Case report: Tremor in the placebo condition of a blinded clinical trial of intermittent theta-burst stimulation for cocaine use disorder

Vaughn R Steele; Alexander Rotenberg; Noah S Philip; Mark Hallett; Elliot A Stein; Betty Jo Salmeron

doi:10.3389/fpsyt.2024.1391771

Case report: Tremor in the placebo condition of a blinded clinical trial of intermittent theta-burst stimulation for cocaine use disorder

Front Psychiatry. 2024 Jul 9:15:1391771. doi: 10.3389/fpsyt.2024.1391771. eCollection 2024.

Authors

Vaughn R Steele^{1

2

3}, Alexander Rotenberg⁴, Noah S Philip^{5

6}, Mark Hallett⁷, Elliot A Stein⁸, Betty Jo Salmeron⁸

Affiliations

¹ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.
² Olin Neuropsychiatry Research Center, The Institute of Living at Hartford Hospital, Hartford, CT, United States.
³ Center for Brain and Mind Health, Yale University, New Haven, CT, United States.
⁴ Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
⁵ Department of Psychiatry and Human Behavior, The Warren Alpert Medical School, Brown University, Providence, RI, United States.
⁶ Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System & Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, United States.
⁷ National Institute of Neurological Disorders and Stroke, Intramural Research Program, National Institutes of Health, Bethesda MD, United States.
⁸ Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, United States.

Abstract

We report a case of a new-onset, persistent tremor that developed during a clinical trial (NCT02927236) of intermittent theta burst stimulation [iTBS, a form of repetitive magnetic transcranial magnetic stimulation (rTMS)] for cocaine use disorder. Although the participant exhibited an exceptionally strong clinical response, subsequent unblinding revealed that they received sham iTBS. This case highlights the potential for strong functional neurological placebo responses in rTMS trials, and functional disorders might be a marker of a placebo response. Additionally, we note the possibility that the weak e-fields produced by some sham rTMS systems may induce clinically relevant effects.

Keywords: cocaine use disorder; iTBS; low-intensity rTMS; placebo effect; sham rTMS.

Publication types

Case Reports

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the NIDA-IRP and the NIH Center on Compulsive Behaviors. VS is supported by grants from the National Institute on Mental Health (R01MH132044) and the National Institute on Drug Abuse (K12DA000167).