Are there diseases for which a placebo treatment is state of the art?

Are there diseases for which a placebo treatment is state of the art?

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I was reading about the placebo effect, and I wondered if there exists or ever existed a disease with the following properties:

  1. There are no known treatments for the disease that perform better than a placebo.
  2. The placebo has a positive effect on patient outcomes.

If there is a disease like this, what do doctors do? Do they give out prescriptions for sugar pills because the pills will do better than nothing?

Doctors sometimes use "open-label placebos" - substances that have no known physiological effect on the treated disease, but have been associated with symptoms improvement in some studies. Open-label means doctors openly tell people it's placebo. The example is treatment of irritable bowel syndrome.

Doctors use not only fake drugs, but also real drugs as placebos. There are some doctors who don't have a courage to say they don't know how to help, so they just prescribe "something" (a real but ineffective drug) in the hope they will convince someone that they provided some help.

Prescribing "placebo treatments": results of national survey of US internists and rheumatologists (BMJ, 2008)

Prescribing placebo treatments seems to be common and is viewed as ethically permissible among the surveyed US internists and rheumatologists. Vitamins and over the counter analgesics are the most commonly used treatments. Physicians might not be fully transparent with their patients about the use of placebos and might have mixed motivations for recommending such treatments.

There is a common practice to prescribe:

  • Vitamins or antibiotics for common cold, flu and other viral infections (Montana DPHHS ; JRSM Open)
  • Antipsychotics, antidepressants and sedatives for personal problems that can't really help to solve those problems
  • Various drugs for fibromyalgia

The seeming effect of placebo can discourage a person to seek for the real treatment.

Placebos Without Deception: Outcomes, Mechanisms, and Ethics

Scientific research indicates that open-label and dose-extending placebos (that patients know are placebos) can elicit behavioral, biological, and clinical outcome changes. In this chapter, we present the state-of-the-art evidence and ethical considerations about open-label and dose-extending placebos, discussing the perspective of giving placebos with a rational, as dose extension of active drugs, or expectancy boosters. Previous comprehensive reviews of placebo use have considered how to harness placebo effects in medicine and the need to focus on elements of the clinical encounter as well as patient𠄼linician relations. Here, we illustrate the similarities and differences between standard (deceptive) placebos, open-label placebos and dose-extending placebos. We conclude that placebos without deception would override ethical barriers to their clinical use. This paves the way to future large-scale, pragmatic randomized trials that investigate the potential of ethical open-label and dose-extending placebos to improve patients’ outcomes, and reduce side effects.

Medical Definition of Placebo effect

Placebo effect: Also called the placebo response. A remarkable phenomenon in which a placebo -- a fake treatment, an inactive substance like sugar, distilled water, or saline solution -- can sometimes improve a patient's condition simply because the person has the expectation that it will be helpful. Expectation to plays a potent role in the placebo effect. The more a person believes they are going to benefit from a treatment, the more likely it is that they will experience a benefit.

To separate out this power of positive thinking and some other variables from a drug's true medical benefits, companies seeking governmental approval of a new treatment often use placebo-controlled drug studies. If patients on the new drug fare significantly better than those taking placebo, the study helps support the conclusion that the medicine is effective.

The power of positive thinking is not a new subject. The Talmud, the ancient compendium of rabbinical thought, states that: "Where there is hope, there is life." And hope is positive expectation, by another name. The scientific study of the placebo effect is usually dated to the pioneering paper published in 1955 on "The Powerful Placebo" by the anesthesiologist Henry K. Beecher (1904-1976). Beecher concluded that, across the 26 studies he analyzed, an average of 32% of patients responded to placebo.

It has been shown that placebos have measurable physiological effects. They tend to speed up pulse rate, increase blood pressure, and improve reaction speeds, for example, when participants are told they have taken a stimulant. Placebos have the opposite physiological effects when participants are told they have taken a sleep-producing drug.

The placebo effect is part of the human potential to react positively to a healer. A patient's distress may be relieved by something for which there is no medical basis. A familiar example is Band-Aid put on a child. It can make the child feel better by its soothing effect, though there is no medical reason it should make the child feel better.

People who receive a placebo may also experience negative effects. They are like side effects with a medication and may include, for example, nausea, diarrhea and constipation. A negative placebo effect has been called the nocebo effect.

A clinical study of lupron depot in the treatment of women with Alzheimer's disease: preservation of cognitive function in patients taking an acetylcholinesterase inhibitor and treated with high dose lupron over 48 weeks

To test the efficacy and safety of leuprolide acetate (Lupron Depot) in the treatment of Alzheimer's disease (AD), we conducted a 48-week, double-blind, placebo-controlled, dose-ranging study in women aged 65 years or older with mild to moderate AD. A total of 109 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 24 inclusive were randomized to low dose Lupron Depot (11.25 mg leuprolide acetate), high dose Lupron Depot (22.5 mg leuprolide acetate), or placebo injections every 12 weeks. There were no statistically significant differences in primary efficacy parameters (ADAS-Cog and ADCS-CGIC), although there was a non-statistically significant trend in favor of the high dose Lupron group on the ADAS-Cog. There were no statistically significant differences in secondary efficacy parameters (NPI, ADCS-ADL, BI, and ADCS-Severity Rating). However, in the a priori designated subgroup analysis of patients taking an acetylcholinesterase inhibitor (AChEI), there was a statistically significant benefit in the high dose group compared to both the low dose and placebo groups as determined by ADAS-Cog (mean decline: 0.18, 4.21, and 3.30), ADCS-CGIC (% subjects experiencing decline: 38, 82, and 63), and ADCS-ADL (mean decline: -0.54, -8.00, and -6.85), respectively. No differences between treatment groups were seen on the NPI, ADCS-CGI Severity Rating, or the BI in the subgroup analysis. These data indicate that cognitive function is preserved in patients treated with high dose Lupron who were already using AChEIs. The positive interaction between Lupron and AChEIs warrants further investigation for the treatment of AD.

Keywords: 17β-estradiol Alzheimer's disease Lupron acetylcholinesterase inhibitor apolipoprotein E clinical trial cognitive testing gonadotropin-releasing hormone luteinizing hormone women.

Treatment of acute GVHD

aGVHD classically affects skin, liver and gastrointestinal tract. It is staged and graded based on the degree of organ involvement and clinical status of the patient [73]. The clinical feature and staging and grading of aGVHD are described in Tables 1 and 2, respectively. It is established that the overall grade of aGVHD has major impact on outcomes post HSCT, with transplant-related mortality ranging from 28 for stage 0 to 92 % for stage IV disease [74]. aGVHD can occur any time around engraftment to day 100 or so, but most likely develops in second month after allogeneic HSCT during CI-based prophylaxis [75].

First-line treatment of acute GVHD

Steroid and CI remain the gold standard for initial treatment of aGVHD. Mild skin aGVHD (grade I) can be treated with topical steroids alone. For more severe disease or any visceral involvement (grade II–IV) high-dose systemic steroid and CI are the mainstay of treatment. Studies using multiple different doses, schedules and duration of treatment have been published. In a retrospective study of 740 patients treated for grade II–IV aGVHD, 531 patients were treated with steroid and complete or partial responses were achieved in 44 % patients with improvement in skin, liver and gut disease at 43, 35 and 53 %, respectively [8]. Similar results have been seen in other retrospective studies as well [15]. The response to initial treatment correlates directly with post-transplant survival [76, 77]. The treatment for grade II–IV aGVHD is usually started with methylprednisolone at 2 mg/kg/day with CI. An exception is the aGVHD of the upper GI tract which presents with symptoms of anorexia, nausea/vomiting and dyspepsia that is more responsive to lower doses (1 mg/kg) of methylprednisolone/prednisolone. Also in skin GVHD treatment steroid is being started often at a lower dose. In gut GVHD, steroid and CI are usually started with IV due to a concern for appropriate absorption of oral medications. Higher doses of steroids have been tested in treatment of aGVHD. In a prospective study methylprednisolone 2 mg/kg/day was compared with 10 mg/kg/day. No difference in response rates, progression from grade II to III or IV or overall survival was observed [78]. In a retrospective study compared methylprednisolone 1 vs 2 mg/kg/day, no difference was seen in outcomes of patients with grade I or II aGVHD, but this study was limited by small numbers of patients with grade III and IV aGVHD [79].

Treatment with steroids especially at higher doses can lead to significant side effects including immunosuppression, hyperglycemia and osteopenia. Very few studies have evaluated effects of short vs long taper of steroids. A prospective randomized trial including 30 patient compared taper of steroids over a period of 86 vs 147 days after initial response to treatment. The short taper arm achieved resolution in 42 vs 30 days for long taper arm. No difference was observed in toxicity of steroids, development of cGVHD or 6-month overall survival [80].

Authors usually start methylprednisolone intravenously at 2 mg/kg/day, continue at that dose between 1 and 2 weeks depending on the response, then if the patient responds well to the steroid, taper down to 1.5 mg/kg/day for 1 week, 1 mg/kg/day for 1 week, then continue to taper at the rate of 10 mg/week. We often use even slower taper at doses lower than 30 mg. If initial response to steroid is not ideal, introduce a secondary agent, and taper 10 % or 10 mg every week from 2 mg/kg/day dose. The rate of the taper later on depends on the response.

Many agents in addition to steroid and CI have been evaluated for initial treatment of aGVHD, but most of them have failed to show significant benefit. In a large-scale phase II trial conducted by BMT Clinical Trial Network (BMT-CTN) patients were randomized into 4 arms to receive methylprednisolone 2 mg/kg/day and CI in addition to either etanercept, mycophenolate (MMF), denileukin or pentostatin as the initial therapy. Complete response rates at 28 days were 26, 60, 53 and 38 %, respectively, with overall survival of 47, 64, 49 and 47 % at 9 months [81]. Based on these encouraging results, a randomized phase III trial of steroid and CI with MMF vs steroid and CI has started (BMT CTN Study 0802), but the study was terminated as preliminary results did not show any difference with addition of MMF [82]. Other agents such as basiliximab, daclizumab, antithymocyte globulin (ATG), etanercept and infliximab have also been tested without convincing results [83–87]. Based on these findings, the addition of agents to high-dose steroids in first-line treatment is only recommended in the setting of clinical trials.

Treatment of steroid-refractory acute GVHD

The criterion for steroid-refractory acute GVHD is not well defined. It is generally recommended that if aGVHD worsens in any organ during the first 3 days of high-dose steroid treatment or if there is no response during the first 5–14 days second line of therapy should be considered [88]. We generally use the 3-day criterion for lower GI GVHD and introduce secondary agents by fifth day. The decision to add second-line treatment should be made sooner for patients with more severe GVHD and also in patients who cannot tolerate high-dose steroid treatment. Multiple agents have been tested for the treatment of steroid-refractory aGVHD. Unfortunately none of the existing treatments provided convincing evidences for long-term benefits. Thus, the outcome of steroid-refractory aGVHD remains poor with mortality as high as 80 % [76].

