It is standard (and required practice) to give informed consent prior to beginning a new medication during which possible side effects are discussed. While few would argue with this practice, clinicians have wondered about the possibility that the very discussion of potential side effects might actually create an expectation that they will occur and thus increase the likelihood of certain individuals to report them. A recent study from the Journal of Psychopharmacology experimentally tested this hypothesis using college undergraduates with complaints of sleeping difficulty.
The participants were 82 undergraduates at a university in Australia who had difficulty sleeping and believed they were participating in a trial of a new hypnotic medication. The sample was randomly divided into three groups- one that was given a written and verbal warning for the potential for a single side effect (appetite increase or decrease), another that was given warnings about four potential side effects, while a third group was told that they were controls and thus given no side effect warnings. The first two groups received a placebo pill in a red capsule, cleverly labeled SX3752. Subjects returned a week later to complete questionnaires about their sleep as well as any potential adverse effects.
The two groups that took placebo reported an improvement in their sleep by about 47 minutes compared to controls (a finding that has been reported previously). With regard to side effects, the group warned about a single side effect often reported just that. Approximately 25% of the group warned about either an increase or decrease in appetite reported a change in that direction, while no subjects reported a change in appetite in the direction opposite of their warning (i.e. you were warned about appetite increase but reported appetite decrease). An increased reporting of appetite side effects for the group told of only one potential side effect versus four was found, but only at the trend level, and approximately 25% of the control group also reported some appetite change.
The authors concluded that there is modest evidence to support the conclusion that the warning about fewer side effects increases the possibility of them being reported by patients through a placebo effect. This phenomenon likely operates because a smaller number of potential side effects are easier to remember. The authors state that such effects should be considered especially when reviewing side effect data computed in clinical trials.
Thus, it seems somewhat ironic that these data suggest that a more exhaustive informed consent that covers many potential side effects may actually reduce the likelihood of any individual effect being reported. This study is certainly intriguing, although it is not clear exactly how a clinician should use these findings in everyday practice.