Complementary therapies

In reply: Teschke questions the temporal sequence in our reported case1 by raising an ambiguity in dates. We wish to clarify: when the patient first presented on 23 May 2006, lethargy, arthralgia and nausea had been present for only about 3 weeks. This was well after the dose increase in black cohosh in March 2006. As such, the dose escalation definitely preceded the patient’s symptoms and liver failure. To further explore causality would require rechallenge with black cohosh, which we consider dangerous and unethical. Other unlikely causes of liver failure raised by Teschke, although theoretically possible, were not evident. The clinical course and histological findings in the pretransplant biopsy and explanted liver categorically excluded alcoholic cirrhosis and non-alcoholic steatohepatitis as causes of the liver failure. We also reiterate that there was no previous history of liver disease or other medication use. Increasing numbers of case reports are being published showing evidence of hepatotoxicity in patients taking black cohosh. Two well documented cases of seriously deranged liver function in patients taking black cohosh, which resolved on ceasing its use, have just been reported.2 Teschke concedes that four other cases have been reported where some causality between black cohosh and hepatotoxicity was evident.3 Neither Teschke nor Naser and Liske offer any reassurance on the long-term safety or lack of toxicity of black cohosh by referencing any properly conducted safety study. Certainly, there is recent in-vitro and in-vivo evidence in a rat model that black cohosh is toxic to hepatocyte mitochondria and impairs oxidative phosphorylation, resulting in apoptotic hepatocyte death.4 It is notable that, based on available evidence, the Australian Therapeutic Goods Administration requires preparations containing black cohosh to carry a warning of potential liver toxicity, stating that “there appears to be an association between the use of black cohosh and liver damage, but that it is very rare”.5 Furthermore, in the United Kingdom, the Medicines and Healthcare Products Regulatory Agency stated, “Warnings regarding rare adverse reactions in the liver should be added to the product information for black cohosh for both licensed and unlicensed products”.6 Government authorities in Europe3 and Canada7 have raised similar concerns. Long-term studies as well as further animal studies would be welcome in this area.

Elizabeth C-Y Chow · Marcus Teo · John A Ring · John W Chen

A 1978 case report in the Journal described a 25-year-old man with disseminated osteogenic sarcoma whose metastases regressed after treatment with diet and intensive meditation. Thirty years later, there has been no recurrence of his cancer, and a recent pneumonectomy for chronic bronchiectasis revealed mature cancellous bone in the resected lung. The man is otherwise well. (MJA 2008; 189: 663-665) Clinical recordA man who is now 58 years old was diagnosed in 1974, at the age of 24, with histologically confirmed high-grade osteogenic sarcoma of the right femur (Figure, A). His right leg was amputated in January 1975. Histopathologically, the tumour was described (in a 1994 review of the case) as follows: “The tissue is replaced by a cellular malignant spindle cell tumour forming osteoid and bone and having a disorganised pattern of proliferation . . . confirming the diagnosis of a high grade endosteal osteosarcoma (osteogenic sarcoma).” In December 1975, widespread bony and pulmonary metastases were diagnosed. Despite being told in March 1976 that he had only 2–3 weeks to live, the man survived until September that year, when he underwent three cycles of palliative chemotherapy with vincristine, adriamycin, cyclophosphamide and dacarbazine, as well as brief palliative radiation therapy. He elected to discontinue these therapies as his condition deteriorated further. The patient then consulted prominent psychiatrist and hypnotherapist Dr Ainslee Meares, who reported his case and his subsequent remarkable recovery in the Medical Journal of Australia in 1978.1 When Meares first saw the patient, he had visible bony tumours protruding from his ribs, sternum (Figure, B) and iliac crest, and was coughing up blood containing small spicules of bone (Figure, C). Meares taught him how to meditate, and both he and the patient felt this was a key component in recovery, although he also adhered faithfully to a vegan diet and tried many alternative therapies, including massage, acupuncture, faith healing and others. The patient recovered and returned to full-time work, founding and running self-help groups for people with cancer, but had persistent reminders of the original illness. Presumably related to immunosuppression from chemotherapy, he developed pulmonary tuberculosis in June 1978, and was treated for this condition for 12 months. This progressed to cavitation and severe bronchiectasis, causing repeated bouts of pneumonia and persistently elevated erythrocyte sedimentation rate (ESR). Chest x-rays in November 1989, 15 years after the patient’s diagnosis and subsequent recovery, showed evidence of previous tuberculosis and ongoing bronchiectasis, with a left hilar mass compressing the left upper lobe bronchus by 50%. Views of the lumbar spine and pelvis, taken at the same time to investigate ongoing back pain, showed abnormalities initially thought to represent progressive metastatic disease. The report noted “progressive metastatic disease with large osteoblastic deposit right ilium, sacrum, and invasion into L5”. That report was amended 4 days later, after comparison with films from 1978, to state “The appearances in the body of L5 . . . are those of metastatic disease but this appearance is essentially unchanged”. A thoracic computed tomography scan performed a few days later showed evidence of previous left lung tuberculosis. With no further treatment, the patient’s condition remained stable. X-ray images of the chest, pelvis and lumbar spine in 1993 were unchanged from 1989. Lung function testing in 1996 and 1999 showed satisfactory function, with an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio of 2.56 L/3.40 L. Indeed, the patient was well enough to go trekking in Nepal for three weeks in 1999 to a height of about 16 000 feet above sea level. However, two episodes of left lower lobe pneumonia in 2004 and chronic bronchiectasis resulted in referral to a thoracic surgeon with a view to pneumonectomy. Noting the patient’s chronically elevated ESR, indicating ongoing sepsis, and recurrent chest infections, the surgeon recommended left pneumonectomy while the patient was still young enough to tolerate the surgery. In December 2004, pneumonectomy was performed. As the patient had relied on elbow crutches since the original leg amputation, it was hoped that a minimally invasive approach might preserve chest wall skeletal structure and musculature, but because of widespread adhesions and tuberculous scarring, this was not possible. A complicated 5-hour pleuropneumonectomy was performed, with the pericardium being opened to enable access to the pulmonary veins, precipitating a short period of intraoperative ventricular fibrillation. Macroscopic pathological examination showed a small, collapsed, scarred left lung. The lung parenchyma was abnormal, and bronchiectasis, cavitation and scarring were widespread, but there was no obvious tumour. Microscopic examination showed severe bronchiectasis, but there was no evidence of mycobacterial infection. The report noted that “palpation of lung parenchyma deep to the hilum reveals a rock-hard consistency, impossible to section with a knife. Using a saw, horizontal cuts . . . reveal a centrally located bony mass 35 × 30 mm about, surrounding the bifurcation of the left main bronchus.” Histopathological examination of decalcified sections showed “a bony mass surrounding and incorporating large central bronchi and neurovascular structures. Much of the bone has a mature cancellous appearance with normal appearing osteocytes, and mature fat within the intertrabecular spaces. In addition there are foci of coarse sclerotic and heavily calcified bone which are devoid of viable osteocytes. No viable tumour is present.” After steady postoperative recovery, the patient returned to full-time work and remains well. DiscussionOsteosarcomas are rare malignant tumours of the skeleton characterised by formation of immature bone by tumour cells. At the time of this patient’s diagnosis, osteosarcoma was a devastating disease with very low survival rates.2 Most patients died within a year of diagnosis. Management centred around limb amputation, with palliative chemotherapy and radiation therapy for recurrences. Over the past 30 years, management has improved dramatically. With the use of limb-sparing surgery, induction and adjuvant chemotherapy, and surgical excision of metastases, survival rates of around 60% can now be expected for patients presenting with localised disease.3-5 There are limited data examining long-term outcomes among patients recovering from osteosarcoma. A few articles have reported long-term follow-up, including surveillance for recurrence,6 the development of other cancers,7 and cardiac toxicity from chemotherapy agents.8 Metastases have been known to develop as long as 14 years after diagnosis.6 While there is a report of spontaneous regression of a pulmonary metastasis that developed 5 years after treatment for osteosarcoma,9 the fate of regressed secondaries has not been well documented. Today, pulmonary metastases are often resected, but this is while the tumour is active. In this patient’s case, the lung was resected, for other reasons, 30 years after the original diagnosis, and incidentally, a large piece of mature cancellous bone was found surrounding the left main bronchus. This presumably represented bone formation by a long-since regressed secondary tumour, similar to the bone found in the primary tumour at the time of amputation. It is clear from the 1978 report that large sections of the externally visible osteogenic secondaries were resorbed as the cancer regressed. This was most obvious on the patient’s chest wall (Figure, D). However, some spinal and pelvic bone formed by the secondaries appears to have remained intact after tumour disappearance, as illustrated by the fact that x-rays taken of the spine and pelvis 15 years after diagnosis and recovery were identical with films of 11 years earlier and by the presence of bone in the resected lung. It is interesting to consider the possible factors involved in this man’s remarkable recovery. Spontaneous remission is a possibility, although exceedingly unlikely at such an advanced stage of disease, and its coincident timing with a wide range of self-help measures adopted by the patient makes this explanation even more improbable. Certainly, the patient had widespread disease from which recovery, even today, would be very unlikely. Although the patient received a short course of palliative chemotherapy and radiotherapy to his lumbar spine, it is unlikely that this would have been curative with such widespread metastatic disease. Meares and the patient attributed the remarkable recovery to intensive meditation,1 and it is true that the patient meditated from 3 to 5 hours daily after developing secondaries. He still regularly meditates and teaches others with cancer to do so. His fastidious adoption of the Gerson diet10 for 3 months, followed by adherence to a plant-based wholefood vegan diet may also have played some part. Such a lifestyle approach, incorporating meditation and a vegan diet, has recently been shown to cause significant modulation of gene expression and biological processes associated with tumour growth.11 Apart from illustrating the value of maintaining hope in the face of apparent hopelessness, this case shows that, long after tumour regression, metastatic lesions from osteosarcoma may contain significant amounts of residual bone. Even in the absence of tumour, these bony deposits may cause health problems in their own right, depending on their location. Our understanding of such unlikely survival continues to improve with the recent demonstration that modifiable lifestyle factors affect gene expression in patients with cancer.11