Antithymocyte globulin (ATG)

Multiple retrospective studies have shown benefit of ATG in steroid-refractory disease. The benefit is significant when used early especially in skin involvement [75]. The benefit of ATG in overall survival is yet to be shown. In a prospective randomized trial, 61 patients with aGVHD refractory to 2 mg/kg/day of methylprednisolone were treated with 5 mg/kg/day methylprednisolone alone or in combination with rabbit ATG. There was no difference between the two arms in terms of response rates, survival or TRM [89].

Alemtuzumab (Campath)

Alemtuzumab is a humanized monoclonal antibody to CD52 (a pan lymphocyte cell surface marker). In a prospective study of 18 patients with steroid-refractory aGVHD, alemtuzumab 10 mg daily was administered subcutaneously for 5 days. On day 28 of treatment 15 patients had responses and 10 out of the 15 patients were alive at 11 months. Fourteen patients developed infections including 11 who developed CMV reactivation [90]. In another phase II trial of 10 patients with grade III and IV aGVHD, 5 responded to treatment but all 10 died with a median period of 40 days [91]. Alemtuzumab is a very potent antibody but immunosuppression is very strong and life-threatening infections occur. Thus caution should be taken not to use too high dose and it should be introduced earlier than later in the course.

Anti-interleukin 2 receptor antibodies

Daclizumab and basiliximab are monoclonal antibodies directed against IL2 receptor. They have been tested in the treatment of aGVHD in the initial treatment as well as steroid-refractory setting. In a phase II study, daclizumab was given as single second-line agent to 62 patients with steroid-refractory aGVHD. Sixty-nine percent of patients achieved complete responses. Unfortunately most of the patients went on to develop severe cGVHD [92]. In another trial, 12 patients were treated with daclizumab alone or in combination with infliximab. Patients continued to receive cyclosporine and mycophenolate which was initially started as prophylaxis and they were also treated prophylactically with IV antifungal and antibacterial agents. The 200-day mortality was 17 % compared to 89 % in historical matched cohort of 12 patients treated with ATG and MMF [93]. Based on this encouraging data daclizumab was used in a trial for initial treatment for aGVHD along with steroids. The study was terminated early when the interim analysis showed worse survival for the combination arm at 100 days and 1 year [84]. This was thought to be a result of depletion of Tregs and their regulatory role in aGVHD. Other IL2 antibodies are in clinical trials as well [94, 95]. Basiliximab is a shorter acting IL2 receptor antibody. It has been associated with modest responses when used in treatment of aGVHD [95].

Anti-TNFα agents

As described earlier, TNFα plays a critical role in pathogenesis of aGVHD. It is involved in the activation of APCs, localization of effector cells to the affected tissues and cellular apoptosis. Although there are several ways to inhibit TNFα, most of the clinical trials have used either etanercept, a soluble dimeric TNFα receptor 2 that competes for TNFα binding with cellular receptors, or infliximab, a monoclonal antibody that binds to TNFα. A major difference between etanercept and infliximab is that infliximab can induce systemic elimination of monocytes and macrophages that express membrane-bound TNF, whereas etanercept does not [96]. In a retrospective study, infliximab has been shown to be associated with significant response although the proportion of patients with grade III–IV aGVHD was low and treatment was complicated by infections particularly aspergillus which could be explained by elimination of monocytes–macrophages by infliximab [97, 98]. Etanercept also increased infections in clinical trials but not as much as infliximab [81, 86]. In a phase III randomized trial of high-dose corticosteroids with or without infliximab including 63 newly diagnosed GVHD patients, no statistically significant difference was found in GVHD-related mortality, non-relapse mortality or overall survival [87]. In a study of 13 patients with acute GVHD, etanercept was shown to induce responses in 6 patients with maximal benefit seen in patients with GVHD of the gastrointestinal tract [99]. Other small studies have also shown benefit of TNFα inhibitors in treatment of aGVHD [100–102]. Combination therapy has shown to be effective as well. A study of 22 pediatric patients of steroid-refractory aGVHD who were treated with a combination of daclizumab and infliximab response was seen in 19 out of 22 patients [103]. Taken together, the published literature suggests that treatment with TNFα inhibitors is associated with improved responses in steroid-refractory aGVHD, particularly the ones involving gastrointestinal tract.

Extracorporeal photopheresis (ECP)

The majority of experience with extracorporeal photophoresis is in treatment of cGVHD. The treatment consists of a combination of leukapheresis and photodynamic therapy. The patient’s blood is exposed to 8-methoxypsoralen followed by ultraviolet A radiation before being reinfused. This process induces apoptosis of leukocytes leading to their phagocytosis by APCs and a potential switch in activity of APCs in favor of immunomodulation. In a prospective phase II trial of patients with steroid-refractory aGVHD, ECP was done weekly until maximal disease response. CR rate was 82, 61 and 61 % for aGVHD of skin, liver and GI tract, respectively. Transplant-related mortality was only 14 % in patients treated with ECP while 73 % in patients who were not [104]. Other retrospective studies have also shown benefit of ECP in treatment of aGVHD [105]. ECP is safe, without any increase in rate of infections, secondary malignancies or mortality [106].

Mycophenolate mofetil (MMF)

MMF works by inhibition of purine synthesis in lymphocytes. It is available in both oral and IV forms. There have been multiple published studies, both retrospective and prospective, using MMF in the treatment of steroid-refractory aGVHD [81, 107]. In one study it was associated with responses in 9 out of 19 patients, but this did not translate into long-term overall survival [108].


Sirolimus is a mammalian-target-of-rapamycin (mTOR) inhibitor which has been used in the treatment of steroid-refractory aGVHD as well as in GVHD prophylaxis studies [109, 110]. Concerns have been raised over potential side effects of sirolimus which could include seizures, hyperlipidemia, thrombotic microangiopathy and myelosuppression. In a study of 21 steroid-refractory grade III/IV aGVHD patients, treatment with sirolimus was associated with responses in 57 % patients (CR 24 %), but treatment was discontinued in 10 patients due to no response in GVHD or toxicity [109]. Similar results were observed in retrospective studies as well [110]. It should be noted that in the GVHD prophylaxis study conducted by BMT-CTN which compared sirolimus/tacrolimus combination with methotrexate/tacrolimus combination, the option using busulfan/cyclophosphamide as conditioning regimen in sirolimus/tacrolimus arm was closed due to excessive occurrence of veno-occlusive disease (VOD) [111].


Pentostatin is a nucleotide analog and is used in the treatment of lymphoid malignancies due to its anti-lymphocyte activity. In a phase I trial of pentostatin in the treatment of steroid-refractory aGVHD, out of 23 enrolled patients CR was observed in 14, but median survival was only 85 days [112]. These patients were already treated with multiple other lines of treatment for aGVHD. Another retrospective study of 13 patients has reported overall response rates of greater than 50 % [113].

Mesenchymal stem cells (MSC)

The first treatment with MSC was attempted in 2004 in a 9-year-old boy with haploidentical third party MSC [29]. Since then multiple phase I and II studies have been published using MSCs in the treatment of steroid-refractory aGVHD. The MSCs are helpful in the treatment of aGVHD due to their immunomodulatory properties [114]. In a non-randomized phase II trial of 55 patients with steroid-refractory aGVHD, use of HLA identical, haploidentical or HLA-unmatched donor MSCs was associated with CR in 30 patients and improvement in 9 additional patients [28].

Covid-19: What is a placebo? Why is it used in vaccine trials?

After Haryana health minister Anil Vij, who had participated in a vaccine trial, tested positive for the coronavirus disease (Covid-19), it triggered a lot of questions around the efficacy of the vaccine candidate Covaxin, developed by Bharat Biotech. The company later issued a clarification, saying the trial volunteers receive the two vaccine doses 28 days apart and the efficacy of the vaccine can be determined 14 days after the second dose is administered.

The Biotech firm further added that the phase 3 trial is a double-blinded study where half of the participants receive the vaccine and the other half receive a placebo. A double-blinded study means neither the participant nor the investigator knows whether the person was administered a vaccine or a placebo.

According to the dictionary definition, a placebo is a medicine or procedure prescribed for the psychological benefit to the patient rather than for any physiological effect. It is a substance or treatment which is designed to have no therapeutic value, including inert injections, pills, or any other kind of fake treatment.

Why is it used in vaccine trials?

The researchers compare the results of the vaccine with those obtained from the placebo and the placebo-controlled trials are widely regarded as a standard method for testing the efficacy of new treatments. The aim of administering a placebo in trial volunteers is to observe how many people in each group naturally contract the virus and fall ill.

In the United States, if the number of inoculated volunteers contracting Covid-19 is at least 50 per cent lower than the number in the placebo group, Food and Drug Administration (FDA) can grant the emergency use authorisation. The drug regulator requires a longer period of study to grant permanent approval to the vaccine candidates.

The United Kingdom has authorised Pfizer’s vaccine for emergency use and the company is now awaiting emergency use authorisation from the FDA for its roll-out in the US. The biotech firm had announced that the final efficacy analysis of its vaccine candidate, BNT162b2, undergoing Phase 3 trial met all of the study’s primary efficacy endpoints.


The terms alternative medicine, complementary medicine, integrative medicine, holistic medicine, natural medicine, unorthodox medicine, fringe medicine, unconventional medicine, and new age medicine are used interchangeably as having the same meaning, and are almost synonymous in most contexts. [1] [2] [3] [4] Terminology has shifted over time, reflecting the preferred branding of practitioners. [5] For example, the United States National Institutes of Health department studying alternative medicine, currently named the National Center for Complementary and Integrative Health (NCCIH), was established as the Office of Alternative Medicine (OAM) and was renamed the National Center for Complementary and Alternative Medicine (NCCAM) before obtaining its current name. Therapies are often framed as "natural" or "holistic", implicitly and intentionally suggesting that conventional medicine is "artificial" and "narrow in scope". [6] [7]

The meaning of the term "alternative" in the expression "alternative medicine", is not that it is an effective alternative to medical science, although some alternative medicine promoters may use the loose terminology to give the appearance of effectiveness. [8] [9] Loose terminology may also be used to suggest meaning that a dichotomy exists when it does not, e.g., the use of the expressions "Western medicine" and "Eastern medicine" to suggest that the difference is a cultural difference between the Asiatic east and the European west, rather than that the difference is between evidence-based medicine and treatments that do not work. [8]

Alternative medicine

Alternative medicine is defined loosely as a set of products, practices, and theories that are believed or perceived by their users to have the healing effects of medicine, [n 1] [n 2] but whose effectiveness has not been established using scientific methods, [n 1] [n 3] [8] [13] [14] [15] or whose theory and practice is not part of biomedicine, [n 2] [n 4] [n 5] [n 6] or whose theories or practices are directly contradicted by scientific evidence or scientific principles used in biomedicine. [8] [13] [19] "Biomedicine" or "medicine" is that part of medical science that applies principles of biology, physiology, molecular biology, biophysics, and other natural sciences to clinical practice, using scientific methods to establish the effectiveness of that practice. Unlike medicine, [n 4] an alternative product or practice does not originate from using scientific methods, but may instead be based on hearsay, religion, tradition, superstition, belief in supernatural energies, pseudoscience, errors in reasoning, propaganda, fraud, or other unscientific sources. [n 3] [8] [10] [13] [19]

