Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation and Expressive Writing for Post-Traumatic Stress

Efficacy and Safety of a Combined Intervention of Repetitive Transcranial Magnetic Stimulation and Expressive Writing According to Timing of Administration: A Parallel-Group Randomized Controlled Trial in Adults With Post-Traumatic Stress Symptoms

The goal of this clinical trial is to learn if a combined treatment using repetitive transcranial magnetic stimulation (rTMS) and expressive writing works to reduce symptoms of post-traumatic stress in adults. It will also study how safe this treatment is and whether the timing of rTMS changes how well it works.

The main questions it aims to answer are:

• Does this combined treatment lower symptoms of post-traumatic stress?
• Does it work better when rTMS is given before or after expressive writing?

Researchers will compare three groups to see which approach works best:

• rTMS given before expressive writing
• rTMS given after expressive writing
• Sham stimulation (a look-alike procedure that does not provide real stimulation)

Participants will:

• Take part in sessions that include expressive writing about emotional experiences
• Receive either real rTMS or sham stimulation
• Complete questionnaires about post-traumatic stress, anxiety, depression, and mood
• Have their heart rate and skin responses measured during the sessions
• Be assessed before the study, after the sessions, and one month later

This study includes adults aged 18 to 65 who have experienced at least one traumatic or highly stressful event and report symptoms of post-traumatic stress.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adults
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation; Behavioral: Expressive writing; Device: Sham rTMS

Detailed Description

Objective: To evaluate the efficacy and safety of a combined intervention consisting of repetitive transcranial magnetic stimulation (rTMS) and emotional re-experiencing through expressive writing, as well as to analyze the influence of the timing of rTMS application on clinical outcomes in adults with post-traumatic stress symptomatology.

Design: A randomized controlled superiority trial with three parallel groups: (1) rTMS administered 10 minutes prior to emotional re-experiencing via expressive writing, (2) rTMS administered 10 minutes after emotional re-experiencing, and (3) sham stimulation with an equivalent temporal structure. Assessments will be conducted at baseline, post-intervention, and at one-month follow-up.

Study setting: University Institute of Neurosciences (IUNE), University of La Laguna (ULL), located in San Cristóbal de La Laguna, Santa Cruz de Tenerife, Canary Islands, Spain.

Participants: Community-dwelling adults aged 18 to 65 years, exposed to at least one traumatic or highly stressful event, presenting post-traumatic stress symptomatology defined by a score ≥ 24 on the Revised Impact of Event Scale (IES-R). A total sample size of 45 participants is anticipated, distributed across three groups of 15 participants each.

Measures: Post-traumatic stress symptomatology will be assessed using the IES-R; anxiety symptoms using the GAD-7; and depressive symptoms using the PHQ-9. Affect will be assessed with the PANAS. Physiological arousal will be recorded via heart rate and skin conductance using a polygraph. rTMS will be delivered using a Magstim Rapid2 stimulator with a figure-of-eight coil, guided by BrainSight neuronavigation. Emotional re-experiencing will be induced through expressive writing.

Outcomes: The primary outcome will be the change in post-traumatic stress symptomatology. Secondary outcomes will include safety, measured by the frequency and type of adverse events and serious adverse events; changes in anxiety and depressive symptomatology; and situational changes in affect and physiological arousal during expressive writing sessions.

Data analysis: Baseline characteristics of each group will be presented in a descriptive table. Continuous variables will be summarized using means and standard deviations, whereas categorical variables will be reported as absolute and relative frequencies. Between-group differences at baseline will be explored using analysis of variance (ANOVA) for continuous variables and chi-square tests of independence for categorical variables. Assumptions of normality and homogeneity of variances will be assessed beforehand. When these assumptions are violated, non-parametric alternatives will be used, including the Kruskal-Wallis test for continuous variables and Fisher's exact test for categorical variables.

Intervention effects will be analyzed using linear mixed-effects models and, as a complementary approach, repeated-measures ANOVA. Main effects of group (sequential 1, sequential 2, and sham) and time (baseline, post-intervention, and one-month follow-up), as well as the group × time interaction, will be examined for the primary outcome (post-traumatic stress symptomatology) and secondary outcomes (anxiety symptoms, depressive symptoms, and situational changes).

Analyses will be conducted under both an intention-to-treat (ITT) and per-protocol (PP) framework. The ITT population will include all randomized participants who have received at least one rTMS session, consistent with previous research (Philip et al., 2019). The PP population will include participants who completed the assigned treatment without substantial protocol deviations.

For ITT analyses, missing data will be handled using linear mixed-effects models estimated via maximum likelihood, allowing the use of all available data under the assumption that missingness is at random (MAR). If evidence suggests that missing data may depend on unobserved variables (not missing at random, NMAR), sensitivity analyses will be conducted using pattern-mixture models or selection models to assess the robustness of the findings.

