In my office I have a colorful brochure from the makers of the anti-depressant Paxil. It presents a graph of the pooled average reduction in depression symptoms of 271 patients taking either Paxil or a placebo sugar pill. The Paxil graph line drops evenly over 12 weeks from 24 (high depression) to 8. The placebo line drops over 12 weeks from 24 to 11. The drug company expects that I will look at this graph and say “Wow, look how well Paxil works in reducing depression.” But I look at the graph and say “Wow, look how well the sugar pill works. And it only costs 5 cents a tablet.” Of course there are serious research problems with these data. The data are based on the self report of the patients, and we know patients sometimes tell the doctor what they think he or she wants to hear. Also, these are averaged scores. Patients may not have improved as evenly as the graph might suggest. And some patients may have improved only slightly if at all. Nevertheless, the graph illustrates what we have known for some time – that our expectations have a big impact on outcomes. Serious placebo research dates back 30 plus years to the study of the power of thought and belief in reducing pain. A recent Seattle study (Daniel Cherkin) illustrates the findings. 638 patients with chronic lower-back pain received either standard acupuncture therapy, or fake acupuncture (toothpicks that mimic the feel of real acupuncture), or standard back-pain care (anti-inflammatory drugs plus massage). On average, both fake and real acupuncture reduced pain twice as much as standard care. Advocates for acupuncture therapy say “Wow, see how effective acupuncture is.” I look at the data and say “Wow, see how effective the toothpick is. It must be possible to think yourself out of pain.” But how does this work? How does thinking – belief and expectation in the mind – reduce pain in the body? Well, now they have mapped the underlying brain processes. When a doctor tells you that a pill or other treatment will reduce your pain, your expectation that your pain will be reduced triggers activity in the prefrontal cortex (site of higher mental function) which in turn triggers other parts of the brain to release homemade opioids (Benedetti at the University of Turin). In fact, if you give someone a drug that blocks the effects of opioids, that drug will also block the placebo effect on pain. So we know that a placebo works on pain by getting the brain to produce it’s own pain killer. And the greater the expectation, the greater the pain relief. If you give dummy pills to patients, those who are told their pills cost $2.50 each report 85% reduction in their pain, while those who are told their pills cost 10 cents each report 60% reduction in pain. Research has moved far past pain in their study of the placebo effect. We have learned that there is not a single placebo effect, but many placebo effects, each with different mechanisms. For example, if Parkinson patients were told they were receiving Parkinson medication but instead got an injection of simple saline, many of them showed less rigidity and more fluidity of movement (University of British Columbia study). Apparently, the expectation of effective treatment releases dopamine, the brain’s reward molecule and the precise chemical that is scarce in Parkinson patients. We’ve also found that sometimes expectation has nothing to do with placebo effects. Instead the placebo effect occurs because the brain has learned that a certain experience is followed by a specific response. It’s Pavlovian conditioning at work. A Benedetti study showed that when patients were given several injections of a morphinelike drug, a subsequent placebo injection produced the same slow shallow breathing. The brain had learned that an injection equals shallow breathing, and the response was completely unconscious. A similar finding occurred with an immune suppressing drug. Mind over matter. Or sometimes just brain over matter. But it doesn’t work on everyone, and the effect often fades after a while. There are remaining mysteries about placebo responses. For more on this, read Train Your Mind, Change Your Brain by Sharon Begley. Robert Packard, PhD


Familial aggregation in the night eating syndrome

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