Stat Counter

Tuesday, August 3, 2010

Placebos: All you never wanted to know (Part 2) - Theories

Welcome back to this, the second post in my review of placebos. Now, to the fodder that makes us scientists, theories about the placebo. This is important as a good theory can both account for our data and predict new data, while also giving us something to falsify, which is apparently how science progresses.

Steve Stewart Williams (all round good guy) reviewed the state of placebo theorising in 2004, and he specified that there are a number of criteria that a successful placebo theory should meet.

1) Account for both objective and subjective placebo effects (that whole obj vs subj dichotomy is very unsatisfying to me, but thats another post)
2) Should also account for nocebo effects (negative placebo effects)
3) Should account for dose reponse rates of placebos (take more fake pills, get a better effect)
4) Should account for differences between different forms of placebo treatments
5) Should account for stronger effects on subjective than objective measures
6) Must account for active placebos producing stronger effects (active placebos are real drugs prescribed in either conditions for which they have no specificity, or in too small a dose to have a biological effect)
7) Must explain placebo effects in healthy people in non clinical settings
8) Must account for the general and local effects observed in placebo analgesia

Thats a tall order, and none of the theories we have can account for all of these items. That may be because the placebo is ill defined, or down to a lack of awareness of key features of the effect (a problem in many young sciences and fields of study).

Drumroll please......
Theory the First: Conditioning. This draws from work with behaviourists and physiologists. Basically, the idea is that when given an active drug, we learn to associate the physiological response with the treatment, and then a fake treatment can activate the same response in our bodies.
The trouble with this theory is that it cannot account for placebo effects as a result of new drugs or substances that a person has not experienced before.
That being said, conditioning by means of an active drug or experimental manipulation is probably the most reliable way of inducing a placebo response in an experimental setting.
Its also worth noting that conditioning can occur to the other stimuli (like a white coat, hospital, doctor etc) present in the environment at the time of the active treatment, so figuring out what we have conditioned someone to can be quite difficult.

Theory the Second: The current 800pound gorilla in the ring, expectancy theory (developed by the inestimable Irving Kirsch) suggests that we have certain cognitions that relate to particular treatments, and that these can activate physiological responses which create placebo effects. Expectancy theory is very good at explaining placebo effects, but it raises the question of how to explain "expectancies". To be precise, Kirsch talks about response expectancies, which he defines as the expectation of a non-volitional response (Kirsch 1985). However, given that much of what Kirsch calls non-volitional can be manipulated by hypnosis and meditation, it creates problems in the definition (but that seems to be quite common in this field. In fairness to Kirsch, he knows this as he has worked with hypnosis for many years also, but its a point that gets missed by many people.

Theory the Third: Michael Hyland's motivational concordance is a new kid on the block, having been put forth recently. This theory suggests that placebos are generated by a ritual which fits the belief system or goals of the person concerned. This theory is basically a sysnthesis of the expectancy and conditioning theories, drawing upon both cognitive and behavioural features for its explanation. I do like this theories focus on the action, as this seems to be the essential part of placebo responses.

Theory the Fourth: Allan and Siegel proposed a signal detection model of the placebo effect some years ago, which is elegant in its simplicity. They suggest that placebos alter response thresholds encouraging false postive signals on the part of patients. In other words, there is no placebo save that people alter their way of responding because they feel like they should be better. Unfortunately, this theory does not fit the data on releases of opioids at specific sites to create analgesia, so it must be discarded.

Theory the Fifth: Motivation. This theory is synonomous with Andrew L. Geers, who has examined it in many different contexts in his own work. He suggests that placebo effects are mediated by the desire to reach a particular goal and demonstrates that priming techniques can enhance placebo effects. This theory is useful as it can account for larger clinical placebo effects than are typically seen in the lab. However, the problem here is that one would expect motivation to be high in patients suffering from chronic pain but they typically do not respond well to placebo treatment. The issue with these patients could be that negative expectancies and conditioning built up from previous experience inhibit the showing of the response, but thats just a hypothesis.

So, what can we make of these theories?
Expectancy definitely seems to exert a large influence. Motivation is also quite important, and conditioning probably aids in the retention of placebo effects over time. I personally like the motivational concordance theory quite a lot, as it seems to suggest why so many people report good results from alternative medicines where the RCT's suggest (but only suggest) that they are indistinguishable from placebos.The optimal path (for now) seems to be to include measures for all the various effects in large scale studies, to examine which of them contribute the most to healing.

P.S. Some anthropologists propose an embodied cognition approach to placebo, but I currently don't know enough about it to talk about it here.

Next on this series, Interesting Experimental Placebo evidence (now with added optimism!).

Stewart-Williams, S. (2004). The Placebo Puzzle: Putting Together the Pieces. Health Psychology, 23 (2), 198-206 DOI: 10.1037/0278-6133.23.2.198