George A Jelinek MD, FACEM, DipDHM · Ruth H Gawler MB BS, MGPPsych, FACPsyMed

To the Editor: We read Pham and colleagues’ recent article1 with interest, as evidence mounts against the use of probiotics in critically ill patients. Although a plausible and attractive theory, probiotics in the patient with acute illness now appear ineffective, if not positively harmful. A recent randomised trial of probiotics in 298 patients with severe acute pancreatitis showed a non-significant rise in infective complications,2 in keeping with results of previous studies of critically ill patients.3,4 Disturbingly, mortality in the probiotic group was more than double that in the placebo group (P < 0.01). Bowel ischaemia was a prominent feature of deaths in the probiotic group (eight patients), but was not associated with any deaths in the placebo group (P < 0.004). It may be that non-occlusive mesenteric ischaemia in critical illness is exacerbated by the added bacterial load itself, or through a pro-inflammatory response by gut epithelial cells. While probiotics may be a benign and beneficial adjunct to enteral feeding in certain clinical situations, there is persuasive evidence that probiotic therapy is associated with increased infective complications in critically ill patients and significant mortality in patients with severe acute pancreatitis. Until there is evidence to the contrary, we believe probiotics should not be administered to patients with severe acute illness.

Shimonti Chatterjee · John Fraser

To the Editor: Pham and colleagues commented on the effects of probiotics; however, not much is known about the impact of probiotics on weight gain and obesity. It is known that a predominance of certain bacteria, such as Lactobacillus, in the bowel can promote weight gain. Many of these bacteria are found in probiotic products. The human intestinal microbiota is predominantly colonised by the Firmicutes and Bacteroidetes phyla of bacteria. Lactobacillus and Bifidobacterium, found in a number of probiotic products, belong to the Firmicutes phylum. A study has shown that obese people carry a higher proportion of bacteria from the Firmicutes phylum and that there is a statistically significant decrease in the proportion of Firmicutes bacteria as they lose weight.3 A similar pattern of Firmicutes predominance has been found in obese mice. Furthermore, the microbiota of the obese mice were more likely than those of lean mice to break down otherwise indigestible polysaccharides from the diet.4 In other words, a higher proportion of Firmicutes bacteria was associated with increased and more efficient caloric uptake from food. These data did not necessarily imply causation, so the investigators performed another experiment. They transferred intestinal microbiota from obese and lean donor mice to germ-free mice, and found that the mice who received microbiota from the obese donors had a significant increase in body fat after 2 weeks compared with the recipients from the lean donors.4 It is therefore likely that the bacteria often found in probiotics can cause weight gain. Obesity in children and adults is a major health problem in developed nations. Given the increasing use of probiotic products in such countries, large studies should be performed to characterise the association between probiotics and obesity. Such studies may not find any association or may find that there is only a dose-related risk. If there is an association, probiotics may still prove useful in certain circumstances (eg, for weight gain in children failing to thrive).

Sanjaya N Senanayake

In reply: The comments by Chatterjee and Fraser regarding the danger of administering probiotics to patients with acute severe illnesses are important additions to the debate on the risks and benefits of probiotic administration. We also thank Senanayake for his interesting comments on the possible role of probiotics in weight gain. The recently published multicentre trial1 describing unexpected adverse events associated with probiotics in acutely unwell patients with severe pancreatitis is one example of an adverse outcome following probiotic administration. The use of probiotics in patients with severe comorbidities and in those who are immunocompromised is also contraindicated. There are reported cases of Lactobacillus GG sepsis in premature babies with short gut syndrome,2 and Saccharomyces boulardii fungaemia has been described in immunocompromised patients.3 It is interesting to note that two systematic reviews have assessed the efficacy of probiotics in prevention of necrotising enterocolitis in premature (< 33 weeks’ gestation) and very low birthweight (< 1500 g) infants.4,5 Both reviews concluded that probiotics may decrease the incidence of necrotising enterocolitis in preterm infants, and that severe adverse events were not associated with probiotics in these unwell and immunodeficient patients. However, there were insufficient data to comment definitively on the short-term or long-term safety of probiotics in these infants; this will require assessment in future large trials. The increased scrutiny of probiotics resulting from the publication of the adverse outcomes in adults with severe acute pancreatitis1 may, by necessity, slow the commencement and progression of these larger trials in infants in the neonatal intensive care setting.

