Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review

Junjie Wang, Yingqun Zhou, Hong Gan, Jiaoyan Pang, Hui Li, Jijun Wang, Chunbo Li, Junjie Wang, Yingqun Zhou, Hong Gan, Jiaoyan Pang, Hui Li, Jijun Wang, Chunbo Li

Abstract

Background: Negative symptoms are one of the most difficult areas in the treatment of schizophrenia because antipsychotics are often less effective towards them. Repetitive transcranial magnetic stimulation (rTMS) is a new technique for cerebral cortex stimulation and is believed to be a safe and promising method for the treatment of mental disorders. As the clinical research and new treatment models have increased in recent years, the efficacy towards negative symptoms and safety evaluation of rTMS treatment should also be updated.

Aims: To explore the efficacy and safety of rTMS in the treatment of negative symptoms for patients with schizophrenia.

Methods: We searched for relevant controlled clinical trials from the following databases: PubMed, EMBASE, the Cochrane Library, EBSCO, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SINOMED, and Airiti Library. The retrieval time went up to January 2, 2017. The research literature was screened according to the predefined inclusion and exclusion criteria. After data extraction, statistical analysis was conducted by using RevMan 5.3 and Stata 14. Quality evaluation was done on the included research articles. The Cochrane risk of bias assessment tool was adopted for assessing risk of bias. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system recommendation grading method was used as the reference standard.

Results: A total of 3500 articles were retrieved. In the end, there were 29 articles included in the metaanalysis with a total sample size of 1440. After the meta-analysis, it was found that the use of antipsychotic treatment combined with rTMS could improve the negative symptoms of patients (SMD=-0.40, 95% CI= -0.62~-0.18). Based on the bias of the efficacy evaluation assessed by the Cochrane risk of bias assessment tool, there were 6 studies rated as having "high risk of bias" and the rest were rated as "unable to determine". According to the assessment, development and evaluation criteria of the GRADE classification, the evidence quality for the efficacy evaluation index was "moderate". The acceptability of rTMS treatment was better (RR= 0.75, 95% CI= 0.49~1.15, based on the 1492 samples from the 28 studies), however, the patients who received the rTMS treatment had a higher rate of mild adverse effects (RR= 2.20, 95% CI= 1.53~ 3.18, based on the 1296 samples from the 23 studies).

Conclusions: The use of the antipsychotic treatment incorporated with rTMS treatment can slightly improve the negative symptoms of patients with schizophrenia and has better acceptability and fewer adverse effects. Nevertheless, there is publication bias in this study and the heterogeneity of the study is relatively high. Therefore, we need to be cautious when interpreting the results.

Keywords: meta analysis; negative symptoms; repetitive transcranial magnetic stimulation treatment; schizophrenia; systematic review.

Figures

Figure 1.
Figure 1.
Flowchart of the literature search and screening
Figure 2.
Figure 2.
Funnel plot of potential publication bias of the efficacy of antipsychotics combined with rTMS in the treatment of the negative symptoms of schizophrenia
Figure 3.
Figure 3.
Forest plot of efficacy of antipsychotic drugs combined with rTMS in treatment of negative symptoms in schizophrenia
Figure 4.
Figure 4.
Meta-regression analysis of the standardized mean difference (SMD) of the TMS combined with antipsychotic drugs for the treatment of negative symptoms and the baseline PANSS negative symptom score
Figure 5.
Figure 5.
Efficacy of antipsychotic drugs combined with rTMS in the treatment of negative symptoms of schizophrenia: drop outs
Figure 6.
Figure 6.
Adverse effects of antipsychotic drugs combined with the rTMS in treatment of negative symptoms of schizophrenia forest plot

