JAMA: PET uncovers expectation of therapeutic benefit in patients with Parkinsons

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The strength of belief of improvement can directly modulate dopamine release in patients with Parkinson’s disease. Individuals with Parkinson’s disease were more likely to have a neurochemical response to a placebo medication if they were told they had higher odds of receiving an active drug, according to a report in this month's Archives of General Psychiatry.

In patients with Parkinson’s disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition, according to Sarah C. Lidstone, PhD, of Pacific Parkinson’s Research Centre at Vancouver Coastal Health and the University of  British Columbia in Vancouver, B.C., and colleagues.

Lidstone and colleagues studied 35 patients with mild to moderate Parkinson’s disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline 11C- raclopride PET scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response.

On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25 percent, 50 percent, 75 percent or 100 percent chance of receiving active medication before the third scan; however, all patients were given placebo.

The dopaminergic response to placebo was measured using 11C- raclopride PET. The clinical response was also measured (Unified Parkinson Disease Rating Scale) and subjective responses were ascertained using patient self-reporting methods.

Patients who were told they had a 75 percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not, according to Lidstone and colleagues.

Patients’ reaction to the active medication before the first scan was also correlated with their response to placebo. Response to prior medication (i.e., the dopaminergic response to levodopa) was the major determinant of placebo induced dopamine release in the motor striatum. Expectation of clinical improvement was additionally required to drive dopamine release in the ventral striatum, wrote Lidstone and colleagues.

“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,” the authors concluded. “While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson’s disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions.”