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They got a (sugar) pill for that

Can chronic medical conditions, including depression, be treated with placebos? Recent studies suggest they can.

By Deborah Kotz
Globe Staff / March 7, 2011

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Dianne Sanborn admits that “it didn’t make any sense’’ to take a sugar pill to relieve the severe constipation, abdominal pain, and bloating — attributed to irritable bowel syndrome — that she’d suffered from since college. But eager to try anything, the 64-year-old entered a clinical trial last spring at Beth Israel Deaconess Medical Center, where she was told to take placebo caplets twice a day for three weeks.

“Before I took each pill, I had to tell myself that it was going to make me feel better, but I was very skeptical,’’ says the 64-year-old former nurse practitioner who had to quit her job 13 years ago because of her medical problems. “I certainly knew placebos could work but only if you didn’t know it was a placebo.’’ When her symptoms dissipated three days after she started taking the placebos, however, she became a believer.

So did many of the other 36 volunteers who were randomly assigned placebos along with any of their usual treatments in the December study published in the journal PLoS ONE. Nearly 60 percent of them reported an improvement in their irritable bowel symptoms compared to 35 percent of the 43 volunteers who weren’t given placebos but were just told to continue their standard therapy.

Other research had already demonstrated that sham treatments could dull pain, alleviate depression, and even quell Parkinson’s tremors. But this study was the first to show that placebos have power even when patients know they’re taking them. And now placebo researchers are gearing up to figure out ways to move side-effect-free sugar pills into mainstream clinical practice — that’s the goal of a placebo-studies program that Harvard Medical School is launching in July with 30 faculty members. “We’d like to eventually see placebo treatments become a full partner in medical care along with active medications, procedures, and surgery,’’ says PLoS ONE study author Dr. Ted Kaptchuk, who will head the program.

Some questions that still need answers: How much does the simple act of seeing a doctor weigh into the placebo effect? Are there certain people — or certain conditions — that are more likely to respond to placebos? Can fake treatments provide lasting relief over the long haul?

In Kaptchuk’s study, doctor visits probably weighed in significantly, given that more than a third of the participants who went in for frequent visits without getting placebos experienced relief from their symptoms. What’s more, IBS — a condition that can be aggravated by anxiety, lack of sleep, or stress — appears to have a strong mind-body component, suggesting that it’s more responsive to placebo treatments. And in terms of lasting relief, Sanborn says her symptoms returned soon after she stopped taking the placebos once the three-week study ended.

“I tried putting Tic Tacs and M&M’s in my pill bottle,’’ she says, “but got lazy and stopped after a week or two.’’

The power of belief in medical therapies sets off a cascade of reactions in the brain that turns down the pain response. Simply anticipating relief — this pill will help me — causes increased activation in the prefrontal cortex, a region of the brain responsible for your mood and how much control you feel over a situation. And researchers have shown that this triggers the release of pain-relieving and mood-boosting brain chemicals called enkephalins and beta-endorphins. The prefrontal cortex also sends signals to other brain regions that control motor symptoms like tremors and digestive problems. We can’t simply wish our pain or depression away, but we can influence those brain processes that give rise to a wide range of symptoms, says placebo researcher Tor Wager, a professor of psychology and neuroscience at the University of Colorado-Boulder.

But Wager’s latest study published in the Journal of Neuroscience found that the amount of activation in the prefrontal cortex can vary by as much as 40 percent among those given placebos, and this appears to determine how big a response folks get to a sham drug. “We still don’t understand,’’ he says, “why people’s placebo responses are all over the place from strong to medium to weak.’’

There are hints, though, of common threads that tie placebo responders together, Wager adds, like believing in a treatment or having a doctor who does.

The placebo effect appears to play the strongest role, says Kaptchuk, in symptom-driven conditions like chronic pain, irritable bowel syndrome, and mood disorders where a drug’s effectiveness is based on a patient’s subjective assessment rather than on objective measurements like cholesterol levels or the size of a tumor. Previous research has demonstrated that sham knee surgery was just as effective as cartilage-removal surgery to alleviate the pain of arthritis and that Parkinson’s patients who had fetal cell transplant brain surgery experienced the same reduction in tremors as those who had the surgery without the transplant.

Sham acupuncture works just as well as the real thing — but both are better than no treatment.

