St. John’s Wort: No ‘Wonder Remedy’ for Depression

St. John’s wort is a common name for an over-the-counter supplement extracted from a flowering plant called Hypericum perforatum.[1] This herb has been around for centuries, and many patients have been using it in recent years to self-medicate for depression. Even health care professionals, many in Germany, prescribe it for this purpose.[2]

However, the herb — which is not approved by the Food and Drug Administration (FDA) — has not been proven effective in treating depression or any other mental health condition.[3] Instead, it is well known for its unsafe interactions with numerous prescription drugs.

Some people believe that St. John’s wort is safer than prescription antidepressants because it is sold as a dietary supplement. But a recent Australian study — published in the July 2015 issue of Clinical and Experimental Pharmacology and Physiology — showed that reports of side effects related to St. John’s wort are quite similar to those for a commonly used prescription antidepressant drug.[4]

Appraising available evidence

Although dozens of clinical trials have focused on St. John’s wort,[5] the current evidence about the herb’s effectiveness for treating depression remains inconclusive, largely because of varying study designs that make generalization across studies difficult.[6]

A 1996 British Medical Journal meta-analysis (a study analyzing data from multiple clinical trials) — conducted by a German researcher named Klaus Linde, along with other colleagues — was among the first to hype the interest in St. John’s wort.[7] The study reported that the herb was more effective than a placebo and as effective as standard antidepressants in treating mild to moderately severe depression. However, as acknowledged by its own lead author, the study suffered from serious limitations related to the trials it included: They were very short (lasting only two to eight weeks), were conducted in part by primary care physicians who were not experienced in depression research, included patients with symptoms that may not have met standards for diagnosing major depression, and used low doses of standard antidepressants in comparison groups. Therefore, a commentary published in the same issue as this study cautioned, “Although promising, these studies are not sufficient to accept the use of [St. John’s wort] in major depression.”[8]

Linde published a follow-up meta-analysis in 2005 indicating that several trials suggested that St. John’s wort has “minimal beneficial effects” compared with a placebo in treating major depression.[9] However, the study concluded that the evidence was still inconsistent and confusing with regard to the effectiveness of St. John’s wort. Linde and colleagues tried to improve upon the quality of the 1996 and 2005 analyses by conducting a third study in 2008, which was limited to trials with patients meeting standard criteria for major depression.[10] Although they found that St. John’s wort did slightly better than a placebo and similar to standard antidepressants in treating major depression, this finding was almost exclusively true only in German studies.

The researchers acknowledged that all German studies recruited patients during physician office visits (these patients are more likely to have minor depression). In contrast, trials done in other countries included patients in academic research settings or hospital outpatient units (patients who are more likely to have severe depression).

Three federally funded U.S.-based randomized clinical trials investigating the efficacy of St. John’s wort were all negative: The first found St. John’s wort no more effective than a placebo in treating major depression,[11] the second found it not more effective than either a placebo or standard antidepressants[12] in treating major depression, and the third found it no more effective than a placebo or standard antidepressants in treating even mild depression.[13]

The American Psychiatric Association sums it up best: “St. John’s wort would not meet the FDA’s minimum requirements to be declared an effective antidepressant and is not recommended for general use in treating depression.”[14]

Side effects and drug interactions

Side effects associated with St. John’s wort include skin rash (worsened by sunlight), dry mouth, fatigue, dizziness, headache and gastrointestinal symptoms.[15]

Importantly, St. John’s wort has an impressive potential for interacting with a wide range of medications.

If given with certain depression or anxiety medications called selective serotonin reuptake inhibitors (SSRIs) (including fluoxetine [PROZAC] and sertraline [ZOLOFT]) or serotonin[16] and norepinephrine reuptake inhibitors (SNRIs)(including duloxetine [CYMBALTA]), St. John’s wort can increase the risk for serotonin syndrome.[17] Serotonin syndrome is a potentially fatal condition characterized by confusion, tremors, diarrhea and a drop in body temperature.[18]

In addition, St. John’s wort reduces the efficacy of many drugs (see box below).

The recent safety study

The 2015 study used voluntary adverse-drug-reaction reports filed by doctors (on behalf of patients) with Australia’s drug safety agency from 2000 through 2013.[22] The researchers compared the 84 adverse reaction reports related to St. John’s wort with the 447 reports related to fluoxetine.

The overall pattern of reports for the two products was broadly similar in terms of patient characteristics, types of interaction, organ system affected and severity.

The majority of adverse events for St. John’s wort involved the central nervous system. As expected, more severe adverse events occurred when the supplement was taken in combination with other prescription medications. For example, one woman developed serotonin syndrome after she took St. John’s wort in combination with sertraline.

It should be noted that the number and type of side effects associated with St. John’s wort found in this study underestimate the real scope of the problem because many consumers fail to inform their health care providers that they are using this product. Therefore, the majority of the herb’s side effects likely go unreported.

