Why do some promising brain-stimulation devices fail the next steps of clinical development?

Interest in techniques of noninvasive brain stimulation (NIBS) has been growing exponentially in the last decade. Recent studies have shown that some of these techniques induce significant neurophysiological and clinical effects. Although recent results are promising, there are several techniques that have been abandoned despite positive initial results. In this study, we performed a systematic review to identify NIBS methods with promising preliminary clinical results that were not fully developed and adopted into clinical practice, and discuss its clinical, research and device characteristics. We identified five devices (transmeatal cochlear laser stimulation, transcranial micropolarization, transcranial electrostimulation, cranial electric stimulation and stimulation with weak electromagnetic fields) and compared them with two established NIBS devices (transcranial magnetic stimulation and transcranial direct current stimulation) and with well-known drugs used in neuropsychiatry (pramipexole and escitalopram) in order to understand the reasons why they failed to reach clinical practice and further steps of research development. Finally, we also discuss novel NIBS devices that have recently showed promising results: brain ultrasound and transcranial high-frequency random noise stimulation. Our results show that some of the reasons for the failure of NIBS devices with promising clinical findings are the difficulty to disseminate results, lack of controlled studies, duration of research development, mixed results and lack of standardization.