Why Is the “Placebo Effect” Getting Stronger?

The brain has an amazing capacity to help the body heal itself.  The “placebo effect” was first described in a 1955 medical paper:  people given a harmless sugar pill – a “placebo” – will feel less pain if they are first convinced the pill is a medicine that effectively relieves pain.  Placebos are effective for a variety of symptoms like depression and stomach ulcers, too.

Since 1962, the US Food and Drug Administration (FDA) has required drug makers to prove a new medicine is more effective than a placebo before it will approve the drug for market.  For some reason, placebos seem to be more effective than expected in drug trials between 2001-2006, especially for meds targeting the brain and central nervous system.  As a result, more new drugs fail to pass FDA approval because they don’t produce results better than sugar pills.  Even old standbys like Prozac are proving less effective against placebos than when they were first tested in the 80s.

The increase in placebo effectiveness is significant enough that the NIH is studying the phenomena, funded by big pharmaceutical companies.  Wired Magazine has a great article on the increase in placebo effectiveness here.

One study mentioned in the article talks about the placebo effect in Alzheimer’s disease (AD) patients.  To be effective, placebos require the patient to have cognitive ability – you have to understand what the pill will do for you before your brain will activate your body’s natural response.  A person with AD may have suffered enough brain damage that they’re unable to grasp that concept.  As a result, AD patients generally require more painkiller than the average person because the AD patients don’t get the benefit of the placebo “boost” in effectiveness.

I anxiously await the study’s results.  It would be wonderful to learn how to make the placebo effect more powerful and let our brains do more to heal us.

Detecting Alzheimer’s Before Symptoms Appear: ADNI

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) (http://www.adni-info.org/) aims “to study the rate of change of cognition, function, brain structure and function, and biomarkers” over 5 years, starting in October 2004.  Its 800+ participants–which include healthy elderly controls, subjects with mild cognitive impairment (MCI), and those with Alzheimer’s disease (AD)–undergo magnetic resonance imaging (MRI) and positron emission tomography(PET) scans along with laboratory (blood, urine, and cerebrospinal fluid, or CSF) and cognitive tests.   One unique aspect of this huge study is that data from the 58 research sites is posted online and made available free to qualified researchers.  This is the largest public-private brain research project ever funded by the National Institutes of Health.  It has spawned similar efforts in Europe, Australia, Japan, and elsewhere.

ADNI searches for biomarkers that can determine AD risk.  Blood pressure is a biomarker that helps determine risk for heart disease or stroke.  Among other things, ADNI seeks to find a combination of biomarkers that are a clear indicator of AD.

The initial ADNI goal was to create a standard assessment tool for use in AD clinical trials.   Current methods for assessing the progress of AD in patients are slow and not always reproducible.  Clear, precise measures of the disease process would make it easier to determine whether someone is improving or declining on a new treatment.  Also, if all trials were using the same measures of success, it would be easier to compare results of different treatments.  This would make clinical trials less costly and produce reliable results more quickly.

The study is flexible enough to incorporate new technologies.  After the study began, the ability to detect amyloid beta in the brain in living subjects using PET was demonstrated.   This was the first time the characteristic accumulation of the protein in the brain could be confirmed without benefit of autopsy. This measurement was added to the study at some sites.

As ADNI research progressed and scientists became aware of new ways its data could be applied, the study’s goals expanded.  Over 800 blood samples underwent whole genome analysis as part of the search for AD-associated genes.  The ADNI samples have the benefit of donor brain scans and lab data available to researchers.  Analysis has identified several new genes (in addition to the 4 known early onset AD and 1 late onset AD genes) as targets of study, and researchers are working to confirm they are associated with increased risk of AD.  http://homepages.indiana.edu/web/page/normal/10543.html

Near the end of the study, ADNI is yielding fascinating results.  Detecting the beginnings of AD, before the onset of symptoms, might allow treatments that postpone onset of symptoms and maybe someday even prevent symptoms from occurring.  It’s long been known that amyloid beta and tau proteins accumulate in the brains of AD victims.  Tools like MRIs and CSF tests may reliably detect AD before symptoms appear and predict whether MCI will convert to AD.   One ADNI result shows when people develop AD, the concentration of amyloid beta 42 in CSF drops and tau increases.  http://www.medicinenet.com/script/main/art.asp?articlekey=92513

ADNI ends in October 2009, with final results reported in 2010.  To date over 25 papers have been published with many more under review and presented at conferences.  Proposals are in work for ADNI 2.

Article on Alzheimer’s disease research

My article “Preserving the Memory” appears in the July/August 2009 issue of Analog Science Fiction and Fact.   Thanks to Dr. Thomas D. Bird, Professor of Medicine and Neurology at the University of Washington and Chief of their Division of Neurogenetics, for reviewing the article for accuracy.  He said he thought it was “a good review of the state of the art” in Alzheimer’s disease (January 2009).