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St John’s wort (Hypericum perforatum) is a flowering plant in the family Hypericaceae. In the treatment of depression, its active agent, Hypericum, is believed to work by preventing the uptake of neurotransmitters such as noradrenaline, serotonin and dopamine into the nerve endings.
In 2000 the herbal medicine, which many patients used for the relief of depressive symptoms and was available over-the-counter, was removed from the Irish market by the then Irish Medicines Board (IMB), now called the Health Products Regulatory Authority (HPRA). The IMB made the decision due to potential adverse interactions of St John’s wort with other drugs, the quality of the products available and concerns about people self-medicating for depression. Since then the evidence showing the benefits of St John’s wort has grown and the HPRA has recently licensed the product for the first time to be prescribed by doctors for the treatment of mild depression.
Prof Patricia Casey, Consultant Psychiatrist, Mater Hospital, Dublin, welcomed the decision by the HPRA to grant a license for the medicine, citing the findings of a study from the Cochrane Review Group about St John’s wort’s value.
The Group reviewed 29 studies in 5,489 patients with depression that compared treatment with extracts of St John’s wort for four to 12 weeks with placebo treatment or standard antidepressants. The studies came from a variety of countries, tested several different St John’s wort extracts, and mostly included patients suffering from mild to moderately severe symptoms. The range of daily extract doses varied between 240-1,800mg, but in most trials 500-1,200mg was used. The standard antidepressants used as active comparators were fluoxetine (six trials, dosage 20-40mg), sertraline (four trials, 50-100mg), imipramine (in three trials, dosage 100-150mg), citalopram (one trial, 20mg), paroxetine (one trial, 20-40mg), maprotiline (one trial, 75mg), and amitriptyline (one trial, 75mg).
Prof Patricia Casey
The findings were more favourable to St John’s wort extracts in studies from German-speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries St John’s wort extracts seemed less effective. This difference could be due to the inclusion of patients with slightly different types of depression, but it cannot be ruled out that some smaller studies from German-speaking countries were flawed and reported overoptimistic results, according to the authors.
Overall, however, the St John’s wort extracts tested in the trials were superior to placebo, similarly effective as standard antidepressants, and had fewer side effects than standard antidepressants.
“The evidence is that it is an effective antidepressant,” Prof Casey told the Medical Independent.
She pointed out that the systematic review showed that St John’s wort was as effective in major depression as standard antidepressants. The license in this country, however, has been given for those with mild depressive symptoms.
“That, I think, might confuse people because mild depressive symptoms often don’t need any treatment because they resolve spontaneously,” according to Prof Casey.
“However, in the early stages of a depressive illness, there may be mild depressive symptoms as well. If a GP thinks that some of these depressive symptoms are a sign of a depressive illness in evolution rather than just indicators of unhappiness or normal sadness then certainly St John’s wort has a role. For example, if a person had a prior history of depression and had been treated and then came back to the GP with mild depression then St John’s wort could be a valid treatment option. I generally don’t treat people with mild depressive symptoms with antidepressants unless I think that it is an early depressive episode. Generally, I don’t recommend giving antidepressants for mild depressive symptoms because usually they are just indicators of stress or sadness and I certainly don’t believe in medicating the problems of living, but in a group of people who have had prior depression and now present with some symptoms again, but may not yet have a full disorder, St John’s wort can play a role.”
Prof Casey said that the herbal medicine is particularly useful for people who do not want to take synthesised antidepressants.
“The reason this is particularly good news is that there are many people who need antidepressants but refuse them, so I think a naturally occurring product will have a lot more appeal for that group of patients,” Prof Casey argued.
“It will bring people into treatment that otherwise wouldn’t be willing to accept treatment for what is potentially a very serious condition. I think that some people who were opposed to drugs for depression might be tempted to take St John’s wort to relieve their symptoms.”
Prof Casey said that, although not affecting everyone, the issue of patients not wanting to take antidepressants is a common problem that mental health professionals and GPs need to contend with.
“There certainly is a group who are very reluctant to take antidepressants and I can’t make people take medication against their will,” she said.
“Sometimes I would have to say to them ‘I strongly recommend you take antidepressants, this is what you need, talking therapy won’t work for you’ and if they won’t take it, I can’t treat them, they have to find someone who will give them what they want. I can’t give people treatments that aren’t evidence-based and that are not indicated. If somebody goes to an oncologist and doesn’t want to use chemotherapy, they want to use, aromatherapy, for instance, I am sure most oncologists would say ‘I can’t go along with that’. Sometimes I have to say that to patients in psychiatry as well.”
