Placebo effects can be defined as positive responses to the therapeutic context surrounding administration of an active or inactive treatment. These effects are believed to be mediated by a variety of overlapping external (e.g., environmental cues and the patient-physician relationship) and internal (e.g., expectancies, emotions, and cognitive framing) factors (
1). Much of the attention given to placebo effects in medicine has focused on their role in placebo-controlled clinical trials and the nuisance they can pose on measurements of clinical efficacy. However, a growing body of research is demonstrating that placebo effects, in their own right, can meaningfully modulate brain regions/networks and neurotransmitter systems (
1). Thus, there is a strong need to better understand and harness these biologically based changes that now present a new frontier in translational medicine (
2).
The majority of studies interrogating placebo effects have focused on healthy volunteers; however, an increasing number of studies are recruiting clinical populations, such as patients with Parkinson’s disease, chronic pain, and other neuropsychiatric disorders (
3). 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 (
2,
3). Functional neurological disorder (FND) can be briefly defined as the presence of neurological symptoms that are incompatible with recognized neurological/medical disease and may or may not be associated with psychological stressors (
4). These disorders are challenging to manage, have a limited set of treatment options, and pose a large burden on health care system resources (
5). Anecdotally, many clinicians have recognized that patients with FND may have very strong placebo responses, and some of these cases have been described in the literature (
6). However, to the best of our knowledge, no study to date has directly investigated placebo effects in FND, and data demonstrating placebo responses from FND clinical trials are limited.
In this article, we propose that leveraging placebo effects could be meaningfully incorporated into the management of patients with FND. We build on previous discussions of this topic (
6,
7) and offer an argument focusing on the convergent literature revealing the shared neural substrates between the brain’s “placebo network” and the dysfunctional networks implicated in the pathophysiology of FND. Although there are likely many common pathways and nodes of overlap between FND and placebo networks in the brain, we focus on the amygdala for simplicity and clarity. We then conclude by briefly outlining different approaches and strategies for optimizing the translation of placebo effects toward the treatment of FND.
