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PostPosted: Sat Jun 12, 2010 8:46 pm 
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This meta-analysis published recently on nocebo effect shows it's quite significant:

Mult Scler. 2010 Jun 10. [Epub ahead of print]

Nocebo effects in multiple sclerosis trials: a meta-analysis.
Papadopoulos D, Mitsikostas D.

Department of Neurology, Athens Naval Hospital, Athens, Greece/Neurology section, Evangelismos General Hospital, Athens, Greece.

Abstract
Objective: To estimate the incidence and severity of nocebo responses in trials of symptomatic treatments (STs) and disease-modifying treatments (DMTs) for multiple sclerosis (MS).Methods: We conducted a systematic Medline search for all randomised, placebo-controlled MS trials published between 1989 and 2009. Meta-analysis of the incidence of nocebo responses was performed by pooling the percentage of placebo-treated patients that exhibited adverse events.

Nocebo severity was calculated from the percentage of placebo-treated patients that dropped-out due to drug-related adverse events.Results: Data were extracted from 56 DMT and 44 ST eligible trials. The pooled incidence of nocebo responses was 74.4% (95% CI: 69.92-88.30) in DMT trials and 25.3% (95% CI: 15.24-36.90) in ST trials and was significantly higher in the former (p < 0.0001). The pooled nocebo severity was 2.1% (95% CI: 1.6-2.67) in DMT and 2.34% (95% CI: 1.54-3.29) in ST trials.

Meta-regression analysis revealed a higher nocebo incidence in parallel design ST studies compared to crossover ones (p = 0.013) and a higher nocebo severity in phase II ST studies compared to phase III ones (p = 0.0001). Nocebo severity in DMT trials exhibited an association with the year of study publication (p = 0.011) and the frequency of drug administration (p = 0.0082).

Conclusions: Nocebo responses in MS trials are substantial and appear to have increased significantly in recent years with important implications for both trial design and clinical practice. Furthermore, nocebo responses exhibit an association with medication and trial-related factors.

PMID: 20538704 [PubMed - as supplied by publisher]


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PostPosted: Sun Jun 13, 2010 12:59 am 
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A Placebo Effect scenario Bitter pill to swallow. Fiction or fact?
Patient: Multiple sclerosis, may have acute depression, loss of sensitivity in hands and feet, poor hair and nail quality, no energy, tired all of the time, hardly able to get out of bed. Constant pain in muscles and joints, limbs swollen, repeated chest infections, skin in poor condition, overweight, taking drugs to ease pains, depression and to assist sleeping etc. Most of the time unable to stand, so dependant on sitting in armchair, Wheelchair inevitable.

Prescribed: Sugar pills

Doctor: “Take these two tablets three time per day. I am sure that this new drug will help to ease your condition, it should give you enough energy in a few days to enable you to cope a little better”. Please let me know how you get on.

Scenario
Patient is no longer alone, because the Doctor at least appears to care and is observed to be trying to help. The pills initially stimulate a subtle belief in ones ability to at least make the effort to try to get up. Immediately the body becomes upright, gravity starts to work its magic by automatically stimulating an increase in the circulation of fluids throughout the entire complicated network of tubes and cells of the body. And the longer a person is in an upright position, the more benefits the person receives from the healing affects of gravity.

Day 1 of the new treatment requires a great deal of effort, rewarded only by an increased level of pain. It is at this point that anger, determination, call it what you like, takes over from depression, causing an adrenaline rush, which compensates for the discomfort. A bit like a boxer receiving a blow for the first time, following blows appear to be somewhat less painful.
Day 2 requires a similar amount of effort with little obvious benefits except a few more aches and pains developing from the previous day.

By the end of about two weeks, the extra activity has meant that the fluids are now flowing, as they should be, more freely throughout all of the systems within the body. Although aching, it becomes apparent to the patient that they are in fact doing more than they have done for a long time, and the only thing that could possibly be helping are the pills which are prescribed by the Doctor.
Further visits to the surgery, driven by sheer determination to show the improvements which have already been achieved, coupled with a desire to obtain some more of this wonderful stuff, means a further increase in activity and a breath of fresh air.

Over the following months less time is allocated to the poor bed and chair posture, in favour of mobility, which means an inevitable increase in exposure to the beneficial effects that gravity exerts on the circulation. The depression lifts and sleeping pills are abandoned as a genuine feeling of tiredness takes over due to the effort subconsciously put in to proving that ‘the pill is mightier than the sores’.

Eventually, even the damaged nervous system begins to respond again, simply because gravity opens up the damaged fluid pathways and effects repairs on the damaged myelin.

The Doctor who sees the improvements knows that the miracle drug does not exist. A conclusion that either the problem was all in the mind of the recipient, or the placebo somehow fooled the brain into healing the body is understandably drawn from the evidence.
Giving the illusion for a clear case of mind over matter. The placebo wins another place in the battle of medical remedies, when the real effect is postural based.
Andrew K Fletcher 02 July 1998

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