Perceived placebo effect

Fig. 3 Components of a cough medicine. The efficacy of a cough medicine can be attributed to at least five factors pharmacological, physiological, trae placebo, psychological and non-specific effects. The overall placebo response measured in clinical trials can be considered as a perceived placebo effect that is made up of four factors physiological, trae placebo, psychological and nonspecific effects...

The perceived placebo effect is defined as the total effect of the placebo medicine, which includes the true placebo effect and other effects, such as any physiological effect, and non-specific effects such as natural recovery from the disease. The perceived placebo effect is normally measured in a placebo-controlled clinical trial, but it is not possible to estimate the contribution of the true placebo effect to any changes in cough severity from this parameter, as the perceived placebo effect also includes the physiological effect and non-specific effect of treatment as shown in Fig. 3. 

Ernst E (2007) Placebo New insights into an old enigma. Drug Discov Today 12 413 18 Ernst E, Resch KL (1995) Concept of true and perceived placebo effects. Br Med J 311 551-553 Evans D (2003) Placebo. The belief effect. Harper Collins, London... 

But do the clinical-trial data submitted to the FDA even establish proof of principle Recall that the rather small differences found between drug and placebo in the trials submitted to the FDA could have been due to the breaking of blind on the basis of perceived side effects. It may simply be evidence of an enhanced placebo effect, rather than a true drug effect. As I noted in Chapter i, once side effects are taken into account, the difference between SSRI and placebo is not even statistically significant.30... 

There is no conclusive evidence either way on the efficacy of OTC cough preparations, but they are extremely popular. The placebo effect and reassurance derived from using them for self-limiting acute cough probably contribute significantly to their perceived effectiveness. 

One should not underestimate the power ol the placebo effect—that is, the tendency to perceive improvement in a subject who believes that he or she is receiving a potentially beneficial treatment. In a study of arthroscopic surgical treatment for knee pain, for example, subjects who were led to be-ieve that they had received surgery through the use of videotapes and other means showed the same level of improvement, on average, as subjects who were actually operated on. 

The third component of the physiological effect involves the sensory impact of the cough medicine. If the medicine could be administered without any sensory impact, i.e. without the patient perceiving that any treatment had been administered, then it is doubtful that there could be any true placebo effect as this is dependent on the conscious perception that a treatment has been administered. Consciousness... 

In view of the perceived benefit of aspirin in the secondary prevention of stroke and myocardial infarction, two large trials involving physicians as subjects were initiated to study the effect of aspirin in the primary prevention of arterial thrombosis. In the American study, 22,000 volunteers (age 40 to 84 years) were randomly assigned to take 325 mg of aspirin every other day or placebo. The trial was halted early, after a mean follow-up of 5 years, when a 45% reduction in the incidence of myocardial infarction and a 72% reduction in the incidence of fatal myocardial infarction were noted with aspirin treatment. However, total mortality was reduced only 4% in the aspirin group, a difference that was not statistically significant, and there was a trend for a greater risk of hemorrhagic stroke with aspirin. Thus, the prophylactic use of aspirin in an apparently healthy population is not recommended at this time, unless there are risk factors for cardiovascular disease. 

A later study supported the findings that methylphenidate s benefits are most apparent in sleep-deprived/sleep-restricted volunteers. Roehrs et al. (52) compared the effects of 09 00 doses of 10 mg methylphenidate to placebo on sleepiness (Multiple Sleep Latency Test, MSLT), Profile of Mood States (POMS) ratings, and divided-attention performance after either 4 or 8 hr of sleep. After these test days, the 4- and 8-hr sleep conditions were repeated, but this time subjects were given their choice of drug or placebo. Results indicated that performance was improved by methylphenidate, most notably after the 4-hr condition. Methylphenidate also improved sleep latency and mood, but only after restricted sleep. During the choice phase of the study, subjects showed a preference for methylphenidate after 4 hr sleep (in 88% of opportunities), but not after 8 hr sleep (in only 29% of opportunities), suggesting that the preference for methylphenidate depended on the perceived sleepiness level of the individual. 

In a series of studies, Bell et al. assessed the effects of ephedrine mixtures on performance, and found measurable improvement. One and one-half hours after ingesting a placebo (P), caffeine (C) (4 mg/kg), ephedrine (E) (0.8 mg/kg), or caffeine and ephedrine, 12 subjects performed a 10-km run while wearing a helmet and backpack weighing 11 kg. The trials were performed in a climatic suite at 12-13°C, on a treadmill where the speed was regulated by the subject. V02, VC02, V(E), HR, and rating of perceived exer-... 

It is frustrating that the results of the study are somewhat equivocal. We are pleased that the CAMS study confirms the strong anecdotal evidence of the benefit of cannabis for some people with MS. It is particularly encouraging that patients receiving cannabis perceived an improvement in both spasticity and pain, when compared with those on placebo, and that no significant side-effects were reported. However, it is clear that the primary assessment tool used to measure spasticity, the Ashworth Scale, has failed to capture the full impact of this aspect of MS. Spasticity is a complex collection of symptoms encompassing pain and stiffness, some of which can only accurately be as-... 

Foo and Lemon (1997) assessed the acute effects of kava, alone and in combination with alcohol, on subjective measures of impairment and intoxication and on cognitive performance. This was a placebo-controlled study, with ten subjects in each of four conditions placebo, kava, alcohol, and kava plus alcohol. The placebo was pure fruit juice and fruit juice was added to kava and alcohol as well to maintain double blind conditions. A battery of tests was included to measure outcomes, including subjective measures of impairment and intoxication, and visual-motor and cognitive performance. These measures were performed before (time = 0), and 30, 60 and 90 minutes after consumption of the drinks. Each test trial took about 12 minutes. Kava consumption produced no significant effects on perceived or measured competence, while alcohol caused motor and cognitive impairments. However, when kava and alcohol were combined, kava potentiated both the perceived and measured impairment produced by the alcohol alone. This potentiation effect is in accord with the findings of Jamieson and Duffield (1990) on the positive interaction of ethanol and kava resin in mice. 

No formal assessment of the validity of each reference was undertaken in this process, although the levels of evidence afforded by different types of publications (i.e., case report vs. randomized, placebo-controlled double-blind study) were actively considered during the review process. In addition, it was observed that some identified publications were of limited value, especially those that lack sufficient detail about the specific herbal preparation addressed, and case reports that postulate a causal relationship between a specific herbal ingredient and a reported adverse effect, without consideration for confounding factors such as patient history or concomitant drug use. Some such references were nonetheless retained, though the editors attempted to call attention to their perceived flaws. 

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