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Placebos Do Work: Let's Consider Why

New research on the placebo effect has big implications.

"We not only know placebos work," Dr. Harriet Hall explains in a fascinating, well-researched article in Skeptic, "we know there is a hierarchy of effectiveness":

* Placebo surgery works better than placebo injections
* Placebo injections work better than placebo pills
* Sham acupuncture treatment works better than a placebo pill
* Capsules work better than tablets
* Big pills work better than small
* The more doses a day, the better
* The more expensive, the better
* The color of the pill makes a difference
* Telling the patient, "This will relieve your pain" works better than saying "This might help.

To help convey the power of persuasion that doctors routinely wield, Dr. Hall's article opens with a treatment anecdote that gives a flavor of the article to come:

"Jane D. was a regular visitor to our ER," she recalls, "usually showing up late at night demanding an injection of the narcotic Demerol, the only thing that worked for her severe headaches. One night the staff psychiatrist had the nurse give her an injection of saline instead. It worked! He told Jane she had responded to a placebo, discussed the implications, and thought he'd helped her understand that her problem was psychological. But as he was leaving the room, Jane asked, "Can I get that new medicine again next time instead of the Demerol? It really worked great!"

In short, when we think something will work, its chances of doing so increase dramatically. Dr. Hall then refines that idea by giving it a sharper explanation: "What’s effective is not the placebo," meaning the benefit patients derive from a "dummy" pill, "but the meaning of the treatment." She hypothesizes that the power of the effect depends on four variables: patient expectancy; motivation (the desire to improve one's health); a certain amount of conditioning, including from advertising; and endogenous opiates, or pain-relieving chemicals produced in the brain, which copy the effect of pain-relievers such as opiates.

To that end, it isn't so surprising to hear her claim: "A substantial percentage of the effects from antidepressants may be placebo effects." Her assertion jibes with one that PT blogger Dr. Philip Newton made on this site last December: "In some controversial cases, such as selective serotonin reuptake inhibitor (SSRI) anti-depressants," he wrote, "placebo effects are thought to account for a major proportion of the positive effects of a drug."

Researchers have of course long-known and long-studied the effect of placebos, and just as obviously try to minimize the effect by controlling for it. In "Listening to Prozac but Hearing Placebo," however, a significant meta-analysis of SSRI antidepressants given to 2,318 patients with depression, Drs. Irving Kirsch and Guy Sapirstein found in 1998 that "the placebo response is a predictor of the drug response," which is rather telling, and a relation they chart quite dramatically on the following graph:

Not only that, but "the placebo response was constant across different types of medication (75%), and the correlation between placebo effect and drug effect was .90." As they put it, "These data indicate that virtually all of the variation in drug effect size was due to the placebo characteristics of the studies," which calculated placebo as the single largest factor, accounting for 50.97% of SSRI efficacy.

"Our results are in agreement with those of other meta-analyses," Kirsch and Sapirstein explained, "revealing a substantial placebo effect in antidepressant medication." "They also indicate that the placebo component of the response to medication is considerably greater than the pharmacological effect."

Kirsch and Sapirstein's study never got the airtime it deserved. A serious, well-executed meta-analysis, it was quickly drowned out by a litany of other studies that assessed the efficacy of antidepressants in comparative terms with each other, rather than as a base-level investigation of efficacy, with each drug studied relative to placebo alone. The shift in emphasis played a big role in tilting interest more toward comparative pharmacology, shunting the effect of placebos aside.

Still, Dr. Hall's striking article hopefully will return our attention to the exciting opportunities and real quandaries (medical and ethical) that the placebo effect poses, in so far as it can have a documented, substantial, and lasting impact on patients without costs or side effects. Hence the pun in my title: placebos do work—which is to say, they have effects that are part of the treatment process and should not be discounted as such.

The placebo indicates that the mind and its sometimes unconscious effects are incredibly powerful instruments in treatment, and that we're getting but half the story in focusing so relentlessly on biology and genes, to the expense of so much else.

Granted, offering placebo alone to patients (something I'm not advocating) would raise charges of quackery and suspicions that the doctor or psychiatrist is inherently against medication, a position viewed with great skepticism today. To put that another way, patients so often expect medication that if the doctor or psychiatrist doesn't prescribe any the patient can view that outcome (and physician) negatively, as minimizing their problem and even as hinting that they've wasted time.

With that level of expectancy, however, the placebo effect is doubtless ramped up even more, accounting for still-greater pharmaceutical effects, something that's worth taking into consideration, not least because it adds a benefit or a wrinkle—depending on perspective—to the treatment options available.

I am suggesting that we pay a lot more attention to how those forms of persuasion influence medical and psychiatric practice across the board. Follow me on Twitter @christophlane

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