Many people do not want to go on antidepressants because they fear dependence. However, Prof Casey said that this perception is not based on fact.
“Antidepressants don’t cause dependence; that is a mistake that is out there in the public domain. People do not become dependent on them in the way that they do with benzodiazepines,” she explained.
“What happens is that some people need long-term antidepressants and when they discontinue them their symptoms may reoccur in the same way that if somebody has hypertension and stops taking an anti-hypertensive, their blood pressure will shoot up. So that is an erroneous belief about dependence on antidepressants. There certainly is no evidence that I am aware of that St John’s wort is dependence inducing. It has got the same problems as any other antidepressant, which is mainly interactions with other drugs.”
Prof Casey believes that the decision to take St John’s wort off the Irish market was a wise one at the time given that is was available over-the-counter. Due to its potential interactions with various drugs – including warfarin, the contraceptive pill, and antibiotics – it is important that the medicine is only available through medical supervision, she maintained.
“People shouldn’t be self-medicating for depression,” Prof Casey stressed.
“Depression and depressive symptoms have various causes and they need medical assessment when they occur as to whether they need antidepressants or talking therapy or whether they need anything or whether they are indicating a physical illness. Another consideration is that people should not be self-medicating for what is potentially a serious illness. People think that naturally-occurring products by some magical way make people feel better. It [St John’s wort] is an antidepressant. It acts on serotonin and dopamine neurotransmitters the same as other antidepressants do. For that reason it is going to interact with other substances too. So because it has active ingredients in it, it is not a placebo and it has to be done under supervision.”
Prof Casey believes that the psychiatric community will welcome the reintroduction of the medicine into the Irish market, though she suggested it will primarily be prescribed by GPs.
“It has just come on the market so many people might not yet know about it,” noted Prof Casey.
“I think it is mainly in general practice it is going to be used. That is my sense of it. They are the first port of call for people. I think when GPs know that St John’s wort is available they will be prescribing it for the reasons I have given, and because it is non-stigmatising. I think they would find it easier to persuade people rather than the other antidepressants. That is my feeling, but we will have to wait and see what the sales data shows in the coming weeks, but that is my sense.”
Prof Casey said that the use of St John’s wort within an Irish clinical setting will be a “learning experience” for all involved.
“Most of us in clinical practice for any number of years won’t have experience in using it so this will be a learning experience for all of us,” she said. “It will be interesting to see the benefit that this group of patients, who maybe don’t want to go on regular medication, will derive from it. Time will tell.”
Changes to the sale and supply of St John’s wort in Ireland
The HPRA confirms that following assessment of the clinical, quality and safety data, it has granted a marketing authorisation permitting the product Pacifa, Hypericum perforatum (St John’s wort), to be placed on the Irish market as a prescription-only medicine.
Pacifa is indicated for the short-term treatment of mild depressive symptoms in adults over 18 years of age. Treatment of mood disorders and in this case ‘mild depressive symptoms’ are considered a serious medical condition and it is recommended that patients are under the supervision of an appropriately trained healthcare professional for diagnosis and monitoring of treatment, the HPRA says.
Pacifa contains 23.6mg of hyperforin (a major active constituent of St John’s wort) per tablet, which exceeds the levels set by the European Medicines Agency (EMA) for traditional herbal medicinal products (THMPS) used for self-medication. St John’s wort formulations that contain higher levels of hyperforin are subject to prescription.
Pacifia is a different formulation to the unauthorised medicines containing St John’s wort, which were available on the Irish market prior to 2000, the HPRA notes.
There were no licensed preparations of St John’s wort available at that time or up until Pacifa was authorised this year. In the absence of an authorised medicine containing St John’s wort, a registered medical practitioner could prescribe an unauthorised medicine for a patient under his/her care (Medicinal Products (Prescription and Control of Supply) Regulations, 2003 (as amended)). The medicine would be imported for use by a wholesaler registered with the HPRA and supplied by a pharmacist to the patient.
Since the introduction of herbal medicines legislation, which came into effect in Ireland in July 2007, the HPRA says it has actively sought applications for medicines containing St John’s wort, adding it is pleased that a medicine of appropriate quality, safety and efficacy is now available to Irish patients.
Topical formulations containing St John’s wort are permitted to be sold in pharmacies without prescription.