Is St. John’s Wort a safe and effective treatment for depression?

By Marissa Nolan

Depression:  Diagnoses and Outcomes

            People suffering from depression have both physical and psychological symptoms.  While some people may have many symptoms, others only have a few.  Some of the symptoms may include:  negative thoughts, problems communicating or interacting with people, a messy appearance, low self-esteem, suicidal thoughts, fatigue, insomnia, increase or decrease in appetite resulting in weight loss or weight gain, difficulty concentrating and loss of interest in the things they once enjoyed (http://www.depressionet.com.au/sod.html).  Even though they feel lonely, they often push others away who try to encourage them to interact with people.  Depression makes it difficult for a person to trust individuals they have in the past.  A depressed person may distance their self from friends because they feel as though they are not worthy of their friendship.  As a result, depressed people are often difficult to be around.  They push the people they love away, yet they need their love and support more than ever. 

            Depression is often diagnosed by a complete physical and psychological evaluation.  Lab tests and interviews should be used by the physician in order to rule out any possibility of the depression resulting from the presence of certain medical conditions or medications.  A thorough evaluation will include a complete history of the patient’s symptoms, how long the symptoms have lasted, how severe the symptoms are, and whether they have received treatment for these symptoms in the past.  A physician should also ask the patient if they have had any suicidal thoughts.  Lastly, an examination should be used to determine if the patient’s speech, memory or thought patterns have been affected, which often happens in the presence of depression.

            Depression comes in many different forms.  In order to diagnose a person with a specific type of depression, the number of symptoms, the type of symptoms, and the severity of symptoms must all be taken into account.  People with moderate depression usually have symptoms which can make it difficult for them to pursue their everyday social and work activities.  While those suffering from severe depression, or major depression, have symptoms so severe that they might be unable to continue with normal everyday work and social activities.  Major depression causes a person to have a range of symptoms that can last for more than two weeks at a time.  While a person with moderate depression may experience only a couple of symptoms associated with depression, a person with major depression will often suffer from most, if not all symptoms of depression (http://www.depressionet.com.au/sod.html).  People with major depression are often at higher risk for suicide.  The person may feel at fault for their depression and they may sometimes suffer from hallucinations.  Thus, majority of cases involving individuals with major depression need immediate medical treatment.

            Depression often leaves people feeling worthless and lonely.  As a result, depressed people sometimes turn to suicide as a solution to what may feel like an endless problem.  They don’t feel optimistic about living everyday life, so they turn to suicide instead.  And yet others find a way out of depression.  With the help of psychological counseling and antidepressants, some individuals are able to return to somewhat of a normal lifestyle.  St. John’s wort is believed to be one of the medications making it possible for depressed patients to live life to its fullest. 

The Purpose of St. John’s Wort

            St. John’s wort, also known as Hypericum perforatum, is a wildly grown herb composed of bright yellow flowers found in several parts of the world.  St. John’s wort has several uses, but today it is mostly used to treat mild to moderate depression.  Physicians often prescribe St. John’s wort than a synthetic drug for the treatment of depression (http://www.tnp.com/encyclopedia/substance/89/).  It is believed by some that “…St. John’s wort is one of the best-documented herbal treatments….” (http://www.tnp.com/encyclopedia/substance/89/). Compared to standard anti-depressants, St. John’s wort has less severe side effects.  In the United States, most pharmacies and natural health food stores sell the herb. Most sufferers of mild to moderate depression choose to take St. John’s wort because of its availability and convenience without a prescription

How St. John’s Wort Works

            St. John’s wort is available in several forms, but most patients choose to take the pill form.  Most patients do not use St. John’s wort for more than six months at a time, but there are some cases where patients have used the herb for a longer amount of time.  Due to evidence of St. John’s wort resulting in fewer side effects than antidepressant drugs, most doctors would rather patients use prolonged therapy of the herb than with other antidepressant drugs. 

There are several different theories of how St. John’s wort actually works.  Some research suggests that “…St. John’s wort may inhibit the reuptake of serotonin, norepinephrine, and dopamine….” (http://www.tnp.com/encyclopedia/substance/89/).  One of the most recent theories suggests that the herb may actually have some kind of an effect on the connection between the immune system and mood (http://www.doctormurray.com/articles/worteditorial.htm).  This theory states that the active ingredient in St. John’s wort is hyperforin, which may be the cause of the change in mood.  However, some research states that the component hypericin is the active ingredient in St. John’s wort.  The misconception of hypericin to be the active element has long been believed because of the extracts of St. John’s wort “...are usually standardized to the substance hypericin….” (http://www.tnp.com/encyclopedia/substance/89/).  Studies of standardized hypericin extracts have found them to be more effective than other antidepressants and placebo.  Most recent evidence has not shown hypericin to be an actual antidepressant itself.  The newest of the supposed active ingredients, hyperforin, was thought in the past to not play a major role in the herb’s actual effectiveness.  However, it has now been shown through recent studies that hyperforin makes up one to six percent of the St. John’s wort extract (http://www.tnp.com/encyclopedia/substance/89/).  But, there may also be other components of the herb which may contribute to its effectiveness.  It is not known exactly which components of St. John’s wort are effective.

