From the Editor 

“To a degree which has never been suspected, what powerful influence upon diseases is produced by mere imagination.” British physician John Haygarth wrote those words more than two centuries ago when considering the placebo effect.

Is it possible to successfully treat people with placebo in an open-label trial? That is, if people know they are taking placebo, will they still experience the benefit of placebo?

painCan a fake intervention help real pain?

In this week’s selection, we look at a new study where participants were offered placebo for back pain. Spoiler alert: it worked.

And, in a new feature for the Reading of the Week, we include an invited letter to the editor from Dr. Albert H. C. Wong who writes about the best way of preventing depression.



 Pain and Placebo

“Open-label placebo treatment in chronic low back pain: a randomized controlled trial”

Cláudia Carvalho, Joaquim Machado Caetano, Lidia Cunha, Paula Rebouta, Ted J. Kaptchuk, Irving Kirsch

Pain, December 2016


Low back pain (LBP) causes more disability than any other medical condition worldwide. It is the most common occupational disorder globally and, in the United States, is ranked third among all diseases by disability-adjusted life-years. Researchers and clinicians have identified a pressing need for innovative treatments and management tools.

Recent studies have demonstrated that some commonly prescribed front-line therapies for LBP are actually not superior to placebo controls in double-blind randomized clinical trials (RCTs) or are of only marginal increased efficacy. In themselves, placebo responses in trials for LBP can be large and clinically significant. Undoubtedly, some of these improvements are due to normal waxing and waning of symptoms and regression to the mean. Recent evidence suggests that beyond such spontaneous improvement, a significant percentage of these responses are due to placebo effects: ie, the psychosocial effects of the therapeutic encounter, including its interactions, rituals, and symbols.

Administrating fake pills to harness placebo effects poses an ethical conundrum for physicians in clinical practice due to the widespread belief that deception is necessary for placebo pills to work (eg, pretending sugar pills are drugs or, more commonly, giving genuine medications that have no known effect on the condition). However, 4 studies have directly tested the effect of an open-label placebo (OLP) prescription, and all indicated that patients reported benefits after taking pills presented honestly as placebos.

carvalho-picCláudia Carvalho

So begins a paper by Cláudia Carvalho that looks at using placebo for back pain – identified to the patients as placebo.

Here’s what they did:

  • Between November 2013 and December 2015, people with back pain were randomized to two groups: a usual treatment and usual treatment plus open-label placebo.
  • Recruitment included ads, referrals, and Facebook posts.
  • Participants were over 18, and needed to have more than 3 months of persistent lower back pain, confirmed by a nurse practitioner or a pain specialist.
  • Participants receiving placebo were told “4 discussion points”: “(1) the placebo effect can be powerful, (2) the body automatically can respond to taking placebo pills like Pavlov dogs who salivated when they heard a bell, (3) a positive attitude can be helpful but is not necessary, and (4) taking the pills faithfully for the 21 days is critical.”
  • Participants did several scales, at baseline, and days 11 and 21, including a Roland-Morris Disability Questionnaire.

Here’s what they found:

  • 239 people completed the initial telephone/email screening; with those who were ineligible dropped from the study, 41 people were randomized to the open-label placebo and 42 people to treatment as usual.
  • Demographics: Participants tended to be female, employed, and taking NSAIDs.
  • At 3 weeks,OLP elicited greater pain reduction on the composite pain measure (P<0.001). Open-label placebo also reduced disability compared to TAU (P<0.001), with a large effect size…” “Effect sizes ranged from medium (g = 0.46) to large (g = 0.76).”
  • A reduction in pain of 27.9% has been found to correspond to clinical ratings of ‘much improved’ and a 30% reduction has been recommended as an indication clinical significance. There was a clinically significant 30% reduction in both usual and maximum pain in the placebo group compared to reductions of 9% and 16% in usual and maximum pain, respectively, in the continued usual treatment group. Open-label placebo reduced minimum pain by 16% compared to an increase in pain of 25% with TAU. There was also a 29% reduction in pain-related disability in placebo group compared to 0.02% in the TAU arm.”


They conclude:

The study is the first to demonstrate potential clinically significant benefits of OLP treatment in cLBP. We found that adding OLP to TAU resulted in significantly greater reductions in cLBP and pain related disability than TAU alone. The amount of additional pain reduction produced by OLP was approximately 30% of baseline pain and disability ratings.

A few thoughts:

  1. Wow.
  1. The topic of placebo remains fascinating even two centuries after John Haygarth first wrote about it.
  1. It should be noted that the actual number of participants who reached the follow up phase was relatively small – just 31 in the non-placebo group. We can take these results then with a bit of skepticism. But it also should be noted that other studies (albeit small in number) have looked at open-label placebo for illness and found similar findings.
  1. This is an interesting way of incorporating placebo into treatment – in a sense, participants were given something of a pep talk. Would the result have been the same without that conversation?
  1. Who best to target with placebo and what are the larger implications? The use of placebo and neuroimaging is an evolving field; see the Pecina et al. paper, considered in a past Reading. You can find it here:


Depression and Treatment

To the Editor:

The Reading of the Week on 23 February 2017 was very interesting: “Has increased provision of treatment reduced the prevalence of common mental disorders? Review of the evidence from four countries” Anthony F. Jorm, Scott B. Patten, Traolach S. Brugha, Ramin Mojtabai. World Psychiatry, February 2017.

The general conclusion was that increased mental health spending and antidepressant medication treatment did not alter the prevalence of depression and anxiety disorders or symptoms. In Australia, anxiety symptoms actually increased. The authors make a logical call for more preventative interventions.

Perhaps treatment is not reducing overall prevalence because some anxiety and mood disorders arise, in part, from the modern taming of physical threats in the environment. Without real fear of being mauled by a bear or being killed by other humans in the daily life of residents of Canada, UK, Australia and the US, anxiety finds a new (and inappropriate) focus. This hypothesis is conceptually similar to the hygiene hypothesis for the putative increase in food and environmental allergies: by cleaning a baby’s environment too much, we remove exposure to antigens needed for the immune system to practice distinguishing antigens and thus promote the emergence of allergies.

For example, the lifetime prevalence of anxiety disorders in Canada, one of the richest and safest countries in the world has been estimated to be 16%.(1) In comparison, the lifetime prevalence of anxiety disorders in Ethiopia was only 8%.(2) Ethiopia is one of the poorest countries in the world, and in addition to meagre health care resources, suffers from recurrent famine and political violence.

New attempts at prevention could take a fresh approach, and aim to reintroduce a controlled element of risk and excitement into anodyne modern life, rather than the sedate counselling and therapy interventions that are often promoted.

Albert H. C. Wong, MD, FRCPC, PhD

Professor of Psychiatry

University of Toronto


  1. Somers JM, Goldner EM, Waraich P, Hsu L. Prevalence and incidence studies of anxiety disorders: a systematic review of the literature. Canadian journal of psychiatry Revue canadienne de psychiatrie. 2006;51(2):100-13.
  2. Kebede D, Alem A. Major mental disorders in Addis Ababa, Ethiopia. III. Neurotic and somatoform disorders. Acta psychiatrica Scandinavica Supplementum. 1999;397:24-9.



Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.