Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis

Highlights

• This is the most up-to-date, large-scale meta-analysis of St John’s wort.

• Studies published in English, German and Chinese were examined.

• 27 clinical trials with a total of 3808 patients were reviewed.

• St John’s wort had comparable efficacy as SSRIs for mild-moderate depression.

• Lower discontinuation or dropout rate as compared to SSRIs.

Abstract

Introduction

St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. However, conflicting data regarding its benefits and risks exist, and the last large meta-analysis on St John's wort use for depression was done in 2008, with no updated meta-analysis available.

Methods

Using the keywords [St John's Wort OR Hypericum perforatum OR hypericin OR hyperforin OR johanniskraut OR圣约翰草] AND [depression OR antidepressant OR SSRI], a preliminary search (without language restriction) on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group, Cochrane Field for Complementary Medicine, China National Knowledge Infrastructure and WanFang database yielded 5428 papers between 1-Jan-1960 and 1-May-2016.

Results

27 clinical trials with a total of 3808 patients were reviewed, comparing the use of St John's wort and SSRI. In patients with depression, St John's wort demonstrated comparable response (pooled RR 0.983, 95% CI 0.924–1.042, p<0.001) and remission (pooled RR 1.013, 95% CI 0.892–1.134, p<0.001) rate, and significantly lower discontinuation/dropout (pooled OR 0.587, 95% CI 0.478–0.697, p<0.001) rate compared to standard SSRIs. The pooled SMD from baseline HAM-D scores (pooled SMD −0.068, 95% CI −0.127 to 0.021, p<0.001) also support its significant clinical efficacy in ameliorating depressive symptoms.

Limitations

Evidence on the long-term efficacy and safety of St. John's wort is limited as the duration of all available studies ranged from 4 to 12 weeks. It is also unclear if St John's wort would be beneficial for patients with severe depression, high suicidality or suicide risk.

Conclusion

For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs. Follow-up studies carried out over a longer duration should be planned to ascertain its benefits.

Introduction

According to the World Health Organisation (WHO), depression is a common mental disorder with over 350 million sufferers worldwide (Depression Internet, 2016). Currently, depression is the second leading cause of Disability Adjusted Life Years (DALYs) in people aged 15–44 years. By the year 2020, it is expected that depression would be the second leading cause of DALYs for all age groups (Reddy, 2010). Due to its enormous associated disability, depression is a major public health issue with significant direct and indirect health costs (Scott and Dickey, 2003). For example, it is estimated that the National Health Service (NHS) in UK spends more on treating depression than diabetes and hypertension combined (Scott and Dickey, 2003). Additionally, depression accounts for around 60–85% of the cost of illness. This cost is mainly attributed to the amount of productive hours lost that in turn has a substantial drag on a country's Gross National Product (GNP) (Scott and Dickey, 2003).

Therefore, effective management of depression is imperative to reduce the significant morbidity and disability associated with the disease. Hypericum perforatum (more commonly known as St John's wort) is an herbaceous perennial plant commonly found in Asia and Europe. It is a popular herbal remedy recommended by TCM practitioners for treating depression (Freeman, 2009). Furthermore, it is licensed and widely prescribed for depression in many European countries. Additionally, St John's wort is also gaining popularity in Western countries, with at least 40% of the sufferers consuming at least 1 TCM in the US annually (Hypericum Depression Trial Study Group, 2002). The burgeoning usage of St John's wort on a global scale warrants accurate information on (1) its efficacy compared to placebo and other conventional antidepressants and (2) its risks-benefits analysis.

However, the literature on St John's wort is rather outdated and conflicting. The last large meta-analysis on the subject was completed in 2008, which showed that the efficacy of St John's wort is superior to placebo and similar to other conventional antidepressants while having less side effects (Linde et al., 2008). However, several other studies have since questioned the efficacy of St John's wort (Hypericum Depression Trial Study Group, 2002, Linde et al., 2005, Freeman et al., 2010). Moreover, while some studies (Linde et al., 2008, Whiskey et al., 2001, Henderson et al., 2002 Oct 1) reported St John's wort to be safer than conventional antidepressants, other studies (Hypericum Depression Trial Study Group, 2002) did not support this conclusion. Therefore, given the outdated and conflicting nature of literature on this issue, this systematic review and meta-analysis is relevant and aims to provide a more updated and clear answer to these questions.