Key messages
• rTMS probably does not reduce the severity of PTSD symptoms by the end of treatment compared with placebo rTMS (sham stimulation) in adults. These findings, however, were limited by wide variations in how the treatment was delivered and the small number of participants.
• Occurrences of serious unwanted effects in studies of rTMS for PTSD have been rare.
• We need more studies investigating rTMS for PTSD in adults. It would be helpful if future studies reported on unwanted effects in greater detail, and followed participants for longer after treatment to assess PTSD severity.
What is post-traumatic stress disorder?
Post-traumatic stress disorder (PTSD) is a mental health condition characterized by distressing and impairing symptoms that develop in some individuals after exposure to a traumatic event. When left untreated, many individuals with PTSD suffer for years.
How is PTSD treated?
Several treatments exist for PTSD, including medication and psychotherapy. However, existing treatments are associated with high dropout rates, which suggests people may have problems with tolerating treatment and may continue to experience symptoms. More effective treatments for PTSD are needed. Repetitive transcranial magnetic stimulation (rTMS) may be a promising treatment for PTSD.
What is rTMS?
rTMS is a non-invasive treatment that involves inducing an electrical field in brain tissue by placing a coil against the scalp that releases magnetic pulses. The biological pathways by which rTMS produces changes in mental health symptoms remain unclear and are an active area of research. rTMS has proven effective in treating people with major depressive disorder and obsessive-compulsive disorder – two mental health conditions that share important characteristics with PTSD.
What did we want to find out?
We wanted to find out if rTMS is better than placebo treatment (sham stimulation) for reducing the severity of PTSD immediately after treatment, and if it is associated with any serious unwanted effects during treatment. We were interested in the persistence of treatment effects, and so aimed to explore the impact of rTMS on PTSD severity at 1 to 4 weeks and 1 to 3 months after treatment. To investigate how well people tolerate rTMS, we compared the number of participants who dropped out of treatment early in active versus sham rTMS groups. Finally, we wanted to examine the impact of rTMS treatment on anxiety and depression immediately after treatment.
What did we do?
We searched for studies that examined rTMS compared with sham rTMS in adults with PTSD. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and number of participants.
What did we find?
We included data from 577 people who participated in 13 studies. The studies were conducted in countries around the world, with 5 carried out in the USA. Three studies with 99 participants contributed to our main analysis examining the effect of rTMS on PTSD severity immediately after treatment. Five studies with 251 participants contributed to our main estimate of rTMS safety (occurrence of serious unwanted events).
Main results
• rTMS probably makes little to no difference in PTSD symptoms immediately after treatment compared to sham treatment. However, only 3 studies contributed data to this primary analysis. When we analyzed the results from 6 studies, the effectiveness of rTMS compared to sham treatment varied across the studies. We did not have enough information from the studies included in this review to explore reasons for this variation. Other reviews of rTMS for PTSD suggest some ways of delivering rTMS may be more effective than others.
• Serious unwanted effects from rTMS treatment are rare. It is unclear whether rTMS is associated with increased chances of experiencing a serious unwanted effect.
• We do not know if rTMS has an effect on PTSD severity several weeks or months after treatment as there was insufficient information to explore this question.
• rTMS may make little to no difference in the rate of dropout from treatment or in depression and anxiety symptoms immediately after treatment.
What are the limitations of the evidence?
We are moderately confident in our finding that rTMS probably makes little to no difference in PTSD severity immediately after treatment. This means there is a fair chance that our conclusion may change as new evidence emerges. We are not confident in the evidence about serious unwanted events due to limited descriptions of unwanted effects and how they were measured in the included studies. In general, rates of serious unwanted effects are difficult to estimate, given the rarity of such events. This problem was exacerbated in the current review by the small number of study participants able to be included in this analysis.
How current is the evidence?
The evidence is current to January 2023.
