Cordeiro, Quirino

Osoegawa, Caio

Trevizol, Alisson Paulino

English

Cadernos Espinosanos (E-Journal)

Rev Med (São Paulo). 2018 Nov-Dec;97(6):607-8.607doi: http://dx.doi.org/10.11606/issn.1679-9836.v97i6p607-608Letter to the editorNon-invasive brain stimulation for the treatment of the negative symptoms in Schizophrenia: results from an updated systematic review and a meta-analysis Caio Osoegawa1, Quirino Cordeiro1,2, Alisson Paulino Trevizol3Declaration of interest: We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agreed with its submission to Revista de Medicina. We here declare no conflict of interest related to the present manuscript.Panels Awards - Clinical, presented in the XXXVII COMU - Congresso Médico Universitário da Faculdade de Medicina da Universidade de São Paulo - FMUSP, September, 2018.  1. Santa Casa School of Medical Sciences, São Paulo, Brazil. ORCID: https://orcid.org/0000-0002-3117-6223.2. Federal University of São Paulo, São Paulo, Brazil. ORCID: https://orcid.org/0000-0002-4100-8207. Email: qcordeiro@yahoo.com.3. University of Toronto, Canada. ORCID: https://orcid.org/0000-0002-6065-9355. Email: allison.trevizol@hotmail.com.Corresponding author: Caio Vinicius Osoegawa; Santa Casa School of Medical Sciences, São Paulo, Brazil. Rua Doutor Cesário Motta Junior, 112 – Vila Buarque, São Paulo, SP, Brazil. CEP: 01221-020. E-mail: osoegawa.caio@gmail.com.Dears Editors,Negative symptoms in Schizophrenia consist of affective flattening, anhedonia, alogia, asociality, and avolition. These symptoms are the main predictors of functional outcomes resulting in poorer social and occupational functioning, in particular for patients with a young age of onset of the disorder1. Antipsychotic treatment evolved in the last five decades reaching a significant control over positive symptoms but still yield small to no effect results for negative symptoms2–4. Non-invasive brain stimulation (NIBS) techniques emerged as an alternative to standard pharmacological treatment options.The developments in functional neuroimaging and biomarkers enabled the better understanding of the cortical and subcortical areas involved in the negative symptoms of schizophrenia. The idea of modulating such dysfunctional areas in a controlled, focused way, in contrast to electroconvulsive therapy, enabled the rise of the NIBS field of study. This area comprehends the transcranial magnetic stimulation (TMS)5,6 and the transcranial direct current stimulation (tDCS)7. These techniques have been proved efficacious for neuroplasticity enhancement, boosting treatment response for refractory symptoms in different neurological and psychiatric disorders8,9. Although promising results have been previously reported on the effect of TMS and tDCS for negative symptoms in schizophrenia10, they are still controversial8. With the purpose of gathering the knowledge on the randomized controlled trials on NIBS for negative symptoms in schizophrenia, we conducted a systematic review and meta-analysis. We hypothesize that NIBS techniques are superior to sham stimulation for treatment of this symptom domain.Our systematic review yielded 440 studies after duplicates were removed. In the end, 31 studies complied with inclusion criteria and were selected for the quantitative analysis (1272 patients). Studies sample sizes ranged from 11 to 157 subjects, with mean ages of 38.8 years (SD = 7.27) and 39.93 years (SD = 7.75) for the sham and active groups, respectively.Quality assessment revealed that all studies were properly randomized, sham-controlled, with patient and evaluator blinded. Also, all studies scored at least 4 in the Jadad scale11.As our primary outcome we found that active NIBS was significantly superior to sham NIBS calculating the effect size for the endpoint (g = 0.23; 95% CI 0.11 – 0.34). In general, heterogeneity was low and not significant in 608Osoegawa C, et al. Non-invasive rain stimulation for the treatment of the negative symptoms in Schizophrenia.our analysis (I2=2.3%, p=0.429 for the χ2 test) and the Egger’s test was not significant (p=0.179).In accordance with previous meta-analytical studies that reported positive results using TMS and tDCS for the treatment of patients with psychiatric disorders9,12–14, we present compelling positive findings that encourage the perpetuation of the effort to find a way to the successful treatment of negative symptoms in schizophrenia.REFERENCES1.  