Perhaps the most shocking findings have come from studies on antidepressants. Three years ago, British researchers reported that the most widely prescribed antidepressants (Prozac, Effexor, Serzone, and Paxil) benefit only the very severely depressed and are about as effective as placebos for everyone else. They based their finding on a pooled analysis of clinical trials, published and unpublished, that were conducted by antidepressant manufacturers and submitted to the US Food and Drug Administration.

“Perhaps 10 percent of patients who are prescribed antidepressants are really benefiting from the drugs’ active ingredients,’’ says Irving Kirsch, a psychologist at the University of Hull in Great Britain who led the study and will join Harvard’s placebo program in the summer. “I say that cautiously because I’m not convinced these drugs have real effects in anyone.’’

Kirsch says it’s tough to have true “blinded’’ studies of antidepressants — where neither patient nor physician knows whether the drug or placebo has been assigned — since side effects like sexual dysfunction, diarrhea, or insomnia often kick in before the therapeutic benefits. Patients having such side effects may be convinced they’re taking an active drug, rather than a placebo, making them more likely to expect their depression to lift and, hence, it does.

Many experts, however, aren’t ready to completely write off antidepressants. “My view is that antidepressants have some specific efficacy, but we don’t have the right kinds of studies to really discern how much of their effectiveness is due to the placebo component,’’ says Franklin Miller, a bioethicist and placebo researcher at the National Institutes of Health.

If future studies demonstrate that open placebo prescribing really works, Kaptchuk says he thinks many doctors may embrace it. After all, about half of physicians who responded to a survey he conducted for a 2008 British Medical Journal study said they prescribed placebos on a regular basis, mainly in the form of vitamins and over-the-counter analgesics to patients who thought such treatments were proven to fix their condition. (Professional medical societies like the American Medical Association discourage this practice since it doesn’t allow for informed consent.)

Miller, coauthor on the same study, disagrees that doctors will embrace it. “It’s foreign to what doctors are trained to do and patently indicates that it’s not the medicine that’s doing the healing,’’ he explains.

Patients — especially those wary of side effects from medications — may push their doctors to prescribe such completely harmless treatments. Or they may simply purchase the pills themselves. Starting in May, manufacturers of Obecalp (placebo spelled backward) will be launching a new placebo product for adults: caplets, liquid, or tablets for $5.95 for 50 doses, says Dennis Buettner who will be selling Obecalp from his website placebostore.com. The placebos will be similar to those dispensed in clinical trials, he says, except patients will be able to take them for as long as they like.

Irritable bowel study participant Diane Clerico, 58, of Saugus recalls that she enjoyed having a break from painful bouts of uncontrollable diarrhea while she was taking the placebos, but that her worst symptoms have since returned. “It was a nice couple of weeks,’’ she says. “I’d go back to taking the pills if I could.’’

Deborah Kotz writes the Daily Dose blog at www.boston.com/dailydose. She can be reached at dkotz@globe.com.

Are you likely to benefit from a placebo?

While researchers don’t know why some people experience more symptom relief from placebos than others, studies have suggested that certain personality traits and life circumstances may boost the placebo effect. Ask yourself the following questions.

ARE YOU OPTIMISTIC AND DRIVEN?
Placebo responders are more likely to engage positively with the world, and they tend to be risk-seeking, says placebo researcher Tor Wager, a professor of psychology and neuroscience at the University of Colorado-Boulder. It may be that their brains tend to release higher levels of pain-relieving opiates when they take a pill.

DO YOU BELIEVE IN MEDICAL TREATMENTS?
The power of belief probably plays some role in how well a drug works. It creates an anticipatory response in the brain that activates the release of opiates.

DOES YOUR DOCTOR?
Research has shown that placebos work better when doctors believe they’re prescribing real drugs. “They’re probably communicating different kinds of social cues to their patients,’’ explains Wager, “providing a stronger power of suggestion that the treatment will work.’’

ARE YOU PROACTIVE WHEN IT COMES TO GETTING MEDICAL ATTENTION?
The simple act of going to the doctor can activate the placebo response, though it helps to have a compassionate health provider rather than someone who dismisses your pain as “all in your head.’’

DO YOU FEEL SOME SENSE OF CONTROL OVER YOUR TREATMENT?
“Engage as much as you can in your treatment,’’ recommends Wager. Try to do something that will enhance your sense of control, whether it’s practicing those physical therapy exercises or asking your doctor if you can have a say in how much medication you get and at what time. Adopt the attitude that even if this treatment doesn’t work, you’ll find something else that will. All of these things can dial down how the brain perceives pain.

DEBORAH KOTZ

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