What You Can Do

If you suffer from consistent symptoms of depression that last longer than two weeks,[23] it is important to seek professional help as soon as possible. Inadequately treated depression can become severe and, in some cases, may be associated with suicide.[24] Symptoms of major depression include sadness and loss of interest or pleasure in nearly all activities. Loss of appetite, fatigue, insomnia or excessive sleeping, restlessness or irritability, feelings of worthlessness or inappropriate guilt, and difficulty thinking, concentrating or making decisions can also be symptoms.[25]

As a first method of treatment (especially for minor depression), consider nonpharmacological options such as psychotherapy.[26] If depressive symptoms are severe and persistent, consider prescription antidepressants in addition to psychotherapy.[27]

Do not use St. John’s wort or any other supplement as a substitute for seeking medical care for depression or any other condition.[28]

Always tell your health care provider about any herbal supplements you are taking.

References

[1] WorstPills.org. St. John’s wort [hypericum, goatweed, the lord god's wonder plant, witch's herb] (SUN BEAUTY). /monographs/view/299. Accessed November 3, 2015.

[2] Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database of Systematic Reviews. 2008;(4):CD000448.

[3] National Center for Complementary and Integrative Health. Get the facts: St. John’s wort and depression. https://nccih.nih.gov/sites/nccam.nih.gov/files/Get_The_Facts_SJW_and_Depression_09-23-2013.pdf. Accessed November 4, 2015.

[4] Hoban CL, Byard RW, Musgrave IF. A comparison of patterns of spontaneous adverse drug reaction reporting with St. John’s wort and fluoxetine during the period 2000-2013. Clinical and Experimental Pharmacology and Physiology. 2015;42(7):747-751.

[5] WorstPills.org. St. John’s wort [hypericum, goatweed, the lord god's wonder plant, witch's herb] (SUN BEAUTY). /monographs/view/299. Accessed November 3, 2015.

[6] Sarris J. Nutrients and herbal supplements for mental health. Australian Prescriber. 2014;37(3):90-93.

[7] Linde K, Ramirez G, Mulrow CD, et al. St John’s wort for depression — an overview and meta-analysis of randomised clinical trials. BMJ. 1996;313(7052):253-258.

[8] De Smet P, Nolen W. St John’s wort as an antidepressant. BMJ. 1996;313(7052):241-242.

[9] Linde K, Berner M, Egger M. St John’s wort for depression: Meta-analysis of randomised controlled trials. The British Journal of Psychiatry. 2005;186:99-107.

[10] Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database of Systematic Reviews. 2008;(4):CD000448.

[11] Shelton R, Keller M, Gelenberg A, et al. Effectiveness of St John’s wort in major depression: A randomized controlled trial. JAMA. 2001;285(15):1978–1986.

[12] Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John’s wort) in major depressive disorder: A randomized controlled trial. JAMA. 2002;287(14):1807-1814.

[13] Rapaport MH, Nierenberg AA, Howland R, et al. The treatment of minor depression with St. John’s wort or citalopram: Failure to show benefit over placebo. Journal of Psychiatric Research. 2011;45(7):931-941.

[14] American Psychiatric Association. Practice Guideline for the Treatment of Major Depressive Disorder. 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed November 3, 2015.

[15] WorstPills.org. St. John’s wort [hypericum, goatweed, the lord god's wonder plant, witch's herb] (SUN BEAUTY). /monographs/view/299. Accessed November 3, 2015.

[16] Borrelli F, Izzo AI. Herb-drug interactions with St John’s wort (Hypericum perforatum): An update on clinical observations. American Association of Pharmaceutical Scientists Journal. 2009;11(4):710-727.

[17] Eli Lilly and Company. CYMBALTA drug label. 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021427s046lbl.pdf. Accessed November 13, 2015.

[18] National Center for Complementary and Integrative Health. Get the facts: St. John’s wort and depression. https://nccih.nih.gov/sites/nccam.nih.gov/files/Get_The_Facts_SJW_and_Depression_09-23-2013.pdf. Accessed November 4, 2015.

[19] Ibid.

[20] National Center for Complementary and Alternative Medicine. April 2012. St. John’s wort. https://nccih.nih.gov/health/stjohnswort/ataglance.htm. Accessed November 25, 2015.

[21] Hall SD, Wang Z, Huang S-M, et al. The interaction between St John’s wort and an oral contraceptive. Clinical Pharmacology and Therapeutics. 2003;74(6):525-535.

[22] Hoban CL, Byard RW, Musgrave IF. A comparison of patterns of spontaneous adverse drug reaction reporting with St. John’s wort and fluoxetine during the period 2000-2013. Clinical and Experimental Pharmacology and Physiology. 2015;42(7):747-751.

[23] National Institutes of Health. Do you have major depression? NIH Medline Plus. 2009;4(4):17-19.

[24] Ibid.

[25] Ibid.

[26] Royal Australian and New Zealand College of Psychiatrists. Position Statement 41: St John’s Wort. 2009;(June):2-3.  Accessed November 3, 2015.

[27] American Psychiatric Association. Practice Guideline for the Treatment of Major Depressive Disorder. 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed November 3, 2015.

[28] National Center for Complementary and Integrative Health. Get the facts: St. John’s wort and depression. https://nccih.nih.gov/sites/nccam.nih.gov/files/Get_The_Facts_SJW_and_Depression_09-23-2013.pdf. Accessed November 4, 2015.