Based on moderate-certainty evidence, our review suggests that active rTMS probably makes little to no difference to PTSD severity immediately following treatment compared to sham stimulation. However, significant heterogeneity in efficacy was detected when we included a larger number of studies in sensitivity analysis. We observed considerable variety in participant and protocol characteristics across studies included in this review. For example, studies tended to be weighted towards inclusion of either male veterans or female civilians. Studies varied greatly in terms of the proportion of the sample with comorbid depression. Study protocols differed in treatment design and stimulation parameters (e.g. session number/duration, treatment course length, stimulation intensity/frequency, location of stimulation). These differences may affect efficacy, particularly when considering interactions with participant factors.
Reported rates of serious adverse events were very low (< 1%) across active and sham conditions. It is uncertain whether rTMS increases the risk of serious adverse event occurrence, as our certainty of evidence was very low. Studies frequently lacked clear definitions for serious adverse events, as well as detail on tracking/assessment of data and information on the safety population. Increased reporting on these elements would likely aid the advancement of both research and clinical recommendations of rTMS for PTSD.
Currently, there is insufficient evidence to meta-analyze PTSD remission, PTSD treatment response, and PTSD severity at different periods post-treatment. Further research into these outcomes could inform the clinical use of rTMS. Additionally, the relatively large contribution of data from trials that focused on white male veterans may limit the generalizability of our conclusions. This could be addressed by prioritizing recruitment of more diverse participant samples.
The estimated lifetime prevalence of post-traumatic stress disorder (PTSD) in adults worldwide has been estimated at 3.9%. PTSD appears to contribute to alterations in neuronal network connectivity patterns. Current pharmacological and psychotherapeutic treatments for PTSD are associated with inadequate symptom improvement and high dropout rates. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive therapy involving induction of electrical currents in cortical brain tissue, may be an important treatment option for PTSD to improve remission rates and for people who cannot tolerate existing treatments.
To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on post-traumatic stress disorder (PTSD) in adults.
We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two clinical trials registers. We checked reference lists of relevant articles. The most recent search was January 2023.
We included randomized controlled trials (RCTs) assessing the efficacy and safety of rTMS versus sham rTMS for PTSD in adults from any treatment setting, including veterans. Eligible trials employed at least five rTMS treatment sessions with both active and sham conditions. We included trials with combination interventions, where a pharmacological agent or psychotherapy was combined with rTMS for both intervention and control groups. We included studies meeting the above criteria regardless of whether they reported any of our outcomes of interest.
Two review authors independently extracted data and assessed the risk of bias in accordance with Cochrane standards. Primary outcomes were PTSD severity immediately after treatment and serious adverse events during active treatment. Secondary outcomes were PTSD remission, PTSD response, PTSD severity at two follow-up time points after treatment, dropouts, and depression and anxiety severity immediately after treatment.
We included 13 RCTs in the review (12 published; 1 unpublished dissertation), with 577 participants. Eight studies included stand-alone rTMS treatment, four combined rTMS with an evidence-based psychotherapeutic treatment, and one investigated rTMS as an adjunctive to treatment-as-usual. Five studies were conducted in the USA, and some predominantly included white, male veterans.
Active rTMS probably makes little to no difference to PTSD severity immediately following treatment (standardized mean difference (SMD) -0.14, 95% confidence interval (CI) -0.54 to 0.27; 3 studies, 99 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision (sample size insufficient to detect a difference of medium effect size). We deemed one study as having a low risk of bias and the remaining two as having 'some concerns' for risk of bias. A sensitivity analysis of change-from-baseline scores enabled inclusion of a greater number of studies (6 studies, 252 participants). This analysis yielded a similar outcome to our main analysis but also indicated significant heterogeneity in efficacy across studies, including two studies with a high risk of bias.
Reported rates of serious adverse events were low, with seven reported (active rTMS: 6; sham rTMS: 1). The evidence is very uncertain about the effect of active rTMS on serious adverse events (odds ratio (OR) 5.26, 95% CI 0.26 to 107.81; 5 studies, 251 participants; very low-certainty evidence [Active rTMS: 23/1000, sham rTMS: 4/1000]). We downgraded the evidence by one level for risk of bias and two levels for imprecision. We rated four of five studies as having a high risk of bias, and the fifth as 'some concerns' for bias.
We were unable to assess PTSD remission immediately after treatment as none of the included studies reported this outcome.