Some other definitions seek to specify alternative medicine in terms of its social and political marginality to mainstream healthcare. [20] This can refer to the lack of support that alternative therapies receive from medical scientists regarding access to research funding, sympathetic coverage in the medical press, or inclusion in the standard medical curriculum. [20] For example, a widely used [21] definition devised by the US NCCIH calls it "a group of diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine". [22] However, these descriptive definitions are inadequate in the present-day when some conventional doctors offer alternative medical treatments and introductory courses or modules can be offered as part of standard undergraduate medical training [23] alternative medicine is taught in more than half of US medical schools and US health insurers are increasingly willing to provide reimbursement for alternative therapies. [24]

Complementary or integrative medicine

Complementary medicine (CM) or integrative medicine (IM) is when alternative medicine is used together with functional medical treatment, in a belief that it improves the effect of treatments. [n 7] [10] [26] [27] [28] For example, acupuncture (piercing the body with needles to influence the flow of a supernatural energy) might be believed to increase the effectiveness or "complement" science-based medicine when used at the same time. [29] [30] [31] Instead, significant drug interactions caused by alternative therapies may make treatments less effective, notably in cancer therapy. [32] [33] [34] Besides the usual issues with alternative medicine, integrative medicine has been described as an attempt to bring pseudoscience into academic science-based medicine, [35] leading to the pejorative term "quackademic medicine". Due to its many names, the field has been criticized for intense rebranding of what are essentially the same practices. [1]

CAM is an abbreviation of the phrase complementary and alternative medicine. [36] [37] It has also been called sCAM or SCAM with the addition of "so-called" or "supplements". [38] [39]

Other terms

Traditional medicine refers to the pre-scientific practices of a certain culture, in contrast to what is typically practiced in cultures where medical science dominates. "Eastern medicine" typically refers to the traditional medicines of Asia where evidence-based medicine penetrated much later.

Holistic medicine is another rebranding of alternative medicine. In this case, the words balance and holism are often used alongside complementary or integrative, claiming to take into account a "whole" person, in contrast to the supposed reductionism of medicine.

Challenges in defining alternative medicine

Prominent members of the science [40] [41] and biomedical science community [12] say that it is not meaningful to define an alternative medicine that is separate from a conventional medicine, because the expressions "conventional medicine", "alternative medicine", "complementary medicine", "integrative medicine", and "holistic medicine" do not refer to any medicine at all. [12] [40] [41] [42] Others say that alternative medicine cannot be precisely defined because of the diversity of theories and practices it includes, and because the boundaries between alternative and conventional medicine overlap, are porous, and change. [16] [43] Healthcare practices categorized as alternative may differ in their historical origin, theoretical basis, diagnostic technique, therapeutic practice and in their relationship to the medical mainstream. [44] Under a definition of alternative medicine as "non-mainstream", treatments considered alternative in one location may be considered conventional in another. [45]

Critics say the expression is deceptive because it implies there is an effective alternative to science-based medicine, and that complementary is deceptive because it implies that the treatment increases the effectiveness of (complements) science-based medicine, while alternative medicines that have been tested nearly always have no measurable positive effect compared to a placebo. [8] [35] [46] [47] John Diamond wrote that "there is really no such thing as alternative medicine, just medicine that works and medicine that doesn't", [41] [48] a notion later echoed by Paul Offit: "the truth is there's no such thing as conventional or alternative or complementary or integrative or holistic medicine. There's only medicine that works and medicine that doesn't. And the best way to sort it out is by carefully evaluating scientific studies - not by visiting Internet chat rooms, reading magazine articles, or talking to friends." [49] Comedian Tim Minchin has also taken to the issue in his viral animation short Storm: "By definition alternative medicine has either not been proved to work, or been proved not to work. Do you know what they call alternative medicine that's been proved to work? Medicine." [50]

Alternative medicine consists of a wide range of health care practices, products, and therapies. The shared feature is a claim to heal that is not based on the scientific method. Alternative medicine practices are diverse in their foundations and methodologies. [22] Alternative medicine practices may be classified by their cultural origins or by the types of beliefs upon which they are based. [10] [8] [19] [22] Methods may incorporate or be based on traditional medicinal practices of a particular culture, folk knowledge, superstition, [51] spiritual beliefs, belief in supernatural energies (antiscience), pseudoscience, errors in reasoning, propaganda, fraud, new or different concepts of health and disease, and any bases other than being proven by scientific methods. [10] [8] [13] [19] Different cultures may have their own unique traditional or belief based practices developed recently or over thousands of years, and specific practices or entire systems of practices.

Unscientific belief systems

Alternative medicine, such as using naturopathy or homeopathy in place of conventional medicine, is based on belief systems not grounded in science. [22]

Proposed mechanism Issues
Naturopathy Naturopathic medicine is based on a belief that the body heals itself using a supernatural vital energy that guides bodily processes. [52] In conflict with the paradigm of evidence-based medicine. [53] Many naturopaths have opposed vaccination, [54] and "scientific evidence does not support claims that naturopathic medicine can cure cancer or any other disease". [55]
Homeopathy A belief that a substance that causes the symptoms of a disease in healthy people cures similar symptoms in sick people. [n 8] Developed before knowledge of atoms and molecules, or of basic chemistry, which shows that repeated dilution as practiced in homeopathy produces only water, and that homeopathy is not scientifically valid. [57] [58] [59] [60]

Traditional ethnic systems

Alternative medical systems may be based on traditional medicine practices, such as traditional Chinese medicine (TCM), Ayurveda in India, or practices of other cultures around the world. [22] Some useful applications of traditional medicines have been researched and accepted within ordinary medicine, however the underlying belief systems are seldom scientific and are not accepted.

Traditional medicine is considered alternative when it is used outside its home region or when it is used together with or instead of known functional treatment or when it can be reasonably expected that the patient or practitioner knows or should know that it will not work – such as knowing that the practice is based on superstition.

Claims Issues
Traditional Chinese medicine Traditional practices and beliefs from China, together with modifications made by the Communist party make up TCM. Common practices include herbal medicine, acupuncture (insertion of needles in the body at specified points), massage (Tui na), exercise (qigong), and dietary therapy. The practices are based on belief in a supernatural energy called qi, considerations of Chinese astrology and Chinese numerology, traditional use of herbs and other substances found in China, a belief that the tongue contains a map of the body that reflects changes in the body, and an incorrect model of the anatomy and physiology of internal organs. [8] [61] [62] [63] [64] [65]
Ayurveda Traditional medicine of India. Ayurveda believes in the existence of three elemental substances, the doshas (called Vata, Pitta and Kapha), and states that a balance of the doshas results in health, while imbalance results in disease. Such disease-inducing imbalances can be adjusted and balanced using traditional herbs, minerals and heavy metals. Ayurveda stresses the use of plant-based medicines and treatments, with some animal products, and added minerals, including sulfur, arsenic, lead and copper sulfate. [ clarification needed ] Safety concerns have been raised about Ayurveda, with two U.S. studies finding about 20 percent of Ayurvedic Indian-manufactured patent medicines contained toxic levels of heavy metals such as lead, mercury and arsenic. A 2015 study of users in the United States also found elevated blood lead levels in 40 percent of those tested. Other concerns include the use of herbs containing toxic compounds and the lack of quality control in Ayurvedic facilities. Incidents of heavy metal poisoning have been attributed to the use of these compounds in the United States. [66] [67] [68] [69] [70] [71] [72] [73]

Supernatural energies

Bases of belief may include belief in existence of supernatural energies undetected by the science of physics, as in biofields, or in belief in properties of the energies of physics that are inconsistent with the laws of physics, as in energy medicine. [22]

Claims Issues
Biofield therapy Intended to influence energy fields that, it is purported, surround and penetrate the body. [22] Advocates of scientific skepticism such as Carl Sagan have described the lack of empirical evidence to support the existence of the putative energy fields on which these therapies are predicated. [74]
Bioelectromagnetic therapy Use verifiable electromagnetic fields, such as pulsed fields, alternating-current, or direct-current fields in an unconventional manner. [22] Asserts that magnets can be used to defy the laws of physics to influence health and disease.
Chiropractic Spinal manipulation aims to treat "vertebral subluxations" which are claimed to put pressure on nerves. Chiropractic was developed in the belief that manipulating the spine affects the flow of a supernatural vital energy and thereby affects health and disease. Vertebral subluxation is a pseudoscientific concept and has not been proven to exist.
Reiki Practitioners place their palms on the patient near Chakras that they believe are centers of supernatural energies in the belief that these supernatural energies can transfer from the practitioner's palms to heal the patient. Lacks credible scientific evidence. [75]

Herbal remedies and other substances

Substance based practices use substances found in nature such as herbs, foods, non-vitamin supplements and megavitamins, animal and fungal products, and minerals, including use of these products in traditional medical practices that may also incorporate other methods. [22] [76] [77] Examples include healing claims for non-vitamin supplements, fish oil, Omega-3 fatty acid, glucosamine, echinacea, flaxseed oil, and ginseng. [78] Herbal medicine, or phytotherapy, includes not just the use of plant products, but may also include the use of animal and mineral products. [76] It is among the most commercially successful branches of alternative medicine, and includes the tablets, powders and elixirs that are sold as "nutritional supplements". [76] Only a very small percentage of these have been shown to have any efficacy, and there is little regulation as to standards and safety of their contents. [76]

Religion, faith healing, and prayer

Claims Issues
Christian faith healing There is a divine or spiritual intervention in healing. Lack of evidence for effectiveness. [79] Unwanted outcomes, such as death and disability, "have occurred when faith healing was elected instead of medical care for serious injuries or illnesses". [80] A 2001 double-blind study of 799 discharged coronary surgery patients found that "intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit." [81]

NCCIH classification

A US agency, National Center on Complementary and Integrative Health (NCCIH), has created a classification system for branches of complementary and alternative medicine that divides them into five major groups. These groups have some overlap, and distinguish two types of energy medicine: veritable which involves scientifically observable energy (including magnet therapy, colorpuncture and light therapy) and putative, which invokes physically undetectable or unverifiable energy. [82] None of these energies have any evidence to support that they effect the body in any positive or health promoting way. [6]

  1. Whole medical systems: Cut across more than one of the other groups examples include traditional Chinese medicine, naturopathy, homeopathy, and ayurveda.
  2. Mind-body interventions: Explore the interconnection between the mind, body, and spirit, under the premise that they affect "bodily functions and symptoms". A connection between mind and body is conventional medical fact, and this classification does not include therapies with proven function such as cognitive behavioral therapy.
  3. "Biology"-based practices: Use substances found in nature such as herbs, foods, vitamins, and other natural substances. (Note that as used here, "biology" does not refer to the science of biology, but is a usage newly coined by NCCIH in the primary source used for this article. "Biology-based" as coined by NCCIH may refer to chemicals from a nonbiological source, such as use of the poison lead in traditional Chinese medicine, and to other nonbiological substances.)
  4. Manipulative and body-based practices: feature manipulation or movement of body parts, such as is done in bodywork, chiropractic, and osteopathic manipulation.
  5. Energy medicine: is a domain that deals with putative and verifiable energy fields:
      therapies are intended to influence energy fields that are purported to surround and penetrate the body. The existence of such energy fields have been disproven. -based therapies use verifiable electromagnetic fields, such as pulsed fields, alternating-current, or direct-current fields in a non-scientific manner.

