‘Lessebo’ effect implications for Parkinson’s therapies

By Eleanor McDermid, Senior medwireNews Reporter

Patients with Parkinson’s disease (PD) have a reduced objective response to treatment given in a clinical trial if they know they may be taking a placebo, research shows.

This “lessebo effect” is the negative aspect of the well-recognised placebo effect, where patients’ belief that they are receiving treatment can cause improvement in the absence of active treatment. As illustrated in the present meta-analysis, patients’ knowledge that they may be taking a placebo drug can also dampen the effects of active treatment, causing the lessebo effect.

Anthony Lang (University of Toronto, Ontario, Canada) and team compared the treatment response of 3277 patients given active treatment in 28 blinded trials where the comparator group also received active treatment with that of 4554 patients given active treatment in the setting of one of 42 placebo-controlled trials.

Across the studies, the overall improvement in the motor section of the Unified Parkinson’s disease Rating Scale (mUPDRS) was 6.0 points for patients in placebo-controlled trials and 7.6 points for those in active-controlled trials. This equated to a significant 1.6-point difference.

“A ‘minimal clinically important difference,’ i.e., the smallest change perceived and valued by a patient, is reported to be in the range of 1.5 to 5.1 mUPDRS units in PD”, say the researchers. “Thus, the lessebo effect is within this clinically relevant range.”

Trials with active comparators were significantly longer than placebo-controlled trials, at 28.1 versus 19.1 weeks, on average, and less often focused on patients with early PD, at 28.6% versus 59.5%.

These two factors were also associated with the largest differences between mUPDRS response in active- versus placebo-controlled trials: 4.1 points in trials lasting up to 12 weeks versus 0.5 points in longer trials, and 3.3 points in those focused on early PD versus –0.7 in those involving patients with motor fluctuations.

In an accompanying editorial, Ronald Postuma (Montreal General Hospital, Canada) and Roger Albin (University of Michigan, Ann Arbor, USA) note that as well as affecting the number of trial participants needed for adequate statistical power, the lessebo effect also has implications for gauging the relative efficacy of antiparkinsonism drugs.

“There is perhaps a natural tendency to regard placebo/lessebo effects as a hindrance to clinical research”, they add. “In the case of PD, placebo/lessebo effects provide considerable insight into the neurobiology of striatal dopaminergic signaling.”

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