The placebo effect in general practice

Abstract

The placebo effect has been used to make people feel better since ancient times. The improvement in symptoms from placebos can be dramatic, yet the medical profession gives this relatively little attention. Neurobiological explanations for the placebo effect have been uncovered in recent years, and there is a growing interest in understanding and harnessing it within the consultation – where the placebo effect is known as the context-mediated effect. Using the placebo effect without care and skill can leave patients in a worse position, facing adverse effects, unnecessary costs and unhelpful health-seeking behaviour. This article will offer a guide to the placebo effect and its less well known sibling the nocebo effect, to help readers be more aware of its presence and value in the GP consultation.

The GP curriculum and the placebo effect

Professional module 2.01: The GP consultation in practice states that:

As a GP you should understand that consultations have a clinical, a psychological and a social component, with the relevance of each component varying from consultation to consultation (the ‘triaxial’ model)

Professional module 2.04: Enhancing professional knowledge states that:

As a GP you should be aware of how you impart information about evidence so that patients can best understand relevant evidence and be helped in making a decision

I shall please: The history of placebo

Placebo derives from the Latin for I shall please. In the 13th century placebo became a pejorative term for a sycophant, in reference to professional mourners who were paid to chant at funerals. The first word of the chants was ‘placebo’. Placebo entered medical use in the 18th century: A medicine given to patients to please them rather than to cure. Only in modern times has it come to mean a medication or treatment with no pharmacological activity. The first controlled trial of a placebo is thought to have taken place in 1931 (Amberson et al., 1931). Since then modern medicine has focused on the benefits of various treatments over and above the effects of placebos, typically ignoring the often dramatic benefits of taking a placebo. Until the last hundred years, almost every treatment given by doctors was no more effective than placebo (opium, digitalis and quinine being notable exceptions) and often considerably more harmful. However, despite this, people have sought out the healing effects of doctors and placebo treatments for millennia.

The placebo effect

The Oxford Dictionary defines the placebo effect as:

A beneficial effect produced by a placebo drug or treatment, which cannot be attributed to the properties of the placebo itself and must therefore be due to the patient's belief in that treatment.

That beneficial effect, when measured in a placebo-controlled trial, can produce up a to 50% reduction in symptoms in chronic musculoskeletal pain (Derry, 2016), and accounts for an estimated 75% of the effects of antidepressants (Kirsh, 2014).

Importantly, placebo effects have not been shown to alter the pathophysiology of disease. They cannot cure cancer or eradicate a virus or lower cholesterol. However, throughout healthcare, from osteoarthritis to depression to Parkinson’s disease, the symptoms of disease have been shown consistently to be altered by placebos (Kaptchuk and Miller, 2015). Take asthma as an example: in one small study that compared the effect of taking a beta-agonist inhaler with that of a placebo inhaler, there was no significant effect on forced expiratory volume in 1 second (FEV1) with the placebo, yet a similar improvement in patient reported symptoms was seen in both groups (Wechsler et al., 2011).

Explanations for the placebo effect

Placebo effects are complex, and various explanations have been proposed (Lucan, 2011). The simplest is that improvements in symptoms after taking a dummy pill can reflect the regression to the mean. The classic example is the person who goes to their GP with a cold virus on the day that the symptoms peak: it usually gets better within a day or two whatever happens in the consultation. Another explanation, seen in clinical trials, is known as the Hawthorne effect: the psychological effect of being singled out and made to feel important.

However, the placebo effect has been shown to be more than just regression to the mean or an artefact within clinical trials. Recent research is revealing a neurobiological mechanism for it, explaining how symptoms can change according to what we expect to happen (Kaptchuk and Miller, 2015). Ted Kaptchuk, a prominent researcher in this field, explains this observation through the metaphor of a walk through the forest (Kaptchuk, 2014). This imaginary forest is known for its deadly snakes, of which you are very conscious as you walk through it. As you walk, you see a long slender object on the ground in the corner of your eye, and immediately think it is a snake – when in fact it is just a stick. In the same way, when you take a medication you do so with a certain expectation, and that can be enhanced by being advised to take it by your doctor, how much it costs, and what it says on the packet. The brain anticipates the positive effects of treatment, which in itself can start to alleviate symptoms. A striking example of this has been demonstrated in Parkinson's disease (De la Fuente-Fernández et al., 2001). Patients expecting l-dopa treatment but who were actually given a placebo had a 200% increase in dopamine levels in the brain on positron emission tomography scanning, even though no dopamine had been taken. Similarly, in pain control, activation of endogenous opioids and dopamine has been found in people given placebo (Finniss et al., 2010).