The history of alternative medicine may refer to the history of a group of diverse medical practices that were collectively promoted as "alternative medicine" beginning in the 1970s, to the collection of individual histories of members of that group, or to the history of western medical practices that were labeled "irregular practices" by the western medical establishment. [8] [83] [84] [85] [86] It includes the histories of complementary medicine and of integrative medicine. Before the 1970s, western practitioners that were not part of the increasingly science-based medical establishment were referred to "irregular practitioners", and were dismissed by the medical establishment as unscientific and as practicing quackery. [83] [84] Until the 1970s, irregular practice became increasingly marginalized as quackery and fraud, as western medicine increasingly incorporated scientific methods and discoveries, and had a corresponding increase in success of its treatments. [85] In the 1970s, irregular practices were grouped with traditional practices of nonwestern cultures and with other unproven or disproven practices that were not part of biomedicine, with the entire group collectively marketed and promoted under the single expression "alternative medicine". [8] [83] [84] [85] [87]

Use of alternative medicine in the west began to rise following the counterculture movement of the 1960s, as part of the rising new age movement of the 1970s. [8] [88] [89] This was due to misleading mass marketing of "alternative medicine" being an effective "alternative" to biomedicine, changing social attitudes about not using chemicals and challenging the establishment and authority of any kind, sensitivity to giving equal measure to beliefs and practices of other cultures (cultural relativism), and growing frustration and desperation by patients about limitations and side effects of science-based medicine. [8] [84] [85] [86] [87] [89] [90] At the same time, in 1975, the American Medical Association, which played the central role in fighting quackery in the United States, abolished its quackery committee and closed down its Department of Investigation. [83] : xxi [90] By the early to mid 1970s the expression "alternative medicine" came into widespread use, and the expression became mass marketed as a collection of "natural" and effective treatment "alternatives" to science-based biomedicine. [8] [90] [91] [92] By 1983, mass marketing of "alternative medicine" was so pervasive that the British Medical Journal (BMJ) pointed to "an apparently endless stream of books, articles, and radio and television programmes urge on the public the virtues of (alternative medicine) treatments ranging from meditation to drilling a hole in the skull to let in more oxygen". [90]

An analysis of trends in the criticism of complementary and alternative medicine (CAM) in five prestigious American medical journals during the period of reorganization within medicine (1965–1999) was reported as showing that the medical profession had responded to the growth of CAM in three phases, and that in each phase, changes in the medical marketplace had influenced the type of response in the journals. [93] Changes included relaxed medical licensing, the development of managed care, rising consumerism, and the establishment of the USA Office of Alternative Medicine (later National Center for Complementary and Alternative Medicine, currently National Center for Complementary and Integrative Health). [n 9]

Medical education

Mainly as a result of reforms following the Flexner Report of 1910 [95] medical education in established medical schools in the US has generally not included alternative medicine as a teaching topic. [n 10] Typically, their teaching is based on current practice and scientific knowledge about: anatomy, physiology, histology, embryology, neuroanatomy, pathology, pharmacology, microbiology and immunology. [97] Medical schools' teaching includes such topics as doctor-patient communication, ethics, the art of medicine, [98] and engaging in complex clinical reasoning (medical decision-making). [99] Writing in 2002, Snyderman and Weil remarked that by the early twentieth century the Flexner model had helped to create the 20th-century academic health center, in which education, research, and practice were inseparable. While this had much improved medical practice by defining with increasing certainty the pathophysiological basis of disease, a single-minded focus on the pathophysiological had diverted much of mainstream American medicine from clinical conditions that were not well understood in mechanistic terms, and were not effectively treated by conventional therapies. [100]

By 2001 some form of CAM training was being offered by at least 75 out of 125 medical schools in the US. [101] Exceptionally, the School of Medicine of the University of Maryland, Baltimore includes a research institute for integrative medicine (a member entity of the Cochrane Collaboration). [102] [103] Medical schools are responsible for conferring medical degrees, but a physician typically may not legally practice medicine until licensed by the local government authority. Licensed physicians in the US who have attended one of the established medical schools there have usually graduated Doctor of Medicine (MD). [104] All states require that applicants for MD licensure be graduates of an approved medical school and complete the United States Medical Licensing Exam (USMLE). [104]

There is a general scientific consensus that alternative therapies lack the requisite scientific validation, and their effectiveness is either unproved or disproved. [10] [8] [105] [106] Many of the claims regarding the efficacy of alternative medicines are controversial, since research on them is frequently of low quality and methodologically flawed. [107] Selective publication bias, marked differences in product quality and standardisation, and some companies making unsubstantiated claims call into question the claims of efficacy of isolated examples where there is evidence for alternative therapies. [108]

The Scientific Review of Alternative Medicine points to confusions in the general population – a person may attribute symptomatic relief to an otherwise-ineffective therapy just because they are taking something (the placebo effect) the natural recovery from or the cyclical nature of an illness (the regression fallacy) gets misattributed to an alternative medicine being taken a person not diagnosed with science-based medicine may never originally have had a true illness diagnosed as an alternative disease category. [109]

Edzard Ernst characterized the evidence for many alternative techniques as weak, nonexistent, or negative [110] and in 2011 published his estimate that about 7.4% were based on "sound evidence", although he believes that may be an overestimate. [111] Ernst has concluded that 95% of the alternative therapies he and his team studied, including acupuncture, herbal medicine, homeopathy, and reflexology, are "statistically indistinguishable from placebo treatments", but he also believes there is something that conventional doctors can usefully learn from the chiropractors and homeopath: this is the therapeutic value of the placebo effect, one of the strangest phenomena in medicine. [112] [113]

In 2003, a project funded by the CDC identified 208 condition-treatment pairs, of which 58% had been studied by at least one randomized controlled trial (RCT), and 23% had been assessed with a meta-analysis. [114] According to a 2005 book by a US Institute of Medicine panel, the number of RCTs focused on CAM has risen dramatically.

As of 2005 [update] , the Cochrane Library had 145 CAM-related Cochrane systematic reviews and 340 non-Cochrane systematic reviews. An analysis of the conclusions of only the 145 Cochrane reviews was done by two readers. In 83% of the cases, the readers agreed. In the 17% in which they disagreed, a third reader agreed with one of the initial readers to set a rating. These studies found that, for CAM, 38.4% concluded positive effect or possibly positive (12.4%), 4.8% concluded no effect, 0.7% concluded harmful effect, and 56.6% concluded insufficient evidence. An assessment of conventional treatments found that 41.3% concluded positive or possibly positive effect, 20% concluded no effect, 8.1% concluded net harmful effects, and 21.3% concluded insufficient evidence. However, the CAM review used the more developed 2004 Cochrane database, while the conventional review used the initial 1998 Cochrane database. [115]

Alternative therapies do not "complement" (improve the effect of, or mitigate the side effects of) functional medical treatment. [n 7] [10] [26] [27] [28] Significant drug interactions caused by alternative therapies may instead negatively impact functional treatment by making prescription drugs less effective, such as interference by herbal preparations with warfarin. [116] [33]

In the same way as for conventional therapies, drugs, and interventions, it can be difficult to test the efficacy of alternative medicine in clinical trials. In instances where an established, effective, treatment for a condition is already available, the Helsinki Declaration states that withholding such treatment is unethical in most circumstances. Use of standard-of-care treatment in addition to an alternative technique being tested may produce confounded or difficult-to-interpret results. [117]

Cancer researcher Andrew J. Vickers has stated:

Contrary to much popular and scientific writing, many alternative cancer treatments have been investigated in good-quality clinical trials, and they have been shown to be ineffective. The label "unproven" is inappropriate for such therapies it is time to assert that many alternative cancer therapies have been "disproven". [118]

Anything classified as alternative medicine by definition does not have a healing or medical effect. However, there are different mechanisms through which it can be perceived to "work". The common denominator of these mechanisms is that effects are mis-attributed to the alternative treatment.

Placebo effect

A placebo is a treatment with no intended therapeutic value. An example of a placebo is an inert pill, but it can include more dramatic interventions like sham surgery. The placebo effect is the concept that patients will perceive an improvement after being treated with an inert treatment. The opposite of the placebo effect is the nocebo effect, when patients who expect a treatment to be harmful will perceive harmful effects after taking it.

Placebos do not have a physical effect on diseases or improve overall outcomes, but patients may report improvements in subjective outcomes such as pain and nausea. [119] A 1955 study suggested that a substantial part of a medicine's impact was due to the placebo effect. [120] [119] However, reassessments found the study to have flawed methodology. [120] [121] This and other modern reviews suggest that other factors like natural recovery and reporting bias should also be considered. [119] [121]

All of these are reasons why alternative therapies may be credited for improving a patient's condition even though the objective effect is non-existent, or even harmful. [116] [35] [47] David Gorski argues that alternative treatments should be treated as a placebo, rather than as medicine. [35] Almost none have performed significantly better than a placebo in clinical trials. [8] [46] [122] [76] Furthermore, distrust of conventional medicine may lead to patients experiencing the nocebo effect when taking effective medication. [116]

Regression to the mean

A patient who receives an inert treatment may report improvements afterwards that it did not cause. [119] [121] Assuming it was the cause without evidence is an example of the regression fallacy. This may be due to a natural recovery from the illness, or a fluctuation in the symptoms of a long-term condition. [121] The concept of regression toward the mean implies that an extreme result is more likely to be followed by a less extreme result.

