Placebo: general

The need for placebos generally from the first human study onwards t)q)ically involves manufacture of dummy capsules or tablets, and if oral solutions or suspensions are to be used, these must be matched as closely as possible for taste, colour and appearance. 

The precise use of the placebo will depend on the study design, e.g. whether crossover, when all patients receive placebo at some point in the trial, or parallel group, when only one cohort receives placebo. Generally, patients easily understand the concept of distinguishing between the imagined effects of treatment and those due to a direct action on the body. Provided research subjects are properly informed and freely give consent, they are not the subject of deception in any ethical sense but a patient... 

Orthopedic Hospitalized adults 22-87 years 2 g prop vs. 1 g para vs. placebo General Given post-op every 6 hours for 24 hours VAS, VRS Prop and para both significantly reduced morphine consumption over 24-h period 4... 

Cardiac surgery Adults 45-79 years 1 g para vs. placebo General 15 min before end of surgery and every 6 hours for 72 hours VAS Para significantly reduced pain at rest and at 12 hours, nonsignficant reduction in morphine consumption 6... 

Total abdominal hysterectomy Hospitalized women 1 g para vs. placebo General Given once either 30 min before surgery or prior to skin closure VAS Preemptive para significantly reduced post-op morphine consumption, no hemodynamic effects 7... 

Nestler EJ, Hyman SE, Malenka RC Molecular Neuropharmacology A Foundation for Clinical Neuroscience. New York, McGraw Hill, 2001 Novick DM, Pascarelli EE, Joseph H, et al Methadone maintenance patients in general medical practice a preliminary report. JAMA 259 3299—3302, 1988 Nunes EV, Quitkin EM, Donovan SJ, et al. Imipramine treatment of opiate-dependent patients with depressive disorders a placebo-controlled trial. Arch Gen Psychiatry 55 153-160, 1998... 

Ezetimibe 1 0 mg tablet 10 mg once daily The overall incidence of adverse events reported with ezetimibe alone was similar to that reported with placebo and generally similar between ezetimibe with a statin and statin alone. The frequency of increased transaminases was slightly higher in patients receiving ezetimibe plus a statin compared with those receiving statin monotherapy (1.3% versus 0.4%). 

Imipramine treatment resulted in a higher rate of remission of anxiety symptoms than trazodone, diazepam, or placebo (e.g., 73% versus 69% versus 66% versus 47%) in an 8-week controlled trial of DSM-III-diagnosed GAD patients. Antidepressants were more effective than diazepam or placebo in reducing psychic symptoms of anxiety. The use of TCAs generally is limited by bothersome adverse effects (e.g., sedation, orthostatic hypotension, anticholinergic effects, and weight gain). 

Conner, K. M. 8c Davidson, J. R. (2002). A placebo-controlled study of kava kava in generalized anxiety disorder. Int. Clin. Psychopharmacol., 17, 185-8. 

So how can we judge the clinical significance of the 1.8-point difference between improvement on antidepressants and improvement on placebos One way is to look at the Hamilton scale and see how a difference of that size could be obtained. There are two common versions of the Hamilton scale a 17-item version and a 21-item version. Fortunately, we do not have to be concerned about differences between these two versions, because only the first 17 items on the 21-item scale are generally scored. So as far as scores are concerned, the 17-item version and the 21-item version are identical. 

There is yet another possibility. The general assumption is that the effect of a drug adds to the placebo effect, so that the total improvement that patients experience is the drug effect in addition to the placebo effect. This assumption is implicit in the design of placebo-controlled clinical trials, in which the drug effect is assessed as the difference between the response to the drug and the response to the placebo. Anne Harrington, an historian of science at Harvard University and the London School of Economics, calls it the oil-and-water hypothesis. 

Although the routine use of placebo-controlled trials in medicine is relatively new, the logic behind it is not. Ted Kaptchuk at Harvard University has traced the use of placebo controls, although without the term placebo , to rites of exorcism in the 16th century.6 The general belief was that demons could not... 

The placebo effect also depends on what people are told about the treatment they are given. The effect is smaller when patients are told that their treatment might be a placebo, as is routinely done in clinical trials, and is larger when people are told that their treatment has been shown to be powerful.17 Because the placebo effect can vary so much, attempts to estimate its power in general, without specifying the condition being treated and the conditions under which the placebo was administered, are meaningless. 

Although placebo effects are generally referred to as nonspecific, there is also a sense in which they are very specific. The effect of the placebo is specific to the beliefs that people have about the substance they are ingesting. Placebo morphine, for example, reduces pain, whereas placebo antidepressants reduce depression. Even the side effects that people report when given a placebo tend to be the same side effects that are produced by the real drug.12 In other words, the effect of a placebo is specific to the effect that the person expects it to have. When given placebo stimulants like decaffeinated coffee (presented as regular coffee), people feel more alert, and their heart rate and... 

The obvious problem with prescribing placebos is the fact that it generally entails deception. When physicians prescribe placebos, they don t tell their patients that the treatment is a placebo.13 Instead, the patients are led to believe that they are receiving an active treatment. This raises a serious ethical question. Is it ethical to deceive patients if the deception is likely to make them better ... 

G. S. Sachs, A. F. Schatzberg and S. Solomon, National Depressive and Manic-Depressive Association Consensus Statement on the Use of Placebo in Clinical Trials of Mood Disorders , Archives of General Psychiatry 59, no. 3 (2002) 262-70... 

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