Mimi Pham · Daniel A Lemberg · Andrew S Day

To the Editor: In the January issue of the Journal, Harvey et al raised some serious concerns about the listing system for complementary medicines.1 In particular, they suggest scrapping the listing system (AUST L) and requiring complementary medicine (CM) products to be evaluated by the Therapeutic Goods Administration (TGA) for efficacy. Scrapping the system would be a significant setback for natural medicines, which have an important role to play in the health system. Such a move would be likely to remove products from the market, while the problem outlined by Harvey et al is more about the claims made for products rather than the products themselves. Certain CM products play a valuable role in many chronic diseases, in situations where existing synthetic products are often lacking. The regulatory system should encourage evidence-based CM products, and appropriate sanctions and enforcement should downgrade the claims made on products that don’t have a specific evidence base. CMs, especially herbal medicines, are complex products with numerous biologically active components. This means that the evidence is specific to the product and cannot be extrapolated. This fact has two important consequences for practitioners and the health system as a whole: the “generic” concept of synthetic pharmaceuticals (eg, interchangeability of paracetamol-containing products) is invalid for CM, meaning that a prescription for “St John’s wort” for example is not reliable, as St John’s wort is not one substance; and meta-analyses and systematic reviews of a “substance” (eg, a herb, or glucosamine) are easily misinterpreted because the products made from that “substance” are so different, any conclusions drawn can only be applied to the particular products that have been trialled.2 While the health system fails to discriminate between products that have specific trial evidence and those that do not, practising evidence-based complementary medicine will remain difficult. Encouraging evidence-based use of CM products, including supporting specifically clinically proven products, will lead to further research and better integration of CM into our health system for the benefit of the Australian public.

Nigel A Pollard

To the Editor: I am writing in response to the recent article by Harvey and colleagues about complementary medicines in Australia.1 Rottapharm is the developer and manufacturer of DONA glucosamine, a patented form of glucosamine. DONA is a registered medicine in 54 countries, in many on the equivalent of the Pharmaceutical Benefits Scheme. DONA is the leading glucosamine product in the world measured by specific trial evidence, sales and registration approvals. The fundamental issue is that different products that contain glucosamine and other complementary medicine (CM) products should be considered to be distinct products. Standards of active ingredients and methods of manufacture of finished products are substantially different between companies. Specific clinical trial evidence for glucosamine is essential because of: formulation differences (DONA glucosamine is a patented formulation of crystalline glucosamine sulfate, which is not comparable with glucosamine hydrochloride or other glucosamine sulfate formulations); bioavailability of glucosamine sulfate (unlike all other formulations on the Australian market, DONA has proven plasma concentrations and synovial fluid levels consistent with a clinical effect at a dosage of 1500 mg once a day, and is the only glucosamine product available with proven human bioavailability and pharmacokinetics);2 and results of specific clinical trials (studies of non-DONA glucosamine products [unknown formulations] have had mixed results while DONA has shown consistent efficacy across all trials, and has been assigned level 1A evidence by the European League Against Rheumatism).2-6 Not requiring sponsors to have evidence to support claims made about their products encourages low quality. For example, the market-leading glucosamine products in Australia have not been subject to independent peer review to establish whether they are effective. As the claims allowed on such products are identical to the claims allowed on DONA, there is no incentive for the industry to source the “real thing” or conduct their own clinical trials. In the interests of their patients, we believe that health professionals have a right to be able to identify specific products that have been clinically proven. Use of CMs that is not evidence-based is likely to lead to failure to realise significant health benefits of CM for the Australian public.

Antonino Santoro

To the Editor: The article by Harvey et al raises important concerns about the complementary medicine (CM) industry, particularly with respect to inappropriate marketing and advertising by some sponsors.1 The role of the Therapeutic Goods Administration (TGA) in setting standards and regulation of CMs should not be taken lightly. Australia has one of the highest quality standards for CMs internationally. Many CM products in Australia are assessed by expert authorities within the Office of Complementary Medicines and the Complementary Medicines Evaluation Committee of the TGA for safety and (where appropriate) efficacy relating to claims made for products.2 This is not fully appreciated by the authors. While many CMs may lack high-quality research to validate efficacy, this does not necessarily mean they are not clinically effective. Many clinicians and consumers find CMs to be of clinical value in improving health status. By suggesting that “the listing system should be scrapped, and CAMs [complementary and alternative medicines] . . . be assessed for efficacy and delisted if evidence is lacking” would be to deny consumers choice of treatment and potential health benefits, and lead to a “black market” or buying products from overseas which may not compare in quality. The authors fail to acknowledge that much of the drive for CM sales is actually coming from consumers through their choice of health care treatment.3 Consumers have the right to trial CMs. It is our role to ascertain safety issues and encourage clinical trials where they are lacking. For thousands of years, populations have relied on some CMs for health benefits, not having the advantage of any trials, but relying solely on traditional use. If the risk of harm to human health from the use of a CM outweighs any proven or unproven efficacy, consideration should be given to delisting the product or restricting its use. More research is required to assess safety data and efficacy for CMs. Australia has come a long way in regulating CMs. To say the “listing system should be scrapped” does not appreciate the tremendous efforts and gains made by the TGA compared with international efforts to enforce good manufacturing practice and various methods to better safeguard consumers. The authors do raise a valid point in saying that sponsors should provide “key evidence supporting each indication of the ARTG [Australian Register of Therapeutic Goods] . . . [which] should be publicly available on the Internet”. This may be useful for consumers and health practitioners, but requires appropriate funding to be viable. Furthermore, codes of conduct and complaints procedures for CMs, such as through the Complaints Resolution Panel, need to be strengthened, particularly with respect to breaches in the advertising code.4 To date, the Parliamentary Secretary has asked the TGA for advice on the proposals put forward by Harvey and colleagues.1,5 The government will consider its response to these proposals in the context of taking forward legislative changes that were deferred in anticipation of the establishment of an Australian New Zealand Therapeutic Products Agency (TGA advice, 28 May 2008).

