You've had brain surgery... just kidding

Controversial study shows overwhelming placebo effect in invasive treatment for Parkinson's

By Tony Craig

How far would you expect patients to go for the advancement of medical science? Would they put up with a hole in the head? How about four? That's what subjects agreed to in a recent Parkinson's study that's as remarkable for its methods as it is for its conclusions.

Sham surgery is hardly a frequent component of even the most carefully blinded trial. However, 40 American and Canadian patients suffering from Parkinson's disease participated in a trial during which half underwent a fake surgical procedure that involved the drilling of four holes into the skull. The other 20 in the treatment arm had human embryonic dopamine neurons implanted into their brains.

The April issue of the Archives of General Psychiatry includes this study, headed by Dr Cynthia McRae of the University of Denver. The researchers followed 30 of the 40 patients who were in the original transplantation study. Of these, 12 had received real implants and 18 had undergone sham surgery.

Implanting human embryonic dopamine neurons is a relatively new experimental approach to treating Parkinson's disease, and less thoroughly blinded trials have shown symptomatic improvements, especially in younger patients.

The researchers went to extraordinary lengths to keep patients and doctors in the dark as to who had received active treatment. But a key parameter in this study was whether the patients believed they were treated or not. Wishful thinking being what it is, a week after surgery 22 of 30 believed they'd received real treatment. After a year, only 10 still believed themselves so favoured. However, there was no statistical relationship between the type of treatment patients actually received and what they thought they received.

Patients were measured on a wide range of scales yet none of these showed any clear added benefit in the actual treatment group, except in tremor and rigidity as reported by medical staff.

Differences between perceived treatment groups were more significant. Those who believed they'd received real transplants continued to improve their global rating scores, while these declined in patients who felt their surgery was faked.

"Expectancy regarding which type of treatment patients received had a statistically significant effect not only on subjective parameters but also on motor symptoms," conclude the authors. "The placebo effect seems to be very strong in this disease.... Medical staff, who didn't know which treatment each patient received, also reported more differences and changes at 12 months based on patients' perceived treatment than on actual treatment."

The trial's results, the authors feel, vindicate its methodology. "Although the sham surgery research design is currently regarded as somewhat controversial, the investigators of the parent study determined that the scientific benefits of this design outweighed potential ethical considerations. The results of this study demonstrate the importance of a double-blind design to distinguish the actual and perceived values of a treatment intervention."