Other factors

There are also reasons why a placebo treatment group may outperform a "no-treatment" group in a test which are not related to a patient's experience. These include patients reporting more favourable results than they really felt due to politeness or "experimental subordination", observer bias, and misleading wording of questions. [121] In their 2010 systematic review of studies into placebos, Asbjørn Hróbjartsson and Peter C. Gøtzsche write that "even if there were no true effect of placebo, one would expect to record differences between placebo and no-treatment groups due to bias associated with lack of blinding." [119] Alternative therapies may also be credited for perceived improvement through decreased use or effect of medical treatment, and therefore either decreased side effects or nocebo effects towards standard treatment. [116]


Practitioners of complementary medicine usually discuss and advise patients as to available alternative therapies. Patients often express interest in mind-body complementary therapies because they offer a non-drug approach to treating some health conditions. [123]

In addition to the social-cultural underpinnings of the popularity of alternative medicine, there are several psychological issues that are critical to its growth, notably psychological effects, such as the will to believe, [124] cognitive biases that help maintain self-esteem and promote harmonious social functioning, [124] and the post hoc, ergo propter hoc fallacy. [124]


Alternative medicine is a highly profitable industry, with a strong lobby. This fact is often overlooked by media or intentionally kept hidden, with alternative practice being portrayed positively when compared to "big pharma". [6]

The popularity of complementary & alternative medicine (CAM) may be related to other factors that Edzard Ernst mentioned in an interview in The Independent:

Why is it so popular, then? Ernst blames the providers, customers and the doctors whose neglect, he says, has created the opening into which alternative therapists have stepped. "People are told lies. There are 40 million websites and 39.9 million tell lies, sometimes outrageous lies. They mislead cancer patients, who are encouraged not only to pay their last penny but to be treated with something that shortens their lives." At the same time, people are gullible. It needs gullibility for the industry to succeed. It doesn't make me popular with the public, but it's the truth. [125]

Paul Offit proposed that "alternative medicine becomes quackery" in four ways: by recommending against conventional therapies that are helpful, promoting potentially harmful therapies without adequate warning, draining patients' bank accounts, or by promoting "magical thinking." [40] Promoting alternative medicine has been called dangerous and unethical. [n 11] [127]

Social factors

Authors have speculated on the socio-cultural and psychological reasons for the appeal of alternative medicines among the minority using them in lieu of conventional medicine. There are several socio-cultural reasons for the interest in these treatments centered on the low level of scientific literacy among the public at large and a concomitant increase in antiscientific attitudes and new age mysticism. [124] Related to this are vigorous marketing [128] of extravagant claims by the alternative medical community combined with inadequate media scrutiny and attacks on critics. [124] [129] Alternative medicine is criticized for taking advantage of the least fortunate members of society. [6]

There is also an increase in conspiracy theories toward conventional medicine and pharmaceutical companies, [34] mistrust of traditional authority figures, such as the physician, and a dislike of the current delivery methods of scientific biomedicine, all of which have led patients to seek out alternative medicine to treat a variety of ailments. [129] Many patients lack access to contemporary medicine, due to a lack of private or public health insurance, which leads them to seek out lower-cost alternative medicine. [130] Medical doctors are also aggressively marketing alternative medicine to profit from this market. [128]

Patients can be averse to the painful, unpleasant, and sometimes-dangerous side effects of biomedical treatments. Treatments for severe diseases such as cancer and HIV infection have well-known, significant side-effects. Even low-risk medications such as antibiotics can have potential to cause life-threatening anaphylactic reactions in a very few individuals. Many medications may cause minor but bothersome symptoms such as cough or upset stomach. In all of these cases, patients may be seeking out alternative therapies to avoid the adverse effects of conventional treatments. [124] [129]

Prevalence of use

According to recent research, the increasing popularity of the CAM needs to be explained by moral convictions or lifestyle choices rather than by economic reasoning. [131]

In developing nations, access to essential medicines is severely restricted by lack of resources and poverty. Traditional remedies, often closely resembling or forming the basis for alternative remedies, may comprise primary healthcare or be integrated into the healthcare system. In Africa, traditional medicine is used for 80% of primary healthcare, and in developing nations as a whole over one-third of the population lack access to essential medicines. [132]

Some have proposed adopting a prize system to reward medical research. [133] However, public funding for research exists. In the US increasing the funding for research on alternative medicine is the purpose of the US National Center for Complementary and Alternative Medicine (NCCAM). NCCAM has spent more than US$2.5 billion on such research since 1992 and this research has not demonstrated the efficacy of alternative therapies. [122] [134] [135] [136] [137] [138] The NCCAM's sister organization in the NIC Office of Cancer Complementary and Alternative Medicine gives grants of around $105 million every year. [139] Testing alternative medicine that has no scientific basis has been called a waste of scarce research resources. [140] [141]

That alternative medicine has been on the rise "in countries where Western science and scientific method generally are accepted as the major foundations for healthcare, and 'evidence-based' practice is the dominant paradigm" was described as an "enigma" in the Medical Journal of Australia. [142]

In the US

In the United States, the 1974 Child Abuse Prevention and Treatment Act (CAPTA) required that for states to receive federal money, they had to grant religious exemptions to child neglect and abuse laws regarding religion-based healing practices. [143] Thirty-one states have child-abuse religious exemptions. [144]

The use of alternative medicine in the US has increased, [10] [145] with a 50 percent increase in expenditures and a 25 percent increase in the use of alternative therapies between 1990 and 1997 in America. [145] According to a national survey conducted in 2002, "36 percent of U.S. adults aged 18 years and over use some form of complementary and alternative medicine." [146] Americans spend many billions on the therapies annually. [145] Most Americans used CAM to treat and/or prevent musculoskeletal conditions or other conditions associated with chronic or recurring pain. [130] In America, women were more likely than men to use CAM, with the biggest difference in use of mind-body therapies including prayer specifically for health reasons". [130] In 2008, more than 37% of American hospitals offered alternative therapies, up from 27 percent in 2005, and 25% in 2004. [147] [148] More than 70% of the hospitals offering CAM were in urban areas. [148]

A survey of Americans found that 88 percent thought that "there are some good ways of treating sickness that medical science does not recognize". [10] Use of magnets was the most common tool in energy medicine in America, and among users of it, 58 percent described it as at least "sort of scientific", when it is not at all scientific. [10] In 2002, at least 60 percent of US medical schools have at least some class time spent teaching alternative therapies. [10] "Therapeutic touch" was taught at more than 100 colleges and universities in 75 countries before the practice was debunked by a nine-year-old child for a school science project. [10] [75]

Prevalence of use of specific therapies

In Britain, the most often used alternative therapies were Alexander technique, aromatherapy, Bach and other flower remedies, body work therapies including massage, Counseling stress therapies, hypnotherapy, meditation, reflexology, Shiatsu, Ayurvedic medicine, nutritional medicine, and Yoga. [150] Ayurvedic medicine remedies are mainly plant based with some use of animal materials. [151] Safety concerns include the use of herbs containing toxic compounds and the lack of quality control in Ayurvedic facilities. [69] [71]

According to the National Health Service (England), the most commonly used complementary and alternative medicines (CAM) supported by the NHS in the UK are: acupuncture, aromatherapy, chiropractic, homeopathy, massage, osteopathy and clinical hypnotherapy. [152]

In palliative care

Complementary therapies are often used in palliative care or by practitioners attempting to manage chronic pain in patients. Integrative medicine is considered more acceptable in the interdisciplinary approach used in palliative care than in other areas of medicine. "From its early experiences of care for the dying, palliative care took for granted the necessity of placing patient values and lifestyle habits at the core of any design and delivery of quality care at the end of life. If the patient desired complementary therapies, and as long as such treatments provided additional support and did not endanger the patient, they were considered acceptable." [153] The non-pharmacologic interventions of complementary medicine can employ mind-body interventions designed to "reduce pain and concomitant mood disturbance and increase quality of life." [154]


The alternative medicine lobby has successfully pushed for alternative therapies to be subject to far less regulation than conventional medicine. [6] Some professions of complementary/traditional/alternative medicine, such as chiropractic, have achieved full regulation in North America and other parts of the world [155] and are regulated in a manner similar to that governing science-based medicine. In contrast, other approaches may be partially recognized and others have no regulation at all. [155] In some cases, promotion of alternative therapies is allowed when there is demonstrably no effect, only a tradition of use. Despite laws making it illegal to market or promote alternative therapies for use in cancer treatment, many practitioners promote them. [156] [157]

Regulation and licensing of alternative medicine ranges widely from country to country, and state to state. [155] In Austria and Germany complementary and alternative medicine is mainly in the hands of doctors with MDs, [36] and half or more of the American alternative practitioners are licensed MDs. [158] In Germany herbs are tightly regulated: half are prescribed by doctors and covered by health insurance. [159]

Government bodies in the US and elsewhere have published information or guidance about alternative medicine. The U.S. Food and Drug Administration (FDA), has issued online warnings for consumers about medication health fraud. [160] This includes a section on Alternative Medicine Fraud, [161] such as a warning that Ayurvedic products generally have not been approved by the FDA before marketing. [162]

Negative outcomes

According to the Institute of Medicine, use of alternative medical techniques may result in several types of harm:

  • "Economic harm, which results in monetary loss but presents no health hazard"
  • "Indirect harm, which results in a delay of appropriate treatment, or in unreasonable expectations that discourage patients and their families from accepting and dealing effectively with their medical conditions"
  • "Direct harm, which results in adverse patient outcome." [163]

Adequacy of regulation and CAM safety

Many of the claims regarding the safety and efficacy of alternative medicine are controversial. Some alternative therapies have been associated with unexpected side effects, which can be fatal. [164]

A commonly voiced concerns about complementary alternative medicine (CAM) is the way it's regulated. There have been significant developments in how CAMs should be assessed prior to re-sale in the United Kingdom and the European Union (EU) in the last two years. Despite this, it has been suggested that current regulatory bodies have been ineffective in preventing deception of patients as many companies have re-labelled their drugs to avoid the new laws. [165] There is no general consensus about how to balance consumer protection (from false claims, toxicity, and advertising) with freedom to choose remedies.

Advocates of CAM suggest that regulation of the industry will adversely affect patients looking for alternative ways to manage their symptoms, even if many of the benefits may represent the placebo affect. [166] Some contend that alternative medicines should not require any more regulation than over-the-counter medicines that can also be toxic in overdose (such as paracetamol). [167]

Interactions with conventional pharmaceuticals

Forms of alternative medicine that are biologically active can be dangerous even when used in conjunction with conventional medicine. Examples include immuno-augmentation therapy, shark cartilage, bioresonance therapy, oxygen and ozone therapies, and insulin potentiation therapy. Some herbal remedies can cause dangerous interactions with chemotherapy drugs, radiation therapy, or anesthetics during surgery, among other problems. [37] [116] [33] An example of these dangers was reported by Associate Professor Alastair MacLennan of Adelaide University, Australia regarding a patient who almost bled to death on the operating table after neglecting to mention that she had been taking "natural" potions to "build up her strength" before the operation, including a powerful anticoagulant that nearly caused her death. [168]

To ABC Online, MacLennan also gives another possible mechanism:

And lastly there's the cynicism and disappointment and depression that some patients get from going on from one alternative medicine to the next, and they find after three months the placebo effect wears off, and they're disappointed and they move on to the next one, and they're disappointed and disillusioned, and that can create depression and make the eventual treatment of the patient with anything effective difficult, because you may not get compliance, because they've seen the failure so often in the past. [169]


Conventional treatments are subjected to testing for undesired side-effects, whereas alternative therapies, in general, are not subjected to such testing at all. Any treatment – whether conventional or alternative – that has a biological or psychological effect on a patient may also have potential to possess dangerous biological or psychological side-effects. Attempts to refute this fact with regard to alternative therapies sometimes use the appeal to nature fallacy, i.e., "That which is natural cannot be harmful." Specific groups of patients such as patients with impaired hepatic or renal function are more susceptible to side effects of alternative remedies. [170] [171]