Vicki Kotsirilos

To the Editor: Harvey et al1 have a right to be concerned about the parlous state of regulation in the billion-dollar complementary medicine (CM) industry. They are not alone, with various leaders from CM doctor groups and other leaders also expressing concern.2,3 Predictably, those in the CM industry itself are denying any problems exist, and just repeat their mantra that their products are safe and effective.3 As business people, the leaders of the CM industry must be pleased with the unchallenged run they have had over the past 20 years (except for one challenge with the Pan Pharmaceuticals debacle4). Consider one company (Mannatech) whose multilevel marketed products are promoted by their associates (natural drug representatives) as useful for arthritis, diabetes, dementia, attention deficit hyperactivity disorder, Parkinson’s disease, asthma, cancer and various other chronic diseases. The associates promoted claims that a product, Ambrotose, would assist with the above conditions using literature that did not carry the company logo, and used the company literature for non-specific claims and testimonials, thus absolving the company of responsibility. The Therapeutic Goods Administration is helpless in such a situation, and it was only when a medical practitioner started selling Mannatech products, including Ambrotose, from his surgery that the state medical board took an interest.5 However, the medical board has no jurisdiction over the company, and when the doctor was deregistered, he would have been able to keep marketing the product for the company. Mannatech launched Ambrotose in Australia, quoting the benefits of their product from a trial conducted and published in the Journal of the American Nutraceutical Association by American immunologist Dr See and colleagues.6 Eighteen months later, the published trial was the subject of much controversy.7 There was little if any effect on the company from this, in stark contrast with what one would expect in the pharmaceutical industry. Yes, Harvey and colleagues are just starting to scratch the surface of controversies that are decades old in this unregulated industry. For the good of the public and for the good of the CM industry, there needs to be a watchdog, similar to Medicines Australia, to regulate CM.

C Scott Masters

In reply: We agree with Kotsirilos that the current listing process of the Therapeutic Goods Administration (TGA) provides some protection for consumers by ensuring that complementary medicines (CMs) are manufactured in accordance with good manufacturing practice. The TGA claims that about 25% of new listings are assessed in detail each year for compliance with requirements, including that sponsors must hold evidence to support promotional claims made.1 However, we understand that the TGA does not assess this evidence for quality, and that literature searches are not performed to see if more recent evidence2 contradicts that submitted by the sponsor.3 In addition, sponsors can make a conservative claim at the time of listing but then make very different claims in promotional campaigns. An under-resourced, laboriously slow and largely impotent complaint system provides little disincentive to such unethical (but profitable) behaviour. While the Medicines Australia code of conduct (for prescription medicines) still has room for improvement, we agree with Masters that it currently provides more effective sanctions for breaches (eg, fines up to $200 000) than the options currently available to the TGA. Medicines Australia also proactively monitors compliance with the code of conduct and provides useful annual reports.4 Regardless, claims for CM that cannot be substantiated by appropriate evidence are better dealt with at the time of a marketing application rather than many months after advertisements have been published and when consumers have long been misled. We also recommended that therapeutic equivalence of the product in question should also be assessed at this time; a point reiterated by Santoro and Pollard. We support the right of consumers to choose from a variety of therapeutic modalities offered in the market place. However, good decision making requires evidence-based information about risks and benefits, regardless of whether the medicine in question requires a prescription, can be obtained over the counter or is a CM. Even if the risks of CMs are relatively low, the financial and opportunity cost for consumers can be significant. A pragmatic compromise to delisting CMs that lack evidence of effectiveness would be an opt-in system, funded by an additional fee, that would independently evaluate the effectiveness of specific CM products. A product with reasonable evidence of effectiveness could be awarded a symbol similar to the the National Heart Foundation “red tick”. Implementing this measure, together with the disclaimer and other recommendations we made in our article,5 would assist consumer choice and provide a market advantage for the sponsors of evidence-based, ethically promoted CMs. These proposals have received support from health professional and consumer organisations as well as sections of the CM industry. They have been put to the Parliamentary Secretary who assists the Minister for Health and Ageing.3

Ken J Harvey · Viola S Korczak · Loretta J Marron · David B Newgreen

Objective: To review the evidence for the effectiveness of complementary and self-help treatments for anxiety disorders and situational anxiety in children and adolescents.Data sources: Systematic literature search using PubMed, PsycINFO and the Cochrane Library for 111 treatments up to February 2006.Study selection: There were 11 treatments for which intervention studies had been undertaken and reported.Data extraction: Studies on each treatment were reviewed by one author and checked by a second. A consensus was reached for level of evidence.Data synthesis: Relevant evidence was available for bibliotherapy, dance and movement therapy, distraction techniques, humour, massage, melatonin, relaxation training, autogenic training, avoiding marijuana, a mineral–vitamin supplement (EMPower +) and music therapy. Findings from case–control studies, individual cohort studies or low quality randomised controlled trials indicated that several treatments may have potential to reduce anxiety, including bibliotherapy, massage, melatonin, and relaxation training.Conclusions: Although some complementary and self-help treatments might be useful for children and adolescents with anxiety, they need to be tested adequately through randomised controlled trials before they could be recommended.

Ruth Parslow PhD · Amy J Morgan BASc, BAppSci(Psychol)(Hons) · Nicholas B Allen BSc(Hons), MSc, PhD · Anthony F Jorm PhD, DSc · Colin P O’Donnell MB BCh, BAO, MRCPsych · Rosemary Purcell PhD

Paracetamol is involved in a large proportion of accidental paediatric exposures and deliberate self-poisoning cases, although subsequent hepatic failure and death are both uncommon outcomes. The optimal management of most patients with paracetamol overdose is usually straightforward. However, several differing nomograms and varying recommendations regarding potential risk factors for hepatic injury introduce complexity. In order to reconcile management advice with current Australasian clinical toxicology practice, revised guidelines have been developed by a panel of clinical toxicologists consulting to the poisons information centres in Australia and New Zealand using a workshop and consultative process. This article summarises the rationale for the recommendations made in these new guidelines.

Frank F S Daly MB BS, FACEM · John S Fountain MB ChB · Lindsay Murray MB BS, FACEM · Andis Graudins MB BS, PhD, FACEM, FACMT · Nicholas A Buckley MD, FRACP

Probiotics consist of yeast or bacteria, especially lactic acid bacteria. They are available as capsules, powder, fermented milks or yoghurts. Probiotics exhibit strain-specific differences in their resistance to acid and bile, ability to colonise the gastrointestinal tract, clinical efficacy, and benefits to the health of the host. There is level I evidence for the use of probiotics in treating acute infectious diarrhoea and preventing antibiotic-associated diarrhoea, with Lactobacillus rhamnosus GG and Saccharomyces boulardii having the most evidence to support their use for these conditions. There is level II evidence that S. boulardii combined with high-dose vancomycin is more effective than the antibiotic alone in preventing recurrent Clostridium difficile diarrhoea. There is level I evidence that probiotics prevent traveller’s diarrhoea. There is level I evidence for use of the high-potency probiotic VSL#3 in preventing pouchitis, and level II evidence for this agent in preventing relapse in patients with ulcerative colitis. Probiotics are generally regarded as safe and well tolerated. Some probiotics may be contraindicated in patients who are immunocompromised or have severe underlying illness, as they have been reported to cause fungaemia and bacteraemia.

