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St. John’s Wort: Not the Foolproof Miracle Drug

Ellin Herward

Date: 11/16/2005

Rates of major and single depressive episodes increase every year.  As of 1999, 19 million Americans experience some form of clinical depression each year, including a major depressive disorder, manic depression or dysthymia (http://www.nmha.org/infoctr/factsheets/21.cfm#_ednref1).  With so many people across the country and across the world experiencing the debilitating effects of depression, there is a great need and search for the most effective treatment and therefore, some disagreement over what is this most effective treatment. 

Interestingly, people are turning to self diagnosis and herbal or dietary supplements in place of more conventional treatments and medications, such as psychotherapy or antidepressant medications.  A quick internet search on depression treatment reveals an overwhelming amount of information.  Perhaps one of the most frequently cited alternative to conventional treatment is hypericum perforatum, or St. John’s wort.

St. John’s Wort Historically

St. John’s wort is a yellow-flowering plant grown throughout the world (http://www.kcweb.com/herb/stjohn2.htm).  Used for over 2,400 years in herbal and folk medicine, St. John’s wort was prescribed by Hippocrates as an herbal medicine (http://www.hypericum.com/nuts.htm).  Historically, this herb was used to treat mental disorders, nerve pain, malaria, as a sedative, and as a balm for wounds, burns, and insect bites (http://nccam.nih.gov/health/stjohnswort/ ).  Now, St. John’s wort is being used in treatment for depression, HIV, and certain cancers.  Following great popularity and use in Germany, St. John’s wort is becoming increasingly more popular as a preferred form of dietary supplement and depression treatment in the United States. 

St. John’s Wort and the Media

            Popularity brings power, the power to sell and the power to capture more attention and spread in use.  For St. John’s wort, the overabundance of media attention on television commercials, the internet, and magazines helps its popularity.  In a report conducted at the Medical College of Georgia, potential patients self report in interviews that “depression, ease of access to alternative medicines, and a history of exposure to and belief in the safety of herbal remedies” motivate their use of St. John’s wort (http://hbcprotocols.com/edgeoff.html). 

            In addition, St. John’s wort is less expensive than other antidepressant treatments.  When a depressed patient can buy 90 caps of a supplement promising “to promote emotional wellbeing and positive mood” for $7.95, many patients will try the product (http://www.vitacost.com/Store/Products/ProductsList.cfm?cid=90&scid=3112&bt=categories).  In addition to websites and internet sources, local stores including Eckerd’s, Wal-Mart, and even the local grocery store sell bottles of St. John’s wort at a more cost-affordable price than other antidepressants.  No prescription is needed and so consumers avoid seeking professional help. 

            Some sources quote that ingredients in St, John’s wort increase theta brain waves, normally “associated with deep meditation, serene pleasure and heightened creative activity (http://www.kcweb.com/herb/stjohn2.htm ).  Compared with Prozac and Zoloft which have side-effects including dry mouth, urinary retention, blurred vision, constipation, sedation, sleep disruption, weight gain, headache, nausea, gastrointestinal disturbance and diarrhea, abdominal pain, inability to achieve an erection or orgasm, loss of libido, agitation and anxiety (http://www.clinical-depression.co.uk/Treating_Depression/side_effects.htm), St. John’s wort has much less risk.  St. John’s wort is associated with potential minor weight loss, some fatigue, and patients should avoid certain foods including cheese, alcohol, and sausage.  In addition, pregnant women and patients using other medications should avoid using St. John’s wort (http://www.kcweb.com/herb/stjohn2.htm).  Yet, a large majority of information on proponents and success rates come from testimonials and non-credible sources.  Only scientific research can tell whether St. John’s wort is actually beneficial and effective in treating depression over a long course. 

Research

St. John’s Wort Role

St. John’s wort has three main components, hypericin, hyperforin, and flavonol, but its role is based on the inhibitory action of hypericin in the brain to breakdown certain neurotransmitters, monamine oxidase (MAO), and work as a serotonin reuptake inhibitor (SRI) (Herbal Information Center); from a biological theory, depression is linked with low levels of serotonin.   It is important to note that St. John’s wort, which is not approved by the Food and Drug Administration, is not effective for severe depression.  Evidence from a randomized controlled trials study by Barnes, Anderson, and Phillipson (2004), “confirmed the efficacy of St John's wort extracts over placebo in the treatment of mild-to-moderately severe depression. Other randomised controlled studies have provided some evidence that St John's wort extracts are as effective as some standard antidepressants in mild-to-moderate depression”.  Yet, there is not an abundance of evidence to support efficacy over standard antidepressant medications.  In a second randomized, double blind trial, researchers at Duke University Medical Center compared St. John’s wort extract to a placebo and then to the FDA approved drug Zoloft in treating major depression of moderate severity (National Institute of Health).  Researchers found that St. John’s wort was no more effective in treating major depression of moderate severity than a placebo.  While in mild to moderately severe depression, St. John’s wort is as effective as placebos and standard antidepressant, but not as effective for treating moderate to severe depression.  Yet, if St. John’s wort is comparable to standard antidepressants, why do patients continue to take the dietary supplement over more conventional treatment options?  

            More promising from the study is the evidence that “St John's wort does appear to have a more favourable short-term safety profile than do standard antidepressants, a factor that is likely to be important in patients continuing to take medication” (Barnes et al. 2004). 

St. John’s Wort Side Effects

Clearly, St. John’s wort has several effective outcomes and slightly better side effects than other pharmacological options for treating depression.  Yet, it has been proven only to be effective in treating mild to moderate depression and not necessarily major depression (http://nccam.nih.gov/health/stjohnswort/).  In addition, despite apparent benefits to using St. John’s wort in place of over the counter medications, there are several suspected negative side effects, the most significant being that St. John’s wort interferes with other medications and can causes them to metabolize too quickly (http://www.netdoctor.co.uk/special_reports/depression/stjwort.htm).  More specifically, St. John’s wort can affect contraceptive dugs, and medications for asthma, epilepsy, migraines and heart problems. 

