Efficacy of repetitive transcranial magnetic stimulation combined with horticultural therapy for post-stroke depression: A randomized controlled trial

Abstract

Post-stroke depression (PSD) affects approximately one-third of stroke survivors, and current treatments often present limitations. Non-invasive therapies such as repetitive transcranial magnetic stimulation (rTMS) and horticultural therapy (HT) are gaining interest as alternative approaches. This study aimed to evaluate the clinical efficacy of rTMS combined with HT in treating PSD. Eighty PSD patients (aged 30 - 75 years old; 1 month - 2 years post-stroke), diagnosed according to the Chinese Expert Consensus on Clinical Practice of Post-Stroke Depression, were randomly assigned to one of four treatment groups: Group A (antidepressant alone—escitalopram, 10 mg/day), Group B (antidepressant + rTMS), Group C (antidepressant + HT), and Group D (antidepressant + rTMS + HT). rTMS was administered to the left dorsolateral prefrontal cortex (10 Hz, 110% motor threshold, 15 min/session, 5 days/week), while HT consisted of 45-min gardening activities (e.g., planting, pruning, watering) conducted 5 days/week. Patients were evaluated using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Stroke-Specific Quality of Life Scale (SS-QOL) before and after the 28-day intervention. Seventy-seven patients completed the trial, with three dropouts. All groups showed significant reductions in HAMD and HAMA scores post-treatment compared to baseline (p<0.01). Group D demonstrated a statistically significant improvement in SS-QOL scores (p<0.01), while other groups did not (p>0.01). No significant difference in HAMD scores was found between Groups B and C (p=0.399). These results suggest that combining rTMS and HT provides greater benefits in managing PSD compared to either intervention alone. No serious complications were reported. This study supports the integration of rTMS and HT as an effective adjunct to standard antidepressant therapy for PSD.

Keywords

Horticultural therapy / Repetitive transcranial magnetic stimulation / Depression / Stroke / Stroke rehabilitation

Funding

This study was funded by the Guangxi Medical and Health Appropriate Technology Development, Promotion, and Application Project (grant number: S2022059).

Conflict of interest

The authors declare no conflicts of interest.

References

[1] Jufang L, Yun L, Weiwei D, et al. Current status of research on symptom clusters in depressed patients after stroke. Nurs Res. 2019; 17:2977-2978.

[2] Zhou H, Wei YJ, Xie GY. Research progress on post-stroke depression. Exp Neurol. 2024; 373:114660. doi: 10.1016/j.expneurol.2023.114660

[3] Zeng Y, Cheng H, Cheng L, et al. Comparison of poststroke depression between acute ischemic and hemorrhagic stroke patients. Int J Geriatr Psychiatry. 2020; 36(4):493-499. doi: 10.1002/gps.5444

[4] Liu L, Xu M, Marshall IJ, Wolfe CD, Wang Y, O’Connell MD. Prevalence and natural history of depression after stroke: A systematic review and meta-analysis of observational studies. PLoS Med. 2023; 20(3):e1004200. doi: 10.1371/journal.pmed.1004200

[5] Wang ZJ, Gu SN, Liu YJ, Zhou FP, Huang SE. Study on the combination of serum miR-191-5p and miR-20a-5p as a diagnostic marker of post-stroke cog-nitive impairment. J Pract Med. 2020; 36(5):593-596, 601. doi: 10.3969/j.issn.1006-5725.2020.05.0010

[6] Liu F, Ren RF, Zhang ZH, Song JG. Research progress of repetitive transcranial magnetic stimulation for post-stroke depression. J Hebei Med Univ. 2021; 42(9):1099-1103. doi: 10.3969/j.issn.1007-3205.2021.09.022

[7] Grace AA. Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nat Rev Neurosci. 2016; 17(8):524-532. doi: 10.1038/nrn.2016.57

[8] Li HN, Chen YD, Huang M, et al. Effects of repetitive transcranial magnetic stimulation on cognitive function, central motor conduction time and balance in patients with poststroke cognitive dysfunction. China Rehabil. 2023; 38(3):140-143.

[9] Cao J, Lv YH, Gou MN, Liang WJ. Effects of horticultural therapy combined with limb functional exercise on negative emotions and limb motor function in hemiplegic patients with stroke. Clin Med Res Pract. 2021; 6(31):159-161. doi: 10.19347/j.cnki.2096-1413.202131050

[10] Yuan Y, Yang FX, Zeng WS, et al. Effect of repeated transcranial magnetic stimulation on cerebral hemodynamics and activation of primary motor areas in mild to moderate postpartum depression. Chin J Mod Med. 2023; 33(22):12-18.

