The efficacy of transcranial alternating current stimulation for treating post-stroke depression: Study Protocol Clinical Trial (SPIRIT Compliant)

Hongxing Wang, Wenrui Zhang, Wenfeng Zhao, Kun Wang, Zu Wang, Li Wang, Mao Peng, Qing Xue, Haixia Leng, Weijun Ding, Yuan Liu, Ning Li, Kai Dong, Qian Zhang, Xiaoqin Huang, Yunyan Xie, Changbiao Chu, Sufang Xue, Liyuan Huang, Hui Yao, Jianping Ding, Shuqin Zhan, Baoquan Min, Chunqiu Fan, Aihong Zhou, Zhichao Sun, Lu Yin, Qingfeng Ma, Andrius Baskys, Ricardo E Jorge, Haiqing Song, Hongxing Wang, Wenrui Zhang, Wenfeng Zhao, Kun Wang, Zu Wang, Li Wang, Mao Peng, Qing Xue, Haixia Leng, Weijun Ding, Yuan Liu, Ning Li, Kai Dong, Qian Zhang, Xiaoqin Huang, Yunyan Xie, Changbiao Chu, Sufang Xue, Liyuan Huang, Hui Yao, Jianping Ding, Shuqin Zhan, Baoquan Min, Chunqiu Fan, Aihong Zhou, Zhichao Sun, Lu Yin, Qingfeng Ma, Andrius Baskys, Ricardo E Jorge, Haiqing Song

Abstract

Background: The treatment of post-stroke depression (PSD) with anti-depressant drugs is partly practical. Transcranial alternating current stimulation (tACS) offers the potential for a novel treatment modality for adult patients with PSD. In this study, we will assess the efficacy and safety of tACS for treating PSD and explore its effect on gamma and beta-oscillations involving in emotional regulation.

Methods: The prospective study is an 8-week, double-blind, randomized, placebo-controlled trial. Seventy eligible participants with mild to moderate PSD aged between 18 years and 70 years will be recruited and randomly assigned to either active tACS intervention group or sham group. Daily 40-minute, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), and an additional 4-week observational period (week 8) will be followed up. The primary outcome is the proportion of participants having an improvement at week 8 according to the Hamilton Depression Rating Scale 17-Item (HAMD-17) score, including the proportion of participants having a decrease of ≥ 50% in HAMD-17 score or clinical recovery (HAMD-17 score ≤ 7). Secondary outcomes include neurological function, independence level, activities of daily living, disease severity, anxiety, and cognitive function. The exploratory outcomes are gamma and beta-oscillations assessed at baseline, week 4, and week 8. Data will be analyzed by logistical regression analyses and mixed-effects models.

Discussion: The study will be the first randomized controlled trial to evaluate the efficacy and safety of tACS at a 77.5-Hz frequency and 15-mA current in reducing depressive severity in patients with PSD. The results of the study will present a base for future studies on the tACS in PSD and its possible mechanism.

Trial registration number: NCT03903068, pre-results.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flowchart of the study design.

