Statins and the Nocebo Effect?

There have been numerous and relentless attempts to play down the extent and severity of statin adverse effects. One of these relates to the nocebo effect.

The nocebo effect suggests that health problems from other causes are blamed on a prescribed medication. The idea is that after taking the tablet the patient reports adverse effects from the medication but these adverse effects have a different cause or may be induced through an expectation of adverse effects due to a widespread belief that the medication can be harmful. In some ways the opposite of the placebo effect.

The nocebo idea, in general, is an interesting concept worthy of debate, however, I believe the way this idea has been applied to statins does not represent what's really happening concerning statin adverse effects.

Claims that statin adverse effects are due to the nocebo effect arose from studies that have found the same number of adverse effects in the statin group as the placebo group. The most recent of these, and probably the most cited, is a study published in the Lancet in May 2017:

Gupta, A, Thompson, D and Whitehouse, A et al. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet 2017 Vol 389 No. 10088 p2473-2481.

This study looked at data from the ASCOT trial. Researchers compared data from the trial period itself with data from a follow-up period where patients were told if they were receiving the statin or a placebo and also given the option to start a statin. During the trial itself about the same number of patients in both the statin group and the placebo group reported muscle aches and pains. But during the follow up period (where patients knew if they were taking a statin or not) considerably more people started to report muscle aches and pains in the statin group than the non-statin group. The researchers and other commentators have suggested that once patients knew they were taking a statin the rate of muscle aches and pains increased in the statin group. A result of the nocebo effect.


However, the following points have been overlooked or deliberately ignored:

The researchers suggested that the muscle-related adverse effects were the result of patients now knowing they were taking a statin and can blame the statin for any muscle-related problems (real or imaginary) experienced.

This idea of a nocebo effect relies on the idea that patients have an expectation that statins cause muscle problems. It has even been suggested that the nocebo effect is due to exaggerated reports about statin adverse effects in the media. However, the data that was used for the 2017 Lancet paper was actually collected between 1998 and 2005. Long before statins became a household name and patients could create preconceived ideas about statins.

It is also worth mentioning that:

During the initial trial period there was a statistically significant increase in renal and urinary adverse effects in those people who were given the statin. Something that has never been mentioned before when discussing this study.

During the unblinded phase there was also a statistically significant increase in musculoskeletal and connective tissue disorders and blood and lymphatic system disorders in the people who took a statin.

In the ASCOT trial no one lived any longer as a result of taking the statin.

The idea of the nocebo effect is one reason doctors reject their patients’ reports of adverse effects after starting a statin. Doctors are advised by opinion leaders to watch out for these “false” reports of statin adverse effects and have other explanations ready, such as telling the patient its just due to old age.