Table 2.
Previous literature on TMS for adolescent depression.
| Publication | n | Age in years (Mean, Range) | Gender | Protocol | Number of sessions, Frequency of sessions | Depression outcome measure | Subject medications | Estimated effect size | Reported effects for depression outcome measure | Side-effects/Adverse events |
|---|---|---|---|---|---|---|---|---|---|---|
| Walter et al. (141) Journal of Child and Adolescent Psychopharmacology |
n = 3 | Ages: 16, 17, and 17 | 3 males | 10 Hz rTMS, 90–110% RMT, over LDLPFC | 10 treatment sessions over 2 weeks | HAM-D & BDI | None | Hedges's gav = 1.53, Glass's Δpre = 3.37 | Improvement of HAM-D from 28 (baseline) to 8 (week 4) for one participant Improvement of HAM-D from 34 (baseline) to 12 (week 4) for one participant No improvement for one participant |
Adverse effects in only one patient—tension headache in two sessions |
| Loo et al. (140) Australasian Psychiatry |
n = 2 | Ages: 16, 16 | Both female | 10 Hz rTMS at 110% RMT; 40 trains of 5 second duration, 25 second ITI | 29–36 treatment sessions over 6–11 weeks | MADRS, CGIS, BDI, Centre for Epidemiological Studies—Depression-Child Scale | n = 1: “psychotropic medication,” n = 1: venlafaxine and methylphenidate | n/a | “Both subjects improved to a clinically significant degree with rTMS treatment | No adverse effects |
| Bloch et al. (142) The Journal of ECT *Mayer et al. (156) |
n = 9 | M = 17.3 Range = 16–18 |
2 males, 7 females | 10 Hz rTMS at 80% RMT over LDLPFC (5 cm targeted); 20 trains, 2 s per train | 20 treatment sessions over 2 weeks | CDRS, Screen for Child Anxiety-Related Disorders, Suicidal Ideation Questionnaire CGIS, Cambridge Neuropsychological Test Automated Battery |
Not reported | Hedges's gav = 1.50, Glass's Δpre = 2.63 | Response rate of 33% | No adverse effects reported |
| Wall et al. (143) The Journal of Clinical Psychiatry *Croarkin et al. (147) *Wall et al. (146) *Croarkin et al. (153) *Somnez et al. (157) |
n = 7 | M = 16.5 Range =14.6–17.8 |
1 male, 6 females | 10 Hz rTMS at 120% RMT over LDLPFC (5 cm targeted); train duration of 4 s, 26 s ITI, total 3,000 pulses | 30 treatment sessions over 6–8 weeks | CDRS-R, QIDS-A17, CGI-S, Suicide Severity Scale | Not reported | Hedges's gav = 4.51, Glass's Δpre = 5.05 | CDRS-R scores improved from treatment 10 (mean = 50.9, SD = 12, P < 0.02) to treatment 30 (mean = 32.6, SD = 7.3, P < 0.0001), and at 6-month follow-up (mean = 32.7, SD = 3.8, P < 0.0001) | Scalp discomfort in 3 out of 8 participants |
| Yang et al. (106) The Journal of ECT |
n = 6 | M = 18.7Range = 15–21 | 2 males, 4 females | 10 Hz rTMS at 120% RMT over LDLPFC (structural-MRI targeted); 4 s trains, ITI 26 s, 75 trains, 3,000 pulses | 15 treatment sessions over 3 weeks | HAM-D, BDI | Not reported | Hedges's gav = 2.63, Glass's Δpre = 3.18 | Response rate of 66% Responders had an 11% increase in glutamate levels from baseline | No adverse events reported |
| Segev et al. (144) The Journal of ECT |
n = 1 | 17 | 1 male | 10 Hz rTMS, 100% RMT over LDLPFC (5 cm targeted), 42 trains of 4 s with an ITI of 30 s, 1,680 pulses per treatment | 20 treatment sessions over 4 weeks | BDI-II, SIQ, Childhood Anxiety Related Disorder Questionnaire | Not reported | n/a | “…significant clinical improvement was demonstrated in anxiety symptoms and not in clinical measures of depression” | Headache, scalp pain, and scalp burning |
| Croarkin et al. (58) Psychiatry Research: Neuroimaging *Wall et al. (145) *Croarkin et al. (153) *Sonmez et al. (152) |
n = 10 | M = 15.4 Range = 13.9–17.4 |
6 males, 4 females | 10 Hz rTMS at 120% RMT over LDLPFC (structural-MRI targeted); train duration of 4 s, 26 s ITI, total 3,000 pulses | 30 treatment sessions over 6–8 weeks | CDRS-R, QIDS-A17-SR, CGI-S | Not reported | Hedges's gav = 1.89, Glass's Δpre = 2.57 | CDRS-R total score at baseline was 62.9 (SD = 8.2), total score at posttreatment was 41.8 (SD = 13.2), total score at 6-month follow up was 34.2 (SD = 15.3) Also reported, “…throughout the 6-month follow-up period, we estimated that a 1–scale unit increase (or decrease) in the CDRS-R total score (depression severity) was related to a mean decrease (or increase) in each Gln/Glu ratio” |
Scalp discomfort, headaches, dizziness, neck stiffness, eye twitching, nausea, musculoskeletal discomfort |
| MacMaster et al. (149) Frontiers in Psychiatry |
n = 32 | M = 17.57 Range = 13–21 |
17 males, 15 females | 10 Hz rTMS at 120% over LDLPFC (structural-MRI targeted); 4 s trains, ITI 26 s, 75 trains, 3,000 pulses | 15 treatment sessions over 3 weeks | HAM-D | Not reported | Hedges's gav = 1.82, Glass's Δpre = 1.71 | Response rate of 56% Remission rate of 44% |
Limiting headaches and mild neck pain |
| Zhang et al., pooled analysis *Zhang et al. (150) Brain Stimulation *Zhang et al. (155) Journal of Affective Disorders *Zhang et al. (154) Journal of ECT |
n = 70 2 weeks n = 23 4 weeks |
M = 14.86 Range = 10–17 |
26 males, 44 females | 10 Hz rTMS at 120% MT over LDLPFC (5 cm targeted); 80 trains, 30 pulses per train, 12s ITI, 2,400 pulses or 1 Hz rTMS at 120% MT over RDLPFC (5 cm targeted); 2 trains, 700 pulses per train, 1 s ITI, 1,400 pulses | 20 treatment sessions over 4 weeks | HAM-D & HAMA | Sertraline, venlafaxine, duloxetine, mirtazapine n = 1: agomelatine, bupropion, deanxit. and clomipramine | Hedges's gav 2 weeks = 1.65, Glass's Δpre 2 weeks = 1.40 Hedges's gav 4 weeks = 2.85, Glass's Δpre 4 weeks = 1.98 |
2-week response rate of 50% 2-week remission rate of 54.3% 4-week response rate of 100% 4-week remission rate of 91.3% |
No serious adverse events reported. Limited headaches or musculoskeletal discomfort |
| Rosenich et al. (151) Early Intervention in Psychiatry |
n = 15 | M = 20.69 Range = 17–25 |
7 males, 8 females | Unilateral treatment = continuous 1 Hz rTMS over RDLPFC for 15 min (n = 2) or 30 min (n = 9); Bilateral treatment (n = 4) = intermittent 10 Hz rTMS 5 s intervals, 25 s ITI for 1,500 pulses over LDLPFC and followed by 15 min of 1 Hz unilateral treatment for 900 pulses over RDLPFC (all 6 cm targeted). All stimulation at 110% RMT | 18 treatment sessions over 6 weeks | HAM-D, MADRS, and Zung Self Rating Depression Scale | Not reported | Hedges's gav = 1.24, Glass's Δpre = 1.41 | Partial response rate of 86.7% Response rate of 40% Remission rate of 13% |
No serious adverse events, only mild headache, fatigue, and localized discomfort |
| Dhami et al. (148) Journal of Affective Disorders |
n = 20 | M = 20.9Range = 16–24 | 10 males, 10 females | Bilateral theta burst stimulation: iTBS on LDLPFC and cTBS on RDLPFC at 80% RMT (structural-MRI targeted) | 10 treatment sessions over 2 weeks | HRSD-17, BDI-II, Q-LES-Q, CDRS-R | Not reported | Hedges's gav = 2.21, Glass's Δpre = 3.07 | Response rate of 20% Remission rate of 10% |
Headache, scalp pain, chest tightness, anxiety, nausea, gastrointestinal symptoms, nasopharyngitis, restlessness, general discomfort |
| Croarkin et al. (7) NeuropsychopharmacologyActive arm |
n = 48 | M = 17.6Range = 12–21 | 18 males, 30 females | 10 Hz rTMS at 120% over LDLPFC (5 cm targeted); 4 strains, 26 s ITI, 75 trains, total 3,000 pulses | 30 treatment sessions over 6 weeks | HAM-D, MADRS, CRS-R, QIDS-A-SR, CGI-S | zaleplon, zolpidem, zopiclone, or lorazepam | Hedges's gav = 1.27, Glass's Δpre = 1.86 | Response rate of 41.7%; remission rate of 29.2% | Four serious adverse events reported, all having to do with suicidal ideation or worsening depressive symptoms determined unrelated to rTMS treatment |
| Croarkin et al. (7) NeuropsychopharmacologySham arm |
n = 55 | M = 17.4Range = 12–21 | 18 males, 37 females | Sham | 30 treatment sessions over 6 weeks | HAM-D, MADRS, CRS-R, QIDS-A-SR, CGI-S | zaleplon, zolpidem, zopiclone, or lorazepam | Hedges's gav = 1.15, Glass's Δpre = 1.53 | Response rate of 36.4%; remission rate of 29.0% | One serious adverse event of suicidal ideation definitely unrelated to rTMS treatment |
| Croarkin et al. (7) NeuropsychopharmacologyActive vs. Sham | n = 103 (54 active) | M = 17.35Range = 12–21 | 36 males, 67 females | 10 Hz rTMS at 120% over LDLPFC (5 cm targeted); 4 s trains, 26 s ITI, 75 trains, total 3,000 pulses | 30 treatment sessions over 6 weeks | HAM-D, MADRS, CRS-R, QIDS-A-SR, CGI-S | zaleplon, zolpidem, zopiclone, or lorazepam | Hedges's gs = 0.10, | “There were no statistically significant differences in clinical outcomes between the active TMS and sham TMS groups” | Five serious adverse events reported, all having to do with suicidal ideation or worsening depressive symptoms determined unrelated to rTMS treatment |
rTMS, repetitive transcranial magnetic stimulation; iTBS, intermittent theta burst stimulation; cTBS, continuous theta burst stimulation; RMT, resting motor threshold; MT, motor threshold; ITI, intertrain interval; LDLPFC, left dorsolateral prefrontal cortex; RDLPFC, right dorsolateral prefrontal cortex; HAM-D/HRSD, Hamilton depression rating scale; HAM-A, Hamilton anxiety rating scale; BDI, Beck depression inventory; MADRS, Montgomery-Asberg depression rating scale; SIQ, suicidal ideation questionnaire; CGIS, clinical global impressions scale; CDRS-R, depression rating scale for children revised; QIDS, Quick Inventory of Depressive Symptomatology; Q-LES-Q, quality of life enjoyment and satisfaction questionnaire; SSRI, selective serotonin reuptake inhibitor.
*
Follow up studies/post-hoc analysis using the same participant data.