Placebo-induced Dopamine Release in PD Patients Varies with Expectation of Active Medication

Subject: Placebo-induced Dopamine Release in PD Patients Varies with Expectation of Active Medication

Date: 8/26/2010

The degree of dopamine release induced by placebo varies with the patient’s expectation of receiving active medication, according to a new study, with the greatest dopamine release when the patient believes there is a 75% chance of receiving levodopa.

Thirty-five patients with mild to moderate PD consented to enroll in a study involving an unspecified deception. They were then informed they had a particular probability of receiving levodopa (25%, 50%, 75%, or 100%). All patients received placebo, and underwent raclopride PET imaging to determine degree and location of dopamine release.

Dopamine release was significantly higher than baseline in the group informed they had a 75% chance of receiving levodopa, but not in other groups. Degree of release in response to placebo was correlated with the release in response to open-label administration of levodopa. “Response to prior medication was the major determinant of placebo-induced
dopamine release in the motor striatum,” the authors report, while “expectation of clinical improvement was additionally required to drive dopamine release in the ventral striatum.”

The response at 75% but not other probabilities “is in keeping with studies on conditioned learning in which dopaminergic activation is seen when reward is deemed likely but not certain,” they state.

“Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome,” they conclude.

Effects of expectation on placebo-induced dopamine release in Parkinson disease
SC Lidstone, M Schulzer, K Dinelle, E Mak, V Sossi, TJ Ruth, R de la Fuente-Fernandez, AG Phillips, J Stoessl
Arch Gen Psychiatry 2010;67:857-865