Differential response to H-coil repetitive transcranial magnetic stimulation before versus after the first COVID-19 shutdown

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Differential response to H-coil repetitive transcranial magnetic stimulation before versus after the first COVID-19 shutdown
Dear Editor, Depression rates increased following the onset of the COVID-19 pandemic in 2020 [1,2]. To our knowledge, no studies have investigated the impact of the COVID-19 pandemic on rTMS effectiveness for depression. We hypothesized that rTMS response rates increased after the first COVID-19 shutdown. The rTMS protocol remained unchanged during the pandemic, but secondary factors related to rTMS treatment (e.g., behavioral activation, therapeutic alliance, socialization, etc.) might be more impactful during an extended period of social isolation. We tested this hypothesis by investigating change in rTMS response rates over the course of the pandemic.
We conducted a retrospective chart review of outpatients who completed a course of H-coil rTMS (25-35 sessions) for depression at McLean Hospital in Belmont, MA between June 2015 and April 2022. All patients completed the Quick Inventory of Depressive Symptomatology (QIDS) before and after their rTMS treatment course.
Patients were divided into two groups-pre-shutdown and postshutdown-based on whether treatment concluded before or after March 15, 2020, the first COVID-19 shutdown in the United States [3]. As a secondary analysis we compared patients who completed treatment pre-shutdown, post-shutdown 2020, 2021, and 2022. Unpaired two-tailed t-tests were conducted to assess between-group differences in percentage change and total change in QIDS. Z-tests for proportions were used to assess between-group differences in response rate (≥50% improvement on QIDS) and remission rate (post-treatment QIDS ≤5) [4]. An autoregressive integrated moving average (ARIMA) was used to assess for a long-term time trend independent of the shutdown. Finally, to determine whether the effect was unique to the shutdown relative to other time points, we compared the change in percentage improvement at the shutdown to the change in percentage improvement at every other monthly time point (the first and last 6-month periods were excluded from because it would lead to a small sample size at the tails).
In this naturalistic study, nearly all metrics suggest that H-coil rTMS was significantly less effective for depression after the first COVID-19 shutdown. We originally hypothesized that the post-shutdown groups would show greater improvement than the pre-shutdown group because of the heightened importance of psychosocial (non-rTMS) benefits (e.g., behavioral activation, therapeutic alliance, socialization, etc.) during shutdown. Our results argue against this theory. These findings are relevant because, if replicated, they could help inform predictive factors of mental health treatments or provide additional insight into the impact of social isolation on psychiatric treatments. One possible explanation for our findings is that social distancing policies and protective equipment implemented after shutdown diminished the quality and quantity of these psychosocial benefits. Furthermore, reduced access to more acute interventions like inpatient hospitalization or electroconvulsive therapy may have funneled more severely depressed patients to TMS who were less likely to respond, or reduced access to adjunctive therapies such as partial hospitalization programs and in-person psychotherapy may have confounded our findings [5].
An alternative explanation for our findings is that patient illness was more complex after the shutdown. Our groups did not differ in baseline QIDS, but QIDS may not accurately capture the burden of specific symptoms or comorbidities that increased after shutdown (e.g., suicidality, insomnia, anxiety, etc.) [6,7]. With fewer psychiatric referrals after shutdown [8], it is possible that only patients with more complex or treatment-resistant illness received rTMS [9]. If so, our observations may also extend to pharmacotherapy and psychotherapy. While ketamine response has been previously shown to remain unchanged after the first shutdown [10], this study was limited to patients treated before February 2021. Additional studies may be warranted to determine if our observations extend to other pharmacotherapy, psychotherapy, and There are several limitations to consider. Without a matched control group, we cannot assess the impact of other unmeasured confounding variables. For instance, patients who sought treatment after shutdown may have many biopsychosocial differences from those who sought treatment before shutdown. Our findings may also reflect unknowns about how COVID-19 illness or COVID-19 vaccines may impact brain stimulation itself. Additionally, we did not systematically collect participants' antidepressant treatment history. Finally, our study only included individuals from one hospital site receiving treatment with one type of TMS device. Future work could examine more data from more sites, providing a way to determine if our findings reflect a pre-existing trend, a direct effect of COVID-19, an effect of changes in psychiatric treatment trends, or other factors.

Declaration of competing interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shan H. Siddiqi serves as a scientific consultant for Magnus Medical and a clinical consultant for Kaizen Brain Center and Acacia Mental Health. Shan H. Siddiqi has received research support from Neuronetics Inc and Brainsway Ltd. Shan H. Siddiqi owns shares in Brainsway Ltd (publiclytraded) and Magnus Medical (not publicly traded). Shan H. Siddiqi has served as a speaker on behalf of Otsuka (unbranded educational material) and Brainsway (unbranded scientific material). None of these entities were involved in the present work.