Inflow-Frequency Transcranial Magnetic Stimulation Associates With Decreased Anxiety in Generalized Anxiety Disorder

For this study, patients with generalized anxiety disorder were recruited from the Nanfang Hospital in China between 2018 and 2020.

Inflow-frequency transcranial magnetic stimulation (ILF-TMS) was associated with improved symptoms of anxiety among patients with generalized anxiety disorder (GAD), according to results of a study published in Comprehensive Psychiatry.

Patients (N=62) with GAD were recruited from the Nanfang Hospital in China between 2018 and 2020. Patients were randomized to receive 10 sessions over 2 weeks of active (n=31) or sham (n=31) ILF-TMS. Active ILF-TMS was delivered by a treatment cap at 1 mHz for 30 minutes with a magnetic intensity of 500 Gs. The primary outcome was change in the Hamilton Anxiety Rating Scale (HAMA).

The active and sham groups were aged mean 39.8 (SD, 13.5) and 42.6 (SD, 9.8) years, 51.6% and 64.5% were women, the mean duration of disease was 29.9 and 43.6 months, 74.2% and 77.4% had chronic GAD, and 41.9% and 45.2% were affected moderately by their disease, respectively.

At week 12, 80.6% of active and 54.8% of sham ILF-TMS recipients responded to treatment (P =.03).

Among the ILF-TMS recipients, average HAMA scores decreased from 23.48 (SD, 6.51) at baseline to 14.19 (SD, 8.34) at week 2 and 7.97 (SD, 8.77) at week 12. For the controls, scores decreased from 22.71 (SD, 5.26) at baseline to 13.29 (SD, 5.12) at week 2 and 10.00 (SD, 6.60) at week 12. There was a significant time effect (P <.001) but not a group or group-by-time interaction.

Similar trends were observed for Hamilton Depression Rating Scale (HAMD), Clinical Global Impression (CGI), and Treatment Emergent Symptom Scale (TESS).

There was a significant group effect observed for CGI-Efficacy Index (EI), in which the active and sham groups reported CGI-EI scores of 1.89 and 1.69 at week 2, 2.36 and 1.85 at week 4, and 2.79 and 2.13 at week 12 (P =.01), respectively.

In addition, at week 2 the active ILF-TMS treatment was associated with improved reaction time during the psychomotor vigilance task (P =.01) and the percentage of targets hit when n=1 during the N-back test (P =.01).

Among both groups, the daily defined dose (DDD) of antidepressant equivalents increased significantly from baseline to week 12 (P <.001) from 18.06 DDD to 34.83 DDD among the active cohort and from 15.05 DDD to 30.68 DDD among the sham cohort.

At least 1 side-effect was reported by 12 of the active and 16 of the sham cohorts (P =.14). The most common effects were constipation (24.1% vs 15.4%) and dry mouth (20.9% vs 19.2%).

The major limitation of this study was that patients increased their antidepressant dosage during the study period, which may have had effects of GAD symptomology.

The study authors concluded, “These results showed that ILF-TMS over the whole brain may be a promising and safe adjunctive treatment for reducing anxiety symptoms in GAD patients. Based on the results of this study, further studies should be carried out to explore the optimum treatment regimen (in terms of number of sessions, site of stimulation, etc) and investigate the effect of ILF-TMS in the treatment of cognitive dysfunction, depressive disorders, and other mental disorders.”


Zeng S, Tang C, Su M, et al. Infralow-frequency transcranial magnetic stimulation as a therapy for generalized anxiety disorder: A randomized clinical trial. Compr Psychiatry. 2022;117:152332. doi:10.1016/j.comppsych.2022.152332