[11] Lee HN, Chen YD, Huang M, et al. Effect of repeated TMS on cognitive function, central motor conduction time and balance ability in patients with cognitive dysfunction after stroke. Chinas Rehabil. 2023; 38(3):140-143. doi: 10.3870/zgkf.2023.03.003

[12] Zhang YW, Wang J, Fang TH. The effect of horticultural therapy on depressive symptoms among the elderly: A systematic review and meta-analysis. Front Public Health. 2022; 10:953363. doi: 10.3389/fpubh.2022.953363

[13] Wang SS, Zhou XY, Zhu CY. Chinese expert consensus on clinical practice of post-stroke depression. Chin Stroke J. 2016; 11(8):685-693. doi: 10.3969/j.issn.1673-5765.2016.08.015

[14] Sharp R. The hamilton rating scale for depression. Occup Med (Lond). 2015; 65(4):340. doi: 10.1093/occmed/kqv043

[15] Schneider H, Esbit S, Gonzalez JS, et al. Hamilton anxiety rating scale. In: Gellman MD, editor. Encyclopedia of Behavioral Medicine. Cham: Springer; 2020. doi: 10.1007/978-3-030-39903-0_197

[16] Williams LS, Weinberger M, Harris LE, Clark DO, Biller J. Development of a stroke-specific quality of life scale. Stroke. 1999; 30(7):1362-1369. doi: 10.1161/01.str.30.7.1362

[17] Simning A, Bermann G, Elashoff J, Li M. Sample size calculation for clinical trials: A unified approach. Stat Med. 2015; 34(14):2167-2186.

[18] Cardenas VA, Bhat JV, Horwege AM, et al. Anatomical and fMRI-network comparison of multiple DLPFC targeting strategies for repetitive transcranial magnetic stimulation treatment of depression. Brain Stimul. 2022; 15(1):63-72. doi: 10.1016/j.brs.2021.11.008

[19] Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev. 2012; 64(2):238-258. doi: 10.1124/pr.111.005108

[20] Chang WH, Shin MA, Lee A, Kim H, Kim YH. Relationship between serum BDNF levels and depressive mood in subacute stroke patients: A preliminary study. Int J Mol Sci. 2018; 19(10):3131. doi: 10.3390/ijms19103131

[21] Li Y, Peng C, Guo X, You JJ, Yadav HP. Expression of brain-derived neurotrophic factor and tyrosine kinase B in cerebellum of poststroke depression rat model. Chin Med J (Engl). 2015; 128(21):2926-2931. doi: 10.4103/0366-6999.168058

[22] Na KS, Won E, Kang J, et al. Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder. Sci Rep. 2016; 6:21089. doi: 10.1038/srep21089

[23] Phillips C. Brain-derived neurotrophic factor, depression, and physical activity: Making the neuroplastic connection. Neural Plast. 2017; 2017:7260130. doi: 10.1155/2017/7260130

[24] Yang XR, Kirton A, Wilkes TC, et al. Glutamate alterations associated with transcranial magnetic stimulation in youth depression: A case series. J ECT. 2014; 30(3):242-247. doi: 10.1097/YCT.0000000000000094

[25] Strafella AP, Paus T, Fraraccio M, Dagher A. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain. 2003; 126(Pt 12):2609-2615. doi: 10.1093/brain/awg268

[26] Cho SS, Strafella AP. rTMS of the left dorsolateral prefrontal cortex modulates dopamine release in the ipsilateral anterior cingulate cortex and orbitofrontal cortex. PLoS One. 2009; 4(8):e6725. doi: 10.1371/journal.pone.0006725

[27] Etiévant A, Manta S, Latapy C, et al. Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation. Sci Rep. 2015; 5:16873. doi: 10.1038/srep16873

[28] Chervyakov AV, Chernyavsky AY, Sinitsyn DO, Piradov MA. Possible mechanisms underlying the therapeutic effects of transcranial magnetic stimulation. Front Hum Neurosci. 2015; 9:303. doi: 10.3389/fnhum.2015.00303

[29] Herremans SC, Van Schuerbeek P, De Raedt R, et al. The impact of accelerated right prefrontal high-frequency repetitive transcranial magnetic stimulation (rTMS) on cue-reactivity: An fMRI study on craving in recently detoxified alcohol-dependent patients. PLoS One. 2015; 10(8):e0136182. doi: 10.1371/journal.pone.0136182

[30] Holtzheimer PE 3^rd, McDonald WM, Mufti M, et al. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010; 27(10):960-963. doi: 10.1002/da.20731

