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An Effective Alternative in Treating Depression

Anna Yanker

November 12, 2008






Depression is one of the most frequent psychological problems encountered in the medical profession. Approximately one out of every five people will experience an episode of major depression in his or her life (Bilia, 2001).


Most individuals experiencing depression are treated through medication, psychotherapy, or a combination of the two. Prescribed medications are usually divided into two categories, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). Imbalances of the neurotransmitters serotonin, norepinenphrine, and/or dopamine are thought to be a biological basis for depression. SSRIs work by blocking the reabsorption of serotonin by nerve cells in the brain. TCAs inhibit the transport proteins that return neurotransmitters, such as serotonin and norepinephrine, back to the nerve cells from which they originated (Muller, 2002). Thus, these two types of medication restore healthy levels of neurotransmitters, promoting emotional stability in the individual.


While conventional prescription medications have proven to be effective in treating depression in some individuals, the numerous adverse side effects associated with their use tend to limit their efficacy and acceptance. These side effects may cause some patients to take medication erratically or discontinue its use altogether. According to some statistics, successful treatment of depression with currently available drugs is achieved only in 65-75% of patients (Bilia, 2001). This leads many physicians and patients alike to seek effective alternative treatments.


ST. JOHNís WORT (Hypericum Perforatum)



The use of St. Johnís Wort can be traced back thousands of years to ancient Greece. Originally used as a treatment against demonic possession, hypericum perforatum has since evolved to be used for everything from insect bites to diuretics. One of its most notable, and scientifically supported, uses is as an alternative treatment for depression (Woelk, 2000). The leaves and flowers of hypericum are harvested and dried for use in tablets, capsules, drops, and teas ( While there have been many positive scientific findings in favor of hypericum perforatum, not all of the claims made about its properties and effects are true.




It is not yet fully understood how the compounds in St. Johnís Wort work to treat depression. However, studies suggest that its effectiveness may work by preventing nerve cells in the brain from reabsorbing serotonin, similar to the effect of SSRIs ( Hyperforin, another compound in St. Johnís Wort, is said to act as a ďreuptake inhibitor,Ē increasing the levels of neurotransmitters in the brain which can improve mood and restore emotional balance (






It has been estimated that 50-65% of depressed patients treated with conventional antidepressants fail to respond to the treatment, and 50% of those prescribed experience side effects which 3 out or 10 times are so severe as to warrant to discontinuation of treatment (


Specialists have suggested that some 80-90% of all cases of depression can be helped by conventional or alternative treatments ( St. Johnís Wort has been claimed to be just as effective as prescription antidepressants and, in addition, is considerably less expensive, available without a prescription, and presents far fewer and much milder side effects. Some sources claim there are no side effects at all ( Medical studies have shown that 50-80% of depressed patients have a significant decrease in symptoms of depression and a corresponding increase in well-being as a result of using hypericum perforatum ( †Some studies have even found that St. Johnís Wort is superior to some antidepressants, such as Paxil, as a treatment even in severe depression

(, and claim that hypericum can enhance oneís social abilities (


Twenty-five controlled double blind studies have been conducted with reference to the efficacy of St. Johnís Wort in treating depression. Sixteen of the studies compared hypericum with a placebo, and nine with reference treatments.† In a majority of these studies, depressive symptoms and secondary symptoms improved significantly. It is important to note that most scientific experimentation has been performed on mild to moderate forms of depression. Hypericum is not yet recommended for treatment of more severe forms of depression (







There have been numerous clinical trials dedicated to verifying the claims made about the effects and safety of St. Johnís Wort in alleviating depressive symptoms. A majority of these trials utilize the Hamilton Rating Scale for Depression (HAMD). The HAMD is the standard measure used in research for the effectiveness of depression treatments. It measures the severity of depressive symptoms in individuals who have already been diagnosed with a depressive disorder († The results of the following studies will be partially expressed in the context of the HAMD.


