Neuromodulatory treatments for psychiatric disease: A comprehensive survey of the clinical trial landscape

• Main Authors: Gavin J.B. Elias, Alexandre Boutet, Roohie Parmar, Emily H.Y. Wong, Jürgen Germann, Aaron Loh, Michelle Paff, Aditya Pancholi, Dave Gwun, Clement T. Chow, Flavia Venetucci Gouveia, Irene E. Harmsen, Michelle E. Beyn, Emiliano Santarnecchi, Alfonso Fasano, Daniel M. Blumberger, Sidney H. Kennedy, Andres M. Lozano, Venkat Bhat
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Series: Brain Stimulation
• Subjects: Neuromodulation; Psychiatry; Clinical trials; Transcranial magnetic stimulation; Deep brain stimulation; Transcranial electrical stimulation
• Online Access: http://www.sciencedirect.com/science/article/pii/S1935861X21002230

Background: Numerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions. Objective/hypothesis: We sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field. Methods: ClinicalTrials.gov (https://www.clinicaltrials.gov/) and the International Clinical Trials Registry Platform (https://www.who.int/ictrp/en/) were queried in March 2020 for trials assessing the outcome of neuromodulation for psychiatric disorders. Relevant trials were categorized by variables such as neuromodulation modality, country, brain target, publication status, design, and funding source. Results: From 72,086 initial search results, 1252 unique trials were identified. The number of trials registered annually has consistently increased. Half of all trials were active and a quarter have translated to publications. The largest proportion of trials involved depression (45%), schizophrenia (18%), and substance use disorders (14%). Trials spanned 37 countries; China, the second largest contributor (13%) after the United States (28%), has increased its output substantially in recent years. Over 75% of trials involved non-convulsive non-invasive modalities (e.g., transcranial magnetic stimulation), while convulsive (e.g., electroconvulsive therapy) and invasive modalities (e.g., deep brain stimulation) were less represented. 72% of trials featured approved or cleared interventions. Characteristic inter-modality differences were observed with respect to enrollment size, trial design/phase, and funding. Dorsolateral prefrontal cortex accounted for over half of focal neuromodulation trial targets. The proportion of trials examining biological correlates of neuromodulation has increased. Conclusion(s): These results provide a comprehensive overview of the state of psychiatric neuromodulation research, revealing the growing scope and internationalism of this field.