The placebo effect in general practice

If we consider the experience of going to see a GP, we can begin to see how many different ways the placebo effect can be generated. Placebo effects are ‘about the rituals, the words, the engagement, the costumes and the diplomas’; ‘They’re about how the drama of healthcare can alleviate symptoms, even without pharmaceuticals’ (Kaptchuk, 2014). As such, the placebo effect can be thought of as something dynamic that can be enhanced or dampened by the interaction between the patient, their surroundings and their doctor. Discussing the placebo effect in The Lancet, GP and academic KB Thomas wrote (Thomas, 1994):

The placebo effect in general practice is the power of the doctor alone to make the patient feel better, irrespective of medication. It is one of the most important factors in the consultation, yet generally it is neglected, unrecognized, and untaught. A better appreciation of this power would change doctors’ attitudes to the consultation and would result in the making of less illness, the prescribing of less medication, and a better understanding by the patient of his or her condition.

Twenty-five years on, is the placebo effect any better understood and utilised in general practice? The word placebo is perhaps, ironically, too toxic to gain approval from the mainstream medical profession, due to its association with sham treatments. ‘Context-mediated effect’ has been offered as an alternative, more palatable, term (Olesen, 2015). Box 1 offers some examples within general practice where the context-mediated effect can be found and utilised.

Box 1.

Context-mediated effects in general practice.

The rituals, the costumes and the diplomas

Even before the consultation has begun, many things can influence its impact and effect: the waiting room environment, the layout of the consulting room, the clothes the doctor wears, and the way in which the patient is greeted. Consider what you can do where you work to make this a positive experience, which encourages the healing effect of the consultation that follows

Using the placebo effect as a shortcut

Be wary of using the placebo effect as a shortcut to end a consultation or avoid exploring a patient's ideas and concerns: Patient: ‘Doctor this headache has been going on for 3 days and I think it should have gone by now’.

Doctor: ‘Well, I have a very strong painkiller that is only available on prescription. It is sure to help’.

When running late and with so little time in a consultation, it is tempting to ignore the cue (‘I think it should have gone by now’) and try to get the patient out of the door with your ‘strongest’ and most ‘powerful’ drug, that you think will work because the patient will expect it to rather than because it is much stronger than what they have already had (e.g. naproxen versus ibuprofen). However, the chances are, they will be back next week demanding an magnetic resonance imaging scan

Doctor as the ‘drug’

A major theme of Balint's seminal work The Doctor, his Patient and the Illness is that of the doctor as ‘the drug’ – how the interaction between patient and doctor can in itself be therapeutic (Balint 1957). Many an hour has been spent unpicking consultations in Balint groups ever since. Identifying and addressing someone's ideas and concerns about their symptoms is often all that is required to alleviate them

Being positive

What effect does being positive have on symptoms? One GP did an experiment to see if people with non-specific symptoms who he consulted in a positive manner got better quicker than those who had a negative consultation (Thomas, 1987). Two weeks later there was a statistically significant difference: 64% of those receiving a positive consultation got better, compared with 39% of those who received a negative consultation. Those who were given treatment did no better than those who were not given treatment. These findings should be viewed with caution, it was not the most robust study, but reinforce the idea that what you say and how you say it can be as important as what you do

Health anxiety and external locus of control

A lot of people will look to either tablets or you, their GP, to make everything better when they feel unwell. There may be a powerful placebo effect, which can initially be quite satisfying for the doctor: every time you suggest something it works! The patient keeps coming back to you, praising your clinical skills, but soon becomes a frequent attender. Identifying these patients, who may have health anxiety or feel they need their problems fixed by someone else (an external locus of control), early on is hard. Helping them to worry less about their symptoms or take back control of their health is often even harder

Is it ethical for GPs to prescribe placebos?

If much of the beneficial effect of some medications is placebo, should doctors be prescribing dummy pills to their patients? Applying the Hippocratic principle of ‘do no harm’ this seems to make sense, but this is of course overshadowed by the need for honesty and trust between doctor and patient. However, what happens if you give someone a placebo and tell them that it is a placebo? A 2017 systematic review and meta-analysis found five trials where ‘open label' placebos were given alongside no treatment (Charlesworth et al., 2017). It found that people given placebos report an improvement in their symptoms. The evidence is not strong enough to form any firm conclusions; the studies were small and not blinded. However, these trials raise interesting questions. One hypothesis is that the positive suggestion alongside giving the placebo is responsible for the effect, but this needs to be tested in larger, more robust studies.