References

    1. Wang H, Zhang W, Yang X, et al. Deeply understanding clinic status of post-stoke depression: a clinic syndrome following brain injury. Zhonghua Yi Xue Za Zhi 2019;99:1611–4.
    1. Towfighi A, Ovbiagele B, El Husseini N, et al. Poststroke depression: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2017;48:e30–43.
    1. Villa RF, Ferrari F, Moretti A. Post-stroke depression: mechanisms and pharmacological treatment. Pharmacol Ther 2018;184:131–44.
    1. Robinson RG, Jorge RE, Long J. Prevention of poststroke mortality using problem-solving therapy or escitalopram. Am J Geriatr Psychiatry 2017;25:512–9.
    1. Robinson RG, Jorge RE. Post-stroke depression: a review. Am J Psychiatry 2016;173:221–31.
    1. Robinson RG, Jorge RE, Clarence-Smith K, et al. Double-blind treatment of apathy in patients with poststroke depression using nefiracetam. J Neuropsychiatry Clin Neurosci 2009;21:144–51.
    1. Mikami K, Jorge RE, Moser DJ, et al. Prevention of post-stroke generalized anxiety disorder, using escitalopram or problem-solving therapy. J Neuropsychiatry Clin Neurosci 2014;26:323–8.
    1. Hackett ML, Kohler S, O’Brien JT, et al. Neuropsychiatric outcomes of stroke. Lancet Neurol 2014;13:525–34.
    1. Ayerbe L, Ayis S, Wolfe CD, et al. Natural history, predictors and outcomes of depression after stroke: systematic review and meta-analysis. Br J Psychiatry 2013;202:14–21.
    1. Bartoli F, Lillia N, Lax A, et al. Depression after stroke and risk of mortality: a systematic review and meta-analysis. Stroke Res Treat 2013;2013:862978.
    1. Robinson RG, Jorge RE, Moser DJ, et al. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA 2008;299:2391–400.
    1. Jorge RE, Robinson RG, Tateno A, et al. Repetitive transcranial magnetic stimulation as treatment of poststroke depression: a preliminary study. Biol Psychiatry 2004;55:398–405.
    1. Deng L, Sun X, Qiu S, et al. Interventions for management of post-stroke depression: A Bayesian network meta-analysis of 23 randomized controlled trials. Sci Rep 2017;7:16466.
    1. Hackett ML, Anderson CS, House A, et al. Interventions for treating depression after stroke. Cochrane Database Syst Rev 2008. Cd003437.
    1. Jorge RE, Moser DJ, Acion L, et al. Treatment of vascular depression using repetitive transcranial magnetic stimulation. Arch Gen Psychiatry 2008;65:268–76.
    1. Jorge RE, Acion L, Moser D, et al. Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry 2010;67:187–96.
    1. Mikami K, Jorge RE, Moser DJ, et al. Prevention of poststroke apathy using escitalopram or problem-solving therapy. Am J Geriatr Psychiatry 2013;21:855–62.
    1. Coupland C, Dhiman P, Morriss R, et al. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ 2011;343:d4551.
    1. Paolucci S. Advances in antidepressants for treating post-stroke depression. Expert Opin Pharmacother 2017;18:1011–7.
    1. Connolly KR, Helmer A, Cristancho MA, et al. Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. J Clin Psychiatry 2012;73:e567–73.
    1. Brunoni AR, Moffa AH, Sampaio-Junior B, et al. Trial of electrical direct-current therapy versus escitalopram for depression. N Engl J Med 2017;376:2523–33.
    1. Brunoni AR, Chaimani A, Moffa AH, et al. Repetitive transcranial magnetic stimulation for the acute treatment of major depressive episodes: a systematic review with network meta-analysis. JAMA Psychiatry 2017;74:143–52.
    1. Rosa MA, Lisanby SH. Somatic treatments for mood disorders. Neuropsychopharmacology 2012;37:102–16.
    1. Bikson M, Grossman P, Thomas C, et al. Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul 2016;9:641–61.
    1. Fertonani A, Ferrari C, Miniussi C. What do you feel if I apply transcranial electric stimulation? Safety, sensations and secondary induced effects. Clin Neurophysiol 2015;126:2181–8.
    1. Lafon B, Henin S, Huang Y, et al. Low frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings. Nat Commun 2017;8:1199.
    1. Merton PA, Morton HB. Stimulation of the cerebral cortex in the intact human subject. Nature 1980;285:227.
    1. Machado D, Unal G, Andrade SM, et al. Effect of transcranial direct current stimulation on exercise performance: A systematic review and meta-analysis. Brain Stimul 2019;12:593–605.
    1. Wang HX, Wang L, Zhang WR, et al. Effect of transcranial alternating current stimulation for the treatment of chronic insomnia: a randomized, double-blind, parallel-group, placebo-controlled clinical trial. Psychother Psychosom 2020;89:38–47.
    1. Antal A, Alekseichuk I, Bikson M, et al. Low intensity transcranial electric stimulation: safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol 2017;128:1774–809.
    1. Philip NS, Nelson BG, Frohlich F, et al. Low-intensity transcranial current stimulation in psychiatry. Am J Psychiatry 2017;174:628–39.
    1. Frase L, Selhausen P, Krone L, et al. Differential effects of bifrontal tDCS on arousal and sleep duration in insomnia patients and healthy controls. Brain Stimul 2019;12:674–83.
    1. Shekelle PG, Cook IA, Miake-Lye IM, et al. Benefits and harms of cranial electrical stimulation for chronic painful conditions, depression, anxiety, and insomnia: a systematic review. Ann Intern Med 2018;168:414–21.
