Repetitive transcranial magnetic stimulation for psychiatric symptoms in long-term hospitalized veterans with schizophrenia: A randomized double-blind controlled trial

Xiuru Su, Long Zhao, Yujie Shang, Yingnan Chen, Xiaowen Liu, Xuan Wang, Meihong Xiu, Huijing Yu, Lijun Liu, Xiuru Su, Long Zhao, Yujie Shang, Yingnan Chen, Xiaowen Liu, Xuan Wang, Meihong Xiu, Huijing Yu, Lijun Liu

Abstract

Multiple lines of evidence demonstrate that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve clinical outcomes in patients with schizophrenia (SCZ). However, the efficacy of HF-rTMS on psychiatric symptoms remains unknown in veterans with SCZ. This study aimed to investigate whether HF-rTMS was beneficial in alleviating the clinical symptoms in veterans with SCZ. Forty-seven long-term hospitalized veterans with SCZ were randomly allocated to receive neuronavigated 10 Hz rTMS or sham stimulation over the left dorsolateral prefrontal cortex once daily for four consecutive weeks. Symptoms were assessed by using the Positive and Negative Syndrome Scale at baseline and at the end of week 4. We also collected easily available routine biochemical markers including blood sugar, lipid profiles, hormone, and blood cell counts, considering that these markers may potentially be used to predict the outcomes of rTMS treatment. We found that there was a significant interaction effect of time and group on the positive symptoms. Compared with the sham group, the positive factor score of veterans with SCZ was significantly decreased after treatment in the real rTMS group. Interestingly, the improvement of positive symptoms from baseline to 4-week follow-up was significantly associated with the whole white blood cells (WBC) counts at baseline in the real rTMS group, and baseline WBC counts were predictive of the symptom improvement after rTMS treatment. Our findings indicate that add-on 10 Hz rTMS is beneficial for clinical symptoms in veterans with SCZ. In addition, the baseline WBC counts were predictive of the outcomes after treatment.

Clinical trial registration: clinicaltrials.gov, identifier NCT03774927.

Keywords: clinical outcome; rTMS; randomized controlled trial; schizophrenia; veteran.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Su, Zhao, Shang, Chen, Liu, Wang, Xiu, Yu and Liu.

Figures

FIGURE 1
FIGURE 1
Flowchart.