Precautions for Taking St. John’s Wort

            St. John’s wort should not be used to treat severe depression.  In the case of more severe forms of depression, a patient should contact a physician immediately.  If a patient is suffering from any other medical illness, not associated with depression, they should contact a physician and find out whether or not they should take St. John’s wort.  It usually takes about two to four weeks for St. John’s wort to start having an affect, and   patients should take this into consideration before starting the treatment.  St. John’s wort should not be taken by women who are pregnant or breastfeeding.  St. John’s wort should not be taken with pharmaceutical antidepressants, due to possible complications resulting from interactions between the medications.             

Although St. John’s Wort is relatively safe, there are a very small number of patients who may experience some side effects.  Some of these side effects may include:  stomach ache, restlessness, tiredness, and allergic reactions such as a skin rash (http://www.tnp.com/encyclopedia/substanceprint/89/).  St. John’s wort, like any other antidepressant, can cause patients with bipolar disorder to experience episodes of mania.  This is can especially be the case if the patient is not on mood-stabilizers.  Recently, there has been a study on the affects of St. John’s wort that may suggest that the herb can cause cataracts.  Evidence has shown that this may be possible by the herb allowing for the absorption of “…UV rays, which can result in damage of both the lens and the retina….” (http://www.raysahelian.com/stjohn.html).  Recent studies have also shown that St. John’s wort, when taken with anti-viral medications, can cause the medications to be less effective. 

Claims about the Effectiveness of St. John’s Wort and Evidence to Support Them

            Several claims have been made about the effectiveness of St. John’s wort.  Many of which have shown evidence of favoritism of positive trials.  In the case of one clinical trial published in the British Medical Journal in 1996, it was investigated whether or not St. John’s wort was “…more effective than placebo in the treatment of depression, as effective as standard antidepressive treatment, and had fewer side effects than standard antidepressant drugs….” (http://www.raysahelian.com/stjohn.html).  The trial conducted the study on patients with mostly mild to moderate forms of depression.  The clinical trial used a placebo controlled method in order avoid the expectations patients have when they know they are placed on a medicine.  The results showed that the herb to be “…significantly superior to placebo and was as effective as a pharmaceutical antidepressant—and with much fewer side effects….” (http://www.raysahelian.com/stjohn.html). 

However, a study conducted by the Journal of the American Medical Association resulted in the finding of St. John’s wort to not be effective in the treatment of moderate depression.  The study was also a placebo controlled study of patients with major depression.  The results showed that after an eight week study that there was no difference in the two groups of patients, one given St. John’s wort and the other given placebo (http://www.tnp.com/news/article/283/).  Authors of the JAMA study believe that previous studies of the effectiveness of St. John’s wort were flawed and therefore are incorrect. 

The difference in the results of the two studies, leads people to wonder which result is correct.  The truth is that most studies done on the effectiveness of medications on depression are flawed.  For example, most studies done on St. John’s wort suggest that it is only effective for mild to moderate depression.  Where as, the JAMA study conducted the herb’s effectiveness on major depression.  This is an example of the misclassification of the types of depression.  The JAMA study stated that they evaluated the effectiveness of St. John’s wort on major depression, when it was actually the same level of depression at which St. John’s wort has been proved by other studies to be effective (http://www.tnp.com/news/article/283/).  Most studies on the effectiveness of St. John’s wort on depression are conducted with patients suffering from major depression.  But, few cases of are of the same intensity.  The different levels of intensity of major depression are mild, moderate, and severe.  St. John’s wort is effective in the treatment of mild or moderate levels of major depression. Due to the relatively small number of trials conducted, it has not been proven that St. John’s wort is an effective treatment for patients suffering from severe depression.  The National Institute of Mental Health is at work on a $4.3 million clinical trial to compare the effects of St. John’s wort, a placebo, and a standard pharmaceutical antidepressant on patients with depression.  The results of the clinical trial are not expected to be release for at least another year (http://www.quackwatch.com/01QuackeryRelatedTopics/DSH/stjohn.html). 