Immonen J, Jaaskelainen E, Korpela H, Miettunen J. Age at onset and the outcomes of schizophrenia: a systematic review and meta-analysis. Early Interv Psychiatry. 2017;11(6):453-60. doi: 10.1111/eip.12412.2.  Green MF, Harvey PD. Cognition in schizophrenia: past, present, and future. Schizophr Res Cogn. 2014;1(1):e1-9. doi: 10.1016/j.scog.2014.02.001.3.  Kahn RS, Keefe RS. Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry. 2013;70(10):1107-12. doi: 10.1001/jamapsychiatry.2013.155.4.  Robinson DG, Schooler NR, John M, Correll CU, Marcy P, Addington J, et al. Prescription practices in the treatment of first-episode schizophrenia spectrum disorders: data from the national RAISE-ETP study. Am J Psychiatry. 2015;172(3):237-48. doi: 10.1176/appi.ajp.2014.13101355.5.  Farzan F, Barr MS, Sun Y, Fitzgerald PB, Daskalakis ZJ. Transcranial magnetic stimulation on the modulation of gamma oscillations in schizophrenia. Ann N Y Acad Sci. 2012;1265:25-35. doi: 10.1111/j.1749-6632.2012.06543.x.6.  Rabany L, Deutsch L, Levkovitz Y. Double-blind, randomized sham controlled study of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia. J Psychopharmacol. 2014;28(7):686-90. doi: 10.1177/0269881114533600.7.  Gomes JS, Shiozawa P, Dias ÁM, Valverde Ducos D, Akiba H, Trevizol AP, et al. Left dorsolateral prefrontal cortex anodal tDCS effects on negative symptoms in schizophrenia. Brain Stimulation. 2015;8:989-91. doi: 10.1016/j.brs.2015.07.033.8.  Fusar-Poli P, Papanastasiou E, Stahl D, Rocchetti M, Carpenter W, Shergill S, et al. Treatments of negative symptoms in schizophrenia: meta-analysis of 168 randomized placebo-controlled trials. Schizophr Bull. 2015;41(4):892-9. doi: 10.1093/schbul/sbu170.9.  Brunoni AR, Chaimani A, Moffa AH, Razza LB, Gattaz WF, Daskalakis ZJ, 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(2):143-52.  doi: 10.1001/jamapsychiatry.2016.3644.10.  Shi C, Yu X, Cheung EF, Shum DH, Chan RC. Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: a meta-analysis. Psychiatry Res. 2014;215(3):505-13. doi: 10.1016/j.psychres.2013.12.019.11.  Moher D, Jadad AR, Tugwell P. Assessing the quality of randomized controlled trials. Current issues and future directions. Int J Technol Assess Health Care. 1996;12(2):195-208. 12.  Trevizol AP, Barros MD, Silva PO, Osuch E, Cordeiro Q, Shiozawa P. Transcranial magnetic stimulation for posttraumatic stress disorder: an updated systematic review and meta-analysis. Trends Psychiatry Psychother. 2016;38(1):50-5. doi: 10.1590/2237-6089-2015-0072.13.  Trevizol AP, Shiozawa P, Cook IA, Sato IA, Kaku CB, Guimarães FB, et al. Transcranial magnetic stimulation for obsessive-compulsive disorder: an updated systematic review and meta-analysis. J ECT. 2016;32(4):262-6. doi: 10.1097/YCT.0000000000000335.14.  Enokibara M, Trevizol A, Shiozawa P, Cordeiro Q. Establishing an effective TMS protocol for craving in substance addiction: Is it possible? Am J Addict. 2016;25(1):28-30. doi: 10.1111/ajad.12309.Received: November 19, 2018.Accepted: November 19, 2018.

Non-invasive brain stimulation for the treatment of the negative symptoms in Schizophrenia: results from an updated systematic review and a meta-analysis

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Non-invasive brain stimulation for the treatment of the negative symptoms in Schizophrenia: results from an updated systematic review and a meta-analysis

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