Introduction - Uppsala Monitoring Centre

Placebo
Placebo-controlled studies allow the establishment of the common ADR pattern of
new drugs prior to marketing. Ethically, placebo treated patients should be kept to a
minimum, but from the point of view of establishing the factors responsible for the
ADR pattern as well as those factors affecting efficacy large numbers are important.
The adverse events occurring whilst on placebo are grouped together in the
analysis and allow one to define the adverse events due to the drug, but these
‘placebo’ adverse events consist at least three different elements:
1. Adverse events that have occurred because the patient believes that they may
be on an active drug. These are the true ‘placebo effects’.
2. Those adverse events, which are due to the underlying disease(s) or new
diseases (diseases in this context includes the minor symptoms of everyday life).
3. Adverse events due to unidentified parallel interventions, e.g. ‘white coat
hypertension’.
It has been suggested that where there is also an untreated group one is able to
define more accurately those adverse events due to the giving of placebo by
subtracting those of the untreated group from those on placebo. (Ernst & Resch,
1995), The adverse events occurring whilst on placebo have been called Nocebo
(Kitchener et al., 1996) or ‘Placebo-induced side effects’ (Schindel, 1968),
‘Nonspecific medication side effects and Nocebo phenomena’ (Barsky et al., 2002).
Introduction of the term ‘nocebo’ meaning the patient’s expectations producing
adverse effects from placebo, from ‘nocere’ meaning ‘to harm’ (Kennedy, 1961).
From what has been said above many of the adverse events are not true
‘effects’ of placebo or nocebo.
Secret Remedies
Since the beginning of time medicines had been sold without any description of their
contents. In 1731 the French King’s physician authorized remedies that had been
prepared in advance for the cure of certain illnesses after taking the advice of a
committee representing the physicians, surgeons and apothecaries. In 1778 The
Société Royale de Medicine was charged with examining new drugs giving royal
warrants authorising their sale and distribution and this legalised the secret
remedies. On 8 th August 1793 all the licensed academies and societies were
suppressed and as a result the secret remedies multiplied (Kassel, 2002). The
French law of 1803 specifically banned secret remedies and they were defined as
‘those of which the formula is kept secret by their inventors’. Only those drugs that
were mentioned in the ‘Codex’ and those preparations magistral 163 could be
provided by pharmacists. The pharmacists probably felt aggrieved by this especially
163 Magistral – medicines prescribed by a physician