Studies in Support of St. John’s Wort

            In a study in the British Medical Journal (Philipp M., Kohnen R., Hiller K.O., 1999), the safety and effectiveness of St. John’s wort compared with imipramine and placebo was tested on 263 people with moderate depression over an eight-week study.  Patients were screened one week before starting the study to make sure they had no antidepressants in their systems.  Patients were evaluated at the end of every first, second, fourth, sixth, and eighth week.  The Hamilton depression scale was used to determine the level of depression of each patient at the time of each evaluation.  Also, the clinical global impression scale was used to keep track of the improvement of each patient.  All patients were given three capsules of trial drugs each day.  Either 1050 mg of hypericum, 100 mg of imipramine or placebo were given each day.  The pills were made to look and taste identical so that patients would not know what they were taking.  If patients had known what drug they were taking, the results of the study would have been insufficient.  Patients were watched closely for compliance with the study by using pill counts at each evaluation.  In the end 100 patients were treated with hypericum daily, 105 with imipramine daily, and 46 with placebo daily.  Patients treated with either hypericum or imipramine had more improvement than those who were treated with placebo.  Although, the patients treated with placebo did see improvements as well. There were side effects experienced by all patients in the study.  The most common side effect was dry mouth.  Patients treated with imipramine were found to have the most side effects.  However, no serious side effects were found in the use of any of the drugs.  Results from the study showed that hypericum and imipramine were equal in effectiveness of treating moderate depression.  These results also showed that hypericum was more effective than placebo on patients with moderate depression.  Researchers in this study believe that based on this study St. John’s Wort is the most safe and effective way to treat moderate depression. 

            Yet another study in support of St. John’s Wort in the Clinical Therapeutics (Brenner R., Azbel V., Madhusoodanan S., Pawlowska M., 2001), compared hypericum and SSRI sertaline in the treatment of mild to moderate depression.  The double-blind study treated 30 patients with 300 mg pills of hypericum or 25 mg pills of sertaline for six weeks.  Each patient was given six pills daily.  Patients were told to take two in the morning, two in the afternoon, and two at night after meals.  Patients who were given the hypericum were given 600 mg of the extract only for the first week, and 900 mg for the rest of the study.  Over the weeks of the study, patients were evaluated using the clinical global impression scale and the Hamilton depression scale.  Any adverse reactions experienced by each patient were recorded as well.  If any patients decided to stop the study because of the presence of any adverse reactions, they were given follow-ups until the reactions discontinued.  5 patients who were taking hypericum and 3 patients taking sertaline dropped out of the study before the end.  So the end results of the study are actually based upon the evaluations of only 20 patients, 8 taking hypericum and 12 taking sertaline.  The results of the study showed that there was improvement in both patients taking hypericum and patients taking sertaline.  However, four patients, 2 from each treated group, discontinued the study because of the presence of adverse reactions.  Some of the reactions were headache, dizziness, and nausea.  Both drugs were well tolerated by the patients with no presence of severe side effects.  Therefore, the results of this study show that hypericum is as effective as the SSRI sertaline.  It also concluded that hypericum is a safe treatment for mild to moderate depression.  

            Another supporting study in the British Medical Journal (Woelk, H., 2000), was done to compare the effectiveness and acceptability of imipramine and hypericum using 324 patients with mild to moderate depression.  The patients were given either 75 mg of imipramine twice daily or 250 mg of hypericum twice daily.  All patients received a placebo along with the active pill every treatment.  Each patient was carefully evaluated every first, third, and sixth week.  The Hamilton depression rating scale was used at each evaluation to keep track of the amount and severity of depression symptoms in each patient.  A clinical global impression scale was used to monitor the improvement of a patient at each evaluation.  Compliance was recorded by pill counts at each evaluation.  The results of the study showed that patients treated with hypericum showed the same amount of improvements as the patients treated with imipramine.  However, results also showed that imipramine did have adverse effects in patients more than hypericum.  Some of these adverse reactions were nausea, headache, dizziness, and dry mouth, which was also experienced by patients treated with hypericum.  So, although hypericum and imipramine were shown to have the same amount of effectiveness, hypericum was proven to be a safer method to treat mild to moderate depression.  This study also found that in patients who suffer from anxiety, hypericum seems to alleviate symptoms better than imipramine. 

