Novel TMS for Stroke and Depression (NoTSAD): Accelerated Repetitive Transcranial Magnetic Stimulation as a Safe and Effective Treatment for Post-stroke Depression

Abstract

Background: Post-stroke depression (PSD) affects up to 50% of stroke survivors, reducing quality of life, and increasing adverse outcomes. Conventional therapies to treat PSD may not be effective for some patients. Repetitive transcranial magnetic stimulation (rTMS) is well-established as an effective treatment for Major Depressive Disorder (MDD) and some small trials have shown that rTMS may be effective for chronic PSD; however, no trials have evaluated an accelerated rTMS protocol in a subacute stroke population. We hypothesized that an accelerated rTMS protocol will be a safe and viable option to treat PSD symptoms. Methods: Patients (N = 6) with radiographic evidence of ischemic stroke within the last 2 weeks to 6 months with Hamilton Depression Rating Scale (HAMD-17) scores >7 were recruited for an open label study using an accelerated rTMS protocol as follows: High-frequency (20-Hz) rTMS at 110% resting motor threshold (RMT) was applied to the left dorsolateral prefrontal cortex (DLPFC) during five sessions per day over four consecutive days for a total of 20 sessions. Safety assessment and adverse events were documented based on the patients' responses following each day of stimulation. Before and after the 4-days neurostimulation protocol, outcome measures were obtained for the HAMD, modified Rankin Scale (mRS), functional independence measures (FIM), and National Institutes of Health Stroke Scales (NIHSS). These same measures were obtained at 3-months follow up. Results: HAMD significantly decreased (Wilcoxon p = 0.03) from M = 15.5 (2.81)−4.17 (0.98) following rTMS, a difference which persisted at the 3-months follow-up (p = 0.03). No statistically significant difference in FIM, mRS, or NIHSS were observed. No significant adverse events related to the treatment were observed and patients tolerated the stimulation protocol well overall. Frey et al. NoTSAD: Accelerated rTMS for PSD Conclusions: This pilot study indicates that an accelerated rTMS protocol is a safe and viable option, and may be an effective alternative or adjunctive therapy for patients suffering from PSD. Future randomized, controlled studies are needed to confirm these preliminary findings.

Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation for Post-stroke Vascular Cognitive Impairment: A Prospective Pilot Study

“…The effect of a protocol applying high-frequency stimulation to the left dorsolateral prefrontal cortex (DLPFC) region is gaining popularity ( 17 ), and rTMS' therapeutic effect on post-stroke depression is becoming an established fact. Most of the protocols used involved the administration of a high frequency of 5 Hz or more to the left DLPFC region ( 18 , 19 ). Nevertheless, there is no definitive protocol for the use of rTMS to enhance cognition in post-stroke patients ( 20 ).…”

Neural Substrates of Poststroke Depression: Current Opinions and Methodology Trends

“…As shown in Table 1 , the PFC as replicated across studies of various methodologies may be the structure most heavily implicated in the pathogenesis of PSD. The role of PFC in depressive disorders has been confirmed by multiple clinical trials, showing that rTMS targeted at the left DLPFC can significantly alleviate the symptoms of PSD, vascular depression, and MDD ( Jorge et al, 2004 ; O’Reardon et al, 2007 ; George et al, 2010 ; McIntyre et al, 2016 ; Gu and Chang, 2017 ; Shen et al, 2017 ; Frey et al, 2020 ; Sackeim et al, 2020 ). We believe that the PFC is most promising as the avenue for future research or the target for treatment of PSD and other depressive disorders.…”

“…Although inconclusive, some researchers still believe that there is an association between left frontal strokes and PSD within the first 2 months after stroke based on some converging evidence ( Astrom et al, 1993 ; Shimoda and Robinson, 1999 ; Rajashekaran et al, 2013 ; Robinson and Jorge, 2016 ). The role of the left prefrontal cortex (PFC) in PSD was further supported by multiple clinical trials showing that repetitive transcranial magnetic stimulation (rTMS) targeted at the left dorsolateral PFC (DLPFC) can significantly alleviate the symptoms of PSD and vascular depression ( Jorge et al, 2004 ; McIntyre et al, 2016 ; Gu and Chang, 2017 ; Shen et al, 2017 ; Frey et al, 2020 ).…”

Transcranial Magnetic Stimulation for the Neurological Patient: Scientific Principles and Applications

“…For example, TMS has been explored as a means of treating depression in the setting of PD 70 and in post-stroke depression. 71 Despite these preliminary findings, no specialized protocols have been adopted for treating depression or OCD in neurological conditions, and default parameters used in for treating these in non-neurological populations are often used.…”