Deconstructing the placebo response: Why does it work in treating depression?

In the past three decades, the power of placebos has gone through the roof in treating major depressive disorder. In clinical trials for treating depression over that period of time, researchers have reported significant increases in patient’s response rates to placebos — the simple sugar pills given to patients who think that it may be actual medication.

New research conducted by UCLA psychiatrists helps explain how placebos can have such a powerful effect on depression.

“In short,” said Andrew Leuchter, the study’s first author and a professor of psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior, “if you think a pill is going to work, it probably will.”

The UCLA researchers examined three forms of treatment. One was supportive care in which a therapist assessed the patient’s risk and symptoms, and provided emotional support and encouragement but refrained from providing solutions to the patient’s issues that might result in specific therapeutic effects. The other two treatments provided the same type of therapy, but patients also received either medication or placebos.

The researchers found that treatment that incorporating either type of pill — real medication or placebo — yielded better outcomes than supportive care alone. Further, the success of the placebo treatment was closely correlated to people’s expectations before they began treatment. Those who believed that medication was likely to help them were much more likely to respond to placebos. Their belief in the effectiveness of medication was not related to the likelihood of benefitting from medication, however.

“Our study indicates that belief in ‘the power of the pill’ uniquely drives the placebo response, while medications are likely to work regardless of patients’ belief in their effectiveness,” Leuchter said.

The study appears in the current online edition of the British Journal of Psychiatry.

At the beginning and end of the study, patients were asked to complete the Hamilton Rating Scale for Depression, giving researchers a quantitative assessment of how their depression levels changed during treatment. Those who received antidepressant medication and supportive care improved an average of 46 percent, patients who received placebos and supportive care improved an average of 36 percent, and those who received supportive care alone improved an average of just 5 percent.

“Interestingly, while we found that medication was more effective than placebo, the difference was modest,” Leuchter said.

The researchers also found that people who received supportive care alone were more likely to discontinue treatment early than those who received pills.

People with major depressive disorder have a persistent low mood, low self-esteem and a loss of pleasure in things they once enjoyed. The disorder can be disabling, and it can affect a person’s family, work or school life, sleeping and eating habits, and overall health.

In the double-blind study, 88 people ages 18 to 65 who had been diagnosed with depression were given eight weeks of treatment. Twenty received supportive care alone, 29 received a placebo with supportive care and 39 received actual medication with supportive care.

The researchers measured the patients’ expectations for how effective they thought medication and general treatment would be, as well as their impressions of the strength of their relationship with the supportive care provider.

“These results suggest a unique role for people’s expectations about their medication in engendering a placebo response,” Leuchter said. “Higher expectations of medication effectiveness predicted an improvement in placebo-treated subjects, and it’s important to note that people’s expectations about how effective a medication may be were already formed before they entered the trial.”

Leuchter said the research indicates that factors such as direct-to-consumer advertising may be shaping peoples’ attitudes about medication. “It may not be an accident that placebo response rates have soared at the same time the pharmaceutical companies are spending $10 billion a year on consumer advertising.”

(Image credit: © Chris Lamphear)

Placebo and the Brain: How Does it Work?

Placebo, the positive effect of a drug that lacks any beneficial ingredients, has been researched for centuries but remain a mystery for psychologists and neuroscientists alike. Although there is now a considerable amount of amassed knowledge of how placebo can be induced, through which mechanisms it works, and which individuals are susceptible to the effect, the explicit answer to why and how our brains have the ability to ‘cure’ themselves under certain circumstances is yet to be found. Having dived into the literature on the phenomenon, a picture has emerged in which one of the brain’s greatest tricks can be better understood and the fascinating implications it has for how we look at the body-mind distinction.

What is termed a placebo is usually defined in research trying to pin down its nature as the treatment that results in a change in symptom or condition that differs from the natural course of the specific disease. Placebo effects have been shown for mainly relief of pain, but also in studies of depression, parkinson’s, and anxiety. While the sugar pill is still in use, we now know that there are a two factors that are crucial for a placebo effect to occur. These are the level of expectancy and desire to get better/not get worse that the patient feels and both are in turn sensitive to a host of psychosocial variables such as their faith in medical staff, the emotional tone of the physician-patient interaction (whether it is optimistic or pessimistic for example), memories of past experiences with the effects of medicine, and so on.

