Modeling the antidepressant treatment response to transcranial magnetic stimulation using an exponential decay function.

Recovery from depression often demonstrates a nonlinear pattern of treatment response, where the largest reduction in symptoms is observed early followed by smaller improvements. This study investigated whether this exponential pattern could model the antidepressant response to repetitive transcranial magnetic stimulation (TMS). Symptom ratings from 97 patients treated with TMS for depression were collected at baseline and after every five sessions. A nonlinear mixed-effects model was constructed using an exponential decay function. This model was also applied to group-level data from several published clinical trials of TMS for treatment-resistant depression. These nonlinear models were compared to corresponding linear models. In our clinical sample, response to TMS was well modeled with the exponential decay function, yielding significant estimates for all parameters and demonstrating superior fit compared to a linear model. Similarly, when applied to multiple studies comparing TMS modalities as well as to previously identified treatment response trajectories, the exponential decay models yielded consistently better fits compared to linear models. These results demonstrate that the antidepressant response to TMS follows a nonlinear pattern of improvement that is well modeled with an exponential decay function. This modeling offers a simple and useful framework to inform clinical decisions and future studies.

Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder: Prevention in the Context of New Trauma.

Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that can result from experiencing a traumatic event. While a single index trauma can result in PTSD, patients often have additional traumatic events over the course of their lives. Despite this, little research to date has focused on prevention of PTSD recurrence following a novel traumatic experience. We present three cases of individuals with chronic PTSD who experienced an additional traumatic experience during treatment with transcranial magnetic stimulation (TMS) at VA Providence. Despite expectations to the contrary, TMS appeared to prevent a recurrence or worsening of their PTSD symptoms. We discuss possible neurobiological explanations for these outcomes and implications for possible use of TMS to prevent PTSD following trauma.

Repetitive Transcranial Magnetic Stimulation for Depression and Posttraumatic Stress Disorder in Veterans With Mild Traumatic Brain Injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) is a signature injury of military conflicts and is prevalent in veterans with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Although therapeutic transcranial magnetic stimulation (TMS) can reduce symptoms of depression and PTSD, whether traumatic brain injury (TBI) affects TMS responsiveness is not yet known. We hypothesized mTBI would be associated with higher pretreatment symptom burden and poorer TMS response. MATERIALS AND METHODS: We investigated a registry of veterans (N = 770) who received TMS for depression across the US Veterans Affairs system. Of these, 665 (86.4%) had data on TBI and lifetime number of head injuries while 658 had complete data related to depression outcomes. Depression symptoms were assessed using the nine-item Patient Health Questionnaire and PTSD symptoms using the PTSD Checklist for DSM-5. Linear mixed effects models and t-tests evaluated whether head injuries predicted symptom severity before treatment, and how TBI status affected clinical TMS outcomes. RESULTS: Of the 658 veterans included, 337 (50.7%) reported previous mTBI, with a mean of three head injuries (range 1-20). TBI status did not predict depressive symptom severity or TMS-associated changes in depression (all p's > 0.1). TBI status was associated with a modest attenuation of TMS-associated improvement in PTSD (in patients with PTSD Checklist for DSM-5 scores > 33). There was no correlation between the number of head injuries and TMS response (p > 0.1). CONCLUSIONS: Contrary to our hypothesis, presence of mTBI did not meaningfully change TMS outcomes. Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness. Limitations include those inherent to retrospective registry studies and self-reporting. Although these findings are contrary to our hypotheses, they support the safety and effectiveness of TMS for MDD and PTSD in patients who have comorbid mTBI.

Transdiagnostic Symptom Subtypes to Predict Response to Therapeutic Transcranial Magnetic Stimulation in Major Depressive Disorder and Posttraumatic Stress Disorder.

The diagnostic categories in psychiatry often encompass heterogeneous symptom profiles associated with differences in the underlying etiology, pathogenesis and prognosis. Prior work demonstrated that some of this heterogeneity can be quantified though dimensional analysis of the Depression Anxiety Stress Scale (DASS), yielding unique transdiagnostic symptom subtypes. This study investigated whether classifying patients according to these symptom profiles would have prognostic value for the treatment response to therapeutic transcranial magnetic stimulation (TMS) in comorbid major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). A linear discriminant model was constructed using a simulation dataset to classify 35 participants into one of the following six pre-defined symptom profiles: Normative Mood, Tension, Anxious Arousal, Generalized Anxiety, Anhedonia and Melancholia. Clinical outcomes with TMS across MDD and PTSD were assessed. All six symptom profiles were present. After TMS, participants with anxious arousal were less likely to achieve MDD remission compared to other subtypes (FET, odds ratio 0.16, p = 0.034), exhibited poorer PTSD symptom reduction (21% vs. 46%; t (33) = 2.025, p = 0.051) and were less likely to complete TMS (FET, odds ratio 0.066, p = 0.011). These results offer preliminary evidence that classifying individuals according to these transdiagnostic symptom profiles may offer a simple method to inform TMS treatment decisions.