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   Sep 23

St John’s Wort returns to Ireland

Director Rory O’Riordan discusses with Lloyd Mudiwa the reintroduction of the popular herbal medicine St John’s Wort, some 14 years after its withdrawal from the Irish market.

St John’s Wort (SJW) — botanical name Hypericum perforatum L — is a “very well known” herbal medicine all around Europe and was on sale across Ireland up to the year 2001.

“You could get it in pharmacies, in health food stores, in groceries, in petrol stations like any other herbal medicine or food supplement. There was no control on it and it came in all sorts of doses and forms, from capsules, to tablets and infusion bags,” according to Rory O’Riordan, a trained pharmacist and Executive Director of Fannin Ltd, part of the DCC Vital group, who put the versions on the market here at the time at more than 20.

However, nobody had actually presented any evidence-based data on the efficacy and safety of the product for the Irish Medicines Board (IMB) — now the Health Products Regulatory Authority (HPRA) — to approve.

“Because the versions on the market were unregulated, you couldn’t be sure how pure they were, or whether the dose was there or not? They were just various dosage forms, mostly imported from across Europe.”

Regulatory concerns

Uniquely in Ireland, the IMB removed the product from the market because it was “very concerned” about two things, according to O’Riordan.

“One was the level of interactions that they were picking up from doctors and pharmacists of people on other medicines who were taking SJW, unbeknownst to either the doctor or the pharmacist. The second was that some people were using it to treat depressive symptoms and the IMB had the view that ‘you shouldn’t really be self-medicating depression and that this should be something that your doctor is involved in’.”

The medicines regulatory body indicated that any medicine or any form of SJW that did not have a licence could not be sold here anymore. Also, O’Riordan said, the IMB believed that if SJW was an effective product then it ought to be of a certain standard of quality, and “we can’t have all sorts of forms of doses with questionable amounts of the drug”.

Meanwhile, the EU in general brought in licensing of herbal medicines in 2000. In countries such as the UK, hypericum is licensed as a traditional herbal medicine product (THMP), which tends to be available without prescription.

The IMB was unusual in the sense that it regarded the natural medicine as something that should be managed by a doctor rather than self-managed. In most other EU countries people can still buy SJW in a pharmacy or health foods store, O’Riordan observed. Fannin has the first and only legal version of St John’s Wort in the Irish marketplace.

One could drive to Belfast and buy a packet of it in many pharmacies. “You don’t need a prescription for it. Equally none of the SJW products in that pharmacies in Northern Ireland are actually licensed here, so this is the only product licensed we have,” he stressed.

‘Some people are particularly sensitive to St John’s Wort and others perhaps need two tablets a day’.

Cochrane Review

Fannin has returned St John’s Wort, branded as Pacifa, to the Irish market, this time as a prescription-only medicine. O’Riordan explained: “What the IMB/HPRA had said is ‘we are not opposed to the substance, but we want it to be regularised and licensed’. So we are the first company to actually have done that.”

The Executive Director had sourced a form of this product in Germany, where herbal medicine is a very strong part of medical practice. “I found it to be a very high-quality, standardised pharmaceutical grade of St John’s Wort and I bought the dossier and submitted it to the IMB,” he added.

Interestingly, the Cochrane Review, a group of independent physicians who assess medicines, evaluated this product in 2008 and, according to O’Riordan, “made strong recommendations” for it.

The group investigated whether extracts of hypericum, prescribed widely for the treatment of depression in other countries, were more effective than placebo and as effective as standard antidepressants in the treatment of major depression; and whether they had fewer adverse effects than standard antidepressant drugs.

They reviewed nearly 30 studies involving a combined total of more than 5,400 patients with depression that compared treatment with hypericum for four to 12 weeks with placebo treatment or standard antidepressants.

The studies conducted in a variety of countries tested several different extracts of the plant, and mostly included patients suffering from mild to moderately severe symptoms. Trials were searched in computerised databases, by checking bibliographies of relevant articles, and by contacting manufacturers and researchers.

Trials that were randomised and double-blind; that included patients with major depression; compared extracts of SJW with placebo or standard antidepressants; and included clinical outcomes assessing depressive symptoms, were all reviewed.

At least two independent reviewers extracted information from study reports. The main outcome measure for assessing effectiveness was the responder rate ratio (the relative risk of having a response to treatment).

The main outcome measure for adverse effects was the number of patients dropping out due to adverse effects.

Some 29 trials (5,489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28, and in nine smaller trials it was 1.87. Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 and 1.00.

