Effectiveness and safety of repetitive transcranial magnetic stimulation for generalized anxiety disorder: A meta-analysis and trial sequential analysis of randomized controlled trials

Background

Generalized anxiety disorder (GAD) is a chronic disorder characterized by uncontrollable, excessive, widespread anxiety lasting for over six months. Repetitive transcranial magnetic stimulation (rTMS) has been used in treating anxiety disorders, but previous studies have yielded contradictory results. We performed a meta-analysis and trial sequential analysis to investigate the effectiveness and safety of rTMS for GAD and explore the optimal treatment protocol of rTMS for GAD.

Methods

Eight databases were systematically searched to identify randomized controlled trials (RCTs) of rTMS for GAD. The primary outcome was the Hamilton Anxiety Scale. Secondary outcomes included a self-rating anxiety scale, clinical global impression-severity of illness, and incidence of adverse events. Data synthesis was conducted using Review Manager (version 5.4) and Stata software (version 12.0).

Results

A total of 29 eligible trials were included. The rTMS combined with medication was more effective than the medication alone in alleviating symptoms of patients with GAD (mean difference [MD] = −3.38, 95 % confidence interval [CI]: from −4.47 to −2.28). Compared with sham-rTMS combined with medication, rTMS combined with medication exhibited a significant effect in improving symptoms of GAD (MD = −2.80, 95 % CI: from −3.71 to −1.89). No serious adverse events were reported between rTMS treatment and medication therapy.

Conclusion

The rTMS could be an effective and safe treatment for patients with GAD. However, these findings should be interpreted with caution due to high heterogeneity and limited number of RCTs.