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St. John's Wort and Depression: In Depth

St Johns Wort Hypericum-perforatum-h29417

What’s the Bottom Line?

How much do we know about St. John’s wort for depression?

  • We know a fair amount about the short-term effects of St. John’s wort on depression but less about its long-term effects.

What do we know about the effectiveness of St. John’s wort for depression?

  • St. John’s wort isn’t consistently effective for depression. Do not use it to replace conventional care or to postpone seeing your health care provider.

What do we know about the safety of St. John’s wort for depression?

  • St. John’s wort limits the effectiveness of many prescription medicines.
  • Combining St. John’s wort and certain antidepressants can lead to a potentially life-threatening increase in your body’s levels of serotonin, a chemical produced by nerve cells.
  • Don’t try to treat depression on your own. Depression can become severe if you don’t get effective, professional help. For some people, depression can increase the risk of suicide. Talk to your health care provider if you or someone you know may be depressed.

About St. John’s Wort

  • St. John’s wort (Hypericum perforatum), a plant that grows in the wild, has been used for centuries for mental health conditions. It’s widely prescribed for depression in Europe.
  • St. John’s wort is sold as a dietary supplement in the United States, where the standards for selling supplements are less strict than the standards for prescription or over-the-counter drugs.

For more information, see the National Center for Complementary and Integrative Health (NCCIH) Web page about St. John’s wort.

About  Depression

Depression (major depressive disorder or clinical depression) is a common but serious mood disorder. It causes severe symptoms that affect how you feel, think, and handle daily activities, such as sleeping, eating, or working. In 2015, almost 7 percent of U.S. adults had at least one episode of major depression in the past year. Symptoms of depression vary but can include

  • Feeling sad or anxious often or all the time
  • Not wanting to do activities that used to be fun
  • Feeling irritable‚ easily frustrated‚ or restless
  • Having problems with sleep and feeling tired
  • Eating more or less than usual or having no appetite
  • Experiencing pain that doesn’t improve with treatment
  • Having trouble concentrating, remembering details, or making decisions
  • Feeling guilty, worthless, or helpless
  • Thinking about suicide or hurting yourself.

Antidepressants and certain types of psychotherapy help treat depression.

For more information on depression, visit the National Institute of Mental Health (NIMH) webpage on depression.

What the Science Says About the Effectiveness of St.  John’s Wort for  Depression

The results of studies on the effectiveness of St. John’s wort for depression are mixed.

  • In a 12-week, 2011 clinical trial with 73 participants, neither St. John’s wort nor a standard antidepressant medication called citalopram, a selective serotonin reuptake inhibitor (SSRI), decreased symptoms of minor depression better than a placebo. The study was funded by NCCIH and NIMH.
  • In a 26-week clinical trial with 124 participants, St. John’s wort, a standard antidepressant (sertraline, an SSRI), and a placebo were similarly effective in treating major depression of moderate severity. NCCIH and NIMH funded this 2012 analysis of data collected in 2002.
  • A 2008 review of 29 international studies suggested that St. John’s wort may be better than a placebo and as effective as different standard prescription antidepressants for major depression of mild to moderate severity. St. John’s wort also appeared to have fewer side effects than standard antidepressants. The studies conducted in German-speaking countries—where St. John’s wort has a long history of use by medical professionals—reported more positive results than those done in other countries, including the United States.
  • St. John’s wort was no more effective than placebo in treating major depression of moderate severity, an NCCIH- and NIMH-funded study of 340 participants reported in 2002.
The Placebo Effect
  • The placebo effect is when patients’ health improves because they think that an intervention—a pill, procedure, or injection, for example—will help. In a clinical trial of St. John’s wort for major depression, what participants guessed they were taking may have affected their recovery from depression more than what they actually received. A health care provider’s style in talking with patients also may have a positive effect on patient health that is separate from the treatment.