[31] McGirr A, Van den Eynde F, Tovar-Perdomo S, Fleck MP, Berlim MT. Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: An open label trial. J Affect Disord. 2015; 173:216-220. doi: 10.1016/j.jad.2014.10.068

[32] Baeken C, Vanderhasselt MA, Remue J, et al. Intensive HF-rTMS treatment in refractory medication-resistant unipolar depressed patients. J Affect Disord. 2013; 151(2):625-631. doi: 10.1016/j.jad.2013.07.008

[33] Divarco R, Ramasawmy P, Petzke F, Antal A. Stimulated brains and meditative minds: A systematic review on combining low intensity transcranial electrical stimulation and meditation in humans. Int J Clin Health Psychol. 2023; 23(3):100369. doi: 10.1016/j.ijchp.2023.100369

[34] Guo Z, Jin Y, Peng H, et al. Ipsilesional high frequency repetitive transcranial magnetic stimulation add-on therapy improved diffusion parameters of stroke patients with motor dysfunction: A preliminary DTI study. Neural Plast. 2016; 2016:6238575. doi: 10.1155/2016/6238575

[35] Guan YZ, Li J, Zhang XW, et al. Effectiveness of repetitive transcranial magnetic stimulation (rTMS) after acute stroke: A one-year longitudinal randomized trial. CNS Neurosci Ther. 2017; 23(12):940-946. doi: 10.1111/cns.12762

[36] Conforto AB, Anjos SM, Saposnik G, et al. Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: A proof of principle and novel approach to improve motor function. J Neurol. 2012; 259(7):1399-1405. doi: 10.1007/s00415-011-6364-7

[37] Rossini D, Magri L, Lucca A, Giordani S, Smeraldi E, Zanardi R. Does rTMS hasten the response to escitalopram, sertraline, or venlafaxine in patients with major depressive disorder? A double-blind, randomized, sham-controlled trial. J Clin Psychiatry. 2005; 66(12):1569-1575. doi: 10.4088/jcp.v66n1212

[38] Taylor R, Galvez V, Loo C. Transcranial magnetic stimulation (TMS) safety considerations and recommendations. In: Transcranial Magnetic Stimulation. Vol. 89. New York: Humana Press; 2014. p. 15-30. doi: 10.1007/978-1-4939-0879-0_2

[39] O’Reardon JP, Solvason HB, Janicak PG, et al. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biol Psychiatry. 2007; 62(11):1208-1216. doi: 10.1016/j.biopsych.2007.01.018

[40] Berlim MT, van den Eynde F, Tovar-Perdomo S, Daskalakis ZJ. Response, remission and drop-out rates following high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) for treating major depression: A systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. Psychol Med. 2014; 44(2):225-239. doi: 10.1017/S0033291713000512

[41] Fitzgerald PB, Benitez J, de Castella A, Daskalakis ZJ, Brown TL, Kulkarni J. A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic stimulation for treatment-resistant depression. Am J Psychiatry. 2006; 163(1):88-94. doi: 10.1176/appi.ajp.163.1.88

[42] Li T, Zeng X, Lin L, Xian T, Chen Z. Effects of repetitive transcranial magnetic stimulation with different frequencies on post-stroke aphasia: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 2020; 99(24):e20439. doi: 10.1097/MD.0000000000020439

[43] Duan X, Yao G, Liu Z, Cui R, Yang W. Mechanisms of transcranial magnetic stimulation treating on post-stroke depression. Front Hum Neurosci. 2018; 12:215. doi: 10.3389/fnhum.2018.00215

[44] Currier MB, Murray GB, Welch CC. Electroconvulsive therapy for post-stroke depressed geriatric patients. J Neuropsychiatry Clin Neurosci. 1992; 4(2):140-144. doi: 10.1176/jnp.4.2.140

[45] Paus T, Castro-Alamancos MA, Petrides M. Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation. Eur J Neurosci. 2001; 14(8):1405-1411. doi: 10.1046/j.0953-816x.2001.01757.x

[46] Espárrago Llorca G, Castilla-Guerra L, Fernández Moreno MC, Ruiz Doblado S, Jiménez Hernández MD. Post-stroke depression: An update. Neurologia. 2015; 30(1):23-31. doi: 10.1016/j.nrl.2012.06.008

[47] Shen XY, Liu MY, Cheng Y, et al. Repetitive transcranial magnetic stimulation for the treatment of post-stroke depression: A systematic review and meta-analysis of randomized controlled clinical trials. J Affect Disord. 2017; 211:65-74. doi: 10.1016/j.jad.2016.12.058