St John’s Wort, botanical name Hypericum perforatum, is considered a weed in temperate climates outside its native homelands of Europe, Asia and North Africa. The flowering tops and aerial parts of the plant are used medicinally in the form of tinctures and tablets to treat a number of conditions affecting the nervous and immune systems.
Records of the medicinal use of St John’s Wort date back to ancient Greece. It is believed Dioscorides and Hippocrates used it to cleanse the body of evil spirits. Since the times of the Swiss physician and botanist Paracelsus (1493-1541), St John’s Wort has traditionally been used to treat nerve pain, anxiety, neurosis and depression and externally for bruises, wounds and shingles.
How is it used today?
In modern times, St John’s Wort has been shown to be as effective as placebo and standard antidepressants in the treatment of mild to moderate depression.
In Australia, St John’s Wort is mainly purchased through pharmacies and health food stores with or without the guidance of a health-care professional.
The St John’s Wort products vary in the amount of key constituents they contain. Only a few products actually match what was trialled in the studies with positive clinical outcomes. Variations in the active constituent content will affect the strength and effectiveness of the medicine and its possible safety.
It has become more common for complementary medicine manufacturers to include a standardised amount of the herb constituents on the label. The daily dose range for total hypericin content is 0.75mg to 2.7mg of hypericin daily. The published studies generally used standardised extracts to contain 0.3% hypericin and 2-5% hyperforin.
In 2000, St John’s Wort made up 25% of all antidepressant prescriptions in Europe. A more recent Australian study reported 4.3% or 17,780 patients who had visited a GP for depression had taken or were taking St John’s Wort.
How does it work?
St John’s Wort has been reported as containing many constituents and demonstrating multiple and simultaneous mechanisms of action.
While individual key constituents have been identified as hypericin (a naturally occurring substance with a few different applications including antidepressive), pseudohypericin and hyperforin (a phytochemical produced in some plants), collectively they exert a number of pharmacological effects including antidepressant activity.
The hypericin and flavonoids (namely hyperforin) and other flavonoid molecules that are found in some fruits and vegetables are thought to play a role in exerting an antidepressant effect by altering nerve chemical messengers known as neurotransmitters. It is considered important available products contain standardised amounts of these components.
St John’s Wort has been shown in non-human studies to assist in keeping the circulating levels of four key neurotransmitters (serotonin, noradrenaline, dopamine and gamma-aminobutyric acid) at levels that improve depressive symptoms.
This is a very distinctive feature of St John’s Wort. No other drug has been demonstrated to affect all four of these chemical messengers with similar potencies. Studies comparing the effectiveness of St John’s Wort with different classes of other anti-depressants that target these neurotransmitters support the proposed multi-targeted mechanism of action of St John’s Wort.
Antidepressants Citalopram (Celexa) and Sertraline (Zoloft) belong to a class of antidepressants known as selective serotonin re-uptake inhibitors (SSRIs). These block the reabsorption of the neurotransmitter serotonin in the brain, making more serotonin available to assist the brain cells to send and receive chemical messages. This in turn boosts mood.
A high-standard systematic review conducted in 2009 concluded St John’s Wort extract was superior to placebo in patients with major depression and similarly effective to standard treatment with SSRIs. They also found fewer people taking St John’s Wort discontinued their treatment. This was due to them experiencing fewer side effects.
The same review also found no significant difference in the effectiveness of St John’s Wort and the older class of antidepressants known as “tri-cyclic”. These work by blocking the absorption of serotonin to improve their availability for sending and receiving chemical messages that improve our mood.
St John’s Wort was reported as more effective in German studies compared to those in non-European-based populations, but it is thought these results were over-optimistic.
Safety and side-effects
Like standard antidepressants, it may take up to four weeks to judge how effective St John’s Wort has been. It is generally well tolerated, but adverse effects may occur. These include mild gastrointestinal symptoms, skin reactions, increased sensitivity to sunlight, fatigue, sedation, restlessness, dizziness, headache and dry mouth.
St John’s Wort affects enzymes in the gastrointestinal tract and liver that are involved in drug metabolism. It can reduce how much of a drug is available in the body by reducing how much is absorbed and excreted. Therefore the potential effectiveness of many drugs can be limited.
This includes drugs used to treat serious conditions such as AIDs, cancer and epilepsy. St John’s Wort can also reduce the effectiveness of the oral contraceptive pill. It should not be taken along with standard antidepressant drugs.
Anyone suspecting they may have symptoms of depression should consult their doctor to ensure a correct diagnosis is made. The use of St John’s Wort should be guided by a health-care professional who is knowledgeable about the quality of available products, effective dosing and safety considerations, including known drug interactions associated with its use.