Mimi Pham MB BS · Daniel A Lemberg FRACP · Andrew S Day MD, FRACP

Complementary and alternative medicines (CAMs) are being used increasingly in Australia, often in conjunction with conventional medicines.1 While the demand for CAMs is growing, the regulatory framework is weak. The electronic lodgement facility, introduced in 1996, has made it easier to place new CAMs on the Australian Register of Therapeutic Goods (ARTG). Concern about the regulation of CAMs has been growing among organisations such as CHOICE.2 Here, we review the regulatory requirements for CAMs, compare weight-loss products listed on the ARTG with registered pharmaceutical products, analyse complaint procedures and advocate policy change. We have focused on weight-loss products because of widespread concern about an obesity “epidemic”, extensive advertising of the products and the large number on the market. Regulation of therapeutic goods in AustraliaIn 1989, the federal Parliament passed the Therapeutic Goods Act 1989 (Cwlth), which created the ARTG. The ARTG has two parts: one for “registered goods” and the other for “listed goods”. Some goods captured by the Act are classified as “exempt goods” and are not entered in the ARTG (ss. 9A, 18). Box 1 shows the differences between the various categories of therapeutic goods. “Registered” medicines are considered to be of relatively higher risk and are individually evaluated by the Therapeutic Goods Administration (TGA) for quality, safety and efficacy before market entry. “Listed” medicines are considered to be of relatively lower risk (Box 2).3 Most, but not all, CAMs are listed medicines.4 Initially, the TGA did not require sponsors to have evidence to support claims made about their products. In 1999, concern that improbable therapeutic claims were being made about CAMs led to the introduction of a requirement that sponsors hold substantiating evidence.5 Further, since a report by the Expert Committee on Complementary Medicines in the Health System, a random sample of about 20% of new listings is said to be assessed each year for compliance with TGA requirements.6 Both these measures have been introduced to increase monitoring of CAMs. In 1991, the government introduced fees and charges to industry for services provided by the TGA, such as ARTG applications, good manufacturing practice inspections and annual licensing. The aim was to achieve 50% cost recovery. In 1998, the government determined that 100% of costs would be recovered.7 Illustrative TGA fees (at 1 July 2007) were $170 200 for registering and evaluating a new prescription medicine (a new chemical entity); $990 for registering and evaluating an over-the-counter product or CAM (plus $6570–$46 000, depending on the number of pages of data submitted); and $540 for listing a medicine. The annual charge for a registered (non-biological) prescription medicine was $3030; for a registered over-the-counter product, conventional or CAM, $920; and for a listed medicine, $690.7 Sponsors self-assess their medicines as being listable using the web-based electronic listing facility (ELF) of the ARTG. The ELF system automatically checks that the ingredients entered are consistent with those allowed in listed medicines and asks the sponsors to certify that they hold evidence to support the indications (and thus claims) made. Sponsors may pick either a coded indication such as “May aid or assist weight loss . . .” or a custom indication entered as free text in a memo field. More than one entry into either field is allowed. After payment of a fee, the ELF system automatically generates an “AUST L” number and a certificate of listing. Since the introduction of the ELF, the time taken to list a product has been reduced from around 5 months to 10 days or less for about 90% of applications.8 Complaints from the public about listed products need to be submitted to various authorities, as summarised in Box 3.9 In February 2007, the Australian Government reintroduced a provision of the Therapeutic Goods Advertising Code, which had existed before August 2005, prohibiting health care professionals from endorsing therapeutic goods in advertisements to consumers. This provision took effect from 8 March 2007, but allowed existing advertisements to continue for either 2 years after approval (eg, in print) or 1 year if approval had not been required (eg, Internet advertisements).10 An example: weight-loss productsIn Australia, both listed and registered weight-loss products are available. To determine the numbers of each and compare them, we asked the TGA to search the ARTG for registered or listed products with the indication “weight loss”, or similar, for the period 1996 to 2006. We then supplemented the list by searching the shelves of pharmacies and health food shops and Australian Internet sites. Because of problems encountered, the TGA made available a subset of the ARTG database so that we could refine their search for weight-loss products. For the registered and listed products found, we compared the therapeutic claims with the published evidence. The website of the Therapeutic Goods Advertising Code Council was used to identify complaints and select illustrative case studies. Products identifiedThe initial search output received from the TGA failed to show some registered weight-loss products, such as orlistat (Xenical [Roche]) and sibutramine (Reductil [Abbott]). It also failed to show many listed CAMs that were being actively promoted for weight loss. Some of these problems resulted because the ELF system allowed sponsors of listed products to enter information into the ARTG in free text without verification by TGA staff. Some non-standard indications had been used for weight-loss products (such as “thermogenic”, “body sculpting”, “reduce carb cravings”), which made a complete search for such products difficult, if not impossible. Our own search found over 1000 new weight-loss products listed on the ARTG from 1996 to 2006. New listings generally increased over the period, from 45 in 1996 to 144 in 2006. Most contained multiple ingredients (herbs, vitamins, minerals). Homoeopathic products are not included on the ARTG. Over the same period, 10 conventional medicines for weight loss were registered with the ARTG, each containing one ingredient, (orlistat, diethylpropion, phentermine, sibutramine). All these substances are officially scheduled poisons, and products containing them are registered for the management of obesity, unless the product is for export. Those containing orlistat and sibutramine have been fully evaluated. Phentermine-containing medicines were “grandfathered” on to the ARTG because they were already on the Australian market when the Act took effect in February 1991. Diethylpropion is no longer marketed. The safety and efficacy of these agents has been comprehensively reviewed.11 Thus, sponsors could decide not to market products they had placed on the ARTG or to take them off the market but leave them on the ARTG. Taking into account these limitations, we found about 100 times as many listed weight-loss products on the ARTG as registered products. It is not possible to be too specific about numbers because there were confounding factors, such as the inclusion in the listed goods part of the ARTG of prescription-only medicines that were destined for export. In our opinion, the indications for weight-loss products listed on the ARTG (and thus their promotional claims) were often not in accord with the limited scientific evidence available. Furthermore, the number of such listed products is increasing each year at a much greater rate than registered products. It is possible that this has been influenced by the decision not to evaluate listed products for efficacy and also the lower fees for listing a product compared with registration. A typical weight-loss productAn example of a publicly available, listed weight-loss product is shown in Box 4. We are unaware of publicly available evidence from clinical trials to support the therapeutic claims made for this product or for many other listed (and homoeopathic) weight-loss products. Several systematic reviews have evaluated the commonly included ingredients and have concluded that, at best, more definitive clinical trials are required before conclusions can be drawn.12,13 While these products are of relatively low risk, some herbal ingredients can cause harm by themselves and also by interacting with conventional medicines; both kinds of event may be under-reported.14,15 The Complaints Resolution Panel found that the claims made about the illustrated product, Xantrax (Hershel-Beck Laboratories), breached the Therapeutic Goods Advertising Code as they were misleading and likely to arouse unwarranted and unrealistic expectations of product effectiveness.16 In our experience, it usually takes 3 to 4 months for submitted complaints to be adjudicated by the Complaints Resolution Panel and several more months before the results are made public. Meanwhile, promotional campaigns continue. In addition, the sanctions imposed appear ineffectual, as shown by the fact that some companies repeatedly breach the Therapeutic Goods Advertising Code. For example, from March 