Table 4.
RCTs of combination of TMS and psychotherapy for PTSD.
| Study | Participants | n | TMS type | Psychotherapy type | Groups (frequency, target) | MT (%) | Total dose | Outcome measures | Assessment times | Main outcomes |
|---|---|---|---|---|---|---|---|---|---|---|
| Osuch et al. 58 | PTSD | 9 | rTMS | Imaginal exposure: Participants completed a personalized list of 10 events or cues related to their trauma which would elicit graduated levels of distress. During the TMS session, participants spoke aloud about the events or cues. The exposure was self-guided: participants could speak as much or as little about any of the cues. | 1 Hz right DLPFC + exposure Sham (coil rotated vertically) + exposure |
100% | 20 active + 20 sham sessions (crossover design) 36,000 active pulses |
CAPS HAM-D IES Serum hormonal measures Urine hormonal measures |
Pre-Condition 1 Post-Condition 1 Pre-Condition 2 Post-Condition 2 |
The active TMS group showed moderate reductions in hyperarousal symptoms compared with no significant reduction in sham. Avoidance, intrusion, and depression scores did not improve significantly in either group. The active TMS group showed trends for increased 24 h urinary norepinephrine and serum T4 levels, as well as decreased serum prolactin levels. |
| Isserles et al. 59 | PTSD | 30 | dTMS (H1-coil) | Ultra-brief exposure procedure using script-driven imagery: Participants completed a structured form describing three life events: positive, neutral, and traumatic. Thirty-second audio scripts written in the second person were recorded for each life event. For those randomized to groups with trauma exposure, the trauma script was first played, followed by a 30-s silent imaginal period, followed by the neutral script and imaginal period. For those randomized to the nontrauma exposure group, the positive script was first played instead of the trauma script. | 20 Hz bilateral MPFC + trauma exposure 20 Hz bilateral MPFC + nontrauma exposure Sham coil + trauma exposure |
120% | 12 sessions 20,160 pulses |
CAPS PSS-SR HAM-D BDI Heart rate Skin conductance |
Baseline Post-dTMS Follow-up 2 weeks and 2 months |
Compared with both control groups, the active dTMS plus brief trauma exposure group showed significant improvement in intrusive symptoms on the CAPS (response rate 44% versus 12.5% and 0%) as well as significant reduction in heart rate response to traumatic scripts. Significant within-group reductions in total CAPS, avoidance, and hyperarousal measures were shown in the active dTMS plus exposure group only. |
| Kozel et al. 60 | PTSD (veterans) | 103 | rTMS | CPT: In CPT, traumatic memories are elicited and patients are supported through direct confrontation of conflicts and maladaptive beliefs associated with their memories. In this study, CPT Veteran Military Version manual was used for 12–15 weekly sessions by CPT-trained therapists. Each CPT session followed immediately after a 30-min TMS session. | 1 Hz right DLPFC + CPT Sham coil + CPT |
110% | 12–15 sessions 216,000–27,000 pulses |
CAPS PCL M-PTSD QIDS IPF |
Baseline Sessions 5 and 9 Follow-up 1, 3, and 6 months |
Compared with sham, the group receiving active TMS immediately prior to CPT sessions showed significantly greater reductions in PTSD symptoms across all assessment times, including sustained response at 6-month follow-up. |
| Fryml et al. 61 | PTSD (veterans) | 8 | rTMS | PE: Participants received PE according to a standardized protocol. An audio recording of their own PE session was played during the once weekly TMS session. | 10 Hz right or left DLPFC + PE Sham + PE |
120% | 8 sessions 48,000 pulses (one session per week) |
CAPS HAM-D HAM-A PCL |
Baseline Weekly |
This was a small pilot study (5 active, 3 sham) that demonstrated feasibility of simultaneous TMS and PE. Participants showed a nonsignificant trend in reduction of PTSD symptoms on the CAPS favoring active TMS with PE. |
| Isserles et al. 62 | PTSD | 125 | dTMS (H7-coil) | Ultra-brief exposure procedure using script-driven imagery: Performed as described above in Isserles et al., 59 with the exception of the neutral script that played following the trauma script being removed in this study. | 18 Hz bilateral MPFC/ACC + trauma exposure Sham + trauma exposure |
100% | 12 sessions 34,560 pulses |
CAPS MPSS HAM-D |
Baseline Week 5 post-dTMS Week 9 (follow-up 1 month) |
Both sham and dTMS groups showed significant PTSD improvement at weeks 5 and 9, though contrary to the hypothesis dTMS was significantly inferior to sham at both time points. This raised questions about the efficacy of the brief script-driven imagery procedure as well as the possibility that active dTMS with the H7-coil may interfere with trauma-memory mediated extinction, with the authors highlighting the differential targeting of the H7-coil (versus the H1-coil used in the Isserles et al. pilot study). |
ACC, anterior cingulate cortex; BDI, Beck Depression Inventory; CAPS, Clinician Administered PTSD Scale; CPT: cognitive processing therapy; dTMS, deep transcranial magnetic stimulation; HAM-A, Hamilton Anxiety Rating Scale; HAM-D, Hamilton Depression Rating Scale; IES, Impact of Event Scale; IPF, Inventory of Psychosocial Functioning; MPFC, medial prefrontal cortex; MPSS, Modified PTSD Symptom self-report Scale; M-PTSD, Mississippi Scale for Combat-Related PTSD; MT, motor threshold; PCL, PTSD Symptom Checklist; PE: prolonged exposure; PSS-SR, PTSD Symptom Scale–Self-Report; PTSD, post-traumatic stress disorder; QIDS, Quick Inventory of Depressive Symptomatology–Self Report version; RCTs, randomized controlled trials; rTMS, repetitive transcranial magnetic stimulation.