References

    1. Barnett R. Schizophrenia. Lancet. (2018) 391:648. 10.1016/S0140-6736(18)30237-X
    1. Chwastiak LA, Rosenheck RA, Kazis LE. Association of psychiatric illness and obesity, physical inactivity, and smoking among a national sample of veterans. Psychosomatics. (2011) 52:230–6. 10.1016/j.psym.2010.12.009
    1. Lafeuille MH, Gravel J, Lefebvre P, Fastenau J, Muser E, Doshi D. Patterns of relapse and associated cost burden in schizophrenia patients receiving atypical antipsychotics. J Med Econ. (2013) 16:1290–9. 10.3111/13696998.2013.841705
    1. Thieda P, Beard S, Richter A, Kane J. An economic review of compliance with medication therapy in the treatment of schizophrenia. Psychiatr Serv. (2003) 54:508–16. 10.1176/appi.ps.54.4.508
    1. Pesa JA, Doshi D, Wang L, Yuce H, Baser O. Health care resource utilization and costs of California Medicaid patients with schizophrenia treated with paliperidone palmitate once monthly or atypical oral antipsychotic treatment. Curr Med Res Opin. (2017) 33:723–31. 10.1080/03007995.2016.1278202
    1. Joshi K, Lafeuille MH, Brown B, Wynant W, Emond B, Lefebvre P. Baseline characteristics and treatment patterns of patients with schizophrenia initiated on once-every-three-months paliperidone palmitate in a real-world setting. Curr Med Res Opin. (2017) 33:1763–72. 10.1080/03007995.2017.1359516
    1. Ascher-Svanum H, Furiak NM, Lawson AH, Klein TM, Smolen LJ, Conley RR. Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States. J Med Econ. (2012) 15:531–47. 10.3111/13696998.2012.662923
    1. Biagi E, Capuzzi E, Colmegna F, Mascarini A, Brambilla G, Ornaghi A. Long-acting injectable antipsychotics in schizophrenia: Literature review and practical perspective, with a focus on aripiprazole once-monthly. Adv Ther. (2017) 34:1036–48. 10.1007/s12325-017-0507-x
    1. Emsley R, Chiliza B, Asmal L, Harvey BH. The nature of relapse in schizophrenia. BMC Psychiatry. (2013) 13:50. 10.1186/1471-244X-13-50
    1. Chi MH, Hsiao CY, Chen KC, Lee LT, Tsai HC, Lee I. Hui. The readmission rate and medical cost of patients with schizophrenia after first hospitalization - A 10-year follow-up population-based study. Schizophr Res. (2016) 170:184–90. 10.1016/j.schres.2015.11.025
    1. Han X, Jiang F, Tang Y, Needleman J, Guo M, Chen Y. Factors associated with 30-day and 1-year readmission among psychiatric inpatients in Beijing China: A retrospective, medical record-based analysis. BMC Psychiatry. (2020) 20:113. 10.1186/s12888-020-02515-1
    1. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. (2005) 353:1209–23. 10.1056/NEJMoa051688
    1. George MS. Whither TMS: A one-trick pony or the beginning of a neuroscientific revolution?. Am J Psychiatry. (2019) 176:904–10. 10.1176/appi.ajp.2019.19090957
    1. Cosmo C, Zandvakili A, Petrosino NJ, Berlow YA, Philip NS. Repetitive transcranial magnetic stimulation for treatment-resistant depression: Recent critical advances in patient care. Curr Treat Options Psychiatry. (2021) 8:47–63. 10.1007/s40501-021-00238-y
    1. Chervyakov AV, Chernyavsky AY, Sinitsyn DO, Piradov MA. Possible mechanisms underlying the therapeutic effects of transcranial magnetic stimulation. Front Hum Neurosci. (2015) 9:303. 10.3389/fnhum.2015.00303
    1. Guttesen LL, Albert N, Nordentoft M, Hjorthøj C. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation for auditory hallucinations in schizophrenia: Systematic review and meta-analysis. J Psychiatr Res. (2021) 143:163–75. 10.1016/j.jpsychires.2021.09.001
    1. Li J, Cao X, Liu S, Li X, Xu Y. Efficacy of repetitive transcranial magnetic stimulation on auditory hallucinations in schizophrenia: A meta-analysis. Psychiatry Res. (2020) 290:113141. 10.1016/j.psychres.2020.113141
    1. Mitra S, Mehta UM, Binukumar B, Venkatasubramanian G, Thirthalli J. Statistical power estimation in non-invasive brain stimulation studies and its clinical implications: An exploratory study of the meta-analyses. Asian J Psychiatr. (2019) 44:29–34. 10.1016/j.ajp.2019.07.006
    1. Kennedy NI, Lee WH, Frangou S. Efficacy of non-invasive brain stimulation on the symptom dimensions of schizophrenia: A meta-analysis of randomized controlled trials. Eur Psychiatry. (2018) 49:69–77. 10.1016/j.eurpsy.2017.12.025
    1. Siskind D, Honarparvar F, Hasan A, Wagner E, Sinha S, Orr S. rTMS for clozapine refractory schizophrenia - A systematic review and pairwise meta-analysis. Schizophr Res. (2019) 211:113–4. 10.1016/j.schres.2019.07.004
    1. Agha Z, Lofgren RP, VanRuiswyk JV, Layde PM. Are patients at Veterans Affairs medical centers sicker? A comparative analysis of health status and medical resource use. Arch Intern Med. (2000) 160:3252–7. 10.1001/archinte.160.21.3252
    1. O’Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: A multisite randomized controlled trial. Biol Psychiatry. (2007) 62:1208–16. 10.1016/j.biopsych.2007.01.018
    1. George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: A sham-controlled randomized trial. Arch Gen Psychiatry. (2010) 67:507–16. 10.1001/archgenpsychiatry.2010.46
    1. Yesavage JA, Fairchild JK, Mi Z, Biswas K, Davis-Karim A, Phibbs CS. Effect of repetitive transcranial magnetic stimulation on treatment-resistant major depression in US veterans: A randomized clinical trial. JAMA Psychiatry. (2018) 75:884–93. 10.1001/jamapsychiatry.2018.1483
    1. Madore MR, Kozel FA, Williams LM, Green LC, George MS, Holtzheimer PE. Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. J Affect Disord. (2022) 297:671–8. 10.1016/j.jad.2021.10.025
