Emma Williams!

October 22, 2014!

Writing 2010-052!
Prof. Ammar Hussein!

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For over 200,000 years, humans have ingested specific plants and plant parts for

benefits beyond nutrition. The earliest neanderthals have been found to carry pollen
grains from therapeutic plants to ensure the deceased an ample supply of medication in
the afterlife. The biblical story of Adam included the consumption of an apple with
power beyond high fiber. However, it is only within the last 150 years that scientists
have been able to identify and segregate the individual active biological components
that contribute to a plants medicinal properties (Enna and Norton). Health advances
have resulted in the prevalence of man-made medicines worldwide, although herbal
supplements are still used alone and in-addition-to manufactured medicines to treat
certain conditions. Depression is one of these conditions. !
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Depression, defined as prolonged sadness that interferes with daily life, affects

approximately 350 million people globally and is the leading cause of disability
worldwide . Treatments for depression vary depending on the severity of the disease,
but are usually a combination of psychotherapy and medication that help the patient
face their feelings and restructure negative thought patterns while increasing levels of
certain neurotransmitters in the brain (Depression). Interestingly enough, one of the
most cited treatments for depression is an herbal supplement Hypericum perforatum,
commonly known as St. Johns Wort. The active ingredients in St. Johns Wort,

hypericin and hyperforin, are found in the flowers of the plant and have been used to
treat depression for over two hundred years (Shelton, Keller, Helenberg). Indeed,
Roman scholars from 2,000 years ago wrote about the medicinal properties of St.
Johns Wort in treating hysteria (Enna and Norton). Today, doctors are more skeptical.!
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A plethora of studies have been conducted on the efficacy and safety of St.

Johns Wort in treating depression. Unfortunately, the plethora of results from all of
these studies makes it especially hard to determine the actual competence of the herb
in treating depression. Although most studies seem to agree that St. Johns Wort is at
least more effective in treating depression than a placebo, only a few qualify St. Johns
Wort as an adequate treatment and even less recommend it to be used as a sole
treatment of depression. Other studies conclude that St. Johns Wort is only as effective
as a placebo treatment, and instead warn consumers of the potential medicationinteractions. In this paper, I will examine the different results on efficacy of St. Johns
Wort as a depression treatment, as well as the safety of the supplement and the
possible financial benefits of St. Johns Wort.!
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Although several active biological ingredients exist in St. Johns Wort, the two

that contribute to the majority of the herbs properties are hypericin and hyperforin, both
complex molecules known to inhibit neuronal reuptake of norepinephrine and serononin
in the brain. Most prescription medications used to treat depression, known as selective
serotonin reuptake inhibitors (or SSRIs), function in the same way (Dasgupta). Beyond
these facts, opinions vary. Some research has been done that leads scientists to
believe that St. Johns Wort may activate sigma receptors in the brain to cause neuronal
firing, thus activating brain neurotransmission (Dasgupta). Other scientists claim that

although hypericin and hyperforin biologically act as natures SSRIs, the concentrations
of these chemicals in the herbal supplements are too low to penetrate the brain deeply
enough to influence neurotransmission (Enna and Norton). !
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Many studies have been conducted to determine the efficacy of St. Johns Wort

as a treatment against depression, but results vary so widely that they are inconclusive.
Experts S.J. Enna and Stata Norton mention the variations in chemical compositions of
St. Johns Wort extracts as a possible cause for the disparities. Another possible
explanation is the concentration of active ingredients in the actual supplements.
Although supplements are standardized at a 0.3% concentration of hypericin and 4%
concentration of hyperforin, actual concentrations vary widely from bottle to bottle, and
even from pill to pill (Enna and Norton).!
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Despite scrutiny, multiple studies support the positive results. In one study

quoted by scholar Amitara Dasgupta, extracts in St. Johns Wort were found to work
better than the placebo in major depression treatments with response rates as high as
1.28 in nine large trials conducted and 1.87 in nine small trials. Compared against
tricyclic antidepressants and more common SSRIs, St. Johns Wort was found to be just
as effective, with response rates as high as 1.02 in five trials and 1.00 in 12 other trials
(Dasgupta). Unfortunately, since the study was conducted in Germany where the use of
St. Johns Wort is so widespread, possible bias could have skewed the results of the
trials. !
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Other studies show no improvements on depression when treated by St. Johns

Wort. In the late 1990s, the United States National Institutes of Health conducted a
study involving 340 patients diagnosed with moderately-severe major depression.

Results were surprising. Patients response to St. Johns Wort was found to be no better
than the placebo, leading scientists to believe that St. Johns Wort was an ineffective
treatment for depression. However, when scientists compared the results of the placebo
and St. Johns Wort treatments against those of Setraline (a common prescription
antidepressant used as a control in the experiment), they noticed that Setraline also
failed to exhibit a statistically significant benefit in treating depression (Enna and
Norton). !
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While the determined efficacy of St. Johns Wort on treating depression varies

from study to study, one consistent result is the lower level of reported adverse events
from patients taking St. Johns Wort when compared against common depression
prescription medications (Shelton, Keller, Helenberg). One 2006 study by Dr. Shulz
concluded that the total incidence of adverse effects in studies with St. Johns Wort was
10-fold lower than reported incidences in SSRIs. Although 217 out of the 440
depression patients being treated with St. Johns Wort studied reported adverse effects,
only 6% of those effects were probably related to St. Johns Wort. Furthermore, average
HAMD scores decreased from 20.58 to 11.18 over the one year trial, indicating a
positive aesculapian response in treating depression with St. Johns Wort. In the above
2006 study conducted in Germany, patients treated with St. Johns Wort were noted to
have fewer, more mild side effects and dropped out less frequently (Dasgupta). A 2010
study in the United States concluded that patients taking St. Johns Wort improved more
quickly than those taking the placebo with no more greater adverse effects (Enna and
Norton). In a study conducted by doctors from the American Medical Association, only
4% patients treated with St. Johns Wort dropped out of the study due to adverse

effects, compared to 7.7% of patients treated with prescription antidepressants

(Shelton, Keller, Gelenberg). These consistent results advocate the safety of St. Johns
Wort as a safe and effective alternative to prescription medications. !
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Although proven to reduce adverse effects in depression patients, St. Johns