Subgroup analyses are not planned. Results will be reported in tables with descriptive statistics by group and time point. Effect sizes (Cohen's d and partial eta squared) will be reported along with 95% confidence intervals. The statistical significance threshold will be set at α = .05, with Bonferroni correction applied when appropriate for multiple comparisons. All analyses will be performed using R statistical software (R Core Team, 2025).

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lilisbeth Perestelo-Pérez, Doctor in Psychology; Phone Number: +34 922478267; Email: lilisbeth.peresteloperez@sescs.es
• Study Contact Backup: Name: Wenceslao Peñate-Castro, Doctor in Psychology; Email: wpenate@ull.edu.es

Study Locations

• Spain
  • Santa Cruz de Tenerife
    • San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain, 38200
      • Instituto Universitario de Neurociencias (IUNE) de la Universidad de La Laguna (ULL)
      • Contact: Wenceslao Peñate-Castro, Doctor in Psychology; Phone Number: +34 922 31 74 60; Email: wpenate@ull.edu.es
    • Santa Cruz de Tenerife, Santa Cruz de Tenerife, Spain, 38109
      • Servicio de Evaluación del Servicio Canario de Salud
      • Contact: Lilisbeth Perestelo-Pérez, Doctor in Psychology; Phone Number: +34 922478267; Email: lilisbeth.peresteloperez@sescs.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Be between 18 and 65 years of age.
• Have experienced at least one traumatic or highly stressful event, regardless of how much time has passed since the event occurred.
• Present a score ≥ 24 on the Revised Impact of Event Scale (IES-R).
• Have post-traumatic stress symptoms that are not better explained by another clinical condition or mental disorder.

Exclusion Criteria:

• History of epilepsy, seizures, or convulsions.
• Presence of intracranial or cranial metal incompatible with rTMS.
• History of severe traumatic brain injury.
• Pregnancy or reasonable possibility of pregnancy.
• Cochlear implants or internal pulse generators.
• Use of medication that lowers the seizure threshold.
• Current suicidal ideation or behaviour, or recent suicidal ideation within the past month.
• Other medical or psychiatric conditions that contraindicate the use of rTMS.
• Any condition that prevents participation in any of the study interventions.
• Currently receiving psychological and/or pharmacological treatment for PTSD, acute stress, or another disorder that could account for post-traumatic stress symptoms.
• Failure to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rTMS applied 10 minutes after emotional re-experiencing through expressive writing (SG1); Both experimental groups will receive the same excitatory repetitive transcranial magnetic stimulation (rTMS) protocol targeting the right dorsolateral prefrontal cortex (rDLPFC). The stimulation protocol will consist of: Frequency: 10 Hz; Intensity: 80% of resting motor threshold; Train duration: 4 seconds; Inter-train interval: 11 seconds; 50 trains per session; Approximately 12 minutes per session; Total of 2,000 pulses per session Treatment will be administered five days per week over three weeks, for a total of 15 sessions and 30,000 pulses. Emotional re-experiencing will be induced through expressive writing. Participants will write for 15 minutes once per week about the thoughts and emotions associated with their traumatic or highly stressful experiences throughout the treatment period. In this group, expressive writing will take place 10 minutes before the rTMS session.	Device: Repetitive Transcranial Magnetic Stimulation; rTMS will be administered by an experienced technician using a figure-of-eight coil connected to a Magstim Rapid2 stimulator (Magstim, Whitland, Dyfed, United Kingdom). Target localization will be performed using stereotactic neuronavigation with the frameless BrainSight system (Rogue Research, Canada) and a Polaris infrared tracking system (Northern Digital, Canada). Before each session and for each participant, the motor hotspot and resting motor threshold (rMT) will be determined. The hotspot will be defined as the stimulation site over the left primary motor cortex that produces the strongest and most consistent motor-evoked potentials in the first dorsal interosseous muscle, recorded via electromyography using a Biopac MP-35 system. The resting motor threshold will be defined as the minimum stimulation intensity capable of eliciting at least five small-amplitude motor responses out of ten stimuli applied to the relaxed muscle. The rTMS intensity will be individually adjusted; Other Names: rTMS; Behavioral: Expressive writing; Emotional re-experiencing will be induced through expressive writing. Participants will write for 15 minutes once per week about the thoughts and emotions associated with their traumatic or highly stressful experiences throughout the treatment period (Pennebaker & Chung, 2011).
Experimental: rTMS applied 10 minutes before emotional re-experiencing through expressive writing (SG2); Both experimental groups will receive the same excitatory repetitive transcranial magnetic stimulation (rTMS) protocol targeting the right dorsolateral prefrontal cortex (rDLPFC). The stimulation protocol will consist of: Frequency: 10 Hz; Intensity: 80% of resting motor threshold; Train duration: 4 seconds; Inter-train interval: 11 seconds; 50 trains per session; Approximately 12 minutes per session; Total of 2,000 pulses per session Treatment will be administered five days per week over three weeks, for a total of 15 sessions and 30,000 pulses. Emotional re-experiencing will be induced through expressive writing. Participants will write for 15 minutes once per week about the thoughts and emotions associated with their traumatic or highly stressful experiences throughout the treatment period. In this group, expressive writing will take place 10 minutes after the rTMS session.	Device: Repetitive Transcranial Magnetic Stimulation; rTMS will be administered by an experienced technician using a figure-of-eight coil connected to a Magstim Rapid2 stimulator (Magstim, Whitland, Dyfed, United Kingdom). Target localization will be performed using stereotactic neuronavigation with the frameless BrainSight system (Rogue Research, Canada) and a Polaris infrared tracking system (Northern Digital, Canada). Before each session and for each participant, the motor hotspot and resting motor threshold (rMT) will be determined. The hotspot will be defined as the stimulation site over the left primary motor cortex that produces the strongest and most consistent motor-evoked potentials in the first dorsal interosseous muscle, recorded via electromyography using a Biopac MP-35 system. The resting motor threshold will be defined as the minimum stimulation intensity capable of eliciting at least five small-amplitude motor responses out of ten stimuli applied to the relaxed muscle. The rTMS intensity will be individually adjusted; Other Names: rTMS; Behavioral: Expressive writing; Emotional re-experiencing will be induced through expressive writing. Participants will write for 15 minutes once per week about the thoughts and emotions associated with their traumatic or highly stressful experiences throughout the treatment period (Pennebaker & Chung, 2011).
Sham Comparator: Sham stimulation combined with expressive writing, divided equally to mirror the two active arms; Sham stimulation will be delivered using a placebo coil that reproduces the acoustic and procedural characteristics of rTMS without producing effective cortical stimulation. Emotional re-experiencing will be induced through expressive writing. Participants will write for 15 minutes once per week about the thoughts and emotions associated with their traumatic or highly stressful experiences throughout the treatment period. This group will be divided into two halves, each mirroring the timing conditions of each experimental study arm.	Behavioral: Expressive writing; Emotional re-experiencing will be induced through expressive writing. Participants will write for 15 minutes once per week about the thoughts and emotions associated with their traumatic or highly stressful experiences throughout the treatment period (Pennebaker & Chung, 2011).; Device: Sham rTMS; Sham stimulation will be delivered using a placebo coil that reproduces the acoustic and procedural characteristics of rTMS without producing effective cortical stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-traumatic stress symptoms	Post-traumatic stress symptomatology will be assessed using the Revised Impact of Event Scale (IES-R), a 22-item self-report instrument designed to measure subjective distress associated with traumatic or highly stressful events. The scale evaluates three core dimensions: intrusion, avoidance, and hyperarousal. In the present study, the IES-R will be used both to quantify the severity of post-traumatic stress symptoms and to establish eligibility criteria.	Assessment at baseline, immediately after treatment and one month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Safety will be described by the number of participants who experience adverse events (AEs) and serious adverse events (SAEs), as well as by the total number of AEs and SAEs observed. An adverse event is defined as any undesirable experience associated with the use of a medical product in a participant. A serious adverse event, according to the U.S. Food and Drug Administration (FDA), refers to any undesirable experience associated with a medical treatment that results in death, is life-threatening, requires hospitalization, leads to disability or permanent damage, necessitates intervention to prevent further harm, or results in any other significant medical consequence.	Through study completion, an average of 2 months
Anxiety	Anxiety symptomatology will be assessed using the Generalized Anxiety Disorder-7 questionnaire (GAD-7). The GAD-7 is a brief 7-item self-report scale designed to evaluate the severity of generalized anxiety symptoms.	Assessment at baseline, immediately after treatment and one month follow-up
Depression	Depressive symptomatology will be assessed using the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is a 9-item self-report measure designed to evaluate the severity of depressive symptoms.	Assessment at baseline, immediately after treatment and one month follow-up
Positive and negative affect	Affect will be assessed using the Positive and Negative Affect Schedule (PANAS). The PANAS is a 20-item self-report scale composed of two 10-item subscales that measure positive affect and negative affect, respectively.	Assessment immediately after every expressive writing session
Physiological arousal	Physiological arousal will be indexed by heart rate and skin conductance, which will be recorded using a polygraph.	From start to end of every expressive writing session

Collaborators and Investigators

• Sponsor: Servicio Canario de Salud
• Collaborators: University of La Laguna

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: April 21, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: randomized controlled trial; repetitive transcranial magnetic stimulation; rTMS; TMS; transcranial magnetic stimulation; Post-traumatic stress
• Additional Relevant MeSH Terms: Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: PI/FIISC/EMT-TEPT-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant data, together with the statistical procedures used for analysis, will be made available as supplementary material in the final open-access publication of the study. The templates of all self-report measures used in the assessment will also be included. Participants will be informed of this procedure in the participant information sheet and will provide corresponding informed consent.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No