2004 to November 2007, the sponsor of Xantrax, Cat Media Pty Ltd, has had at least 28 complaints about its products, 22 of which have been upheld.16,17 In 2006, the Panel received over 350 complaints, more than twice the number received in 2005. Of these, 170 have been finalised and 100 are still being processed, 60 concerning homoeopathic products and which were referred to the TGA, and 22 referred to other bodies. The system is clearly overloaded and under-resourced. We submitted complaints over 6 months ago that have yet to be addressed. We submitted complaints over 12 months ago that have been referred to other jurisdictions, about which we have heard no more; meanwhile, promotion continues. ImplicationsIn 2003, the Expert Committee on Complementary Medicines in the Health System was established to reassure the public about the safety and quality of CAMs. The Committee said (Finding 4.1.1) that the “Government needs to take a more active role in ensuring that consumers have access to reliable information about complementary medicines, and the skills to interpret information and make informed decisions”.6 In 2005, the government responded to the expert committee report by accepting, noting or supporting all but one of the 49 recommendations. The TGA established the Complementary Medicines Implementation Reference Group to oversee the implementation and has provided progress reports.18 Despite the widespread use of CAMs, many consumers are unaware that listed medicines do not undergo the same stringent evaluation process as registered medicines, or indeed, that there is a difference between the two. Consumers are not sufficiently protected by regulation in this case. It is difficult to reconcile the therapeutic claims made for many CAMs with the objects of the Act: “to provide for . . . a national system of controls relating to the quality, safety, efficacy and timely availability of therapeutic goods...” (s. 4, our italics). In an attempt to explain the difference, the TGA produced a pamphlet in 1995 called Buying medicines — what’s on the label for me? It was available in pharmacies and health food shops and is now on the Internet.19 While the content reflects the legal situation, the omission that AUST L listed medicines are not evaluated for efficacy diminishes the utility of the pamphlet for the very people to whom it is directed. This has financial as well as health implications for consumers. Brian Grogan, national president of the Pharmaceutical Society of Australia, has noted: While those products that lack evidence for effectiveness may not actively harm the physical health of those who take them, they may well be harming patients’ financial health, some of whom may have to forgo other more beneficial evidence-based treatments or other necessities.20 In addition, any herb has many different chemical constituents, the presence and concentration of which vary, depending on the source of the herb, and the extraction and standardisation methods used. Marked variations of chemical constituents have been found in different commercial products that purported to contain the same amount of a particular herb.21 Currently, the TGA accepts crude assays that do not necessarily confirm that one herbal product has the same chemical constituents as another that has been proven to be clinically effective. In addition, the TGA does not require stability data on listed products. Finally, the large number of repeated breaches of the Advertising Code by certain companies, together with an increasing backlog of complaints, shows that complaint procedures are no substitute for adequate regulation at the time of market entry. Consumers (and health professionals) cannot exercise informed choice about CAMs if they are denied information about the quality and efficacy of these products. SolutionsHow could the present situation be improved? We propose the following actions: AUST L medicines (and homoeopathic medicines) should include on their labels a statement, such as “This medicine has not been evaluated by Australian health authorities for efficacy”. A campaign to educate the public about such matters is needed. This would best be done by the National Prescribing Service, which is currently conducting a survey of educational needs in relation to CAMs. Ethical codes of conduct and complaint procedures for CAMs, over-the-counter and prescription drugs should be streamlined, harmonised and brought under one adequately resourced authority. Consistent (and meaningful) sanctions should be imposed on companies that repeatedly breach codes (for example, corrective advertising orders and fines linked to company turnover, with the money used to support the complaint system). The ARTG database should be updated with respect to listed products. Sponsors should be required to add key evidence supporting each indication on the ARTG and entries should be checked by staff of the regulatory body and coded with respect to therapeutic indication. This information should be publicly available on the Internet. The TGA should check the analysis of herbal products more thoroughly and allow sponsors to use clinical trial evidence relating to other products only where their own product has been shown to have an identical herbal preparation, extraction and standardisation process. Finally, we believe that, in the longer term, the listing system should be scrapped, and CAMs (including homoeopathic medicines) should be assessed for efficacy and delisted if evidence is lacking. Public money should be used for this, not listing fees. There is a current perception that 100% cost-recovery by the TGA (as with the Food and Drug Administration in the United States) has led to commercial considerations outweighing the need for consumer protection.22,23 Listed weight-loss products would be a good place to start the regulatory reform, given the increasing problem of obesity in Australia. 1 Contrasting requirements of the Therapeutic Goods Administration (TGA) for different categories of goods Requirement Registered goods (pharmaceutical products) Listed goods (complementary medicines) Exempt goods Label designation AUST R AUST L na Compliance with Code of Good Manufacturing Practice Yes Yes No Manufacturers licensed by TGA Yes Yes No Efficacy evaluated by TGA Yes No No Stability (shelf-life) evaluated by TGA Yes No No Individual ingredients evaluated for safety by TGA Yes Yes Some (eg, those in antiperspirants, fluoride toothpastes) Examples All medicines included in a poisons schedule, all PBS medicines, all other medicines not listed or not exempt goods Most herbal preparations, vitamins, minerals, glucosamine, some homoeopathic medicines (if the sponsors so choose), export goods Homoeopathic medicines, extemporaneously dispensed medicines, dandruff shampoos, antiperspirants, fluoride toothpastes na = not applicable. PBS = Pharmaceutical Benefits Scheme. 2 Main criteria used by the Therapeutic Goods Administration for listed complementary medicines (with the exception of homoeopathic products) They may contain only ingredients approved for use in listed medicines (those with well established quality and safety profiles); They must be labelled and advertised only for indications consistent with low risk (eg, symptomatic relief of non-serious diseases, disorders and conditions) and must not be indicated for the treatment of a serious form of a disease, condition, ailment or defect as specified in the Therapeutic Goods Advertising Code; There must be evidence (which can be either traditional or scientific), held by the sponsor of the product, to support any claim that the sponsor makes relating to the medicine; and They do not contain substances that are scheduled in the Standard for the Uniform Scheduling of Drugs and Poisons or otherwise restricted (eg, included in Part 4 of Schedule 4 of the Therapeutic Goods Regulations 1990). 3 Bodies handling complaints about listed products and registered over-the-counter products Complaint Regulation About product quality or claims made on the pack or pack insert Therapeutic Goods Administration’s Office of Complementary Medicines About promotional claims made in specified media (television, radio, Internet, newspapers, magazines, outdoor signs and cinema) Complaints Resolution Panel assesses concerns against the Therapeutic Goods Advertising Code About other advertising, such as pharmacy window displays, brochures, leaflets and catalogues Complaints Resolution Committee of the Complementary Healthcare Council of Australia or Australian Self-Medication Industry’s Complaints Panel 4 Xantrax (Hershel-Beck Laboratories), an example of a listed weight-loss product Ingredients Each Xantrax tablet contains: Camellia sinensis (green tea) Citrus aurantium fruit (bitter orange) Paullinia cupana (guarana) Panax ginseng (Korean ginseng) Ilex paraguariensis (yerba mate) 11 additional vitamins and minerals Therapeutic claims Xantrax helps by: delaying gastric emptying thus prolonging a sense of fullness suppressing appetite maintaining healthy energy levels improving exercise performance enhancing the body’s ability to cope with stress supporting healthy metabolism Pharmacy poster for Xantrax.

