Creative consulting: what modifies a healing response

In the fourth article in his series David Reilly begins exploring placebo and nocebo responses

You are convinced that you need to make the consultation positive,¹ you have tried to prepare yourself and "made the room disappear," ² and the potential for change sits there waiting in the patient.³ Now what? Remember that your main job is to do no harm, while people recover naturally, remaining vigilant for when this "masterful inactivity" is not safe. Your simple respect, courtesy, and expression of needed technical skill are so often more than enough. Carl Rogers boils down the ingredients that make us effective carers as being one's self, having unconditional positive regard for others, and feeling empathy.⁴ Yes it is easier said than practised. Surgery is not easy at first either, and who said human caring would be? Of the many forces modifying your consultation, affecting the patient's self healing responses, and so reactions to therapy, as the placebo response looms large.

The puzzle: predict--pill or placebo?
So let's jump in with a challenge. You prescribe a drug, herb, whatever, and a strong response occurs. How do you know if it was a "real" response, resulting from the specific intervention or if it was triggered by the non-specific/context/placebo effects? Is there a difference? Take a look at the graphs in the figure and try to work out how many and which of these four patients with asthma had only placebo at each stage in their treatment compared with who had a real drug at some point.⁵ They are part of a group of 35 patients in an asthma clinic's randomised double blinded trial adding of a new allergen desensitising technique to their existing asthma treatments. The consent form explained that they "will have a 50:50 chance of getting only placebo"; and there was "a chance of symptoms getting a bit worse before they would improve." Note carefully that the first prescription is a placebo in every case--the researchers knew this but the patients did not (single blinded), while the second prescription is randomised and double blinded. The placebo and active medicine were exactly matched for taste, colour, form, etc, and were given in the same way by the same people at each visit. Who got "real medicine" and how do you know?

Transmitted expectations
Can a placebo trigger improvements and deteriorations like these? And can people respond differently to two sequential placebos given in identical manner by the same people? The answer is yes. Only patient C got the real medicine, patients A, B, and D had different, even opposite, reactions to two placebos given by the same carers in the same context. So what might have happened? Look again at the graphs and recall that at point 2 on the horizontal axis the prescription changes from single blinded to double blinded. The expectations of the carers change. They knew there was now a chance of an active medicine (with its initial risk of adverse effects), and somehow this seems to have "activated" the placebo's impact on healing, for good or bad, even "cancelling" previous healing responses. Note how these reactions override the current pharmacology. This neural-alchemy is likely triggered by "the transmitted clinician's expectation of outcome."⁶ This matters for study design and treatment comparisons⁷ but even more so for individual patient care and safety. Alter the expectation of carers and you may activate different outcomes, for harm as well as good. Patients pick up these signals,² making them "active ingredients." Think through implications of this for your practice.

Nocebo
You probably knew that a placebo response could sometimes encourage a positive outcome, but did you know that the negative impact seen in the graphs could occur? It is called a nocebo response (originally meaning "I hurt") and is the induced harmful effects of negative beliefs.⁸ Like placebo, the triggers vary as widely as the contexts, but the end results may have final common pathways. Some apparent placebo effects are artefacts, or coincidental,⁹ but, as in a blush, our feelings do affect our body.

Your expectations about a drug and the presciber's influence may enhance or diminish the drug's effect. In laboratory experiments, inhaled saline produced increases or decreases in airways resistance according to what patients were told to expect. When patients were given a true bronchodilator, its effects were twice as great than if patients were told it would produce this effect.^10,11 There are around 2000 deaths a year from asthma in Britain. These modifying factors do not appear in the guidelines for asthma treatment. Yet they could tip the balance. Imagine if the protocol was for "the person with asthma," not just "asthma." To the life-saving measures and drugs we might add: establish a therapeutic bond; address the patient's fear; ensure trust in the prescription; increase self coping; enhance relaxation. We can dream!

Placebos can produce pain in normal subjects. Headaches were reported by 70% of medical students told that a (non-existent) electric current was passing through their heads.¹² A review of 109 double blind trials rated the overall incidence of adverse events in healthy volunteers during placebo administration at 19%.¹³ Negatively impacting consultations do harm,¹⁴ but some shocks do even more.

George Engel (father of the biopsychosocial model') analysed 107 sudden deaths related to emotional shocks. They were mostly linked to personal danger (whether real or symbolic), the collapse or death of a close person, and during acute grief-- that is, situations which cannot be ignored and where you believe you have no control.¹⁵ (Think, have you ever been admitted to hospital?)

The most dramatic extreme of nocebo is voodoo death.⁸ Some anthropologists believe that we are born and die twice: biologically and socially. In voodoo death you die socially first. Reviewing nocebo,¹⁶ Herbert Spiegel describes a "medical voodoo" when a man in hospital was wrongly and unnecessarily given the last rites by a priest and died within 15 minutes. The West brings many forms of social death--imprisonment, old people's home, psychiatric long stay ward, retirement, stigmatised diagnoses--with their resultant impact on health. We can help to neutralise the negative messages of such predicaments (including medical ones) by developing psychological defences. For example, learning to deal with hopelessness was an outstanding feature noted in a group of the women with breast cancer whose longevity was extended on average by 18 months by joining support group meetings.¹⁷

Conclusion
We know a human recovery reaction is a built in potential, we have seen that it can be modified for good and bad by human interaction. Medical research uses placebo controlled trials yet has neglected to study the reasons for the positive and negative impacts of placebo. Doing so helps understand what triggers self healing and self destruction.

David Reilly welcomes correspondence or
questions on this series.

A: No response to the first single blind placebo. Dramatic improvement within hours to the double blind randomised prescription--ran a marathon! Waned to 50% within about a month.	B: No response to the first single blind placebo. Dramatic aggravation within hours to the double blind randomised prescription. "Worst ever." plus return of old symptoms (rhinitis) and a new symptom of mid-thoracic back pain. Settled.
C: No response to the first single blind placebo. A smooth and sustained improvement to the double blind randomised prescription.	D: Marked improvement with the first single blind placebo. Dramatic aggravation within hours to the double blind randomised prescription.
These graphs are scanned from charts completed interactively by four different patients and their doctor at three visits, a month apart, during a randomised double blind study of a treatment for asthma. The vertical scale is +/- 100%, a rise is an improvement, and the line descends in a deterioration. Point 1 on the horizontal axis marks the first visit when each patient had a single blind placebo. Four weeks on at point 2 the patient has been given, randomised and double blind, either a second placebo, or active medication. At point 3 a third prescription is given only if required, with those previously randomised to the placebo group again receiving a placebo treatment. The challenge is to determine who got an active medication at the second visit compared with those who received a second placebo.Reilly DT, Taylor MA. Individual patients and their responses -- OPICS published in pages 26-28 of Developing Integrated Medicine. RCCM Research Fellowship in Complementary Medicine. Complementary Therapies in Medicine 1993;1 Suppl 1:1-50

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