Two types of clinical trials have been conducted in regards to the efficacy of St. Johnís Wort in treating depression, those comparing its effects with a placebo, and those comparing its effects with that of another standard antidepressant medication. A few of these studies are highlighted below.






Clerc et al. (2002) conducted a double-blind, randomized, placebo-controlled study of 375 patients in which they compared the effects and safety of 300 mg of hypericum perforatum with a placebo in treating depression. The study participants were male and female adult outpatients with mild to moderate depression, in accordance with DSM-IV criteria and scored between an 18 and 25 on the HAMD. The patients received a single-blind placebo phase before being randomly assigned, 186 in the hypericum group and 189 in the placebo group, to the double blind treatment for 6 weeks.


††††††††††† Efficacy: In both treatment groups the HAMD score decreased over the †††† course of the trial, by a mean of 9.9 in the hypericum group and 8.1 in the †††† placebo group.

††††††††††† Safety: Of those in the hypericum group 30.6% †††††††††† experienced adverse side effects compared to 37% in the placebo group. ††††††† There was ††† no tolerability related withdrawal in any case.†

††††††††††† Conlusion: Clerc et al. (2002) found that overall the hypericum perforatum †††††††††† was found to be safe and more effective than placebo in the treatment of †††††† mild to moderate depression.


Gelenberg et al. (2001) conducted a similarly structured study testing the effects of St. Johnís Wort against a placebo. Their study included 200 adult outpatients diagnosed as having major depression as specified in the DSM-IV criteria and having a baseline HAMD score of 20.


††††††††††† Results: Unlike the previous study this study found that St. Johnís Wort ††† failed to produce significant differences versus the placebo in the subjects †††† HAMD scores. Even so, the results showed that St. Johnís Wort was ††† better tolerated than the placebo.





Bellevance et al. (2002) conducted a study comparing the efficacy and tolerance of St. Johnís Wort when compared with the antidepressant medication sertraline as a treatment for depression. The study was a double-blind, randomized 12-week trial that included 87 men and women with major depression and HAMD scores over 16. Patients were given either 100 mg of sertraline or 900 mg of St. Johnís Wort. Depression assessments were done at a period of 2, 4, 8, and 12 weeks using the HAMD.


††††††††††† Efficacy: The study found that there were no important differences in the changes of the mean HAMD score between the two groups.

††††††††††† Safety: There were significantly more side effects reported by the †† sertraline group at weeks 2 and 4 follow ups.

††††††††††† Conclusion: The study concluded that St. Johnís Wort was just as effective †††††††† as the antidepressant sertraline and, because of its relatively mild side ††††† effects, would be a ďgood first choiceĒ for patients with mild depression.


A similar study conducted by Jurcic et al. (2007) focused on the efficacy of St. Johnís Wort versus paroxetine (the main ingredient in the antidepressant Paxil) and included 251 adult outpatients from 21 psychiatric primary care practices who scored at least 22 points on the HAMD scale.


††††††††††† Efficacy: The study found that after 6 weeks of treatment the HAMD †††††††††† scores had decreased by an average of 14.4 points in the St. Johnís Wort †††† group and 11.4 points in the paroxetine group.

††††††††††† Safety: adverse events were more common in the patients taking ††† paroxetine, and more of the paroxetine patients discontinued study † medication because of adverse events.

††††††††††† Conclusion: St. Johnís Wort was at least as, if not more, effective than ††††† paroxetine in treating depression and was better tolerated.


A final clinical trial to examine is that of Woelk (2000) which focused on the comparison of St. Johnís Wort to imipramine in treating depression. This also was a randomized, double-blind clinical trial that included 324 outpatients with mild to moderate depression in a 6 week study. Patients had to score above an 18 on the HAMD to be included in the study.