Ken J Harvey FRCPA · Viola S Korczak BEc(SocSc), MIPH · Loretta J Marron BSc, AssocDipBus · David B Newgreen BPharm, MBA

To the Editor: Xue and colleagues reported an interesting randomised, single-blind trial of acupuncture for persistent allergic rhinitis (PAR) and concluded that acupuncture is an effective treatment for this condition.1 I am not entirely sure that this is true. The authors state that “once needling sensation (known as de-qi) was obtained, the needles were manipulated . . .”. In the sham group they inserted needles at non-acupuncture points where, according to acupuncture theory, no de-qi can be elicited. Thus the intervention patients were experiencing de-qi, and the control patients were not. This means that neither the patients nor the therapist were blinded. Consequently, the difference in outcome between the two groups could be unrelated to acupuncture itself, and caused by patient expectation, therapist expectation or both. In addition, the statement of Xue et al that “no other randomised controlled trial of acupuncture in adults with PAR has been reported in the English medical literature”1 was misleading. Our review of this topic2 included no fewer than six randomised controlled trials, all either published in English or, in one case, with an English abstract. Interestingly, three of them suggested acupuncture to be effective, while three failed to do so. I fear that the study by Xue et al does little to resolve this intriguing discrepancy.

Edzard Ernst

In reply: Ernst is concerned about the sham acupuncture procedure used in our trial.1 Although not universally agreed, the sham/placebo control we adopted has been described as best practice.2,3 The assumption that, without de-qi, participants would not be blinded is not supported by the literature. In fact, a sham procedure without de-qi was used in a recent trial reported by Ernst and colleagues on acupuncture for subacute stroke rehabilitation.4 In that study, as in ours, to increase the credibility of blinding, participants with previous experience of acupuncture were excluded, and those assessing the outcomes of treatment were blinded. With regard to previous randomised controlled trials of acupuncture for adults with persistent allergic rhinitis in the English medical literature, Ernst failed to distinguish between seasonal allergic rhinitis (SAR) and persistent allergic rhinitis (PAR).5 Of the six studies included in his review,5 five were on SAR, and the sixth, which was cited in our report (reference 14), was on children with PAR. These reports, therefore, are not inconsistent with our findings.

Charlie C L Xue · David F Story

Objective: To investigate the effectiveness and safety of acupuncture in persistent allergic rhinitis (PAR)Design: Randomised, single-blind, sham-controlled trial conducted from May 2004 to February 2005.Participants and intervention: 80 patients with PAR (age, 16–70 years) were randomly assigned to receive real or sham acupuncture. After a 1-week baseline period, participants were treated twice weekly for 8 weeks and followed up for another 12 weeks.Main outcome measures: Nasal obstruction, sneezing, rhinorrhoea and nasal itch were each self-assessed daily on a 5-point scale, and scores were aggregated weekly. The sum of the symptom scores (total nasal symptom score, TNSS) was also determined. A secondary outcome was use of PAR relief medication.Results: After 8 weeks’ treatment, the weekly mean difference in TNSS from baseline was greater with real (−17.2; 95% CI, −24.6 to −9.8) than with sham acupuncture (−4.2; 95% CI, −11.0 to 2.7) (P = 0.01). The decrease in individual symptom score was also greater with real acupuncture for rhinorrhoea (P < 0.01) but not the other symptoms. At the end of follow-up, the greater difference in TNSS from baseline in the real acupuncture group was still apparent: real, −21.0 (95% CI, −29.1 to −12.9) versus sham, − 2.3 (95% CI, −10.2 to 5.6) (P = 0.001). Moreover, the differences from baseline in all four individual symptom scores were greater for the real than for the sham group (P < 0.05). Real and sham acupuncture were both well tolerated.Conclusion: Our findings suggest that acupuncture is effective in the symptomatic treatment of PAR.Trial registration: Australian Government Therapeutic Goods Administration CTN 034/2004.

Charlie C L Xue BMed, PhD · Xuedong An BMed, MApplSc · Thomas P Cheung MSc · Cliff Da Costa PhD · George B Lenon PhD · Frank C Thien MD · David F Story PhD

Why am I so tired? How to put the fuel back in your tank Ginni Mansberg, Anne Thomson. Melbourne: Michelle Anderson Publishing, 2006 (vi + 151 pp). ISBN 085572 369 6 This book is written for patients who experience tiredness. Most general practitioners appreciate this is a common complaint they see and agree it can be quite challenging to treat, especially within consultation time constraints. There are a number of aspects of this book that I love. It is easy to read. It is written as though the authors are having a friendly, chatty conversation with the reader. The authors encourage patients to attend their GP by making a longer consultation time with them. They also discuss what diseases need to be excluded and why certain tests (such as iron levels and thyroid function) are performed by the GP. The role of depression in fatigue is also given due respect. Mansberg and Thomson focus on lifestyle factors that are known to impact on health and energy. These include improving diet, exercise, sleep, stress management, and avoidance of smoking and alcohol. They also cover the possible role of nutritional supplements and herbs for the treatment of fatigue, but do quite rightly emphasise the lack of research in this area. Tiredness can be a difficult condition to treat and is often confused with chronic fatigue syndrome. The book provides some nice, easy practical lifestyle solutions. It motivates the patient to take control of and responsibility for their health; to be more proactive, taking simple steps to help restore their energy and vitality. So when a GP is next confronted with a tired patient, this would be a useful book to suggest, to reinforce their advice on the importance of lifestyle changes. I have already started recommending this book to my patients. At $19.95, the book is great value for money.

Vicki Kotsirilos

Objective: To determine whether eating Lactobacillus rhamnosus GG (LGG) in the form of commercially available yoghurt improves clearance of vancomycin-resistant enterococci (VRE).Design: Double-blind, randomised, placebo-controlled trial.Setting: Renal ward of Austin Health, a tertiary hospital, Feb–Oct 2005.Participants: 27 VRE-positive patients, 14 receiving active treatment and 13 controls.Interventions: Subjects were randomly assigned to either a treatment group (receiving 100 g daily of yoghurt containing LGG for 4 weeks) or a control group (receiving standard pasteurised yoghurt). Faecal samples were obtained three times at about weekly intervals. Treated patients were tested for VRE again at 8 weeks. Patients in the control group who had failed to clear VRE after 4 weeks were then given LGG-containing yoghurt for 4 weeks, as an open continuation.Main outcome measure: Number of faecal specimens clear of VRE.Results: Of the 27 patients enrolled, 23 completed the study. Two patients were lost to follow-up, one died and one withdrew. All 11 patients in the treatment group who completed the study cleared VRE. Three subjects reverted to VRE positivity after using antibiotics to which LGG is sensitive, while all others remained negative for at least 4 weeks after trial completion. Twelve control subjects completed the study, of whom one cleared VRE and 11 remained VRE-positive. Eight of these 11 patients were subsequently crossed over to receive LGG yoghurt, and all cleared VRE within 4 weeks.Conclusion: To our knowledge, this is the first description of a probiotic therapy to successfully treat gastrointestinal carriage of VRE in renal patients. Further investigation of the use of LGG in VRE-positive patients is warranted.