References

    1. Priebe S, Savill M, Wykes T, Bentall R, Lauber C, Reininghaus U, et al. Clinical effectiveness and cost-effectiveness of body psychotherapy in the treatment of negative symptoms of schizophrenia: a multicentrerandomised controlled trial. Health Technol Assess. 2016; 20(11): vii-xxiii, 1-100. doi:
    1. Mantovani LM, Ferretjans R, Marcal IM, Oliveira AM, Guimaraes FC, Salgado JV. Family burden in schizophrenia: the influence of age of onset and negative symptoms. Trends Psychiatry Psychother. 2016; 38(2): 96-99.doi:
    1. Buckley PF, Stahl SM. Pharmacological treatment of negative symptoms of schizophrenia: therapeutic opportunity or cul-de-sac. Acta Psychiatr Scand. 2007; 115(2): 93-100. doi:
    1. Stahl SM, Buckley PF. Negative symptoms of schizophrenia: a problem that will not go away. Acta Psychiatr Scand. 2007; 115(1): 4-11. doi:
    1. Tsapakis EM, Dimopoulou T, Tarazi FI. Clinical management of negative symptoms of schizophrenia: An update. PharmacolTher. 2015; 153: 135-147. doi: org/10.1016/j.pharmthera.2015.06.008
    1. Priebe S, Savill M, Wykes T, Bentall R P, Reininghaus U, Lauber C, et al. Effectiveness of group body psychotherapy for negative symptoms of schizophrenia: multicentrerandomised controlled trial. Br J Psychiatry. 2016; 209(1): 54-61. doi: bp.115.171397
    1. Kole MH, Fuchs E, Ziemann U, Paulus W, Ebert U. Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats. Brain Res. 1999; 826(2): 309-312.doi:
    1. Shaul U, Ben-Shachar D, Karry R, Klein E. Modulation of frequency and duration of repetitive magnetic stimulation affects catecholamine levels and tyrosine hydroxylase activity in human neuroblastoma cells: implication for the antidepressant effect of rTMS. Int J Neuropsychopharmacol. 2003; 6(3): 233-241. doi: S1461145703003493
    1. Wassermann EM, Lisanby SH. Therapeutic application of repetitive transcranial magnetic stimulation: A review. Clin Neurophysiol. 2001; 112(8): 1367-1377.doi:
    1. Keck ME, Welt T, Muller MB, Erhardt A, Ohl F, Toschi N, et al. Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system. Neuropharmacology. 2002; 43(1): 101-109.doi:
    1. 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:
    1. Franck N, O’leary DS, Flaum M, Hichwa RD, Andreasen NC. Cerebral blood flow changes associated with Schneiderian first-rank symptoms in schizophrenia. J Neuropsychiatry Clin Neurosci. 2002; 14(14): 277-282
    1. Vaiva G, Cottencin O, Llorca PM, Devos P, Dupont S, Mazas O, et al. Regional cerebral blood flow in deficit/nondeficit types of schizophrenia according to SDS criteria. Prog Neuropsychopharmacol Biol Psychiatry. 2002; 26(3): 481–485.doi:
    1. Cohen E, Bernardo M, Masana J, Arrufat FJ, Navarro V, Valls S, et al. Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: A pilot study. J Neurol Neurosurg Psychiatry. 1999; 67(1): 129-130
    1. Holi MM, Eronen M, Toivonen K, Toivonen P, Marttunen M, Naukkarinen H. Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia. Schizophr Bull. 2004; 30(2): 429-434
    1. Novak T, Horacek J, Mohr P, Kopecek M, Skrdlantova L, Klirova M, et al. The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results. Neuro Endocrinol Lett. 2006; 27(1-2): 209-213
    1. Mogg A, Purvis R, Eranti S, Contell F, Taylor J P, Nicholson T, et al. Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: a randomized controlled pilot study. Schizophr Res. 2007; 93(1-3): 221-228. doi:
    1. Hajak G, Marienhagen J, Langguth B, Werner S, Binder H, Eichhammer P. High-frequency repetitive transcranial magnetic stimulation in schizophrenia: A combined treatment and neuroimaging study. Psychol Med. 2004; 34(7): 1157-1163
    1. Jin Y, Potkin SG, Kemp AS, Huerta ST, Alva G, Thai TM, et al. Therapeutic effects of individualized alpha frequency transcranial magnetic stimulation (alphaTMS) on the negative symptoms of schizophrenia. Schizophr Bull. 2006; 32(3): 556-561. doi:
    1. Prikryl R, Kasparek T, Skotakova S, Ustohal L, Kucerova H, Ceskova E. Treatment of negative symptoms of schizophrenia using repetitive transcranial magnetic stimulation in a double-blind, randomized controlled study. Schizophr Res. 2007; 95(1–3): 151-157.doi:
