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 University of California (UCLA) psychiatrists helps explain how placebos can have such a powerful effect on depression.

''In short,'' says 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 per cent, patients who received placebos and supportive care improved an average of 36 per cent, and those who received supportive care alone improved an average of just 5 per cent.

''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.''

Other authors were senior author Ian Cook, Aimee Hunter and Molly Tartter, all of UCLA. Authors' financial disclosures are listed in the paper. Funding for the study was provided by the National Institutes of Health's National Center for Complementary and Alternative Medicine, Eli Lilly and Company, and Wyeth Pharmaceuticals.