Placebo in Functional Neurological Disorders: Promise and Controversy

Abstract

Placebo, nocebo, and lessebo effects are very frequent in patients with both neurological and psychiatric disorders. Interestingly, the neural mechanisms underlying placebo effects have been found to be the same as or similar to mechanisms targeted by active pharmaceutical interventions for many of these disorders. In the case of functional neurological disorders (FNDs), there are shared neural substrates between the central nervous system "placebo network" and the dysfunctional networks implicated in the pathophysiology. These networks are primarily involved in emotion regulation, stress responses, and the sense of self-agency. Therefore, placebo effects have also been discussed as therapeutic interventions in FNDs. Such an approach, however, has a variety of ethical implications evolving around informed consent, autonomy, nonmaleficence, beneficence, and justice. In this paper, we discuss the use of placebo, nocebo, and lessebo in FNDs as well as related ethical issues. Overall, the use of placebo in FNDs is currently still considered controversial both for diagnostic as well as therapeutic purposes. Although it is a safe and almost unique intervention, its use violates the core principles of medical ethics and doctor-patient interactions involving autonomy or openness in the therapeutic relationship.

Keywords: ethics; functional neurological disorders; lessebo effect; nocebo effect; placebo effect.

Figure 1

Integration of placebo mechanisms in functional neurological disorders (FNDs). The schematic illustrates the overlap between brain networks involved in the placebo response (prefrontal cortex, anterior cingulate cortex, insula, amygdala) and those implicated in FNDs. Both engage circuits related to expectation, attention, and emotion regulation, providing a shared neurobiological basis for therapeutic responsiveness.