What the Science Says About the Safety and Side Effects of St. John’s Wort for Depression

  • Combining St. John’s wort with certain antidepressants can lead to a potentially life-threatening increase of serotonin, a brain chemical targeted by antidepressants. Symptoms occur within minutes to hours, and may include agitation, diarrhea, fast heartbeat, high blood pressure, hallucinations, increased body temperature, and more.
  • There are case reports of St. John’s wort having dangerous side effects, such as worsening of psychotic symptoms in people with bipolar disorder or schizophrenia.
  • Taking St.  John’s wort can weaken many prescription medicines, such as:
    • Antidepressants
    • Birth control  pills
    • Cyclosporine, used to prevent the body from rejecting transplanted  organs
    • Digoxin, a heart  medication
    • Oxycodone, a pain medicine
    • Some HIV drugs, including indinavir
    • Some cancer medications, including irinotecan
    • Warfarin, an anticoagulant (blood thinner).
  • Other side effects of St. John’s wort are usually minor and uncommon. They may include upset stomach, dry mouth, headache, fatigue, dizziness, confusion, sexual dysfunction, or sensitivity to sunlight. Also, St. John’s wort is a stimulant and may worsen feelings of anxiety in some people.

NCCIH-Funded Research

NCCIH is studying the potential drug interactions of different herbs, including St. John’s wort.

More To Consider

  • Depression can be a serious illness and lead to an increased risk of suicide. If you or someone you know may have depression, talk to a health care provider. Don’t try to treat depression on your own.
  • Do not use St. John’s wort to replace conventional care or to postpone seeing a health care provider about a mental health problem.
  • Dietary supplements can cause medical problems if you use them incorrectly or in large amounts. Some may interact with medications you take. Your health care provider can advise you.
  • Many dietary supplements haven’t been tested in pregnant women, nursing mothers, or children. We have little safety information on St. John’s wort for pregnant women or children. Talk with health care providers if you’re pregnant or nursing or are considering giving a dietary supplement to a child. To learn more, see NCCIH’s fact sheet Using Dietary Supplements Wisely.
  • Take charge of your health—talk with your health care providers about any complementary health approaches you use. Together, you can make shared, well-informed decisions.

For More Information

NCCIH Clearinghouse

The NCCIH Clearinghouse provides information on NCCIH and complementary and integrative health approaches, including publications and searches of Federal databases of scientific and medical literature. The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.

Toll-free in the U.S.: 1-888-644-6226

Telecommunications relay service (TRS): 7-1-1


Email: (link sends email)


A service of the National Library of Medicine, PubMed® contains publication information and (in most cases) brief summaries of articles from scientific and medical journals. For guidance from NCCIH on using PubMed, see How To Find Information About Complementary Health Approaches on PubMed.



To provide resources that help answer health questions, MedlinePlus (a service of the National Library of Medicine) brings together authoritative information from the National Institutes of Health as well as other Government agencies and health-related organizations.


National Institute of Mental Health (NIMH)

The National Institute of Mental Health’s mission is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.


Toll-free in the U.S.: 1-866-615-6464


Email: (link sends email)

NIH Clinical Research Trials and You

The National Institutes of Health (NIH) has created a website, NIH Clinical Research Trials and You, to help people learn about clinical trials, why they matter, and how to participate. The site includes questions and answers about clinical trials, guidance on how to find clinical trials through and other resources, and stories about the personal experiences of clinical trial participants. Clinical trials are necessary to find better ways to prevent, diagnose, and treat diseases.


Key References

Other References

  • Chen JA, Papakostas GI, Youn SJ, et al. Association between patient beliefs regarding assigned treatment and clinical response: reanalysis of data from the Hypericum Depression Trial Study Group. Journal of Clinical Psychiatry. 2011;72(12):1669-1676.
  • Finniss DG, Kaptchuk TJ, Miller F, et al. Biological, clinical, and ethical advances of placebo effects. Lancet. 2010;375(9715):686-695.
  • Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part 2): drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Medica. 2012;78(13):1490-1514.
  • Joshi KG, Faubion MD. Mania and psychosis associated with St. John’s wort and ginseng. Psychiatry. 2005;2(9):56-61.
  • Knüppel L, Linde K. Adverse effects of St. John’s wort: a systematic review. Journal of Clinical Psychiatry. 2004;65(11):1470-1479.
  • Söderberg Löfdal KC, Andersson ML, Gustafsson LL. Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications. Drugs. 2013;73(6):533-543.


NCCIH thanks the following people for their technical expertise and review of this publication: Jonathan R.T. Davidson, M.D., Duke University; David Mischoulon, M.D., Ph.D., Massachusetts General Hospital; and D. Craig Hopp, Ph.D., and David Shurtleff, Ph.D., NCCIH.

This publication is not copyrighted and is in the public domain. Duplication is encouraged.

NCCIH has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your health care provider(s). We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy is not an endorsement by NCCIH.

Last Updated: December 2017