Theta burst stimulation is not inferior to high frequency repetitive transcranial magnetic stimulation in reducing symptoms of post-traumatic stress disorder in Veterans with depression: a retrospective case series
Authors: Shenasa Mohammad Ali , Em Ellerman , Phil Canet , Martis Brian , Mishra Jyoti , Ramanathan Dhakshin 
Published: September 2022

Background

Two commonly used forms of repetitive transcranial magnetic stimulation (rTMS) were recently shown to be equivalent for the treatment of treatment-resistant depression (TRD): high-frequency stimulation (10 Hz), a protocol that lasts between 19-38 minutes, and intermittent Theta-Burst Stimulation (iTBS), a protocol that can be delivered in just 3 minutes. Intermittent TBS offers significant time advantages to patients and clinics and has thus become a default treatment in many clinics. However, it is unclear whether iTBS treatment offers the same benefits as standard 10 Hz rTMS for comorbid symptoms, such as post-traumatic-stress-disorder (PTSD).

Methods

In this retrospective case series, we analyzed treatment outcomes in Veterans from the VA San Diego Healthcare system (VASDHS) who received 10 Hz (n = 47) or iTBS (n = 51) rTMS treatments for TRD between the dates of Feb 2018 to June 2022. We compared outcomes between these two stimulation protocols used between these dates on symptoms of depression (using changes in the patient health questionnaire-9, or PHQ-9) and PTSD (using changes in the PTSD Checklist for DSM-5, or PCL-5). We hypothesized that there would be no differences in treatment outcomes between 10 Hz and iTBS protocols for either depression (confirming prior RCT) or PTSD.

Results

We initially found that stimulation groups differed in gender (the iTBS group had 16 females and 35 males, the 10 Hz group had 5 females and 42 males, p<0.003). Thus, to analyze whether there was a difference by stimulation protocol, we first implemented a mixed-effects ANOVA model for PHQ-8 scores with gender and stimulation type as between-group fixed effects and treatment (pre-treatment and post-treatment scores) as the repeated measures factor. We found no significant difference by stimulation protocol for either depression (PHQ-9, (F(1,94)= 0.16, p = 0.69, eta-squared = 0.002) or PTSD symptoms (PCL-5, F (1,94) = 3.46, p = 0.067, eta-squared = 0.036). As differences related to PTSD outcomes were close to significance, we did look at the post-hoc treatment effects by stimulation type for PTSD symptoms. The iTBS group showed a reduction from 41.9 +/- 4.4 to 25.1 +/- 4.9 (a difference of 16.8 points) while the 10Hz group showed a reduction from 43.6 +/- 2.9 down to 35.2 +/- 3.2 (a difference of 8.4 points). Follow-up analyses restricting the sample in various ways did not meaningfully change these results (no follow-up analyses showed that there was a significant difference between stimulation protocols).

Conclusions

While limited by small sample size, non-blinded and pseudo-randomized assignment, our data suggests that iTBS is non-inferior to 10Hz stimulation in inducing reductions in PTSD symptoms and depression in military Veterans. Our findings pave the way for further research trials to validate and optimize iTBS for PTSD symptoms.