While some individuals show reliable placebo effects, others do not and the underlying causes have recently been suggested to be tied to our individual genetic makeup. Researchers from the Harvard Program for Placebo Studies found that the magnitude of the placebo effect was tied to genes coding for an anzyme that regulates the levels of dopamine in various regions of the brain. Dopamine plays a key role in processing of reward, pain, memory, and learning, all areas in which the placebo effect has been demonstrated. The study, led by Kathryn Hall, concluded that persons whose genes promote an upregulation of the levels of dopamine in the brain also exhibit the greatest placebo effects. In other studies examining release of another group of transmitters called opioids, which regulate the activity in areas that code for pain, higher amounts of opioids were matched to the size of the placebo effect found.

As for where the effect originates, research using brain imaging have found that when a real drug is compared to the effects of a placebo very similar areas show activation but some areas, such as the lateral and central prefrontal cortex, show a greater response in the placebo condition. This part of the brain is often described as overseeing and exerting control over other processing in the brain and act as a connecting point for different streams of information that build up our expectations and desires.

So, how can this knowledge about the placebo effect influence the way doctors discuss, promote, and administer their own treatments? Surely, if we know that an encouraging prognosis given together with a sugar pill can be as effective in some cases as a pharmacological product but without the side- effects, we should be using that. However, having doctors treat their patients through deception leads to obvious problems such as public mistrust in the profession. A finding from the scientists at the very same Harvard program for placebo studies might have the answer. They namely demonstrated that the placebo effect remained when participants were told explicitly that the treatment they were given was in effect useless.

When the going gets tough, the tough get… more relief from a placebo?

Are you good at coping when life gets tough? Do people call you a straight-shooter? Will you help others without expecting anything in return?

Those personality traits might do more than help you win a popularity contest. According to new University of Michigan-led neuroscience research, those qualities also might make you more likely to get pain relief from a placebo – a fake medicine.

And, the researchers show, it’s not just your mind telling you the sham drug is working or not. Your brain’s own natural painkiller chemicals may actually respond to the pain differently depending on your personality.

If you’re more of an angry, hostile type, they find, a placebo won’t do much for you.

For the first time, the new findings link specific, established personality traits with an individual’s susceptibility to the placebo effect from a sham medicine for pain. The researchers showed a significant link between certain personality traits and how much relief people said they felt when given the placebo – as well as the level of a specific chemical that their brains released.

The work, published online in the journal Neuropsychopharmacology, was done by a team of U-M Medical School researchers and their colleagues at the University of North Carolina and University of Maryland.

Placebo’s Effect May Depend on Your Genes

Your response to placebos, or dummy medicine, may depend on your genes, according to a new study.

People with a gene variant that codes for higher levels of the brain chemical dopamine respond better to placebos than those with the low-dopamine version.

The findings, reported online Oct. 23 in the journal PLoS One, could help researchers design medical studies that distinguish the placebo response from the underlying effect of a medicine — the real aim of drug trials.

Neurobiology of the Placebo Effect by Jorge Cham and Dwayne Godwin

Researchers have identified a novel mechanism that helps explain the power of placebos and nocebos.

Described in the Sept. 10 on-line issue of the Proceedings of the National Academy of Sciences (PNAS), the new findings demonstrate that the placebo effect can be activated outside of conscious awareness, and provide an explanation for how patients can show clinical improvement even when they receive treatments devoid of active ingredients or of known therapeutic efficacy.

"In this study, we used a novel experimental design and found that placebo and nocebo [negative placebo] effects rely on brain mechanisms that are not dependent on cognitive awareness," explains first author Karin Jensen, PhD, of the Department of Psychiatry and the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) and the Program in Placebo Studies (PiPS) at Beth Israel Deaconess Medical Center/Harvard Medical School. "A person can have a placebo or nocebo response even if he or she is unaware of any suggestion of improvement or anticipation of getting worse."

Source: abysmalfailure