The Nocebo Effect


Placebo: A dummy medicine containing no active ingredients;

Nocebo:substance which a patient experiences as harmful due to a previous negative perception, but which is in act pharmacologically (medicinallyinactive.

Nocebo in multiple sclerosis trials: A meta-analysis on oral and newer injectable disease-modifying treatments. Gklinos P, Papadopoulos D, Mitsikostas DD. Mult Scler Relat Disord. 2019 Sep 9;36:101389.

BACKGROUND: Nocebo phenomena are linked to decreased adherence to treatments in clinical practice as well as difficulty in assessing the adverse effect profile in clinical trials.

OBJECTIVE:To estimate the incidence and severity of nocebo responses in clinical trials of oral and newer injectable disease-modifying treatments (DMTs) for relapsing multiple sclerosis (MS).

METHODS:Meta-analysis of the incidence of nocebo responses was performed by pooling the percentage of placebo-treated patients that exhibited adverse events (AEs) in randomized, placebo-controlled MS trials published between 2005 and 2018. Nocebo severity was estimated as a percentage of placebo-treated patients who discontinued the treatment due to drug-related AEs.

RESULTS:The pooled incidence of nocebo was 89% (95% CI: 88%-90%) in trials for oral DMTs (cladribine, fingolimod, teriflunomide and dimethyl fumarate) and 66% (95% CI: 51%-80%) in trials of newer injectable DMTs (biosimilar glatiramer acetate 20 mg, innovator glatiramer acetate 40 mg and pegylated interferon beta). The pooled nocebo severity was 8% (95% CI: 5%-12%) for oral treatments and 2% (95% CI: 0-2%) for newer injectable DMTs.

CONCLUSIONS: Oral DMTs may be associated with a higher incidence and greater nocebo severity than newer injectables.

I think you can’t get the “gain without the pain”, meaning that if there is greater the activity of an agent then it is more likely that it is to have side effects. So it is not surprising that the orals have a greater nocebo effect because they are more active. I suspect eating Poop will be low on the noncebo effect, but it can be harmful to your wallet:-(

This paper also gives me laughter therapy as to suggest there is such a thing and innovator GA, made me chuckle…maybe it should have been “wringing out the last drop of profit” GA. Looking forward to the once a week 120mg variant as the three times a week patent runs out.

Ooops has this idea just stopped someone getting the patent

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  • The nocebo and placebo effect are notoriously difficult to control for, particularly in studies with softer endpoints. The 3 pages of risks that must be included in the informed consent form certainly influences the nocebo effect. Similarly, the way the trial staff interact with a participant (e.g. wow, you are looking much better today) and discuss the potential benefits of the treatment can influence the placebo effect. There are many companies that offer training on controlling these effects in clinical trials are most are 💩 because you just can’t control attribution bias in participants.

    Interestingly, in a recent study I managed the placebo and nocebo effects were much more prevalent in the US when compared to Australia. I wonder whether the direct to consumer advertising in the US is driving this. If you’ve ever been to the US, you know that you get hit with drug adds every 20 minutes, you just can’t avoid them. I think this could result in a very different perception about pharmaceutical products and their risks and benefits.

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