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St. John’s Wort for Major Depressive Disorder

St. John’s Wort may be safe and effective for treating patients with mild-to-moderate Major Depressive Disorder.

Depression can be debilitating and can affect quality of life, relationships, and lead to severe life consequences if left untreated. Major depressive disorder is a common type of depression that lasts more than two months where an individual can feel worthless and hopeless. In addition to conventional medicines, some alternative treatments have been investigated for treating depression – inlcuding St. John’s Wort.

A healthcare professional is required to diagnose Major Depressive Disorder via a physical and mental health assessment. Major Depressive Disorder signs and symptoms include the following: sadness, worthlessness, tearfulness, hopelessness, short temper, irritation, tiredness, loss of interest/pleasure, memory loss, weight loss, and appetite loss.

Psychotherapy and antidepressant medications have shown their effectiveness when treating Major Depressive Disorder. However, the costs, social stigma, and medication side effects are a few factors that cause many to not seek care and treatment.

St. John’s Wort has been used for centuries and studied to safely treat various depressive disorders, including Major Depressive Disorder. St. John’s Wort is available as an over-the-counter herbal supplement in the form of tablets, capsules, topical treatment and tea leaves. Some interesting side effects are increased risk for sun burns, stomach upset and skin reactions. Patients should always discuss with a healthcare professional prior to taking St. John’s Wort, especially with other medications.

A 2016 comprehensive review reported the safety and effectiveness of St. John’s Wort. The review included 35 studies combining 6,993 patients over 18 years-old with Major Depressive Disorder. The studies compared St. John’s Wort against placebo or an antidepressant medication over a treatment period of four to 12 weeks. The reviewers sought to answer two questions: 1) “What are the efficacy and safety of St. John’s Wort in adults with Major Depressive Disorder compared to placebo or active comparator?” and 2) “Is there a difference in effect, depending on the type of Major Depressive Disorder (i.e. mild, moderate, severe)?”

Effectiveness and safety of St. John’s Wort for Depression

The reviewers found that St. John’s Wort significantly improved depression symptoms compared to placebo. Patients who received St. John’s Wort responded well with significantly lower depression scale scores than patients who received placebo. Patients receiving St. John’s Wort were not more likely to experience adverse events than placebo overall. Adverse events in nervous system functions were more prevalent in patients taking St. John’s Wort compared to those taking placebo.

Effectiveness and safety of St. John’s Wort versus antidepressant medications

The reviewers found that the effectiveness of St. John’s Wort was comparable to antidepressant medications. Patients receiving either St. John’s Wort or an antidepressant did not have significantly different depression scale scores nor improvement in depression. Patients taking antidepressants experienced more adverse events in contrast to patients taking St. John’s Wort. Adverse events related to the stomach, nervous system functions, and sexual functions were lower in patients treated with St. John’s Wort.

Effectiveness and safety of St. John’s Wort in mild, moderate, and severe Major Depressive Disorder

The reviewers identified 12 patients with either mild or moderate depression, three studies with patients diagnosed with moderate depression alone and one study with patients diagnosed with severe depression alone. There were no studies with mild depression alone.

Evidence suggested that there is no difference in effectiveness in Major Depressive Disorder severity between St. John’s Wort versus placebo. The results indicated the reporting differences and study comparison inconsistencies, which reduces the integrity of the safety and effectiveness studies on St. John’s Wort. Patient populations varied with mild and moderate depression, while there were no reports of severe depression. The reviewers also discovered that patient’s safety from adverse events varied significantly between mild and moderate depression. The effectiveness and safety between St. John’s Wort versus placebo for patients with mild, moderate, or severe depression could not be determined.

The reviewers also did not find differences in effectiveness between St. John’s Wort and antidepressant medications in the mild-moderate and moderate severity studies. Adverse events due to St. John’s Wort were fewer than those who received antidepressants. The effectiveness and safety between St. John’s Wort versus antidepressants in depression severity could not be determined due to the varying and small number of studies.

The results suggest that St. John’s Wort may be effective and safe in improving patients with mild-to-moderate Major Depressive Disorder. The adverse events reported in patients taking St. John’s Wort’s were also fewer than antidepressants, although these data were inconclusive due to small number of studies and reporting inconsistencies. Further research with larger patient studies, standardized preparations, appropriate dosing and drug interactions are required to provide more insights on St. John’s Wort effectiveness and safety.  

Written by, Manuel Bangsil PharmD, MBA, BCMAS


Health Canada. Mental Health – Depression. 2009.

Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016;5(1):148

Image by Photo Mix from Pixabay.



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