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

And because you didn't do the research correctly you call for future studies. I blame your mentors and senior researchers for not instructing you correctly.

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

Jessica Frey¹, Umer Najib¹, Christa Lilly² and Amelia Adcock^1*

• ¹Department of Neurology, West Virginia University, Morgantown, WV, United States
• ²Department of Biostatistics, West Virginia University, Morgantown, WV, United States

Background: Post-stroke depression (PSD) affects up to 50% of stroke survivors(I've only seen

33% chance survivor depression)

, 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.

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.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04093843.

Introduction

The interplay between depression and cerebrovascular disease is complex and clinically important. Post-stroke depression (PSD) is the most common neuropsychological complication of stroke, with a prevalence of ~33% (1) in stroke survivors. PSD adversely influences outcomes by reducing quality of life, increasing caregiver burden, and increasing early mortality as much as ten-fold (2–4). As acute stroke interventions continue to improve, stroke survivorship and associated morbidity will also increase, making the need to explore innovative treatments for PSD even more urgent.

Despite the significant clinical burden of PSD, there are limited treatment options to prevent or reduce its severity. Psychotherapy and pharmacotherapy are well-established as treatments of choice in major depression, however a subset of patients do not respond to either of these first-line therapies (5). Selective Serotonin Reuptake Inhibitor (SSRI) use has been associated with increased risk of hemorrhagic complications as well as increased risk of falls in the elderly, while other studies have shown that SSRIs are actually associated with increased risk for stroke, myocardial infarction, and all-cause mortality (6). A recent meta-analysis for stroke patients concluded that antidepressants did not significantly improve patients' general recovery, achieved varied response rates, and were not tolerated due to adverse effects (7). Compliance, communication problems, and lack of access to psychiatric care are further challenges to treating PSD.

Repetitive transcranial magnetic stimulation (rTMS) may represent an effective treatment option that mitigates the issues associated with the standard PSD interventions. The FDA approved rTMS for patients with Major Depressive Disorder (MDD) in 2008 (8). The typical rTMS protocol that has been used effectively for major depression is 5 days per week for 4–6 weeks. Conventional rTMS paradigms have been studied in the PSD population, and many studies including a meta-analysis have shown that conventional rTMS is likely effective for chronic, refractory PSD (9, 10). However, these conventional paradigms may be inconvenient for patients with limited transportation access and may limit compliancy of patients. Therefore, an accelerated protocol which minimizes the number of days needed to complete the full treatment may be more accessible to patients and may increase compliancy. While there have been some accelerated rTMS paradigms that have been designed to treat conditions such as alcohol withdrawal and treatment-resistant depression (11–14), similar accelerated protocols have not been studied in patients suffering from PSD. Applying accelerated rTMS to the PSD population comes with unique and complex factors. For example, the theoretical risk of seizure using an accelerated protocol may be higher, and this risk may increase even further in patients in the acute to subacute stroke period. Therefore, it is important to study the safety of an accelerated protocol in this population. In addition, the period immediately following cerebrovascular ischemia potentially represents a biologically unique phase amenable to intervention given that both neuroplasticity as well as recurrent stroke risk are highest during this time (15, 16).

There is a clear medical need to further address the impact of rTMS for PSD and to optimize stimulation parameters. We hypothesized that an accelerated 4-days rTMS protocol would be a safe and viable method for treating PSD and would help ameliorate depressive symptoms.