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St. John's Wort


St. John's Wort

Article Author:
Bahtya Peterson
Article Editor:
Hoang Nguyen
Updated:
6/9/2020 5:24:31 PM
For CME on this topic:
St. John's Wort CME
PubMed Link:
St. John's Wort

Indications

St. John's Wort (Hypericum perforatum) is an herbal medication that consists of anthraquinones, which have displayed anti-inflammatory and anti-cancer effects. It has also been used as an antidepressant. It derives from a flowering plant found in Europe and Asia. It is common in the form of a tablet, capsule, tea, or liquid extract used to treat a handful of medical conditions which include but are not limited to the following: 

  • Depression: The definition of depression is the loss of interest or pleasure in doing things that you used to for over a two week period. Depression can be minor or major. St. John's wort has been shown to treat major depression superior to that of a placebo antidepressant. Patients who are suffering from depression should discuss the usage of St. John's Wort with their health provider.[1] However, in other studies, there was a failure to show the benefit of St. John's Wort over placebo.[2]
  • Emotional and Behavioral complications in children: Attention issues, anxiety, different physical problems, sleep disturbances, depression, and other emotional and behavioral complications are all things that children and young adults must address. A study done with children who were observed to have prolonged emotional or attention problems and were prone to nervous and depressed behavior received St. John's wort in a triad treatment plant extract along with valerian root and passionflower herb. At the end of the study, the extract improved the children's emotional and behavioral complications with the help of no other medications.[3]
  • Obsessive-compulsive disorder: Obsessive-compulsive disorder describes a neurological disorder that pertains to a person having excessive thought that leads to repetitive compulsions. It is a disorder that is difficult to treat. Research is in the beginning stages of how St. John's Wort may be useful in the treatment of OCD, however current clinical evidence is limited, and further research is necessary for efficacy. There is some promise of its effects on OCD, as its current mechanism of action is comparable to today's SSRI therapies.[4][5]
  • Premenstrual syndrome (PMS): PMS refers to a variety of symptoms that some women experience in the days before menstruation that includes bloating, acne, breast swelling and tenderness, pain, irritability, and depression. Treatment of this syndrome often involves SSRIs (selective serotonin reuptake inhibitors). St. John's Wort has been used as an alternative over-the-counter treatment that may lessen PMS symptoms. More research is necessary regarding the efficacy of treatment.[6] 
  • Psoriasis: In a double-blind placebo study, researchers tested the therapeutic effects of H. perforatum for mild to moderate psoriatic lesions. Researchers use topical Hypericum perforatum to treat plaque-type psoriasis, an inflammatory disorder, where tumor-necrosis factor-alpha (TNFα) is commonly found in psoriatic skin tissues. The study found that the anti-inflammatory capabilities of Hypericum perforatum ointment lowered cytokine content, including TNFα in psoriatic lesions. The patients who used the St. John's Wort topical exhibited less erythema, thickness, and scaling compared to those who used the placebo.[7] 

Mechanism of Action

St John's Wort is a xenobiotic or a plant-derived compound composed of five various forms of hypericin and other flavonoids. Many mechanisms of action have been proposed. One of the main mechanisms used in health care is the report that St. John's Wort acts as a serotonin reuptake inhibitor. This works to reduce the uptake of serotonin at neuronal synapses, as well as dopamine and norepinephrine. The elevated levels of neurotransmitters are believed to be helpful when treating depression. The supplement works by activating pregnane-X-receptor (PXR) Cytochromes, which induces the cytochrome P450 system, specifically the CYP3A4 enzyme and P-glycoprotein. P450s or monooxygenase enzymes act through hydroxylation reactions onto the xenobiotic or St. John's Wort to make it more polar and thus increasing its reactivity for conjugation into various polar groups. In the monooxygenase reaction, molecular oxygen (O2) is broken into water and alcohol (R-OH); because of this, only one oxygen of the pair is given to the xenobiotic substrate. To prepare for the monooxygenase reaction, other reactions take place in xenobiotic metabolisms such as hydrolysis, deamination, epoxidation, preoxygenation, reduction, desulfurization, and dehalogenation. St. John's Wort's ability to inhibit monoamine oxidase allows an increase in the formation of norepinephrine. Hyperforin, a St. John's wort component, is believed to be the responsible factor for inducing CYP3A4 by activating a xenobiotic receptor and nuclear steroid/pregnane. Hyperforin itself could be the P-glycoprotein activating compound. Another mechanism that leads to antidepressant activity is the capability of binding to GABA receptors to decrease the binding of GABA, which results in lowered CNS depression. Although St. John's Wort is not yet FDA approved, it is worth noting to acknowledge that some of its proposed mechanisms are in FDA approved drugs that are used for the same variety of health complications.[8][9][10][11]

Administration

St John’s Wort has shown encouraging data in its effectiveness and safety when used as a monotherapy. It is prepared by the grinding of the flowers of the plant as well as its dried leaves. The dried flowers can be used in a tea and ingested orally, or be made into an oil by infusion for topical use. Usually, one would find the ground plant in capsules taken as a dietary supplement. 

Suggested Use: As a dietary supplement, adults are to take one 300 mg capsule with 0.3% hypericin content three times a day. One to three capsules daily can be taken with meals, or as directed by health care providers. The herbal supplement must be stored in a cool and dry place, away from direct light.

