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DURABILITY OF TMS TREATMENT FOR VETERANS WITH MDD EXAMINED VIA SIGNIFICANT PSYCHIATRIC EVENTS ASSOCIATED WITH RELAPSE (SPEAR): A PROPOSED NEW COMPOSITE OUTCOME MEASURE FOR HIGH SEVERITY/LOW FREQUENCY MENTAL HEALTH EVENTS

Zachary Zuschlag — Nupur Kroger1, Athanasios Tsalatsanis2, Michael Norred1, Michelle Madore3 1James A. Haley Veterans Hospital, 2University of South Florida, 3Sierra Pacific MIRECC VA Palo Alto Health Care System; Stanford University School of Medicine Zachary Zuschlag, James A. Haley Veterans Hospital

2026 ASCP Annual Meeting

Background

Transcranial Magnetic Stimulation (TMS) has established efficacy for treatment resistant major depressive disorder (MDD-TR), however, the durability of response to this treatment intervention is an area in need of further investigation particularly in the Veteran population. Historically, TMS durability has been examined utilizing measurement based care (MBC) mental health assessment scale scores given at predetermined time points which allows calculations of durability based on relapse utilizing numerical threshold scores. Although this approach has been the standard for research purposes and allows systematic monitoring with high reproducibility, MBC scales often have poor or limited known correlations to clinically relevant relapse events such as hospitalizations and suicide. Subsequently, the authors developed a new composite marker termed Significant Psychiatric Events Associated with Relapse (SPEAR) consisting of mental health hospitalization, suicide attempt, death by suicide, or requirement for additional neuromodulation interventions; a clinically relevant aggregate marker that represents events that are highly impactful to patients and to health care systems, and may be a more important and accurate marker of true psychiatric relapse. This research report will review data from the national VA Clinical TMS Program looking at TMS durability for MDD utilizing traditional MBC methodology, then will present results from a study analyzing TMS durability utilizing SPEAR criteria.

Methods

A longitudinal retrospective cohort analysis was conducted on all Veterans receiving TMS treatment for MDD at a large academic VA medical center from November 1, 2013, through December 31, 2021. For the primary endpoint, the composite measure SPEAR was utilized to assess relapse. Secondary endpoints included examining post-TMS changes in psychopharmacological regimens as a marker for relapse. Data collected included demographic information, psychiatric history, and psychiatric treatment. Medication data was captured and reported by class. MADRS was used to determine response to treatment. Durability was examined at the 3-month, 6-month, one year and two years post TMS treatment timepoints for primary and secondary outcomes. Associations between covariates of interest and durability of response were analyzed.

Results

Study cohort consisted of 217 Veterans, of whom 159 had the required assessments and were included in analyses. TMS was shown to be a durable treatment for MDD with durability rates of 96.18% at 90 days post treatment, 92.37% at 180 days, 87.79% at one year, and 84.73% at two years when utilizing SPEAR criteria. Durability rates based on pharmacological medication changes were 72.52% at 90 days , 59.54% at 180 days, 44.25% at 1 year, and 35.38% at 2 years. Associations between covariates of interest and durability rates as per SPEAR criteria were analyzed utilizing univariate survival analyses. On initial analysis, prior course of TMS, prior course of ECT, and SSRI at the time of treatment were all associated with differences in durability rates. However, these were no longer significant after adjusting for multiple comparisons.

Conclusions

TMS is a durable treatment for Veterans with MDD with 84.73% of Veterans having at least a 2-year period without significant relapse as defined by SPEAR. No covariates analyzed were associated with differences in TMS durability. Prospective studies analyzing different markers of relapse and larger sample sizes are needed. Further studies are also warranted to assess the utility of SPEAR as a composite measure to capture high severity/low frequency mental health events associated with relapse.

Learning Objective 1: Understand SPEAR (Significant Psychiatry Events Associated with Relapse), a proposed new composite end point to capture high severity/low frequency mental health events

Learning Objective 2: Describe differences between SPEAR and traditional measures or relapse and compare durability rates between approaches

References

  1. Madore MR, Kozel FA, Williams LM, Green LC, George MS, Holtzheimer PE, Yesavage JA, Philip NS. Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. J Affect Disord. 2022 Jan 15;297:671-678. doi: 10.1016/j.jad.2021.10.025. Epub 2021 Oct 20. PMID: 34687780; PMCID: PMC8667345. 2) Lisha I, Godbole Kroger NB, Tsalatsanis A, Norred MA, Daneman LEW, Tindall B, Grewal EP, Araque SM, Zuschlag ZD. The durability of response to transcranial magnetic stimulation in veterans with major depressive disorder. J Affect Disord. 2025 Dec 27;399:121032. doi: 10.1016/j.jad.2025.121032. Epub ahead of print. PMID: 41461238.