Side effects

According to the Cochrane Review, patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants or SSRIs. Overall, extracts tested in the trials were superior to placebo, similarly effective as standard antidepressants, and had fewer side-effects than standard antidepressants.

“Using a St John’s Wort extract might be justified, but important issues should be taken into account: SJW products available on the market vary to a great extent.

The results of this review apply only to the preparations tested in the studies included, and possibly to extracts with similar characteristics. Side-effects of SJW are usually minor and uncommon. However, the effects of other drugs might be significantly compromised,” concluded the Review, which stressed that patients suffering from depressive symptoms who wished to use a SJW product should consult a health professional.

O’Riordan added: “The major thing to note about St John’s is that it interacts with a number of medicines so its interaction with the oral contraceptive pill can reduce its efficacy, and our data sheet has that highlighted — details about what people should not be taking if they are going to be taking SJW.

“It’s a fairly long list of drugs [included in the Summary of Product Characteristics] because SJW interferes with the liver enzymes involved. But the main one that people should be aware of is the oral contraceptive pill. People should use another form of contraception if they are going to take St John’s Wort and remain on contraception.”

Indications and dosage

It took about two years for the IMB to assess Pacifa. “So they didn’t just rush into it,” commented O’Riordan. IMB finally granted the licence in March and Fannin launched Pacifa in July. “This time around it’s got a marketing authorisation so it is classified as a medicine and it’s also prescription-controlled, so that means that people can’t go off self-medicating depression,” O’Riordan mentioned. Interestingly, nurses can also prescribe the product.

Previously, there had been lots of claims in Ireland about the indications for SJW. “If you google it you will see a whole host of claims about the product, but the only one we’ve been granted a licence for, that we can openly say, is that it is approved to treat mild depressive symptoms.”
But, as is, the label indication for the short-term treatment of mild depressive symptoms — though a limited one — was somewhat broad in itself, O’Riordan submitted. “It’s not a strong medicine. It’s at the mild end of depression and clearly is not for major depression. I think a lot of people would use this for what we call the ‘blues’, like when the light declines in winter, and people don’t feel so well and are under the weather.”

Pacifa tablets are sold in packs of 30s and the dosage is one or two tablets daily for a month depending on the individual patient’s level of symptoms, and how well they respond. “Some people are particularly sensitive to St John’s Wort and others perhaps need two tablets a day.”

The list price for the product is €16, rising to between €24 and €25 when a pharmacy mark-up is included. “It’s actually less expensive than most of the branded SSRIs (which are some of the most commonly prescribed antidepressants available),” O’Riordan commented. “We didn’t want to deter people by making the product too expensive.

“We expect this to be a very popular option for doctors in the management of depressive symptoms.

We reckon that a lot of GPs will use this instead of antidepressants because a lot of people don’t like that they are on an anti-depressant, and that it’s a chemical that they are on.” Plus, a lot of antidepressants have side-effects that affect libido, sexual function and weight gain.

“We have started talking to doctors about it over the last month and certainly the initial response is very positive,” he said. “They can see in their mind’s eye the kind of patient that they would use it on instead of an SSRI.”

Fannin has also applied for GMS reimbursement. “We are currently negotiating with the HSE on that. We are expecting to gain general reimbursement on the GMS scheme.” O’Riordan assumes the Executive will give its decision by year-end.

In the meantime, he said the cost was still cheaper than €1 a day for treatment, while acknowledging there were a lot of people who simply could not afford to pay for their own medicine.

“Quite a number of the GPs we have been talking to said that they are going to notify the HSE, that this is a product that should be on the GMS. You would expect the company that brought the product in to ask for reimbursement, but when the prescribers themselves start saying that it should be approved then that should probably add weight to our argument.”

Fannin was also briefing all of the consultant psychiatrists because they would have been aware of the product and, even though they tended to treat the more severe end of depression, their reaction has been “very positive”.
“For instance, Prof Patricia Casey, who is the Head of Psychiatry in UCD, was very welcoming of the product and is, in fact, assisting us in our negotiations with the HSE,” O’Riordan disclosed.

He said that while some people could be tempted to drive to Belfast to buy SJW, the price there was about £15 (€20.42) plus the cost of fuel and the drive, “so it’s not particularly economically worthwhile”.

The total volume of antidepressants sold in Ireland amounts to nearly €70 million per year, “so it is a big therapeutic area”, O’Riordan concluded.

Source: Irish Medical Times

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