Adverse Effects

One of the primary adverse effects is the risk of a life-threatening increase in serotonin when combined with certain antidepressants and the inhibition of monoamine oxidase. Using the supplement with other antidepressant medications may cause serotonin syndrome. Serotonin syndrome may first cause tachycardia, increased blood pressure, mydriasis, and sweating. Some may have a fever, and temperatures can rise above 106 degrees F. Treatment can include serotonin antagonists, benzodiazepine to target GABA receptors. Increased blood pressure can have treatment with short-acting antihypertensives. 

Caution:

  • Exacerbating psychotic symptoms of those with schizophrenia or bipolar disorder 
  • Agitation
  • Diarrhea
  • Tachycardia 
  • Hypertension
  • Hallucinations
  • A rise in body temperature 
  • Photosensitivity 

Contraindications

The positive effects of St John’s Wort are negated when used in conjunction with other medications; sometimes, the effects of drug interactions can be life-threatening. Drugs that also utilize the cytochrome P450 system, specifically CYP3A4, or are substrates of P-glycoproteins in metabolism can have reduced efficacy and produce adverse effects when taken in conjunction with St. John’s Wort. These drugs include HIV protease inhibitors, CYP3A4 HIV non-nucleoside reverse transcriptase inhibitors, ciclosporin, tacrolimus, irinotecan, imatinib mesylate, digoxin, oxycodone, and warfarin. Those on hormonal contraceptives must be aware when taking St. John’s Wort that there have been incidences of unplanned pregnancies and irregular menstrual cycles. Clinicians must be aware that when prescribing serotonergic agents and other antidepressants, there is a potential risk of pharmacodynamic interactions occurring when taken with St. John’s Wort.[8][12][9][13][14]

Monitoring

Healthcare professionals must understand and provide precautions as well as awareness of the contraindications of St. John’s Wort to administer safe and knowledgeable healthcare. As the medication has use for a plethora of medical conditions, health care providers need to be aware of why the patient is using it and monitor as needed. 

Enhancing Healthcare Team Outcomes

Any health care provider (Md, DO, NP, or PA) can encourage the use of St. John's Wort as it can be found over-the-counter. Clinicians should be aware of its use in their patients. Often, general practitioners' lack the knowledge that their patients are using the herbal supplement when they self medicate. The use of H. perforatum without knowledge by a healthcare provider increases the likelihood of harmful implications on the efficacy and safety of the supplement as there are dangerous drug interactions. Patients should receive counsel and monitoring when taking St. John's Wort. 


References

[1] Linde K,Berner MM,Kriston L, St John's wort for major depression. The Cochrane database of systematic reviews. 2008 Oct 8;     [PubMed PMID: 18843608]
[2] Rapaport MH,Nierenberg AA,Howland R,Dording C,Schettler PJ,Mischoulon D, The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo. Journal of psychiatric research. 2011 Jul;     [PubMed PMID: 21632064]
[3] Trompetter I,Krick B,Weiss G, Herbal triplet in treatment of nervous agitation in children. Wiener medizinische Wochenschrift (1946). 2013 Feb;     [PubMed PMID: 23179673]
[4] Camfield DA,Sarris J,Berk M, Nutraceuticals in the treatment of obsessive compulsive disorder (OCD): a review of mechanistic and clinical evidence. Progress in neuro-psychopharmacology     [PubMed PMID: 21352883]
[5] Ayati Z,Sarris J,Chang D,Emami SA,Rahimi R, Herbal medicines and phytochemicals for obsessive-compulsive disorder. Phytotherapy research : PTR. 2020 Mar 2;     [PubMed PMID: 32124509]
[6] Jang SH,Kim DI,Choi MS, Effects and treatment methods of acupuncture and herbal medicine for premenstrual syndrome/premenstrual dysphoric disorder: systematic review. BMC complementary and alternative medicine. 2014 Jan 10;     [PubMed PMID: 24410911]
[7] Mansouri P,Mirafzal S,Najafizadeh P,Safaei-Naraghi Z,Salehi-Surmaghi MH,Hashemian F, The impact of topical Saint John's Wort ({i}Hypericum perforatum{/i}) treatment on tissue tumor necrosis factor-alpha levels in plaque-type psoriasis: A pilot study. Journal of postgraduate medicine. 2017 Oct-Dec;     [PubMed PMID: 28272075]
[8] Nicolussi S,Drewe J,Butterweck V,Meyer Zu Schwabedissen HE, Clinical relevance of St. John's wort drug interactions revisited. British journal of pharmacology. 2020 Mar;     [PubMed PMID: 31742659]
[9] Mannel M, Drug interactions with St John's wort : mechanisms and clinical implications. Drug safety. 2004;     [PubMed PMID: 15350151]
[10] Barnes J,Arnason JT,Roufogalis BD, St John's wort (Hypericum perforatum L.): botanical, chemical, pharmacological and clinical advances. The Journal of pharmacy and pharmacology. 2019 Jan;     [PubMed PMID: 30536388]
[11] Butterweck V, Mechanism of action of St John's wort in depression : what is known? CNS drugs. 2003;     [PubMed PMID: 12775192]
[12] Borrelli F,Izzo AA, Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. The AAPS journal. 2009 Dec;     [PubMed PMID: 19859815]
[13] Spina E,Barbieri MA,Cicala G,Bruno A,de Leon J, Clinically relevant drug interactions between newer antidepressants and oral anticoagulants. Expert opinion on drug metabolism     [PubMed PMID: 31795773]
[14] Berry-Bibee EN,Kim MJ,Tepper NK,Riley HE,Curtis KM, Co-administration of St. John's wort and hormonal contraceptives: a systematic review. Contraception. 2016 Dec;     [PubMed PMID: 27444983]