An exception to the normal thinking regarding side-effects is Homeopathy. Since 1938, the U.S. Food and Drug Administration (FDA) has regulated homeopathic products in "several significantly different ways from other drugs." [172] Homeopathic preparations, termed "remedies", are extremely dilute, often far beyond the point where a single molecule of the original active (and possibly toxic) ingredient is likely to remain. They are, thus, considered safe on that count, but "their products are exempt from good manufacturing practice requirements related to expiration dating and from finished product testing for identity and strength", and their alcohol concentration may be much higher than allowed in conventional drugs. [172]

Treatment delay

Alternative medicine may discourage people from getting the best possible treatment. [173] Those having experienced or perceived success with one alternative therapy for a minor ailment may be convinced of its efficacy and persuaded to extrapolate that success to some other alternative therapy for a more serious, possibly life-threatening illness. [174] For this reason, critics argue that therapies that rely on the placebo effect to define success are very dangerous. According to mental health journalist Scott Lilienfeld in 2002, "unvalidated or scientifically unsupported mental health practices can lead individuals to forgo effective treatments" and refers to this as opportunity cost. Individuals who spend large amounts of time and money on ineffective treatments may be left with precious little of either, and may forfeit the opportunity to obtain treatments that could be more helpful. In short, even innocuous treatments can indirectly produce negative outcomes. [175] Between 2001 and 2003, four children died in Australia because their parents chose ineffective naturopathic, homeopathic, or other alternative medicines and diets rather than conventional therapies. [176]

Unconventional cancer "cures"

There have always been "many therapies offered outside of conventional cancer treatment centers and based on theories not found in biomedicine. These alternative cancer cures have often been described as 'unproven,' suggesting that appropriate clinical trials have not been conducted and that the therapeutic value of the treatment is unknown." However, "many alternative cancer treatments have been investigated in good-quality clinical trials, and they have been shown to be ineffective. . The label 'unproven' is inappropriate for such therapies it is time to assert that many alternative cancer therapies have been 'disproven'." [118]

any alternative cancer cure is bogus by definition. There will never be an alternative cancer cure. Why? Because if something looked halfway promising, then mainstream oncology would scrutinize it, and if there is anything to it, it would become mainstream almost automatically and very quickly. All curative "alternative cancer cures" are based on false claims, are bogus, and, I would say, even criminal. [177]

Rejection of science

There is no alternative medicine. There is only scientifically proven, evidence-based medicine supported by solid data or unproven medicine, for which scientific evidence is lacking.

Complementary and alternative medicine (CAM) is not as well researched as conventional medicine, which undergoes intense research before release to the public. [178] Practitioners of science-based medicine also discard practices and treatments when they are shown ineffective, while alternative practitioners do not. [6] Funding for research is also sparse making it difficult to do further research for effectiveness of CAM. [179] Most funding for CAM is funded by government agencies. [178] Proposed research for CAM are rejected by most private funding agencies because the results of research are not reliable. [178] The research for CAM has to meet certain standards from research ethics committees, which most CAM researchers find almost impossible to meet. [178] Even with the little research done on it, CAM has not been proven to be effective. [180] Studies that have been done will be cited by CAM practitioners in an attempt to claim a basis in science. These studies tend to have a variety of problems, such as small samples, various biases, poor research design, lack of controls, negative results, etc. Even those with positive results can be better explained as resulting in false positives due to bias and noisy data. [181]

Alternative medicine may lead to a false understanding of the body and of the process of science. [173] [182] Steven Novella, a neurologist at Yale School of Medicine, wrote that government-funded studies of integrating alternative medicine techniques into the mainstream are "used to lend an appearance of legitimacy to treatments that are not legitimate." [183] Marcia Angell considered that critics felt that healthcare practices should be classified based solely on scientific evidence, and if a treatment had been rigorously tested and found safe and effective, science-based medicine will adopt it regardless of whether it was considered "alternative" to begin with. [12] It is possible for a method to change categories (proven vs. unproven), based on increased knowledge of its effectiveness or lack thereof. A prominent supporter of this position is George D. Lundberg, former editor of the Journal of the American Medical Association (JAMA). [42]

Writing in 1999 in CA: A Cancer Journal for Clinicians Barrie R. Cassileth mentioned a 1997 letter to the US Senate Subcommittee on Public Health and Safety, which had deplored the lack of critical thinking and scientific rigor in OAM-supported research, had been signed by four Nobel Laureates and other prominent scientists. (This was supported by the National Institutes of Health (NIH).) [184]

In March 2009, a staff writer for the Washington Post reported that the impending national discussion about broadening access to health care, improving medical practice and saving money was giving a group of scientists an opening to propose shutting down the National Center for Complementary and Alternative Medicine. They quoted one of these scientists, Steven Salzberg, a genome researcher and computational biologist at the University of Maryland, as saying "One of our concerns is that NIH is funding pseudoscience." They noted that the vast majority of studies were based on fundamental misunderstandings of physiology and disease, and had shown little or no effect. [183]

Writers such as Carl Sagan, a noted astrophysicist, advocate of scientific skepticism and the author of The Demon-Haunted World: Science as a Candle in the Dark (1996), have lambasted the lack of empirical evidence to support the existence of the putative energy fields on which these therapies are predicated. [74]

Sampson has also pointed out that CAM tolerated contradiction without thorough reason and experiment. [185] Barrett has pointed out that there is a policy at the NIH of never saying something does not work, only that a different version or dose might give different results. [122] Barrett also expressed concern that, just because some "alternatives" have merit, there is the impression that the rest deserve equal consideration and respect even though most are worthless, since they are all classified under the one heading of alternative medicine. [186]

Some critics of alternative medicine are focused upon health fraud, misinformation, and quackery as public health problems, notably Wallace Sampson and Paul Kurtz founders of Scientific Review of Alternative Medicine and Stephen Barrett, co-founder of The National Council Against Health Fraud and webmaster of Quackwatch. [187] Grounds for opposing alternative medicine include that:

  • It is usually based on religion, tradition, superstition, belief in supernatural energies, pseudoscience, errors in reasoning, propaganda, or fraud. [129][10][8][188]
  • Alternative therapies typically lack any scientific validation, and their effectiveness is either unproved or disproved. [8][105][106] [dubious – discuss]
  • Treatments are not part of the conventional, science-based healthcare system. [189][22][190][191]
  • Research on alternative medicine is frequently of low quality and methodologically flawed. [22][192]
  • Where alternative therapies have replaced conventional science-based medicine, even with the safest alternative medicines, failure to use or delay in using conventional science-based medicine has caused deaths. [175][176]
  • Methods may incorporate or base themselves on traditional medicine, folk knowledge, spiritual beliefs, ignorance or misunderstanding of scientific principles, errors in reasoning, or newly conceived approaches claiming to heal. [129][8][193]

Many alternative medical treatments are not patentable, [194] which may lead to less research funding from the private sector. In addition, in most countries, alternative therapies (in contrast to pharmaceuticals) can be marketed without any proof of efficacy – also a disincentive for manufacturers to fund scientific research. [195]

English evolutionary biologist Richard Dawkins, in his 2003 book A Devil's Chaplain, defined alternative medicine as a "set of practices that cannot be tested, refuse to be tested, or consistently fail tests." [196] Dawkins argued that if a technique is demonstrated effective in properly performed trials then it ceases to be alternative and simply becomes medicine. [197]

CAM is also often less regulated than conventional medicine. [178] There are ethical concerns about whether people who perform CAM have the proper knowledge to treat patients. [178] CAM is often done by non-physicians who do not operate with the same medical licensing laws which govern conventional medicine, [178] and it is often described as an issue of non-maleficence. [198]

According to two writers, Wallace Sampson and K. Butler, marketing is part of the training required in alternative medicine, and propaganda methods in alternative medicine have been traced back to those used by Hitler and Goebels in their promotion of pseudoscience in medicine. [8] [199]

In November 2011 Edzard Ernst stated that the "level of misinformation about alternative medicine has now reached the point where it has become dangerous and unethical. So far, alternative medicine has remained an ethics-free zone. It is time to change this." [200]

Conflicts of interest

Some commentators have said that special consideration must be given to the issue of conflicts of interest in alternative medicine. Edzard Ernst has said that most researchers into alternative medicine are at risk of "unidirectional bias" because of a generally uncritical belief in their chosen subject. [201] Ernst cites as evidence the phenomenon whereby 100% of a sample of acupuncture trials originating in China had positive conclusions. [201] David Gorski contrasts evidence-based medicine, in which researchers try to disprove hyphotheses, with what he says is the frequent practice in pseudoscience-based research, of striving to confirm pre-existing notions. [202] Harriet Hall writes that there is a contrast between the circumstances of alternative medicine practitioners and disinterested scientists: in the case of acupuncture, for example, an acupuncturist would have "a great deal to lose" if acupuncture were rejected by research but the disinterested skeptic would not lose anything if its effects were confirmed rather their change of mind would enhance their skeptical credentials. [203]

Use of health and research resources

Research into alternative therapies has been criticized for "diverting research time, money, and other resources from more fruitful lines of investigation in order to pursue a theory that has no basis in biology." [47] [35] Research methods expert and author of Snake Oil Science, R. Barker Bausell, has stated that "it's become politically correct to investigate nonsense." [122] A commonly cited statistic is that the US National Institute of Health had spent $2.5 billion on investigating alternative therapies prior to 2009, with none being found to be effective. [122]

Indian Ayurvedic medicine includes a belief that the spiritual balance of mind influences disease.

