The placebo effect
   The placebo effect is a fascinating phenomenon in clinical practice.
   Studies have shown that there is a significant placebo effect in a wide
   article looks at the background of the placebo effect, defines the
   covers the issue of using placebos in research trials, highlighting the
   The term placebo is derived from the Latin verb ‘placare’, ‘ to
   term ‘ placebo effect’. He reported that, on average, about a third of
   placebos. This subsequently led to the development of
   placebo-controlled trials, whereby a new drug is said to have
   significant benefit only if it shows superiority over placebo. The
   placebo effect has also been a source of recent interesting debate in
   from antidepressant medication derives from the placebo effect (Kirsch
   stressed that response to placebo and to antidepressants involves
   In general, a placebo is an inert substance that has no inherent
   drug with which it is compared. An ‘active placebo’ is one that has its
   antidepressants). A placebo need not always be pharmacological. It
   where the patient is anaesthetised but not given ECT. Surgical placebo
   Placebo equivalents are also employed in complementary medicine. For
Why does the placebo effect occur?
   placebo is coincidental and would have occurred even without it. This
   theory explains the beneficial effects of placebo in short-lived
   or schizophrenia show improvement with placebo.
   improvement by any subsequent prescription, including placebo. Using
   unconditioned response, the placebo is the conditioned stimulus, and
   improvement owing to placebo is the conditioned response.
   Patient expectations are important in determining the placebo effect.
   stronger placebo effect than those that are perceived to be less so.
   Thus, placebo injections have more effect than oral placebos, capsules
   are perceived as being stronger than tablets, bright-coloured placebos
   are more effective than light-coloured ones larger placebos have more
   effect than smaller ones, and two placebos have more effect than one.
   the placebo effect. The same compound has been found to be more
   placebo-induced analgesia. Previous studies had shown that
   placebo-induced analgesia is partially reversed by administering the
   placebo effects on mood and behaviour.
Pattern of placebo improvement
   Among psychiatric disorders, the placebo effect has been most
   the improvement as a result of placebo in depression tends to be
   if the pattern of improvement is consistent with a placebo response
   with either placebo or fluoxetine. Those patients who had shown a
   placebo pattern of improvement during the initial fluoxetine phase
   were switched to placebo, but patients who had shown a true drug
   pattern of improvement relapsed more if they were switched to placebo
   placebo-controlled trials involving 40 clinical conditions, including
   epilepsy. They concluded that placebos tended to have no significant
Use of placebos in clinical trials
   However, the use of placebos for conditions for which effective
   should it only have to demonstrate superiority over placebo in order to
   have criticised the use of placebo-controlled trials to test new drugs
   depression, and the use of placebo-controlled trials to test the
   double-blind study of alprazolam v. imipramine v. placebo could
   correctly guess whether they were on an active drug or placebo. In
   be receiving either an active drug or placebo. Therefore, it may not
   accurately determine whether one is on active medication or placebo.
   In addition to ethical issues, RCTs with a placebo control group have
   In any RCT, the placebo is made by the manufacturer of the active drug.
   Hence, placebos used in one study will be different in form (size,
   variation in placebo response observed for the same condition.
Side-effects of placebos
   When a placebo produces prominent side-effects it is known as a ‘
   resulting from the administration of a placebo. In placebo-controlled
   studies of psychotropic drugs, the placebos tend to cause a similar
   or QT prolongation. ‘Placebo sag’ refers to the attenuation of the
   placebo effect with repeated use (Peck & Coleman, 1991). There are
   historical reports of placebo dependence (Vinar, 1969).
   to follow a chronic course. Hence, even if they are given placebo this
   Just as doubts have been cast on the beneficial effects of the placebo,
   placebo may be a reflection of pre-existing or spontaneously occurring
   symptoms rather than being placebo-induced. Similarly, RCTs may be
   placebo) is mediated by cholecystokinin and is abolished by the
   placebo, Casper et al (2001) found similar rates of placebo response in
   medicine, the placebo effect is still poorly understood. Beecher’s
   (1955) original study, which showed an overall average placebo response
   All discussion regarding placebos is based on the assumption that they
   are inert. But are they really so? Placebos are generally referred to
   that the ‘inert’ chemical in the placebo may be relevant to the
   Whatever the reasons for the placebo effect, the most important message
   for clinicians is that just because someone responds to a placebo does
       BEECHER, H. K. (1955) The powerful placebo. JAMA, 159, 1602 -1606.
       differences in placebo responses of patients with major depressive
       antagonism of placebo analgesia by naloxone. Pain, 16, 129 -143.
       HROBJARTSSON, A. & GOTZSCHE, P. C. (2001) Is the placebo powerless?
       An analysis of clinical trials comparing placebo with no treatment.
       KIENLE, G. S. & KIENE, H. (1997) The powerful placebo effect: fact
       placebo: a meta-analysis of antidepressant medication. Prevention &
       brain function of depressed subjects during treatment with placebo.
       of the placebo‘effect’ is really statistical regression?
       PECK, C. & COLEMAN, G. (1991) Implications of placebo theory for
       Heterogeneity of clinical response during placebo treatment.
       of placebo controls. New England Journal of Medicine, 331, 394
       placebo. Archives of General Psychiatry, 55, 334 -343.
       Ter RIET, G., De CRAEN, A. J., De BOER, A., et al (1998) Is placebo
       VINAR, O. (1969) Dependence on a placebo: a case report. British
    4. Why does the placebo effect occur?
    5. Pattern of placebo improvement
    6. Use of placebos in clinical trials
    7. Side-effects of placebos
         4. The placebo effect