Background: The negative symptoms of schizophrenia are not effectively treated with antipsychotic medications. Repetitive transcranial magnetic stimulation (rTMS) is an alternative approach that may be more effective in treating negative symptoms, but there has been little research comparing the effectiveness of different rTMS stimulation protocols.
Objective: Compare the effect of four different rTMS protocols in the treatment of the negative symptoms of schizophrenia.
Methods: Ninety-six patients with schizophrenia who had prominent negative symptoms were randomly assigned to four treatment groups: 10 Hz, 20 Hz, theta burst stimulation (TBS), and mock rTMS (i.e., the control group). In the first three groups, the left dorsolateral prefrontal cortex was stimulated at 80% of the motor threshold five times per week for four weeks. Before and after the treatment, evaluators who were blind to the group assignment of patients administered the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS) and the Treatment Emergent Symptom Scale (TESS).
Results: Three of the 96 patients dropped out during the trial (two from the control group and one from the 20 Hz group). Compared to the control group, after 4 weeks of rTMS treatment all three treatment groups had lower scores on the PANSS negative symptom subscale, the PANSS general psychopathology subscale, and the SANS. The TBS group had significantly larger reductions in these scores than the 10 Hz group and the 20 Hz group, but there were no significant differences between the 10 Hz and 20 Hz groups. There were no pre- versus post-treatment differences in the PANSS positive symptom subscale scores between the four groups. No serious adverse events occurred and there were no statistically significant differences in the TESS scores across the four groups.
Conclusions: We find that rTMS, particularly the TBS stimulation protocol for rTMS, is a safe and effective treatment method for patients with schizophrenia who have prominent negative symptoms. Longitudinal studies with large samples are needed to optimize the rTMS treatment, to identify the stimulation protocol, duration, intensity and treatment interval that provides the best therapeutic result at the lowest risk to the patient.
背景: 抗精神病药物对精神分裂症阴性症状的疗效欠佳。重复经颅磁刺激（rTMS）或许是治疗阴性症状的另一种更有效的方法，但很少有关于不同模式rTMS治疗有效性比较的研究。
目标: 比较四种不同模式rTMS对治疗精神分裂症阴性症状的效果。
方法: 96例有明显阴性症状的精神分裂症患者随机分为四个治疗组：10赫兹，20赫兹，θ波脉冲刺激（TBS），和模拟rTMS治疗（即对照组）。在前三组，采用运行阈值的80％对左背外侧前额叶皮层进行刺激，每周五次，持续四周。治疗前后，由对患者分组单盲的评估者采用阳性和阴性症状量表（PANSS）、阴性症状评估量表（SANS）和不良反应量表（TESS）进行评估。
结果: 96例患者中3名患者中途退出试验（两个来自对照组和一个来自20赫兹组）。与对照组相比，经rTMS治疗4周后，3个治疗组PANSS阴性症状分量表、PANSS一般精神病理分量表和SANS量表得分较低。TBS组这些量表的减分显著大于10赫兹组和20赫兹组，但10赫兹和20赫兹两组间无显著差异。四组之间PANSS阳性症状分量表评分治疗前后没有显著差异。未发生严重不良事件，并且4组TESS评分无统计学显著差异。
结论: 我们发现rTMS治疗，特别是TBS刺激模式对于伴有明显阴性症状的精神分裂症患者是一种安全有效的治疗方法。我们需要进行大样本的纵向研究，以优化rTMS治疗，并确定刺激模式，持续时间，刺激强度以及治疗时间间隔，从而以最低的风险为患者提供最佳的治疗结果。
Keywords: China; randomized controlled trial; repetitive transcranial magnetic stimulation; schizophrenia; treatment.