††††††††††† Efficacy: mean scores on the HAMD among those in the St. Johnís Wort † group had decreased from 22.4 at the baseline to 12. Among those taking †† imipramine, the score decreased from a mean of 22.1 at the baseline to ††††††† 12.75.

††††††††††† Safety: It was reported that participants tolerated the St. Johnís Wort †††††††††† better than imipramine. Adverse events were reported by 63% of those ††††††††††† taking imipramine versus 39% taking St. Johnís Wort. Only 3% of the ††††††††† participants in the St. Johnís Wort group dropped out of the study due to ††††††††††† adverse events as compared with 1 in every 6 participants in the †††† imipramine group.

††††††††††† Conclusion: The two treatments were ďtherapeutically equivalent, and that †††††††††† St. Johnís Wort was better tolerated.













In reviewing 23 randomized trials, Bilia et al. (2001) concluded that St. Johnís Wort is ďsafe, well tolerated, and more effective than placebo and is at lease as effective as standard antidepressants (amitriptyline, imipramine, maprotiline, fluoxetine) with fewer side effects in the treatment of mild to moderate depression (Bilia et al. 2002, page 3086).Ē


Muller (2002) in comparing several studies from the years 2000 and 2001 concluded, ďToday, the pharmacological action and therapeutic efficacy of St. Johnís Wort extract as an antidepressant must be considered as confirmed (Muller, 2002, page 109).Ē





Treating patients with mild to moderate depression can be challenging. The non severe nature of this form of the disorder can make the adverse side effects of standard treatments preclude their use. In these situations, it would be useful to have an effective antidepressant with comparatively few and mild side effects.


However, there are some things the patients needs to be aware of when considering taking St. Johnís Wort as a treatment for depression. (1) The patient needs to consult with their physician regarding the use of other medication. St. Johnís Wort has been observed to interact negatively and reduce the efficacy of certain medications if taken in conjunction with them. These medications include forms of oral contraception, heart disease medications, and blood pressure medications (Bilia et al., 2002). (2) St. Johnís Wort is an herb and herbal drugs remain largely unregulated by the FDA, therefore preparations of St. Johnís Wort in the market might vary in their quality. Only choose products that state the ingredient hypericum perforatum explicity on their label, also be sure to check that the dose does not exceed the recommended 4-5 grams (Jurcic et al., 2007)


St. Johnís Wort has been proven through numerous clinical studies to be effective and safe for the treatment of mild to moderate depression in individuals. Those experiencing depression and the adverse side effects of conventional antidepressant medication should consider taking St. Johnís Wort as an effective alternative. Consult with your physician before taking St. Johnís Wort and/or discontinuing any current medications.







Bellavance. Francois et al. (2002). St. Johnís Wort or Sertraline?† Canadian††††††††† Family Physician, 48, 905-912.

Bilia, Anna Rita et al. (2001). St. Johnís Wort and depression Efficacy, Safety, †††† and Tolerability-an update. Life Sciences, 70 (26), 3077-3096.

Clerc, G. et al. (2002). Efficacy of St. Johnís Wort Extract WS 5570 in Major†††††††††† Depression: A Double-Blind, Placebo-Controlled Trial. Am J Psychiatry,†††††††† 159, 1361-1366.

Gelenberg, Alan et al. (2001). Effectiveness of St. Johnís Wort in Major††††† Depression: A Randomized Controlled Trial. Journal of the American †††††††††† Medical Association, 285 (15), 1978-1986.

Jurcic, Jane et al. (2007). St. Johnís Wort Versus Paroxetine for Depression. †††††† Canadian Family Physician, 53, 1511-1513.

Muller, William E. (2002). Current St. Johnís Wort Research from Mode of Action ††††††††††† to Clinical Efficacy. †Pharmacological Research, 47 (2), 101-109.

Woelk, Helmut (2000). Comparison of St. Johnís Wort and Imipramine for Treating Depression: Randomised Controlled Trial. British Medical †† Journal, 321, 536-539.





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