    1. Zhen LN, Guo Q, Li H, Li CB, Wang JJ. [Effects of repetitive transcranial magnetic stimulation with different paradigms on the cognitive function and psychotic symptoms of schizophrenia patients]. Beijing Da Xue Xue Bao (Yi Xue Ban). 2012; 44(5): 732-736. Chinese. doi:
    1. Gan JL, Chen ZX, Duan HF, Zhu XQ, Shi ZJ, Gao CY, et al. [A randomized controlled trial of a short pulsed transcranial magnetic stimulation in the treatment of refractory negative symptoms of schizophrenia]. Zhong Hua Jing Shen Ke Za Zhi. 2014; 47(3): 191-192. Chinese. doi:
    1. Xu Q, Zhang YQ, Cheng ZH. [Efficacy and safety of repetitive transcranial magnetic stimulation in the treatment of negative symptoms of chronic schizophrenia]. Zhong Hua Yi Xue Hui Di Shi Qi Ci Quan Guo Xin Wei Yi Xue Xue Shu Hui Yi Lun Wen Ji; 2015. Chinese
    1. Quan WX, Zhu XL, Qiao H, Zhang WF, Tan SP, Zhou DF, et al. The effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia and the follow-up study. Neurosci Lett. 2015; 584: 197-201.doi:
    1. Garg S, Sinha VK, Tikka SK, Mishra P, Goyal N. The efficacy of cerebellar vermal deep high frequency (theta range) repetitive transcranial magnetic stimulation (rTMS) in schizophrenia: A randomized rater blind-sham controlled study. Psychiatry Res. 2016; 243: 413-420. doi:
    1. Tikka S K, Nizamie S H, VenkateshBabu G M, Aggarwal N, Das A K, Goyal N. Safety and efficacy of adjunctive θ burst repetitive transcranial magnetic stimulation to right inferior parietal lobule in schizophrenia patients with first-rank symptoms: A pilot, exploratory study. J ECT. 2017; 33(1): 43-51. doi:
    1. Altman DG. Statistics Notes: Detecting skewness from summary information. BMJ. 1996; 313(7066): 1200
    1. Goyal N, Nizamie SH, Desarkar P. Efficacy of adjuvant high frequency repetitive transcranial magnetic stimulation on negative and positive symptoms of schizophrenia: preliminary results of a double-blind sham-controlled study. J Neuropsychiatry Clin Neurosci. 2007; 19(4): 464-467. doi:
    1. Cordes J, Thünker J, Agelink MW, Arends M, Mobascher A, Wobrock T, et al. Effects of 10 Hz repetitive transcranial magnetic stimulation (rTMS) on clinical global impression in chronic schizophrenia. Psychiatry Res. 2010; 177(1-2): 32-36. doi:
    1. Klein E, Kolsky Y, Puyerovsky M, Koren D, Chistyakov A, Feinsod M. Right prefrontal slow repetitive transcranial magnetic stimulation in schizophrenia: A double-blind sham-controlled pilot study. Biol Psychiatry. 1999; 46(10): 1451-1454.doi:
    1. Fitzgerald PB, Herring S, Hoy K, Mcqueen S, Segrave R, Kulkarni J, et al. A study of the effectiveness of bilateral transcranial magnetic stimulation in the treatment of the negative symptoms of schizophrenia. Brain Stimul. 2008; 1 (1): 27-32.doi:
    1. MS Farzan F, Tran LC, Fitzgerald PB, Daskalakis ZJ. A randomized controlled trial of sequentially bilateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of negative symptoms in schizophrenia. Brain Stimul. 2012; 5(3): 337-346. doi:
    1. Prikryl R, Ustohal L, PrikrylovaKucerova H, Kasparek T, Venclikova S, Vrzalova M, et al. A detailed analysis of the effect of repetitive transcranial magnetic stimulation on negative symptoms of schizophrenia: a double-blind trial. Schizophr Res. 2013;149(1-3):167-173. doi: org/10.1016/j.schres.2013.06.015
    1. 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):686-690. doi:
    1. Dlabac-De Lange JJ, Liemburg EJ, Bais L, Renken RJ, Knegtering H, Aleman A. Effect of rTMS on brain activation in schizophrenia with negative symptoms: A proof-ofprinciple study. Schizophr Res. 2015; 168(1-2): 475-482. doi:
    1. Xu WJ, Jin Y, Huang YQ, Liu ZR, He H, Chen J. [Doubleblind control trial of alpha electroencephalogramguided transcranial magnetic stimulation treatment for schizophrenia]. Zhongguo Lin Chuang Kang Fu. 2006; 10(46): 22-24. Chinese. doi:
    1. Liu H, Li H, Liu R, Wang JJ. [The analysis of curative effect of negative symptoms in schizophrenic patients after the treatment of repetitive transcranial magnetic stimu-lation (rTMS)]. Xian Dai Dian Sheng Li XueZaZhi. 2008; 15(03): 134-137. Chinese. doi:
    1. Zhang JJ, Zhang XK, Li H, Zhong XL, Cheng ZW, Liao LW, et al. [Double-blind randomized controlled trial of repetitive transcranial magnetic stimulation in the treatment of the negative symptoms of schizophrenia]. Shanghai Arch Psychiatry. 2010; 22(05): 262-265. Chinese. doi:
    1. Chen HY, Zhang ZJ, Wang JJ, Chen YM, Xiang ZQ, Shi SX, et al. [Effect of adjunctive treatment with repetitive transcranial magnetic stimulation on exploratory eye movements and negative symptoms in schizophrenic patients:arandomized,double-blind,sham-controlled study]. Shanghai Arch Psychiatry. 2011; 23(4): 200-206. Chinese. doi:
    1. Ren YP, Zhou DF, Cai ZJ, Huang Q, Lu L, Chen Q. [Effects of high frequency repetitive transcranial magnetic stimulation on refractory negative symptom of schizophrenia: A double blind, randomized controlled trial]. Zhongguo Xin Li Wei Sheng Za Zhi. 2011; 25(02): 89-92. Chinese. doi:
    1. Duan HF, Gan JL, Zhu XQ, Cao LJ, Shi ZJ, Gao CY, et al. [Therapeutic effect of repetitive transcranial magnetic stimulation for refractory negative symptom of schizophrenia]. Xinxiang Yi Xue Yuan Xue Bao. 2013; 30(11): 895-897+901. Chinese
    1. Gan JL, Duan HF, Cheng ZX, Shi ZJ, Gao CY, Liang XJ, et al. [Effects of repetitive transcranial magnetic stimulation on schizophrenia with refractory negative symptoms and brain-derived neurotrophic factor]. Zhongguo Shen Jing Jing Shen Ji Bing Za Zhi. 2014; 12: 710-714. Chinese. doi:
    1. Zhao SH, Kong JH, Li SL, Tong ZS, Yang CJ, Zhong HQ. Randomized controlled trial of four protocols of repetitive transcranial magnetic stimulation for treating the negative symptoms of schizophrenia. Shanghai Arch Psychiatry. 2014; 1: 15-21. doi:
    1. Bai L, Gan JL, Liang XJ, Duan HF, Gao CY. [The effect of rTMS on DTI and the Negative Symptoms in patients with schizophrenia]. Zhongguo Jian Kang Xin Li Xue Za Zhi. 2015; 23(5): 649-653. Chinese. doi:
    1. Wang YF, Lv BJ, Teng JB, Xia Y. [Efficacy and safety of Repetitive Transcranial Magnetic Stimulation in the treatment of schizophrenia with negative symptoms]. Zhejiang Zhong Xi Yi Jie He Za Zhi. 2015; 4: 331-333+340. Chinese. doi:
    1. Zhang CH, Yu ZH, Zhang G, Yang GH. [Study on effect of repetitive transcranial magnetic stimulation combined with ziprasidone in the treatment of the negative symptoms of schizophrenia]. Zhongguo Xian Dai Yi Yao Za Zhi. 2015; 9: 26-28. Chinese. doi:
    1. Li Z, Du XD, Zhang LL, Yang JG, Yang L, Yin M, et al. [A control study of high-frequency repetitive transcranial magnetic stimulation in chronic schizophrenia characterized by negative symptoms]. Lin Chuang Xin Shen Ji Bing Za Zhi. 2016; 22(5): 28-31. Chinese. doi:
    1. Ma SJ, Wu ZJ, Huang YQ, Lin LB, Gao ZS. [Clinical efficacy of repetitive transcranial magnetic stimulation on firstepisod schizophrenia patients]. ZhongHua Lin Chuang Yi Shi Za Zhi (Dian Zi Ban). 2016; 40(14): 2063-2067. Chinese. doi:
    1. Gan JL, Duan HF, Cheng ZX, Shi ZJ, Gao CY, Zhu XQ, et al. [Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. Zhong Hua Yi Xue Za Zhi. 2015; 95(47): 3808-3812. Chinese. doi:
    1. Dlabac-De Lange JJ, Bais L, Es FD, Visser BG, Reinink E, Bakker B, et al. Efficacy of bilateral repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: results of a multicenter double-blind randomized controlled trial. Psychol Med. 2015;45(6): 1263-1275. doi:
    1. Dlabac-De Lange JJ, Liemburg EJ, Bais L, Van De Poel-Mustafayeva AT, De Lange-De Klerk ESM, Knegtering H, et al. Effect of bilateral prefrontal rTMS on left prefrontal NAA and Glx levels in schizophrenia patients with predominant negative symptoms: An exploratory study. Brain Stimul. 2017; 10(1): 59-64. doi:
    1. 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): 505-513. doi:
    1. Lage C, Wiles K, Shergill SS, Tracy DK. A systematic review of the effects of low-frequency repetitive transcranial magnetic stimulation on cognition. J Neural Transm (Vienna). 2016; 123(12): 1479-1490. doi: doi:
    1. Dlabacde Lange J J, Knegtering R, Aleman A. Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: review and meta-analysis. J Clin Psychiatry. 2010; 71(4): 411-418. doi:
    1. Freitas C, Fregni F, Pascual-Leone A. Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia. Schizophr Res. 2009; 108(1-3): 11-24. doi:

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