Infralow-frequency Transcranial Magnetic Stimulation As A Therapy For Generalized Anxiety Disorder

Objectives:To evaluate the efficacy and safety of infralow-frequency transcranial magnetic stimulation(ILF-TMS)in the treatment of generalized anxiety disorder(GAD).Besides,whether ILF-TMS can improve depressive symptoms and cognitive function in patients with GAD was explored.Methods:The present study is a randomized controlled clinical trial.A total of 62 participants were recruited and randomly assigned to active group(n=31)or sham group(n=31).ILF-TMS was delivered at a frequency of 0.001-0.2 Hz for 30 min with the magnetic intensity of 500 Gs,for 10 sessions(5 days/week for 2 weeks)applied to the whole brain in the active group.Participants receiving sham ILF-TMS completed the same procedures as those in the active group,but treatment were administered using false coil.This sham coil looks and sounds like the active coil,but doesn’t release any magnetic stimulus.The primary outcome was the response rate and remission rate of anxiety symptom(the Hamilton Anxiety Rating Scale,HAMA).The secondary outcomes were the the Hamilton Depression Rating Scale(HAMD),Clinical Global Impression scale(CGI),Treatment Emergent Symptom Scale(TESS)and neurocognitive tests including Psychomotor Vigilance Task,Go/No-go Association Task and N-back Test.HAMA,HAMD,CGI and TESS were conducted at baseline(T0),week 2(the completion of ILF-TMS treatment,T1),week 4(the first follow-up,T2),week 12(the second follow-up,T3).Neurocognitive tests were evaluated at baseline(T0)and week 2(T1).SPSS26.0 was used for descriptive statistics,t-test,Chi-square test,and repeated measures analysis of variance(RM-ANOVA),etc.Main analyses were on an intent-to-treat(ITT)basis and last observation carried forward(LOCF)method was used to impute any missing data.Results:At week 12,the response rate of anxiety symptom was higher(80.6%[25/31]vs 54.8%[17/31],P=0.030)in the active group than the control group with significant difference.Throughout the trial,no significant difference in antidepressant dosage between two groups was observed(time by group interaction,P>0.05),With the progress of the trial,the total score of HAMD,each factor of CGI and TESS in the active group was significantly decreased(HAMD:η2=0.118;CGI-SI:η2=0.098;CGI-GI:η2=0.008;CGI-EI:η2=0.049;TESS-A:η2=0.033;TESS-B:η2=0.018).However,there was no significant differences between the active group and the sham group(time by group interaction,P>0.05).After the intervention,the response time of the active group was shortened in the PVT task with significant difference(t=2.409,P=0.024).In the N-back test,the accuracy and reaction time of the active group were both improved compared to the baseline(n=1:t=-2.969,P=0.007;t=2.585,P=0.016;n=2:t=3.481,P=0.002;t=2.315,P=0.029).Compared with the baseline data,the accuracy and reaction time of the sham group almost improved(n=1:t=0.296,P=0.770;t=2.563,P=0.020;n=2:t=2.882,P=0.010;t=2.125,P=0.048).However,the changes in cognitive function did not differ between two groups(time by group interaction,P>0.05).At week 2 after finishing the intervention,no significant difference in the incidence of at least one adverse event was observed in two groups.Conclusions:Infralow-frequency transcranial magnetic stimulation applied to the whole brain may be an effective and safe treatment to improve anxiety symptom in patients with generalized anxiety disorder.