Medicinal herbs in a traditional Spanish market

Assorted dried plant and animal parts used in traditional Chinese medicine

Phytotherapy (herbal medicine): an engraving of magnolia glauca in Jacob Bigelow's American Medical Botany

  1. ^ ab "[A]lternative medicine refers to all treatments that have not been proven effective using scientific methods." [10]
  2. ^ ab "Complementary and alternative medicine (CAM) is a broad domain of resources that encompasses health systems, modalities, and practices and their accompanying theories and beliefs, other than those intrinsic to the dominant health system of a particular society or culture in a given historical period. CAM includes such resources perceived by their users as associated with positive health outcomes. Boundaries within CAM and between the CAM domain and the domain of the dominant system are not always sharp or fixed." [11]
  3. ^ ab "It is time for the scientific community to stop giving alternative medicine a free ride. There cannot be two kinds of medicine – conventional and alternative. There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work . speculation, and testimonials do not substitute for evidence." [12]
  4. ^ ab "The phrase complementary and alternative medicine is used to describe a group of diverse medical and health care systems, practices, and products that have historic origins outside mainstream medicine. Most of these practices are used together with conventional therapies and therefore have been called complementary to distinguish them from alternative practices, those used as a substitute for standard care. . Until a decade ago or so, 'complementary and alternative medicine' could be defined as practices that are neither taught in medical schools nor reimbursed, but this definition is no longer workable, since medical students increasingly seek and receive some instruction about complementary health practices, and some practices are reimbursed by third-party payers. Another definition, practices that lack an evidence base, is also not useful, since there is a growing body of research on some of these modalities, and some aspects of standard care do not have a strong evidence base." [16]
  5. ^ "An alternative medical system is a set of practices based on a philosophy different from Western biomedicine." [17]
  6. ^ "CAM is a group of diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine." [18]
  7. ^ ab The Final Report (2002) of the White House Commission on Complementary and Alternative Medicine Policy states: "The Commissioners believe and have repeatedly stated in this Report that our response should be to hold all systems of health and healing, including conventional and CAM, to the same rigorous standards of good science and health services research. Although the Commissioners support the provision of the most accurate information about the state of the science of all CAM modalities, they believe that it is premature to advocate the wide implementation and reimbursement of CAM modalities that are yet unproven." [25]
  8. ^ In his book The Homœopathic Medical DoctrineSamuel Hahnemann the creator of homeopathy wrote: "Observation, reflection, and experience have unfolded to me that the best and true method of cure is founded on the principle, similia similibus curentur. To cure in a mild, prompt, safe, and durable manner, it is necessary to choose in each case a medicine that will excite an affection similar ( ὅμοιος πάθος ) to that against which it is employed." [56]
  9. ^ According to the medical historian James Harvey Young:

In 1991 the Senate Appropriations Committee responsible for funding the National Institutes of Health (NIH) declared itself "not satisfied that the conventional medical community as symbolized at the NIH has fully explored the potential that exists in unconventional medical practices." [94]

Revisiting Daniel Moerman and “placebo effects”

About three weeks ago, ironically enough, right around the time of TAM 9, the New England Journal of Medicine (NEJM ) inadvertently provided us in the form of a new study on asthma and placebo effects not only material for our discussion panel on placebo effects but material for multiple posts, including one by me, one by Kimball Atwood, and one by Peter Lipson, the latter two of whom tried to point out that the sorts of uses of these results could result in patients dying. Meanwhile, Mark Crislip, in his ever-inimitable fashion, discussed the study as well, using it to liken complementary and alternative medicine (CAM ) as the “beer goggles of medicine,” a line I totally plan on stealing. The study itself, we all agreed, was actually pretty well done. What it showed is that in asthma a patient’s subjective assessment of how well he’s doing is a poor guide to how well his lungs are actually doing from an objective, functional standpoint. For the most part, the authors came to this conclusion as well, although their hedging and hawing over their results made almost palpable their disappointment that their chosen placebos utterly failed to produce anything resembling an objective response improving lung function as measured by changes (or lack thereof) in FEV1.

In actuality, where most of our criticism landed, and landed hard—deservedly, in my opinion—was on the accompanying editorial, written by Dr. Daniel Moerman, an emeritus professor of anthropology at the University of Michigan-Dearborn. There was a time when I thought that anthropologists might have a lot to tell us about how we practice medicine, and maybe they actually do. Unfortunately, my opinion in this matter has been considerably soured by much of what I’ve read when anthropologists try to dabble in medicine. Recently, I became aware that Moerman appeared on the Clinical Conversations podcast around the time his editorial was published, and, even though the podcast is less than 18 minutes long, Moerman’s appearance in the podcast provides a rich vein of material to mine regarding what, exactly, placebo effects are or are not, not to mention evidence that Dr. Moerman appears to like to make like Humpty-Dumpty in this passage:

‘When I use a word,’ Humpty Dumpty said, in rather a scornful tone, ‘it means just what I choose it to mean — neither more nor less.’

‘The question is,’ said Alice, ‘whether you can make words mean so many different things.’

‘The question is,’ said Humpty Dumpty, ‘which is to be master — that’s all.’

Elia asks Moerman right off the bat what he sees in medical studies such as the NEJM placebo study that’s common to other human situations. Moerman responds:

…I see actors and responders. I see uniforms. I see symbols of power. I see authoritarian and all sorts of other kinds of interactions between people. I see lots of interactions between people. I see lots and lots and lots of meaning.

And I see dead people. (Sorry, couldn’t resist.)

Time and time again, Moerman returns to this word, “meaning.” But what does he—if you’ll excuse the awkward sentence construction—mean when he uses the word “meaning”? Elia asks him just that question, pointing out that the word featured prominently in the title of his book Medicine, Meaning and the “Placebo Effect”. Moerman responds with a bit of a waffle dance before he tries to actually answer the question:

…given that we’re talking to a bunch of physicians, let me start by saying why it is I put “placebo effect” in quotation marks. What we mean ordinarily by “placebo effect” is unproblematic. It’s an inert substance designed to mimic a medical procedure. The key thing is that it’s inert. If it’s inert, what that means is, it can’t do anything. That’s what “inert” means. But there simply can’t be such a thing as a placebo effect. It’s a contradiction in terms, sort of like “king of America.” So, I think that “placebo effect” is like “king of America.” It doesn’t exist. Now, at the same time we all know that if you give people inert medications they often respond dramatically, and they get a lot better. So, the only thing that we know for sure is that it’s not the placebo that did it. So what did do it? And what I argue is that what did it is all of the other meaningful stuff that’s associated with medicine, starting with the behavior of the parking lot attendant, going through the receptionist, to what’s hanging on the walls to the art in hospital. I said in the article, our hospital has two helipads.

When you walk into a place like that you know you’re in a place of great overweaning power. It’s incredibly meaningful. And I would argue that that meaning, that and all sorts of other kinds of meaning—the stethoscope around the neck, the uniforms, the funny white shoes, you know, on and on and on—all of that stuff goes together to create a generic system of meaning which is then sort of instantiated by the specific red or orange or blue pills that the doctor gives you and tells you when to take it this way and that way and to drink lots of water, which is a healing substance all of its own. And the meaning that’s attached to all of that stuff can be at least as powerful as whatever is in the pill, whether it’s inert or not.

Alright, I’ll give Moerman credit for a bit of a sense of humor. That line about his hospital having two helipads wasn’t half-bad. Of course, back when I was doing residency in Cleveland, our county hospital had three helipads. So there. (Actually, the reason it had three helipads is because it was the main base for Metro LifeFlight, where I actually moonlighted as a flight physician for nearly three years while I was in graduate school.) In any event, Moerman seems to miss a huge point. He seems to be arguing that placebo effects come from the atmosphere of medicine i.e., the lab coats, the halls of “power,” the helipads, the medical jargon, the mysterious language that only medical personnel (the high priests or shamans of whom are, presumably, the doctors) can understand. Here’s the problem. In the NEJM article, the patients in the no-treatment, “watchful waiting” group in the asthma/placebo study experienced all of that medical awesomeness, yet they didn’t feel better. They only felt better after they got either active treatment or placebo treatment. In fact, all that medical awesomeness didn’t affect them very much at all. True, even some of those who received no treatment at all reported feeling better, but that’s not uncommon in a clinical trial, and it was a far fewer number who spontaneously felt better than those who were treated with an albuterol inhaler or placebo treatments. In this study at least, the aura of medicine didn’t do much compared to the actual placebo intervention. Moerman completely missed the point here.

He does a bit better, although not a lot, in one of his articles from 2002 to which he refers in his interview entitled Deconstructing the Placebo Effect and Finding the Meaning Response. After listing studies in which, for example, medical students reported feeling a stimulant response after taking a red placebo and a sedative response after taking a blue placebo people with headache reported more pain relief after taking a branded aspirin as compared to aspirin in a plain bottle and after placebo aspirin in the same branded bottle compared to placebo in a plain bottle and it was found that people who were told that exercise would improve their psychological—surprise! surprise!—reported that exercise improved their psychological well-being. In the article, he also tries to have it both ways. While arguing time and time again that placebos, because they are inert, can’t do anything, he takes pains to point out that placebo responses leading to pain relief can be blocked by an opiate antagonist, naloxone, concluding, rather disingenuously in my opinion, “To say that a treatment such as acupuncture ‘isn’t better than placebo’ does not mean that it does nothing.” This is, of course, a massive straw man. If, as Mark Crislip jokes, placebo effects due to CAM are the “beer goggles of medicine,” altering perceived pain and symptoms without actually affecting the underlying physiology, it is not surprising that the brain function might—oh, you know—actually change in response to placebo.

In the podcast, Moerman chooses two more recent studies to try to make his point—and misinterprets them both. First, he cites a famous article from 2009 in which patients were randomized to individualized acupuncture, standardized acupuncture, simulated acupuncture (twirling a toothpick against the skin), and usual care and makes exactly the same mistake interpreting it that CAM practitioners made in trying to promote the study. In essence, he concluded that because sham acupuncture (the toothpicks) did as well as “real acupuncture” and that both did better than usual care that acupuncture “works.” Wrong, wrong, wrong. Moerman then cites a famous German acupuncture study (the GERAC study, published in 2007) as evidence that acupuncture “works” as a “meaningful” intervention. Wrong, wrong, wrong, wrong, wrong as well. This latter study preselected patients with a long history of back pain whose pain didn’t respond well to standard treatment but who were naive to acupuncture. In other words, these studies do not show that “acupuncture works very well for low back pain, much better than standard care” (Moerman’s exact words). In actuality, they showed the exact opposite.

He then mentions a study on depression in which St. John’s wort, sertraline, and placebo all had similar results in depression and asks:

What do you conclude from that study? That nothing has any effect against depression because a placebo was involved. That doesn’t follow.

Actually, yes it does. It does indeed follow. Well, it doesn’t follow that nothing has any effect against depression rather, it follows that in this study apparently neither sertraline nor St. John’s wort had any effect. This, by the way, appears to be the study to which Moerman referred. If this is the study, then it’s not entirely true that sertraline had no effect different from placebo it only affected one of three measures of depression, but it demonstrated “much improvement” in that measure. Disappointing, but not “no effect,” and there were a number of potential explanations. The authors note that “Failure of established antidepressants to show such superiority occurs in up to 35% of trials, which illustrates the difficulties plaguing randomized placebo-controlled trials in this population.” They also noted that only 36% of the sertraline group had their dose maximized, pointing out that “if any protocol bias existed at all, it would favor hypericum [St. John’s wort], which could be dosed to the maximum of its permissible range, whereas the maximum permitted dose of sertraline was only 50% of its highest recommended amount.” So, in this study, it is reasonable to conclude that neither sertraline nor St. John’s wort “worked” in this population at this time at the doses used, but when the totality of evidence and the shortcomings of this trial are taken into account, sertraline does have an effect.

Another issue that Moerman completely ignores is that placebo responses might very well also be largely influenced by artifacts inherent in the structure of clinical trials. It’s not as though these issues haven’t been heavily studied, including expectancy effects (people are suggestible), observer effects (people often report improvement just from the process of being observed, also known as the Hawthorne effect), observer bias, training effects from repeated testing, and cheerleader effects from being encouraged. One wonders what Moerman would say about recent research, including an (in)famous NEJM meta-analysis and a recently updated Cochrane review, that suggest strongly that, when all these nonspecific effects and experimental biases are controlled for adequately, the placebo effect disappears. I think it’s worth quoting each briefly.