In a study by Trevithick-Sutton, Chin, Contos, and Foote (in press), researchers explain that St. John’s wort is composed of hypericin, hyperforin, and flavonol which show anti-depressant effects and therefore, extracts of St. John’s wort are used to treat depressive activity.  These commercial extracts of St. John’s wort “are typically standardized to 0.3% hypericin, but are not FDA regulated.”  This main component of St. John’s wort, hypericin, is also commonly used in treatment of HIV and cancer patients.  Yet, hypericin may also harm patients taking St. John’s wort as treatment for depression by inducing potential hypericism.  Hypericism is characterized by cellular damage to light-exposed ocular areas in the lens.  The study looked at the effects of hypericin photophysics on the major lens protein, α-crystallin.  It is the reaction on the lens protein by the presence of hypericin and singlet oxygen produced from hypericin in the presence of α-crystallin that causes damage.  Looking at absorption spectra, Trevithick-Sutton and colleagues found that “α-crystallin extends the triplet excited hypericin lifetime and does not inhibit singlet oxygen formation. This suggests that hypericin will be an effective photosensitizer in the lens.”  Therefore, prolonged exposure to hypericin found in St. John’s wort has the potential to cause hypericism and cause ocular damage to patient’s eyes. 

Alternatives to St. John’s Wort

If St. John’s wort and alternative herbal treatments have potential harmful side effects, then what is the answer to treating depression?  Currently, for adolescents and children, the only approved antidepressant by the Food and Drug Administration is fluoxetine, commonly known as Prozac.  Yet, despite success rates for use of Prozac in treating depressive disorders, medications are not enough.  In fact, there is an increased risk for suicidal tendencies among adolescent and pediatric patients taking many antidepressant drugs, including Prozac, Zoloft, Paxil, and Luvox (http://www.fda.gov/bbs/topics/news/2004/NEW01116.html).  Clearly, to any manufacturer or proponent for use of St. John’s wort as an alternative medication, this finding further supports the claim that St. John’s wort is safer. 

However, combining therapy, specifically cognitive behavioral therapy, with antidepressant medications proves promising.  To begin, in a recent study by Compton, S.N, March, J.S., Brent, D., Albano, A.M., Weersing, V.R., Curry, J. (2004), investigators found that, “from an evidence-based perspective, cognitive-behavioral therapy is currently the treatment of choice for anxiety and depressive disorders in children and adolescents”.   A previous study by Fava, G.A., Rafanelli, C., Grandi, S., Conti, S., and Belluardo, P. (1998) found that in addition to pharmacotherapy, cognitive behavioral therapy helps prevent and decrease rates of relapse in patients with major depressive episodes.   In clinical trials, the investigators compared two groups of patients who had completed therapy with antidepressant drug therapy for major depression.  Subjects were assigned to either cognitive behavioral therapy or clinical management.  At the two year follow-up, CBT subjects had fewer residual symptoms and decreased relapse rate, 25% versus 80%, than the clinical management group.  To add to the support for a combination of CBT and pharmacological treatment, in a press release in September 2004, the National Institute of Health (http://www.nimh.nih.gov/press/prtads.cfm) promoted the results on a multi-site trial by researchers at Duke University on the success of the combination of medication and psychotherapy, specifically cognitive behavioral therapy, as the most effective treatment option for adolescents with major depression. 

Conclusion

Whether due to biological, cultural or cognitive factors, depression is a treatable disorder and as with all disorders, early treatment is most promising and the combination of treatments will vary for each patient.  While it is true that St. John’s wort is effective in treating mild and moderate depression with reduced side effects than other antidepressants, the components of the herd are not as well understood as other antidepressant treatments, whether therapy or medications and St. John’s wort is not effective for treating moderate to severe depression over a long time period.  Yet, due to the overabundance of media attention and therefore high exposure to information, St. John’s wort continues to grow in use.  As with all medical and therapy programs, the best treatment is to work with a medical professional to determine the safest treatment. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

References

Barnes, J., Anderson, L.A., & Phillipson, D.J. (2004). St John's wort (Hypericum perforatum L.): A Review of its Chemistry, Pharmacology and Clinical Properties. Journal of Pharmacy and Pharmacology. 53 (5), 583-600.

Compton, S.N, March, J.S., Brent, D., Albano, A.M., Weersing, V.R., & Curry, J. (2004).  Cognitive-Behavioral Psychotherapy for Anxiety and Depressive Disorders in Children and Adolescents: An Evidence-Based Medicine Review.  Journal of the American Academy of Child and Adolescent Psychiatry, 43(8), 930-959. 

Fava, G.A., Rafanelli, C., Grandi, S., Conti, S., & Belluardo, P. (1998).  Prevention of Recurrent Depression with Cognitive Behavioral Therapy: Preliminary Findings.  Archives of General Psychology, 55, 816-820. 

Herbal Information Center. http://www.kcweb.com/herb/stjohn2.htm.

National Institute of Health (2002, April 9). Study Shows St. John's Wort Ineffective for Major Depression of Moderate Severity. Retrieved September 21, 2004, from http://nccam.nih.gov/news/2002/stjohnswort/pressrelease.htm

Trevithick-Sutton, C.C., Chin, K.K., Contos, S.D., & Foote, C.S. (in press). Lens α-Crystallin and Hypericin: A Photophysical Mechanism Explains Observed Lens Damage.  Photochemistry and Photobiology.   

 

 

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