairy) was associated with an increased risk of depression.

Healthy diets that included a high intake of vegetables, fruit, whole grains, fish, low-fat dairy, and fish, on the other hand, were linked to a decreased risk of depression.

In general, an adequate, well-balanced diet will provide all of the vitamins and minerals needed for good health and emotional balance. Alternatively, vitamin and mineral supplements may be used to help fill the gaps. 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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Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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