Wort does has safety concerns that the public should be aware ofindeed, many
scientists say the possible health concerns associated with taking St. Johns Wort
outweigh the positive effects on treating depression. For example, in 2000, the United
States Food and Drug Administration issued a public health advisory letter stating St.
Johns Wort may interfere with other medications in the body (St. Johns Wort and
Depression). This is due to an increased production of drug metabolizing enzymes in
the human body after St. Johns Wort is consumed. These enzymes metabolize drugs
and other transport proteins more quickly than usual, so the transport of drugs, vitamins,
and minerals like calcium are affected (Enna and Norton). For this reason, birth control
and other antidepressants and anti anxiety medications like Xanax are weakened by St.
Johns Wort. Combining St. Johns Wort and antidepressants can also lead to serotonin
syndrome, a life-threatening increase in serotonin levels in the brain (ST. Johns
Wort`). Knowing the risks associated with the consumption of St. Johns Wort can help
patients decide if the herb is a viable treatment for them. !
!

Another reason St. Johns Wort might be considered as a treatment for

depressions is due to economic benefits. One study used a Markov model to estimate
the economic and health impacts of using St. Johns Wort as a treatment instead of
prescription antidepressants. Results concluded that the average person would save
$359.66 compared to Venlafaxine and $202.56 compared to Setraline over 72 weeks.

Similarly, the quality of life increased from 0.08 QALYs to 0.12 QALYs (Adams and
Graves). Scholar Amitara Dasputa argues that the reduced incidence of adverse effects
overall improves the outcome of patients, reducing treatment time and therefore cutting
cost (Dasputa). Since St. Johns Wort is the most commonly used herbal supplement
across Europe (NIH), it has the highest net benefit of any herbal supplement. Using
money to develop and improve treatments of St. Johns Wort could potentially result in a
multi-million dollar industry. !
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St. Johns Wort is still a cited treatment of depression, but results vary so widely

that a conclusion cant be drawn. Several studies indicate St. Johns Wort is an effective
treatment for depression, several others find it no more effective than a placebo pill.
Across all studies St. Johns Wort is noted because it has less adverse effects than
common prescription antidepressants. However, more research has to be conducted to
conclude if St. Johns Wort is actually an effective treatment of depressionmore
effective than a placebo pill and comparable to prescription antidepressants. !
!

Disparities across research may be due to differences in chemical compositions

across different supplements among a variety of other reasons. The two main active
biological ingredients hypericin and hyperforin work in a similar way to SSRIs. There is
also research that supports the theory that St. Johns Wort may active specific brain
receptors to activate brain neurotransmitters (Enna and Norton). Research on the
specific physiological components of St. Johns Wort and their effect on the human body
might lead to a greater understanding of how hyperforin and hypericin work on the
human system, in turn leading to a more specific treatment of depression using St.
Johns Wort. There are definite safety concerns associated with the treatment of

depression by St. Johns Wort. Overall, treating depression by St. Johns Wort would
save patients money and might decrease treatment time due to the decrease in adverse
effects. By studying the mechanics and efficacy of St. Johns Wort in treating
depression, scientists might be able to make other advances in the world of herbal
supplements. The medicines are already waiting in the plants around us. All we have to
do is discover them. !
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Works Cited: !
Dasgupta, Amitava; Hammett-Stabler, Catherine A.. Herbal Supplements : Efficacy,
Toxicity, Interactions with Western Drugs, and Effects on Clinical Laboratory Tests.
Hoboken: Wiley, 2010. Ebook Library. Web. 22 Oct. 2014.!

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"Depression." NIMH RSS. NIH, n.d. Web. 20 Oct. 2014. <http://www.nimh.nih.gov/
health/topics/depression/index.shtml>.!

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Enna, S. J., and Stata Norton. St. John's Wort (Hypericum Perforatum). Herbal
Supplements and the Brain: Understanding Their Health Benefits and Hazards.
Upper Saddle River, NJ: FT, 2012. N. pag. Print.!

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Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's Wort in Major
Depression: A Randomized Controlled Trial. JAMA. 2001;285(15):1978-1986. doi:
10.1001/jama.285.15.1978!

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Solomon, Daniela, Jon Adams, and Nicholas Graves. "Economic Evaluation of St.
John's Wort (Hypericum Perforatum) for the Treatment of Mild to Moderate
Depression." Journal of Affective Disorders 148.2-3 (2013): 228-34. ScienceDirect.
Web. 22 Oct. 2014.!

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ST. Johns Wort. MedlinePlus. U.S. National Library of Medicine, 8 Sept. 2014. Web.
13 Oct. 2014. <http://www.nlm.nih.gov/medlineplus/druginfo/natural/329.html>.

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St. Johns Wort and Depression. National Center for Complementary and Alternative
Medicine. National Institutes of Health, Sept. 2013. Web. 13 Oct. 2014. <http://
nccam.nih.gov/health/stjohnswort/sjw-and-depression.htm>.