    1. Davis C. A commentary on the associations among ‘food addiction’, binge eating disorder, and obesity: Overlapping conditions with idiosyncratic clinical features. Appetite. (2017) 115:3–8. 10.1016/j.appet.2016.11.001
    1. Stice E, Yokum S. Gain in body fat is associated with increased striatal response to palatable food cues, whereas body fat stability is associated with decreased striatal response. J Neurosci. (2016) 36:6949–56. 10.1523/JNEUROSCI.4365-15.2016
    1. Harrison BJ, Yücel M, Shaw M, Brewer WJ, Nathan PJ, Strother SC. Dysfunction of dorsolateral prefrontal cortex in antipsychotic-naïve schizophreniform psychosis. Psychiatry Res. (2006) 148:23–31. 10.1016/j.pscychresns.2006.02.006
    1. Woo TU, Whitehead RE, Melchitzky DS, Lewis DA. A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci USA. (1998) 95:5341–6. 10.1073/pnas.95.9.5341
    1. Akil M, Pierri JN, Whitehead RE, Edgar CL, Mohila C, Sampson AR. Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am J Psychiatry. (1999) 156:1580–9. 10.1176/ajp.156.10.1580
    1. Glantz LA, Lewis DA. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry. (2000) 57:65–73. 10.1001/archpsyc.57.1.65
    1. McCarley RW, Wible CG, Frumin M, Hirayasu Y, Levitt JJ, Fischer IA. MRI anatomy of schizophrenia. Biol Psychiatry. (1999) 45:1099–119. 10.1016/S0006-3223(99)00018-9
    1. Selemon LD. Regionally diverse cortical pathology in schizophrenia: Clues to the etiology of the disease. Schizophr Bull. (2001) 27:349–77. 10.1093/oxfordjournals.schbul.a006881
    1. Brandt SJ, Oral HY, Arellano-Bravo C, Plawecki MH, Hummer TA, Francis MM. Repetitive transcranial magnetic stimulation as a therapeutic and probe in schizophrenia: Examining the role of neuroimaging and future directions. Neurotherapeutics. (2021) 18:827–44. 10.1007/s13311-021-01046-1
    1. De Risio L, Borgi M, Pettorruso M, Miuli A, Ottomana AM, Sociali A. Recovering from depression with repetitive transcranial magnetic stimulation (rTMS): A systematic review and meta-analysis of preclinical studies. Transl Psychiatry. (2020) 10:393. 10.1038/s41398-020-01055-2
    1. Guan HY, Zhao JM, Wang KQ, Su XR, Pan YF, Guo JM. High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: A pilot double-blind, randomized controlled study in Veterans with schizophrenia. Transl Psychiatry. (2020) 10:79. 10.1038/s41398-020-0745-6
    1. Dougall N, Maayan N, Soares-Weiser K, McDermott LM, McIntosh A. Transcranial magnetic stimulation (TMS) for schizophrenia. Cochrane Database Syst Rev. (2015) 8:Cd006081. 10.1002/14651858.CD006081.pub2
    1. Homan S, Muscat W, Joanlanne A, Marousis N, Cecere G, Hofmann L. Treatment effect variability in brain stimulation across psychiatric disorders: A meta-analysis of variance. Neurosci Biobehav Rev. (2021) 124:54–62. 10.1016/j.neubiorev.2020.11.033
    1. Slotema CW, Aleman A, Daskalakis ZJ, Sommer IE. Meta-analysis of repetitive transcranial magnetic stimulation in the treatment of auditory verbal hallucinations: Update and effects after one month. Schizophr Res. (2012) 142:40–5. 10.1016/j.schres.2012.08.025
    1. Xiu MH, Guan HY, Zhao JM, Wang KQ, Pan YF, Su XR, et al. Cognitive enhancing effect of high-frequency neuronavigated rTMS in chronic schizophrenia patients with predominant negative symptoms: A double-blind controlled 32-week follow-up study. Schizophr Bull. (2020) 46:1219–30. 10.1093/schbul/sbaa035
    1. Wallwork RS, Fortgang R, Hashimoto R, Weinberger DR, Dickinson D. Searching for a consensus five-factor model of the positive and negative syndrome scale for schizophrenia. Schizophr Res. (2012) 137:246–50. 10.1016/j.schres.2012.01.031
    1. Smucny J, Dienel SJ, Lewis DA, Carter CS. Mechanisms underlying dorsolateral prefrontal cortex contributions to cognitive dysfunction in schizophrenia. Neuropsychopharmacology. (2021) 47:292–308. 10.1038/s41386-021-01089-0
    1. Stanford AD, Sharif Z, Corcoran C, Urban N, Malaspina D, Lisanby SH. rTMS strategies for the study and treatment of schizophrenia: A review. Int J Neuropsychopharmacol. (2008) 11:563–76. 10.1017/S1461145707008309
    1. Rollnik JD, Seifert J, Huber TJ, Becker H, Panning B, Schneider U. Repetitive transcranial magnetic stimulation and electroconvulsive therapy in a patient with treatment-resistant schizoaffective disorder. Depress Anxiety. (2001) 13:103–4. 10.1002/da.1024
    1. Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nat Neurosci. (2015) 18:199–209. 10.1038/nn.3922
    1. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. (2014) 511:421–7. 10.1038/nature13595
    1. Miller BJ, Gassama B, Sebastian D, Buckley P, Mellor A. Meta-analysis of lymphocytes in schizophrenia: Clinical status and antipsychotic effects. Biol Psychiatry. (2013) 73:993–9. 10.1016/j.biopsych.2012.09.007
    1. Wei L, Du Y, Wu W, Fu X, Xia Q. Elevation of plasma neutrophil gelatinase-associated lipocalin (NGAL) levels in schizophrenia patients. J Affect Disord. (2018) 226:307–12. 10.1016/j.jad.2017.10.002
    1. Penner J, Osuch EA, Schaefer B, Théberge J, Neufeld RWJ, Menon RS. Temporoparietal junction functional connectivity in early schizophrenia and major depressive disorder. Chronic Stress. (2018) 2:2470547018815232. 10.1177/2470547018815232
    1. Valiengo L, Goerigk S, Gordon PC, Padberg F, Serpa MH, Koebe S. Efficacy and safety of transcranial direct current stimulation for treating negative symptoms in schizophrenia: A randomized clinical trial. JAMA Psychiatry. (2020) 77:121–9. 10.1001/jamapsychiatry.2019.3199

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe