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Left prefrontal transcranial magnetic stimulation for treatment-resistant depression in adolescents: a double-blind, randomized, sham-controlled trial


Treatment-resistant depression (TRD) is prevalent and associated with a substantial psychosocial burden and mortality. There are few prior studies of interventions for TRD in adolescents. This was the largest study to date examining the feasibility, safety, and efficacy of 10-Hz transcranial magnetic stimulation (TMS) for adolescents with TRD. Adolescents with TRD (aged 12–21 years) were enrolled in a randomized, sham-controlled trial of TMS across 13 sites. Treatment resistance was defined as an antidepressant treatment record level of 1 to 4 in a current episode of depression. Intention-to-treat patients (n = 103) included those randomly assigned to active NeuroStar TMS monotherapy (n = 48) or sham TMS (n = 55) for 30 daily treatments over 6 weeks. The primary outcome measure was change in the Hamilton Depression Rating Scale (HAM-D-24) score. After 6 weeks of blinded treatment, improvement in the least-squares mean (SE) HAM-D-24 scores were similar between the active (−11.1 [2.03]) and sham groups (−10.6 [2.00]; P = 0.8; difference [95% CI], − 0.5 [−4.2 to 3.3]). Response rates were 41.7% in the active group and 36.4% in the sham group (P = 0.6). Remission rates were 29.2% in the active group and 29.0% in the sham group (P = 0.95). There were no new tolerability or safety signals in adolescents. Although TMS treatment produced a clinically meaningful change in depressive symptom severity, this did not differ from sham treatment. Future studies should focus on strategies to reduce the placebo response and examine the optimal dosing of TMS for adolescents with TRD.

TMS indicates transcranial magnetic stimulation.

Primary efficacy outcome.

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The authors would like to acknowledge the participating clinical trial sites and investigative teams: Dothan Behavioral Medicine, Dothan, Alabama; University of California, Los Angeles, Los Angeles, California; Stanford University, Palo Alto, California; Rocky Mountain TMS, Grand Junction, Colorado; Florida Clinical Practice Association, Inc, Gainesville, Florida; Anchor Neuroscience, Pensacola, Florida; Beacon Medical Group, South Bend, Indiana; Integrative Psychiatry, Louisville, Kentucky; Sheppard Pratt Health System, Baltimore, Maryland; Mayo Clinic, Rochester, Minnesota; University of Cincinnati College of Medicine, Cincinnati, Ohio; The Ohio State University, Columbus, Ohio; and Medical University of South Carolina, Charleston, South Carolina.

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P.E.C.: conceptualization, investigation, data curation, data analysis, writing (original draft, review, and editing), and project administration. A.Z.E.: investigation, data curation, data analysis, writing (review and editing), and project administration. S.T.A.: investigation, data curation, data analysis, writing (review and editing), and project administration. G.R.S. Jr.: investigation, data curation, data analysis, and writing (review and editing). R.C.H.: investigation, data curation, data analysis, writing (review and editing), and project administration. S.V.: conceptualization, data analysis, writing (review and editing), and project administration. K.L.H.: conceptualization, investigation, data analysis, writing (review and editing), and project administration. M.A.D.: conceptualization, investigation, data analysis, writing (review and editing), and project administration. J.R.S.: investigation, data curation, data analysis, writing (original draft, review, and editing), and project administration.

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Correspondence to Paul E. Croarkin.

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Croarkin, P.E., Elmaadawi, A.Z., Aaronson, S.T. et al. Left prefrontal transcranial magnetic stimulation for treatment-resistant depression in adolescents: a double-blind, randomized, sham-controlled trial. Neuropsychopharmacol. (2020).

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