Studies Not in Support of St. John’s Wort

            The study in the Journal of the American Medical Association (Shelton, R., 2001), the effectiveness and safety of St. John’s wort and placebo were compared.  The double-blind, placebo-controlled study treated 200 patients with major depression over a period of 8 weeks.  Any patient who had previously taken St. John’s wort or failed to respond to a treatment of an antidepressant was excluded from the study.  The drugs were prepared so that the smell and taste of each drug could not be told apart.  The patients who qualified for the study were then given placebo for one week.  Those patients who experienced improvement of 25% or more were dismissed from the study.  All the other patients were given their first dosage of 300 mg of St. John’s wort or an identical pill of placebo.  The patient was instructed to take the pill, St. John’s wort or placebo, 3 times a day for at 4 weeks.  After the fourth week, the dosage of St. John’s wort and placebo was increased to 4 pills a day.  Each patient was evaluated using the Hamilton depression scale, the clinical global impression scale and a review of any adverse reactions to the drugs.  The evaluations took place at the end of weeks 1, 2, 4, 6, and 8.  The patients’ compliance with the study was evaluated by recording the number of pills at each evaluation.  The results of this study showed that there were no differences in treatment between the St. John’s wort group and the placebo group.  Researchers realized that St. John’s wort could be effective for patients not suffering from as severe depression.  So, the patients were divided into two groups, based on the scores on the Hamilton depression scale.  Results showed that there was not a significant difference between the St. John’s wort group and the placebo group with less severe depression.  There were only two adverse reactions, abdominal pain and headaches, reported in the study.  More patients treated with St. John’s wort experienced adverse reactions, than those in the placebo group.  Thus, the results of this study concluded that people with major depression should not be treated with St. John’s wort.  Researchers concluded that there is not enough evidence to support the effectiveness of St. John’s wort for people with depression.

Who Is Presenting Information and Why

            Some patients who have used St. John’s wort for the treatment of their depression will often support claims that the herb is effective.  They may want others to know that the treatment worked well for them, so they can help others who may be suffering from depression.  Natural health food stores or pharmacies make claims supporting the effectiveness of St. John’s wort for the treatment of depression.  These companies may support false claims, without any prior knowledge of St. John’s wort, in order to make a profit off of selling the herb to the public.  The public may then be influenced into buying St. John’s wort without actually having any prior knowledge about the herb’s effectiveness in treating depression.  People interested in proving the effectiveness of herbs support studies that do so, but they also suggest that studies which prove otherwise are invalid.  Those people who are in support of standard pharmaceutical antidepressants, support studies suggesting St. John’s wort to be ineffective in the treatment of depression.  However, there have been so many studies proving the effectiveness of St. John’s wort that there is enough evidence to state that St. John’s wort is effective in the treatment of depression (http://www.tnp.com/news/article/283/).   

Conclusion

            St. John’s wort has been proven by several studies to be an effective treatment for mild to moderate depression and this fact alone will always be controversial.  There will always be people who are in favor of the use of herbs to treat medical illnesses such as depression.  But there will always be those who do not support herbs as an effective medical treatment.  After doing extensive research on St. John’s wort, I have concluded that although there may not be enough evidence to fully support the effectiveness of St. John’s Wort, but it is indeed the best treatment for mild to moderate depression.  In several of the studies provided, St. John’s wort was shown to be as effective as some other drugs for the treatment of depression.  Thus, I chose not to conclude that St. John’s wort is the most effective treatment for mild to moderate depression, based upon the lack of evidence to prove so.  In most of the studies provided, St. John’s wort was the most well tolerated drug for depression.  Although some side effects were present in patients treated with St. John’s wort, these side effects were less severe and less occurring than those reported by patients treated with other antidepressant drugs.  I feel that in the case of major depression, a person should immediately receive medical care.  After reviewing information provided, I have concluded that St. John’s wort, as of right now, the safest treatment for mild to moderate depression. 

References

Brenner, R., Azbel, V., Madhusoodanan, S., Pawlowska, M. “Comparison of an extract

of hypericum (LI 160) and sertaline in the treatment of depression: a double blind, randomized pilot study”. Clinical Therapeutics. April 2000 22: 4: 411-419.

Philipp, M., Kohen, R., Hiller, K.O. “Hypericum extract versus imipramine or placebo in

            patients with moderate depression: randomized multicentre study of treatment for

            eight weeks”. British Medical Journal. 11 December 1999; 319: 1534-1539.

Shelton, R., Keller, M., Gelenberg, A., Dunner, D., Hirschfeld, R., Thase, M., Russell, J.,

Lydiard, R., Critis-Cristoph, P., Gallop, R., Todd, L., Hellerstein, D., Goodnick, P., Keitner, G., Stahl, M., Halbreich, U. The Journal of the American Medical Association. 18 April 2001; 285:15: 1978.

 Woelk H. “Comparison of St John's wort and imipramine for treating depression:

 randomized controlled trial”. British Medical Journal. 2 September 2000; 321:

 536-539.