The harmful effects of placebos

It is tempting to see the placebo effect as a benign or even benevolent force, but there are numerous problems associated with it. The first, and perhaps most prevalent, is that if patients attribute all of the benefits seen from taking a drug to the active ingredient alone, this can lead to a skewed view of the effects of the drug and reinforce the idea that every symptom requires a drug or other treatment. For instance, if you take cough mixture for a tickly cough and it gets better, you might think it was all thanks to the cough mixture. In fact, the cough was going to get better anyway (regression to the mean) and the medicine was designed to maximise the placebo effect: a brightly coloured, reassuringly disgusting liquid in packaging that makes lots of claims about making you feel better. This can lead to medicalisation of self-limiting illness, reduced self-efficacy and iatrogenic harm (renal failure due to non-steroidal anti-inflammatory drugs, for example). The healing effect of reassurance from a health professional or investigation can be damaging too, manifesting in what has been described as an epidemic of health anxiety.

Patients will often wisely tell you that they never read the list of side effects included in a box of medication. Others will read them over and over and always seem to report one or more of the side effects. This is the nocebo effect; the harmful effect of a treatment that cannot be attributed to the treatment itself. For example, in a study of men with benign prostatic hypertrophy treated with finasteride, patients informed of the sexual side effect of this drug reported sexual side effects at three times the rate that patients who were not informed. (Kaptchuk and Miller, 2015) An estimated 4 to 26% of patients who are randomly assigned to placebos in trials stop taking them because of perceived adverse effects. The nocebo effect can occur when a drug is stopped too, and likely plays some role in the difficulties that many people have stopping some medications such as antidepressants (see Box 2) and painkillers.

Box 2.

The placebo effect in depression.

High-quality evidence demonstrates the benefits of antidepressants over and above that of placebos in treating symptoms of depression. Nonetheless, there is a strong placebo effect, which may be as high as 75% of that of the drug (Kirsh, 2014). In clinical practice it is not possible to know, in the patient in front of you, to what extend improvements in symptoms are due to placebo or the drug. For many people with mild-to-moderate symptoms of depression there is a large potential for context-mediated effects, as well as the shift in thoughts that can come from seeking help, talking about how they feel, and the simple behavioural steps that may follow (e.g. exercise, stopping alcohol).

Joanna Moncrief, a prominent critic of the place of antidepressants in society, frames antidepressants in terms of their potential to act as placebos (Middleton and Moncrief, 2011). ‘Some patients will want their distress to be acknowledged within a medical framework and may respond to the acknowledgment and hope a prescription can provide.’ This, she argues, can lead to unintended harms:

In the long term, however, the message that is symbolised by medication may be harmful. Symbolically, medication suggests that the problem is within the brain, and that wellbeing is dependent upon maintaining ‘chemical balance’ by artificial means, a message which may encourage people to view themselves as flawed and vulnerable.

Tips for antidepressant prescribing

• Try not to prescribe an antidepressant at the first appointment, particularly in a patient you do not know well. This allows you to make a more detailed assessment and gives the patient time to consider the option of medication more fully. Symptoms often stabilise after seeking help, and with behavioural and cognitive interventions

• When prescribing an antidepressant emphasise its role as a part of the plan, which might typically involve cognitive behavioural therapy, lifestyle modification, and addressing social or systemic factors (e.g. a problem at work, family disputes, etc.)

• Many will worry that when they stop taking an antidepressant it will lead to a relapse. Minimise the potential for a nocebo effect at this point by emphasising from the outset that when they have recovered from the episode of depression they will be very unlikely to relapse when they stop taking it. Use this to stress the importance of talking therapies and lifestyle changes, which are the key to building resilience and reducing the risk of relapse

KEY POINTS

When a treatment is given, the overall response is the combined effect of the treatment itself and the placebo effect

What happens in the consultation can have an effect on the strength of the placebo effect

Be aware of the harm that placebos can cause too, such as medicalisation, reduced self-efficacy and the nocebo effect

Consider how your consulting room and practice environment may have an effect on your consultation and its healing effect

Deferring the start of treatment with medication (such as antidepressants) until a follow-up consultation may reduce the risk of misattributing symptom improvement to use of medication

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