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Eliezer Sobel

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Understanding the Placebo Effect

Posted: 04/30/10 11:41 AM ET

It could be argued that Wikipedia is not the most scholarly or accurate resource for medical information. On the other hand, I am not a physician or a psychologist, so please cut me some slack.

From Wikipedia: "The patient is given an inert pill, told that it may improve his/her condition, but not told that it is in fact inert. Such an intervention may cause the patient to believe the treatment will change his/her condition; and this belief may produce a subjective perception of a therapeutic effect, causing the patient to feel their condition has improved. This phenomenon is known as the placebo effect."

My first foray into the nebulous world of antidepressants was in 1985 when I was put on Sinequan. It gave me severe cotton mouth, didn't do much for my mood, but came with the side benefit of causing rather compelling lucid dreams immediately upon falling asleep every night, which I rather enjoyed. In the quarter century since then, I've experimented, for periods ranging from one night to one year, with Prozac, Zoloft (a one-nighter; it gave me the jumping-out-of-my-skin heebie-jeebies, as did Effexor and Trazadone); Paxil, Serzone (I received a $90 refund from Bristol-Myers when a refill caused six hours of vomiting and a call to Poison Control); Neurontin (stopped after two days when talking to the Assistant Headmaster at my school and noticed that my consciousness seemed to be about two feet behind and slightly above my voice which appeared to be emerging from the area in and around my mouth); Wellbutrin, Buspar, Lamictal (again, only for two days, until I finished reading all the potential side effects including the ominous Black-Box Death Warning on the package, and worse, mention of an incurable rash); Seroquel (one night only, got up to pee, stepped on and broke the cat's water bowl and smashed my head into a floor lamp; when I reported this to my psychiatrist, he said, "Oh, I forgot to mention that that's one of the side effects of Seroquel, except people usually end up banging their head on the bathroom floor."); Abilify, Adderall, and Xanax, Klonopin and/or Valium to take the edge off, Ambien for sleep, and marijuana for energy. (I often had what my doctor called "paradoxical reactions" to medications, meaning, for example, that whereas for many people marijuana is a lethargy-inducing occasion to eat Ring-Dings and watch endless reruns of "Mr. Ed" on Nickelodeon, in my case, one or two tokes and I'd be off on a 20-mile bike ride.)

Thus, it was with great interest that I read Irving Kirsch's recent book, The Emperor's New Drugs: Exploding the Antidepressant Myth. Kirsch makes a compelling, carefully-researched, scientific case for the fact that nearly all of the benefits reported by users of antidepressants are a result of the placebo effect. Note to satisfied users, and I count myself among them, at least sometimes: this does not mean that the results and benefits you experience from these drugs are not real or true; nobody is invalidating the truth of your direct experience.

What Kirsch does explain, however, is that there have been literally thousands and thousands of studies of antidepressants conducted by the big pharmaceutical companies that revealed no significant results whatsoever; however, they generally opted not to publish those particular studies, thus making them unavailable to both the public and to your psychiatrist! Kirsch invoked the Freedom of Information Act to demand the release of the studies by the FDA for his perusal. So that's point number one. Taken. (Buy the book for your shrink!)

"Companies have had to conduct numerous trials to get two that show a positive result, which is the Food and Drug Administration's minimum for approval. The makers of Prozac had to run five trials to obtain two that were positive, and the makers of Paxil and Zoloft had to run even more." (From "Against Depression, a Sugar Pill Is Hard to Beat," The Washington Post, May 7, 2002.)

Worse: the studies that were published and released mostly revealed only negligible and "barely-significant" positive results and benefits over placebos in double-blind experiments. Worse yet: Kirsch demonstrates, again with compelling arguments, that even those slightly beneficial results were themselves the result of the placebo effect, for this reason: in a double-blind study, neither the subjects nor the researchers are aware of who is receiving what. However, those receiving the actual medication would soon start to experience their all-too-real side effects, and thus would conclude early on that they indeed were the lucky ones and the positive benefits of the placebo effect would immediately kick in.

Yes, he's saying that the slight advantage of antidepressants over placebos are the result of the placebo effect.

It's placebo over placebo, by a nose.

But don't knock the placebo effect; it has been demonstrated to not only have countless positive health benefits in unsuspecting patients, it can also produce withdrawal symptoms when discontinued, or, when used in the opposite manner, can produce the "nocebo" effect; that is, cause harm. A placebo described as a muscle relaxant will cause muscle relaxation, but if the identical substance is presented as the opposite, muscle tension will result. A placebo presented as a stimulant will raise heart rhythm and blood pressure, but when administered as a depressant, it will lower both.

The principle behind this phenomenon has been termed "the meaning response," referring to the brain's power to generate effects in response to whatever it believes to be true, positive or negative. If the substance is viewed as helpful, it can heal, but if it is viewed as harmful, it can cause negative effects. Because the placebo effect is based upon expectations and conditioning, when a subject who has benefited from a placebo is later informed that they had in fact not received the genuine medication, their condition would often rapidly deteriorate and the positive placebo effects would disappear.

Even when an inert substance is producing positive, healing results in people, the recipients can nullify the intended placebo effect simply by having a negative attitude toward its effectiveness, often quickly transforming the same substance into a harmful nocebo. One researcher even coined a term for this situation: "the placebo paradox." It states that,

"While it may be unethical to use a placebo, it may also be unethical not to [use one]." (Dr. David Newman, author of Hippocrates' Shadow: Secrets from the House of Medicine-What Doctors Don't Know, Don't Tell You, and How Truth Can Repair the Patient-Doctor Breach.)

When I read Kirsch's book and became convinced of his point of view, I had already been feeling dissatisfied with my latest antidepressant cocktail anyway, so I opted to wean myself once again, for the umpteenth time in as many years (umpteen), armed with the knowledge that my paltry mood improvements were both minimal and placebo-induced, and not worth the principle side effect for me, which is insomnia.