    1. Alekseichuk I, Falchier AY, Linn G, et al. Electric field dynamics in the brain during multi-electrode transcranial electric stimulation. Nat Commun 2019;10:2573.
    1. Lang S, Gan LS, Alrazi T, et al. Theta band high definition transcranial alternating current stimulation, but not transcranial direct current stimulation, improves associative memory performance. Sci Rep 2019;9:8562.
    1. Miyaguchi S, Otsuru N, Kojima S, et al. Transcranial alternating current stimulation with gamma oscillations over the primary motor cortex and cerebellar hemisphere improved visuomotor performance. Front Behav Neurosci 2018;12:132.
    1. Alexander ML, Alagapan S, Lugo CE, et al. Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD). Transl Psychiatry 2019;9:106.
    1. Wang HX, Wang K, Sun ZC, et al. A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder. Zhonghua Yi Xue Za Zhi 2020;100:197–201.
    1. Association AP. Diagnostic and Statistical Manual of Mental Disorders. Fifth edition ed: Arlington. VA: American Psychiatric Publishing;; 2013.
    1. Wang HX, Wang K, Zhang WR, et al. Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial. Chin Med J 2020;133:61–7.
    1. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62.
    1. Brott T, Adams HP, Jr, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20:864–70.
    1. Broderick JP, Adeoye O, Elm J. Evolution of the Modified Rankin Scale and its use in future stroke trials. Stroke 2017;48:2007–12.
    1. van Meijeren-Pont W, Volker G, Vliet Vlieland T, et al. Comparison of the responsiveness of the Utrecht Scale for Evaluation of Rehabilitation (USER) and the Barthel Index in stroke patients. Clin Rehabil 2019;33:1672–81.
    1. McCall WV, Benca RM, Rosenquist PB, et al. Reducing suicidal ideation through insomnia treatment (REST-IT): a randomized clinical trial. Am J Psychiatry 2019;176:957–65.
    1. Shear MK, Vander Bilt J, Rucci P, et al. Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A). Depress Anxiety 2001;13:166–78.
    1. Rosa IM, Henriques AG, Wiltfang J, et al. Putative dementia cases fluctuate as a function of Mini-Mental State Examination cut-off points. J Alzheimers Dis 2018;61:157–67.
    1. Dawes P, Pye A, Reeves D, et al. Protocol for the development of versions of the Montreal Cognitive Assessment (MoCA) for people with hearing or vision impairment. BMJ Open 2019;9:e026246.
    1. Janik AB, Rezlescu C, Banissy MJ. Enhancing anger perception with transcranial alternating current stimulation induced gamma oscillations. Brain Stimul 2015;8:1138–43.
    1. Hsu WY, Zanto TP, Gazzaley A. Parametric effects of transcranial alternating current stimulation on multitasking performance. Brain Stimul 2019;12:73–83.
    1. Zhang B, Tan Y, Zhang W, et al. Repeatable battery for the assessment of neuropsyehological status as a screening test in Chinese: reliability and validity. Chin Ment Health J 2008;12:865–9.
    1. Devinsky O, Gazzola D, LaFrance WC., Jr Differentiating between nonepileptic and epileptic seizures. Nat Rev Neurol 2011;7:210–20.
    1. Chow S-C, Shao J, Wang H. Sample size calculations in clinical research. 2nd edition2008.
    1. Jorge RE, Acion L, Burin DI, et al. Sertraline for preventing mood disorders following traumatic brain injury: a randomized clinical trial. JAMA Psychiatry 2016;73:1041–7.
    1. Schmidt S, Mante A, Ronnefarth M, et al. Progressive enhancement of alpha activity and visual function in patients with optic neuropathy: a two-week repeated session alternating current stimulation study. Brain Stimul 2013;6:87–93.
    1. Vossen A, Gross J, Thut G. Alpha power increase after transcranial alternating current stimulation at alpha frequency (alpha-tACS) reflects plastic changes rather than entrainment. Brain Stimul 2015;8:499–508.
    1. D’Atri A, De Simoni E, Gorgoni M, et al. Electrical stimulation of the frontal cortex enhances slow-frequency EEG activity and sleepiness. Neuroscience 2016;324:119–30.
    1. Kasten FH, Maess B, Herrmann CS. Facilitated event-related power modulations during transcranial alternating current stimulation (tACS) revealed by concurrent tACS-MEG. eNeuro 2018;5: pii: ENEURO. 0069-18. 2018.
    1. Robinson CSH, Bryant NB, Maxwell JW, et al. The benefits of closed-Loop transcranial alternating current stimulation on subjective sleep quality. Brain Sci 2018;8:pii: E204.
    1. Marshall L, Helgadottir H, Molle M, et al. Boosting slow oscillations during sleep potentiates memory. Nature 2006;444:610–3.
    1. Antonenko D, Diekelmann S, Olsen C, et al. Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations. Eur J Neurosci 2013;37:1142–51.
    1. Frankel BL. Research on cerebral electrotherapy (electrosleep): some suggestions. Am J Psychiatry 1974;131:95–8.
    1. Tavakoli AV, Yun K. Transcranial alternating current stimulation (tACS) mechanisms and protocols. Front Cell Neurosci 2017;11:214.
    1. Fertonani A, Miniussi C. Transcranial electrical stimulation: what we know and do not know about mechanisms. Neuroscientist 2017;23:109–23.
    1. Kirsch DL, Nichols F. Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. Psychiatr Clin North Am 2013;36:169–76.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera