Placebo Effect in Parkinson’s Disease

Can patients in clinical trials experience physical benefits because they believe they are receiving a new medical treatment and are expecting improvement?  The placebo effect (see sidebar for definitions) has been studied for nearly 50 years, with the finding that generally about one-third of patients will feel better in response to treatment with placebo. Some scientists believe the effect can be especially strong among patients with Parkinson’s, due to the involvement of dopamine.

PET studies have provided evidence that administration of a placebo can bring on the release of dopamine in the both the dorsal striatum and ventral striatum areas of the brain in patients with Parkinson's disease. The ventral striatum is the reward center of the brain. De la Fuente-Fernandez and Stoessl hypothesized that, “ placebo responses are related to the activation of the reward circuitry.” That is, the expectation of reward, (i.e. clinical benefit) triggers the placebo response — the release of dopamine in the brain.

Other functional imaging studies suggest that although placebo treatment can activate brain regions associated with symptom relief, the expectation of benefit may also activate neurons in other areas of the brain.  Fabrizio Benedetti and colleagues have shown that receiving placebo treatments can modify both the rate and pattern of the firing of neurons in the subthalamic nucleus. The STN is the target area for Deep Brain Stimulation.

Clinical evidence of the placebo effect has also been reported. In a follow up study of quality of life of 30 PD patients who had received either fetal tissue transplants or sham surgery, Dr. Cynthia McRae reported a strong placebo effect.

"Those who thought they had received the transplant at 12 months reported better quality of life than those who thought they received the sham surgery, regardless of which surgery they actually received," … and “objective ratings of neurological functioning by medical personnel showed a similar effect.”

It appears that the placebo effect can have a decisive influence on clinical trial outcomes and perhaps also on how well patients respond to treatments for PD. The importance of the expectation of benefits on treatment outcomes should be considered in the design of clinical trials.  For more information, read, “The healing power of placebos” on the FDA website.

Source:

Benedetti F, Colloca L, Torre E, et al. “Placebo-responsive Parkinson patients show decreased activity in single neurons of subthalamic nucleus.” Nature Neuroscience,  2004; 7: 587-88.

de la Fuente-Fernandez R, Schulzer M, Stoessl AJ. “ Placebo mechanisms and reward circuitry: clues from Parkinson's disease.” Biological Psychiatry. 2004 Jul 15;56(2):67-71. 

“The biochemical bases for reward: Implications for the placebo effect. “  Evaluation & The Health  Professions. Dec 2002.  Vol. 25,  Iss. 4,  p. 387-398.  

McRae C, “Cherin E, Yamazaki TG, et al. Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial.” Archives of General Psychiatry 2004; 61: 412-20.