Placebos and Nocebos in Other Brain Disorders

Abstract

The term placebo refers to any intervention with no therapeutic effect that is used as a control in randomized controlled trials (RCTs). Placebo can produce a beneficial effect that cannot be attributed to the properties of the intervention itself, as it is inactive, and must, therefore, be due to the patient’s belief about treatment. Respectively, adverse events (AEs) may occur when using a placebo intervention, a phenomenon that is called nocebo.

Nocebo has been studied and was found to be very prevalent in various neurological conditions and, in particular, in many brain disorders including headache, Parkinson’s disease, Alzheimer’s disease, depression, epilepsy, multiple sclerosis, and motor neuron disease. Pooled AE rates in the placebo groups (nocebo AE rates) vary from 25% in the symptomatic treatment for multiple sclerosis RCTs to almost 80% in motor neuron disease RCTs. Pooled dropout rates because of AEs in the placebo groups (nocebo dropout rates) vary from 2% in multiple sclerosis RCTs to almost 10% in Parkinson’s disease RCTs. Across all brain disorders, the nature of AEs reported in the placebo-treated subjects mirrors those reported by active drug-treated subjects, suggesting that awareness of drug side effect profiles might have influenced patient expectations and, thus, nocebo responses.

Unexplored areas, where nocebo should be studied further, include psychiatric disorders (i.e., schizophrenia and bipolar disorder), vascular disorders (i.e., acute ischemic stroke, vascular dementia), degenerative disorders (i.e., frontotemporal dementia, Lewy body dementia), and other systemic atrophies of the brain (i.e., hereditary ataxias).