Back to Blog
shelves filled with pill bottles

Supplements for depression and anxiety: Are they safe and effective?

Many people are concerned about the safety of antidepressants and are looking for natural alternatives. Although there are several natural products such as St. John’s Wort, S-adenosyl methionine (SAM-e), Rhodiola rosea, and omega-3 which have been shown to have mood stabilizing effects, supplements cannot substitute medications for people with severe depression. Furthermore, St. John’s Wort and other supplements can significantly impact how people process, or metabolize, many prescription medications. The use of these natural products together with prescription medications may pose significant health risks. In this overview we will discuss how supplements work as mood stabilizers and whether these can be taken along with antidepressants.
Supplements should not be taken lightly – an incorrect supplement or excessive use can lead to worsening of depression and affect the heart and digestive system. Pharmacists know about key drug-food interactions so consult with your pharmacist before you decide if taking a supplement to improve your mood or treat depression and/or anxiety is right for you.

St. John’s Wort is one of most commonly known natural products recommended for depression. Its effectiveness was studied in multiple clinical studies which have not produced strong supporting evidence, hence this supplement cannot replace medications for treating depression. St. John’s Wort can affect certain liver enzymes that are involved in metabolizing many medications, making the medications less effective than they should be or causing side effects. As well, St. John’s Wort is known to block the effectiveness of medications known as MAO’s (similar to MAOI antidepressants). MOA-A and MOA-B inhibitors are used to treat panic disorder, social phobias, treatment-resistant depression and atypical depression, as well as Parkinson’s disease. However, MOA inhibitors and St. John’s Wort cannot be combined with popular antidepressants including SSRIs and SNRIs or other antidepressants as such combinations can lead to serotonin syndrome, which can be fatal. Common side effects associated with St. John’s Wort include upset stomach and diarrhea, fatigue, restlessness, elevated blood pressure, and increased sensitivity to the sun. In patients with bipolar disorder, St. John’s Wort may also induce mania. People suffering from depression and taking antidepressants should not attempt to substitute medications or supplement treatment with St. John’s Wort.

S-adenosyl methionine (SAM-e) is a natural substance that is produced in the body. Synthetic SAM-e is considered a supplement in North America, but it is considered a prescription drug in Europe. SAM-e is used to treat depression and pain. SAM-e works similar to folate – folate deficiency may be one of the causes of depression. Folate deficiency affects synthesis of dopamine, serotonin, and acetylcholine, which are important neurotransmitters. The benefit of SAM-e is that it is not impacted by genes that regulate folate metabolism such as MTHFR. People with folate deficiency have lower levels of SAM-e, therefore SAM-e supplements may improve the synthesis of serotonin and dopamine, producing an antidepressant effect.
Some studies have found that SAM-e is just as effective as NSAIDs like ibuprofen and celecoxib and helps people with osteoarthritis and fibromyalgia. SAM-e also has fewer side effects than NSAIDs. SAM-e is considered safe and can be combined with TCAs, SSRIs, and SNRIs. SAM-e side effects can include insomnia, sweating, loss of appetite, constipation, nausea, dry mouth, dizziness, and anxiety. However, SAM-e is not recommended for people with bipolar disorder because it can induce manic episodes. Please consult with your physician or pharmacist to see if SAM-e supplements are right for your treatment.

Rhodiola rosea root extract is considered to be an adaptogen – i.e., it alleviates physical and mental stress. Rhodiola has been studied extensively in Russia and Scandinavia. Controlled clinical trials support Rhodiola’s efficacy for depression and anxiety. Rhodiola has several chemicals including rosavins, tyrosols, and flavonoids. Rhodiola, like St. John’s Wort, affects monoamine oxidase activity and produces an anti-anxiety and mood stabilizing effect. It may also induce vivid dreams, thus can interfere with sleep. Rhodiola should be taken on an empty stomach at least 30 minutes before food to improve absorption and is considered to be safe. Rhodiola can be combined with tricyclic antidepressants. A mild serotonin syndrome reaction can occur when Rhodiola is combined with paroxetine and other SSRIs. Consult your healthcare provider if you’re interested in supplementing your treatment with Rhodiola rosea.

Omega-3 and Omega-6 are widely recommended by naturopathic doctors and physicians based on claims that these fatty acids significantly improved cardiovascular and mental health. However, recent studies questioned some of these claims. Other studies demonstrated the ratio of omega-6 to omega-3 correlates with depression. If a person has too little Omega 3 versus other fatty acids in their body, they may be more likely to be depressed, while the ratio of Omega 6 to other fatty acids is not related to the risk of depression or anxiety. Some omega-3s including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found primarily in fish oil and in certain types of algae. Another type of omega -3 alpha-linolenic acid (ALA) is found in flaxseed oil and in some other vegetable oils. The omega-6 fatty acids are primarily found in vegetable oils. Studies suggest that essential fatty acids can help in treating depression. Omega-3s are thought to be quite safe at usual doses (up to 3 grams per day) and are mainly used as a supplement for the medical treatment of depression but cannot be used alone. In people with bipolar disorder, mania may occur when high doses (6 -10 grams a day) are used. High doses of Omega-3 can also increase the risk of GI bleeding or excessive bleeding from cuts/surgery, which may be life threatening, particularly for patients taking anticoagulants or antiplatelets for managing the risk of heart disease, or NSAIDs (like Advil and naproxyn) for chronic pain. Because it is a fat-soluble substance, omega-3 can accumulate in the body if taken at high doses for long periods of time, and cause permanent kidney and liver damage.

In summary, some supplements, including Omega-3, Rhodiola rosea, and SAM-e, can be used to support the treatment of anxiety and depression. However, these supplements alone are insufficient to manage anxiety and depression. Your response to antidepressants is impacted by genetic variations in drug metabolizing genes, the function of which can also be affected by supplements such as St. John’s Wort. Pharmacogenetic tests, such as Pillcheck, explain how your body processes antidepressants and can assist your healthcare providers in selecting an appropriate drug and dose. Our clinical pharmacists can advise you which supplements can be used safely along with antidepressants.


Dome P et al., (2018). Natural health products, dietary minerals, and over-the-counter medications as add-on therapies to antidepressants in the treatment of major depressive disorder: a review. Brain Research Bulletin, 146.

Mischoulon D & Rosenbaum J. F. (Eds.). (2008). Natural medications for psychiatric disorders: considering the alternatives. Lippincott Williams & Wilkins.

Maher, A. R., Hempel, S., Apaydin, E., Shanman, R. M., Booth, M., Miles, J. N., & Sorbero, M. E. (2016). St. John’s Wort for Major Depressive Disorder: A Systematic Review. Rand health quarterly, 5(4).
Sharma, A., Gerbarg, P., Bottiglieri, T., Massoumi, L., Carpenter, L. L., Lavretsky, H., … & Mischoulon, D. (2017). S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. The Journal of clinical psychiatry, 78(6), e656.

Tayama, J., et. al. (2018). Omega-3 polyunsaturated fatty acids and psychological intervention for workers with mild to moderate depression: a double-blind randomized controlled trial. Journal of Affective Disorders, 245.

Thesing CS et al., (2018) Omega-3 and omega-6 fatty acid levels in depressive and anxiety disorders. Psychoneuroendocrinology. Jan;87:53-62.

Wang, L.S., et. al. (2013). The influence of St. John’s Wort on CYP2C19 activity with respect to the genotype. Journal of Clinical Pharmacology, 44(6).

Share this post

Back to Blog
Skip to content