St John’s wort (Hypericum perforatum) is a traditional herbal medicine with a long history of use for different conditions. Nowadays, of St John’s wort is mainly as an herbal supplement to help with symptoms of mild depression and anxiety. In this post I am looking at St John’s wort effectiveness and possible side effects associated with taking this herbal product.
Most commonly, St John’s wort is available in tablet and capsule formulations, however other preparations of St John’s wort exist including herbal teas, powders, tinctures (liquid extract).
St John’s wort has been widely researched primarily to study its antidepressant properties as well as to investigate the interactions with other medications. One important message to ‘take home’ is that St John’s wort can interact with many different medicines, having a huge impact on patient’s treatment.
St John’s wort active ingredients and mechanism of action
Two main active ingredients found in St John’s wort are hypericin and hyperforin both believed to have antidepressant properties.
Some studies described St John’s wort mechanism of action through inhibition (block) of the reuptake of serotonin, dopamine, and noradrenaline (norepinephrine) neurotransmitters. Animal studies with rats suggest actions on different receptors including upregulation (increase number) of serotonin receptors which cause changes in the amounts of neurotransmitters in the areas of the brain associated with depression (Butterweck, 2003).
As many studies suggest fluctuations of serotonin, norepinephrine, and dopamine neurotransmitters in the central nervous system is associated with depression and currently available antidepressants act to increase one or more of those neurotransmitters in the brain (Moret & Briley, 2011).
St John’s wort effectiveness
Information from different small clinical trials suggests that St John’s wort is not invariably effective for the treatment of depression (NIH, ND). One clinical trial, for example, showed no difference (lack of efficacy) in the reduction of minor depression symptoms between St John’s wort and citalopram a selective serotonin reuptake inhibitor (SSRI, a type of antidepressants) and placebo (a dummy pill). On the other hand, another small clinical trial showed that St John’s wort is as equally as effective as placebo or SSRI antidepressant (sertraline was used in this trial) in treatment of moderate depression or may be more effective than placebo (ibid). SSRIs are the most commonly prescribed antidepressants in UK.
However, the best evidence behind the effectiveness of St John’s wort comes from a systemic review and meta analysis (summary of results from a number of studies) which looked at a total of 66 studies with 15161 patients. Key findings in relation to the effectiveness of St John’s work from this meta and network analysis:
- St John’s wort is effective for the treatment of acute depression with a small difference when compared to placebo (a dummy pill).
- Network analysis reports that St John’s wort shows similar efficacy to selective serotonin reuptake inhibitors and tricyclic antidepressant with a better ‘acceptability’ then both classes of antidepressants
- St Johns wort has a high risk of negative interactions with other drugs
St John’s wort interaction with drugs
Many drugs commonly used in the treatment of different conditions are metabolised (broken down) by liver’s enzymes such as those produced by the cytochrome P450 genes. St John’s wort can induce (increase activity) of cytochrome p450 enzymes and by doing so it can reduce the concentration of drugs in the body, hence reducing their effectiveness.
Many important interactions between St Johns worth and other drugs have been identified. Some classes of drugs affected include:
- Antidepressants (risk of serotonin syndrome)
- Contraceptive pills (reduced efficacy, with unwanted pregnancies reported (Henderson et al, 2002))
- Anticoagulants like warfarin
- HIV medications and many more
Always speak to a healthcare professional if you take different medication(s) and considering taking St John’s wort.
St John’s wort side effects
Most people who take St John’ wort do not experience side effects, however possible side effects include (eMC, ND):
- Allergic reactions for example skin rash, red and itchy skin, hives
- Upset stomach for example diarrhoea or constipation, indigestion, feeling sick (nausea)
- Headaches and dizziness
- Sensitivity to light
- Nerve pain, tingling, anxiety
St John’s wort & NICE recommendation
The official guide on the treatment of depression in adults (NICE) advices practitioners not to recommend St John’s wort for the treatment of depression, despite evident benefits in the treatment of mild to moderate depression (NICE, 2009). This recommendation comes from lack of information on appropriate doses, variations in preparations which are available on the market and possible risk of side effects with other drugs.
In conclusion St Johns wort shown to be effective in the management of depression symptoms with minor and uncommon side effects. One important aspect of taking St John’s wort is a possible risk of interactions with other medications.
Anyone who experience depression symptoms every day (most of the day) for more than 2 weeks should see their GP. Taking St John’s wort should not substitute for seeing help from their doctor.
eMC (ND). Product information: Max Strength Mood Lift St John’s Wort Tablets 425mg St John’s Wort extract. Available at: https://www.medicines.org.uk/emc/files/pil.8339.pdf Accessed on 22/05/2019
Butterweck Veronica (2003). Mechanism of action of St John’s wort in depression. Available at: https://link.springer.com/article/10.2165%2F00023210-200317080-00001 Accessed on 22/05/2019
Henderson L, Q Y Yue, C Bergquist, B Gerden, and P Arlett (2002). St John’s wort (Hypericum perforatum): drug interactions and clinical outcomes. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874438/ Accessed on 22/05/2019
Moret Chantal, Mike Briley (2011). The importance of norepinephrine in depression. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131098/ Accessed on 22/05/2019
NICE (2009). Do not recommend. Guidance: Depression in adults. Available at: https://www.nice.org.uk/donotdo/although-there-is-evidence-that-st-john-s-wort-may-be-of-benefit-in-mild-or-moderate-depression-practitioners-should-not-prescribe-or-advise-its-use-by-people-with-depression-because-of-uncertainty Accessed on 23/05/2019
NIH (ND). St. John’s Wort and Depression: In Depth. Available at: https://nccih.nih.gov/health/stjohnswort/sjw-and-depression.htm Accessed on 23/05/2019