Efficacy and safety of repetitive transcranial magnetic stimulation combined with antidepressants in children and adolescents with depression: A systematic review and meta-analysis

Repetitive Transcranial magnetic stimulation (rTMS) combined with antidepressants benefited adults with depression while its efficacy and safety in children and adolescents with depression remain controversial. We searched PubMed, Embase, the Cochrane Library, Web of Science, CINAHL, LILACS, PsycINFO, CNKI, Wanfang Data Knowledge Service Platform, a Chinese Biology Medical disc database, and relevant clinical registration databases for randomized controlled trials from their inception to October 18, 2022. The efficacy of the treatment was assessed by changes in depression rating scale scores. Safety was assessed by the incidence of adverse events. Heterogeneity was determined using the Cochrane Q statistics and I2 statistics. Publication bias was assessed by Egger's test. Eighteen studies from 10 datasets (1396 patients, 64.7 % female, age range from 8 to 24 years old). The pooled mean-endpoint scores of the depression scale for rTMS combined with the antidepressant group were significantly lower than those of sham combined with the antidepressant group both in two weeks (MD = -4.68, 95 % CI: [−6.66, −2.69]; I2 = 91 %; P < 0.05) and four weeks (MD = −5.53, 95 % CI: [−9.90, −1.16]; I2 = 98 %; P < 0.05). There were no differences in safety (OR = 0.64, 95 % CI: [0.20, 2.04]; I2 = 64 %; P = 0.45) and acceptability between the two groups (3/70 vs 3/70). Heterogeneity was found in this study due to the limited number of original studies included. rTMS combined with antidepressants enhanced the efficacy of the antidepressant medication. The safety and acceptability of the two groups were comparable. These findings may help guide future research and clinical practice.