St John's Wort

St John's wort is not a licenced medicine but a herbal remedy also called hypericum. Wort is correctly pronounced as wert . It has been used for centuries, if not for a couple of millennia, for depression and anxiety. It is commonly used in Germany and other parts of the world. The flowers and leaves of the plant Hypericum perforatum are used to make the product. They contain many different compounds including hypericin, which is thought to be one of the compounds with pharmacological properties. These compounds are extracted from the plant with alcohol.

Some of the proprietary preparations are standardised for hypericin, making them more consistent than products that are not standardised. It is possible, even likely, that other ingredients in the preparation have some effect on depression but as they are not standardised this is likely to be variable between batches. Different brands will have different amounts of hypericin and other ingredients, so it is best to choose a standardised brand and to stay with the same brand.

St John's Wort looks very promising as a treatment for mild to moderate depression^1,2 and there is some evidence of efficacy in moderate to severe depression.^3,4 There may be benefit in prevention of relapse of depression.⁵ There have been comparisons with other antidepressants such as imipramine and amitriptyline. These studies have been fairly positive for St John's Wort, indicating that it helps with depression and possibly has fewer side effects. Unfortunately the trials have been only for short periods such as 4 or 8 weeks and so it is not certain how well St John's Wort will compare in terms of efficacy and adverse effects over a longer period of use. The numbers in such studies have tended to be small. It would be useful to have more studies comparing St John's Wort with newer antidepressants such as the SSRIs particularly with regard to efficacy and side effects. Larger, more powerful trials are needed.

A Cochrane review from 2005¹ found the evidence inconsistent and confusing. What it found particularly difficult was the variability of the potency of doses. The question of the adequacy of doses of conventional antidepressants also dogs clinical trials.

It is not known how St John's Wort works. It is thought that it may affect serotonin, noradrenaline and dopamine uptake. The usual recommended dose is about 900mg a day of hypericum extract, but much higher doses have been used in trials.⁴

It is not possible to list the indications for which it is licensed as it does not have a product licence. It is almost certain that a licence would be refused on the present sparse level of evidence.

It is recommended for mild to moderate depression but its efficacy in severe depression is dubious. It is probably better in depression with an element of anxiety. The orthodox antidepressants have a number of indications other than the treatment of depression and it would be unsafe to assume that St John's wort would be similarly effective.

In Germany it is used quite often to treat depression in children and adolescents, as are tricyclic antidepressants. In the UK the use of antidepressants in children and adolescents is discouraged in favour of cognitive and behavioural therapy and SSRIs should be used with great caution, if at all. Clinical Evidence, based on a search from April 2005, could not recommend St John's Wort for children and adolescents as they were unable to find any RCTs.⁶ Their searches are usually confined to the English language. There is no evidence of benefit in attention deficit and hyperactivity disorder (ADHD)⁷ or bipolar disorder.⁸

The NICE guidelines on the management of depression⁹ state that "Although there is evidence that St John's wort may be of benefit in mild or moderate depression, healthcare professionals should not prescribe or advise its use by patients because of uncertainty about appropriate doses, variation in the nature of preparations and potential serious interactions with other drugs (including oral contraceptives, anticoagulants and anticonvulsants)".
Other recent systematic reviews all point to a significant lack of methodologically rigorous studies within the field.¹⁰

• It should not be used in pregnancy or lactation, due to lack of evidence of safety.
• It should not be taken at the same time as other antidepressants, especially the SSRIs as there is risk of a serotonergic crisis.¹¹
• For the same reason it should not be used with the triptans including sumatriptan, naratriptan, rizatriptan and zolmitriptan
• It should not be used in bipolar disease as it may be associated with mania.¹²
• Because it induces enzymes associated with cytochrome P450, there are a number of drug interactions with St John's wort.^11,13 For a full list of interactions see current BNF.¹⁴ The doctor must decide if these are a contraindication to advising the treatment or if adjustment of doses is required. The following list is by no means exhaustive:
  • Oral contraceptives
  • Warfarin
  • Ciclosporin
  • Amitriptyline
  • Anticonvulsants including carbamazepine, phenobarbitone and phenytoin
  • Simvastatin
  • Alprazolam
  • HIV treatments including indinavir, nelfinavir, ritonavir, saquinavir, efavirenz and nevirapine.
  • Digoxin
  • Theophyllins

It is of particular concern that despite these significant interactions warnings to patients are inadequate in products on sale.¹⁵ There is concern about safety and a call for more research on interactions.¹⁶

Before a patient is started on a licenced antidepressant he needs to see a doctor for a diagnosis. A prescription is issued that is dispensed by a pharmacist and the doctor will arrange follow up.

None of this is obligatory for St John's wort as it can be bought in health food shops and off the shelves in supermarkets with no supervision with regard to diagnosis or advice.

This is most unsatisfactory for the management of a serious and potentially fatal disease. Ideally patients should consult a doctor first, even if they wish to buy the medicine after. They must tell the doctor of their intention and be followed up as they would be if given a prescription. They should also be advised to find a brand that is standardised and to stay with the same brand.

If a conventional antidepressant is being used there should be a "washout" period before starting a new class, including St John's wort. Some antidepressants like fluoxetine have a very long half-life. The patient should be warned about drug interactions, including with antidepressants and oral contraceptives if appropriate.

• The depression should be monitored to assess progress. The patient should be seen after a week or two and then at intervals dictated by the doctor's clinical acumen and usual practice. It may take 2 to 4 weeks to have effect.
• If the patient is taking other drugs, including anticoagulants, they must be monitored on starting therapy and on stopping it. St John's wort causes enzyme induction.¹⁷ If different brands of different strengths are used this will vary.
• Ask the patient about side effects. Patients on conventional drugs are usually very ready to report adverse reactions and often too eager to blame the medication. With "natural remedies" the opposite may be true.
• The most commonly reported side effects¹⁸ include:
  • Gastrointestinal symptoms such as nausea, vomiting or diarrhoea
  • Allergic reactions
  • Fatigue
  • Dizziness
  • Confusion
  • Dry mouth
  • Photosensitivity is uncommon and tends to be associated with high doses, but people taking it should increase their sun protection and avoid strong sunlight.

If the depression becomes severe, the St John's wort should be abandoned and after a brief "washout" period an adequate dose of a drug of proven value in severe depression should be started.

It must be discontinued if side effects are intolerable or drug interactions are unacceptable.

St John's Wort is a plant named after St John the Baptist, whose feast day on 24th June, occurs when daylight in Europe is longest and the plant is in full bloom. Its five yellow petals resemble a halo, and its red sap symbolises the blood of the martyred saint. He was beheaded after criticising the morality of King Herod, the Jewish king. The name Hypericum comes from the Greek, meaning "greatest health". It is also said to have antibiotic properties.