…we found little evidence that placebos in general have powerful clinical effects. Placebos had no significant pooled effect on subjective or objective binary or continuous objective outcomes. We found significant effects of placebo on continuous subjective outcomes and for the treatment of pain but also bias related to larger effects in small trials. The use of placebo outside the aegis of a controlled, properly designed clinical trial cannot be recommended.

We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.

Be that as it may, in a way Moerman (sort of) agrees with Crislip, just not in a way that supports his argument that the “meaning” behind placebos is this wonderful, powerful thing. Crislip makes a strong argument dismissing placebo effects as a myth. Moerman is dismissing placebo effects in a different manner, but in a way infused with his background as an anthropologist. He’s denying placebo effects by renaming them. In a way, they are (again, sort of) arguing the same thing. Crislip argues that placebo effects are an example of mild cognitive therapy in which the pain stays the same but it’s the perception of pain that changes. Moerman argues something similar, ascribing changes in pain perception to all trappings of “power” and interactions with health care providers in medical settings and the “meaning” that patients find in them. None of this is inconsistent with placebo responses being in actuality altered perceptions of symptoms. It’s just that Moerman seems to think that the “meaning” that alters these perceptions is far more powerful than it is. Unfortunately, while Crislip is rooted in hard-nosed “materialistic” science, Moerman seems more rooted in postmodern, relativistic thinking:

Practitioners can benefit clinically by conceptualizing this issue in terms of the meaning response rather than the placebo effect. Placebos are inert. You can’t do anything about them. For human beings, meaning is everything that placebos are not, richly alive and powerful. However, we know little of this power, although all clinicians have experienced it. One reason we are so ignorant is that, by focusing on placebos, we constantly have to address the moral and ethical issues of prescribing inert treatments (73, 74), of lying (75), and the like. It seems possible to evade the entire issue by simply avoiding placebos. One cannot, however, avoid meaning while engaging human beings. Even the most distant objects—the planet Venus, the stars in the constellation Orion—are meaningful to us, as well as to others (76).

One notes that reference #76 is a book by Timothy P. McCleary entitled, The Stars We Know: Crow Indian Astronomy and Lifeways. Perusing the information about the book, I see that the author states very early on that the purpose of his book was to “provide insight into a little known aspect of Crow culture—Crow ethnoastronomy. Ethnoastronomy, a fairly recent development in human sciences, attempts to elicit how non-Western peoples’ perceptions of cosmic phenomena are utilized in structuring behaviors, values, and mores.” All of this might be fascinating reading as far as learning about the history and culture of various peoples, but it would appear to stretch the bounds of what is a science and what it has to do with medicine I’m having a hard time grasping. It must be that reductionistic “Western” scientist in me. Is Moerman trying to say that because humans find “meaning” (whatever that means) in stars and constellations that placebos work? How would understanding “meaning” improve medicine above and beyond what we currently do to understand the effect of patient-provider interactions on health care delivery. Moerman either can’t or doesn’t specify, nor does he provide concrete examples of how his ideas would improve medicine. Maybe he does so in his book, but given that his article to which he referred is billed as the “abstract” or a “synopsis” of his book, somehow I doubt it. Worse, Moerman adds nothing new to the conversation, nor does he provide any testable hypotheses that would allow us to use his concept of “meaning” to better medical care by maximizing nonspecific effects as we use effective medicines.

The lack of specific examples aside, the problem remains for diseases for which there is a real derangement in physiology, such as asthma, diabetes, and the like. If placebo responses make the patient perceive his symptoms as being less severe, that doesn’t help the underlying pathophysiology or work to prevent the very real, very dangerous complications that can result from that pathophysiology. Again, nowhere in Moerman’s editorial or podcast do I see a recognition of that. What I do see is Moerman trying to make like Humpty-Dumpty and make the word “meaning” mean just what he chooses it to mean—neither more nor less, except that, now having read his NEJM editorial and his earlier paper and listened to his podcast interview, I’m still not sure he even knows what it’s supposed to mean.

The bottom line is that we as physicians are indeed called upon to relieve patients’ symptoms, but our obligation goes far beyond that. As physicians, we understand the pathophysiology of disease we know the consequences of leaving a disease untreated. It is not enough for us to make the patient feel better. If that were the case, then there would be no reason not to give patients sedatives or stimulants for almost everything. Those certainly “make patients feel better”! But there are a lot of conditions where physiology trumps subjective complaints, or at least threatens to. Asthma, the topic of the NEJM placebo study from last month, is, of course, a classic example. A patient can be feeling fine (or at least not too bad) but be perilously close to a respiratory arrest. The same is true of diabetes, where a more or less asymptomatic patient can be on the verge of diabetic ketoacidosis. In these cases, our obligation as physicians is not just to make the patient feel better, but to make the patient better.

All in the mind? How research is proving the true healing power of the placebo

We know that our thoughts and perceptions affect our physiology – in situations from stress to sexual arousal – but when it comes to whether these changes influence health, the question suddenly becomes much more controversial. You get claims of miracle cures at one extreme, while some sceptics argue that any role for the mind is deluded. I wanted to investigate the scientific research in this area to find out what the truth is.

Why is there so much resistance in the scientific community to the idea that the mind could have a role in healing?

Part of it is an understandable reaction to those exaggerated claims of cures. Sceptics may fear that allowing any role for the mind will encourage people to believe in the pseudoscientific ideas of alternative therapists. But there’s more to it than that. Ever since Descartes, scientists have viewed physical, measurable matter as more “real”, a more suitable topic for scientific enquiry, than subjective emotions and beliefs. I think that has led to an ingrained bias that because our thoughts aren’t “real”, they can’t influence the physical body. This makes no sense from a neuroscience perspective – where you can’t have a thought without a concurrent physical change in the neurons of the brain – but it causes a kneejerk reaction against the idea that our mental state might affect our health.

Is there also a problem with how drug trials are designed?

A trial that tests a new treatment against a placebo is perfect for testing the direct biochemical action of a drug. But it can’t assess other elements of care, such as social support or stress reduction and positive expectation, because they are present in the placebo group too. There are studies suggesting that these components matter: patients with irritable bowel syndrome have greater relief from their symptoms when their practitioner is empathic rather than cold patients with acid reflux disease do dramatically better after a 42-minute consultation compared to an 18-minute one. We need to take an evidence-based approach to studying these social and psychological aspects of care, just as we do when testing how drugs work.

Why do people believe in treatments based on evidence-free theories of the body?

Often, they believe they have personally benefited from alternative treatments such as homeopathy or reiki or acupuncture. When scientists then insist these treatments don’t work, these patients may be pushed towards the pseudoscientific explanations of their therapists. But there is a scientific explanation: factors such as social support and positive expectation inherent in these treatments can trigger physiological changes that ease symptoms.

What is the mechanism for how the mind influences health?

There are lots of mechanisms. Our mental state can be crucial in determining our experience of symptoms such as pain, nausea, fatigue and depression. Taking a placebo painkiller causes the release of pain-relieving endorphins in the brain, for example, whereas fake oxygen can reduce levels of neurotransmitters called prostaglandins, which dilate blood vessels and cause many of the symptoms of altitude sickness. When you experience a placebo response, it’s not imaginary or “all in the mind”: your symptoms are eased by physical changes just like those triggered by drugs. This is because warning signals such as pain are ultimately controlled by the brain. Feeling stressed, alone or under threat causes the brain to amplify the warning, whereas feeling safe or optimistic once a crisis is over triggers the brain to ease off. The experience of receiving medical care – whether real or fake – seems to reduce our symptoms for the same reason.

The mind can also affect physiological functions such as digestion, circulation and the immune system, and again there’s nothing mysterious or magical about this. All of these processes are controlled by the brain, via the autonomic nervous system. Feeling stressed or afraid can cause your heart to race and your bowels to empty, for example, and triggers an immune response called inflammation. These processes aren’t usually under conscious control - we can’t will changes to occur - but there are indirect methods we can use to influence them. Reducing stress is an obvious example.

What has been the response to the book. Have you fallen foul of both the alternative health practitioners and the evidence fundamentalists?

I was nervous about how it would be received but I’ve had positive reactions from everyone from neurosurgeons to reiki practitioners. A reviewer on the Science-Based Medicine blog described the book as “fascinating”, adding that it “challenged me to think more deeply about placebos, alternative medicine, and patient comfort”. This topic can be very very polarising but the responses have encouraged me that it is possible to have a rational debate about it after all.

Which was the story or treatment that surprised you the most, ie you went in a sceptic and came out a convert?

I met a transplant patient who drank green, lavender-flavoured milk to suppress immune rejection of his donated kidney. That sounds crazy, but it was part of a trial investigating how we can train our immune systems to respond to sensory cues such as taste or smell. This works through classical conditioning, where we learn to associate a psychological cue with a physiological response (such as when Pavlov’s dogs learned to salivate in response to the sound of a buzzer). Similarly, if you take several doses of a drug that suppresses the immune system, subsequently taking a placebo triggers an identical response, even though it contains no active drug – and regardless of whether you know it’s a placebo. In this trial, researchers used the distinctive green drink to strengthen the learned association and maximise the response. They hope reducing drug doses with placebos in this way could cut side effects for patients with organ transplants, autoimmune disease and cancer

Are some of these treatments just being ignored because they can’t be commodified by pharma companies?

Yes. I heard this over and over again from the researchers I interviewed. The majority of clinical trials are funded by pharma companies, which contributes to a medical system that prioritises the prescription of drugs, even for conditions such as pain that are strongly influenced by social and psychological factors. This serves commercial interests but doesn’t necessarily lead to the best outcomes for patients.

The Implications of the Results for Neurodegenerative Disease Research

One potential reason this clinical trial succeed in demonstrating significant benefits of curcumin supplementation, despite the inconclusiveness of so much of the previous work in the field, is that the researchers used a highly bioavailable form of curcumin. Prior to the study, many researchers blamed the failure of previous clinical trials on the low bioavailability of curcumin, which results from the fact that the natural form of the compound is poorly absorbed, rapidly metabolized, and quickly eliminated. However, the researchers used a form of curcumin that is absorbed more quickly in the GI tract than traditionally formulated curcumin supplements, as demonstrated by blood samples taken at intervals after supplement intake, which meant that the curcumin could actually have an effect on patients’ bodies.

In recent years, researchers have been exploring a variety of possible delivery methods to improve the bioavailability of curcumin supplements. The meaningful results of this study indicate that embracing such supplements can mean the difference between inconclusive results and groundbreaking findings with significant implications for the future of neurodegenerative disease research—not to mention research on other diseases where curcumin may offer protective benefits and/or effectively treat symptoms. As more researchers conduct studies using cutting-edge delivery methods, it will be exciting to see how the field progresses. In the meantime, some cutting-edge nutraceutical manufacturers, such as Tesseract Medical Research, are already offering state-of-the-art ingredients and delivery systems designed to optimize bioavailability, offering clinicians and patients the ability to take advantage of curcumin’s possible therapeutic benefits today.