Feasibility of performing a multi-arm clinical trial examining the novel combination of repetitive transcranial magnetic stimulation and aerobic exercise for post-stroke depression

ABSTRACT

Background

Post-stroke depression (PSD) occurs in approximately one-third of chronic stroke survivors. Although pharmacotherapy reduces depressive symptoms, side effects are common and stroke survivors have increased likelihood of multimorbidity and subsequent polypharmacy. Thus, alternative non-pharmacological treatments are needed. Combining two non-pharmacological anti-depressant treatments, aerobic exercise (AEx) and repetitive transcranial magnetic stimulation (rTMS), has been demonstrated to be feasible and well-tolerated in chronic stroke survivors.

Objectives

The purpose of this trial was to determine the feasibility of conducting a multi-arm combinatorial trial of rTMS and AEx and to provide an estimate of effect size of rTMS+AEx on PSD symptoms.

Methods

Twenty-four participants were allocated to one of four treatment arms AEx, rTMS, rTMS+AEx, or non-depressed Control receiving AEx. All participants received a total of 24 treatment sessions. Participant adherence was the primary outcome measure for feasibility and within group effect sizes in Patient Health Questionnaire-9 (PHQ-9) score was the primary outcome for preliminary efficacy.

Results

Mean adherence rates to the exercise intervention for AEx, rTMS+AEx, and Control subjects were 83%, 98%, and 95%, respectively. Mean adherence rates for rTMS and rTMS+AEx subjects were 97% and 99%, respectively. The rTMS and rTMS+AEx treatment groups demonstrated clinically significant reductions of 10.5 and 6.2 points in PHQ-9 scores, respectively.

Conclusion

Performing a multi-arm combinatorial trial examining the effect of rTMS+AEx on PSD appears feasible. All treatment arms demonstrated strong adherence to their respective interventions and were well received. rTMS and the combination of AEx with rTMS may be alternative treatments for PSD.

KEYWORDS:

• Stroke
• depression
• post-stroke depression: repetitive transcranial magnetic stimulation (rTMS)
• aerobic exercise
• rehabilitation

Disclosure statement

No potential conflicts of interest were reported by the authors. Neuronetics Inc. donated SenStars (inserts needed between the TMS coil and the subject’s head for the device to work) for the rTMS treatments. However, Neuronetics Inc. had no role in the study design, study implementation, data analysis, or interpretation of results.

Disclaimer

The views expressed by the authors do not represent the views of the U.S. Department of Veterans Affairs, U.S. National Institutes of Health, or the United States Government.

Additional information

Funding

This work was supported by an Institutional Development Award from the National Institute of General Medical Science of the National Institute of Health [grant number P20-GM109040 (CMG)], Promotion of Doctoral Studies (PODS I) Scholarship from the Foundation for Physical Therapy (CJV), and a grant from the United States Department of Veterans Affairs ([RER] grant number RR&D IK1 RX002962).