Karen J Manley BSc, MHumNutr, GradDipDiet · Margaret B Fraenkel BM BS, PhD, FRACP · Barrie C Mayall MB BS, FRACP, FRCPA · David A Power BM BS, PhD, FRACP

To the Editor: St John’s wort (SJW) (Hypericum perforatum) is a natural medicine commonly used for treating depression. We recently encountered a case of an overdose of SJW leading to serious manifestations in the patient. A 16-year-old girl presented to the emergency department with seizures and confusion. She was intubated and admitted to the intensive care unit. The only relevant history was of febrile convulsions at the age of 4 years. There had been no head trauma. Results of a computed tomography brain scan and cerebrospinal fluid examination were unremarkable. Electrolyte levels were normal, and standard drug toxicological screens were negative. An electroencephalogram (EEG) confirmed diffuse spike wave activity consistent with generalised epileptic activity. On further questioning, it was found that she had taken large quantities of SJW — up to fifteen 300 μg tablets a day in the 2 weeks leading up to admission and an additional 50 tablets just before presentation — for a recent “depressive episode”. Depression had not been formally diagnosed, and the tablets had been obtained “over the counter” from a local pharmacy. A provisional diagnosis of seizures due to an overdose of SJW was made. High performance liquid chromatography was not performed to quantify hypericum extract in serum and urine, as these tests are not available in our hospital. A repeat EEG at discharge on Day 6 was normal, and there were no further seizures in the following 6 months. Psychiatric assessment during the patient’s hospital stay revealed a likely suicide attempt following recent social stresses. There is some evidence for the efficacy of SJW in treating depression.1 In the United States and Australia it is available without prescription, but in Germany, where it is prescribed more frequently than fluoxetine for depression, it is available by prescription only. The reported incidence of adverse drug reactions to SJW is 0–5.7%.2 Although these are usually minor and transient, more serious adverse reactions (such as serotonin syndrome) have been reported.3 SJW was implicated as a likely, but unproven, cause of seizure-related events in a recent review,4 but our case appears to be the most severe reported so far. Adverse reactions are thought to be more common if SJW is taken in conjunction with selective serotonin reuptake inhibitors, but have also been described when SJW is taken alone.5

Dharshi C Karalapillai · Rinaldo Bellomo

To the Editor: Sanderson et al provide an interesting viewpoint about how the community, including medical practitioners, have embraced complementary and alternative medicine (CAM).1 However, if we were reviewing this article for publication, we would ask the authors to: make a valid distinction between those complementary and alternative therapies promoted as curative versus those considered palliative; define how they decided which therapies belong to one or other side of the arbitrary CAM boundary; review and justify the boundaries for the “therapeutic footprint” in a more evidence-based and rigorous way; locate specific therapies inside the footprint; locate where chemotherapy lies within the footprint, in light of the recent review showing, for the vast majority of adult malignancies, its marginal survival benefits considering its high costs, both monetary and healthwise;2 emphasise that there are relatively few recorded adverse events for CAM compared with conventional cancer care (Therapeutic Goods Administration Medicine Summary reports 2003, 2004, 2005 — Dr K Mackay, Acting Director, Adverse Drug Reactions Unit, TGA, personal communication); and vigorously question the marketing of conventional medicines, such as trastuzumab (Herceptin, Roche), to vulnerable patients and an uncritical public when the evidence suggests huge expense and little, if any, survival benefit.3 Perhaps a distinction also needs to be made between CAM therapies, many of which provide proven symptomatic relief, and those lifestyle interventions, such as exercise,4 dietary change,5 and social support, which provide symptomatic relief and may also confer a survival benefit. It does not serve the profession well when many cancer patients and their carers have to go outside the medical system to access information, advice and therapies which they should have easy access to within the system. In fact, we might even question how helpful these arbitrary boundaries are when all that patients and doctors want is to use what works and what is safe.

Craig S Hassed · Vicki Kotsirilos · Marie Pirotta · Avni Sali

In reply: We would like to thank Hassed and colleagues for their comments on the “therapeutic footprint” and their questions about locating specific therapies within the model. While it was outside the scope of our article to critically analyse different treatments using the model (as benefits and risks will vary from patient to patient), we would like to direct Hassed et al to a more detailed consideration of the risks and benefits of chemotherapy.1 We do not see our model as a tool to categorise or economically appraise specific treatments, but rather as one to help conceptualise the key issues to be considered when proposing treatment — the evidence for benefits and risks, contextualised according to treatment goals. The model provides a basis for comparison, taking us beyond arbitrary and unhelpful arguments about the distinctions between complementary and alternative therapies and their boundaries. We hope that the model will encourage evaluation of evidence for all therapies and support critical evaluation not only of drugs, but also lifestyle interventions that may benefit patients. The primary or essential purpose of the model is to encourage the posing of questions like those articulated by Hassed and colleagues to any therapist — whether they identify as medical, complementary or alternative.

Christine R Sanderson · Bogda Koczwara · David C Currow

Objective: To collect contemporary accounts of celebrity use of complementary and alternative medicine (CAM), to aid clinicians in determining which CAM treatments patients are likely to use.Design: Articles published during 2005 and 2006 reporting celebrity use of CAM.Results: 38 celebrities were found to use a wide range of CAM interventions. Homeopathy, acupuncture and Ayurveda were the most popular modalities.Conclusions: There may be many reasons why consumers use CAM, and wanting to imitate their idols is one of them.

Edzard Ernst MD, PhD, FRCP · Max H Pittler MD, PhD

Objective: To review the evidence for the effectiveness of complementary and self-help treatments for depression in children and adolescents.Data sources: Systematic literature search using PubMed, PsycINFO and the Cochrane Library for 131 treatments up to February 2006.Study selection: There were 13 treatments that had been evaluated in intervention studies.Data extraction: Studies on each treatment were reviewed by one author and checked by a second. A consensus was reached for level of evidence.Data synthesis: Relevant evidence was available for glutamine, S-adenosylmethionine, St John’s wort, vitamin C, omega-3 fatty acids, light therapy, massage, art therapy, bibliotherapy, distraction techniques, exercise, relaxation therapy and sleep deprivation. However, the evidence was limited and generally of poor quality. The only treatment with reasonable supporting evidence was light therapy for winter depression.Conclusions: Given that antidepressant medication is not recommended as a first line treatment for children and adolescents with mild to moderate depression, and that the effects of psychological treatments are modest, there is a pressing need to extend the range of treatments available for this age group.

Anthony F Jorm MPsychol, PhD, DSc · Nicholas B Allen MSc, PhD, MAPS · Colin P O'Donnell MB BCh, BAO, MRCPsych · Ruth A Parslow PhD · Rosemary Purcell PhD · Amy J Morgan BASc, BAppSci(Psychol)(Hons)