MST Shows Age-Related Differences in MDD Outcomes, With Lina Jia, MD, PhD

Adolescents with treatment-resistant major depressive disorder (MDD) receiving magnetic seizure therapy (MST) experienced faster symptom improvement, fewer cognitive adverse events, and better overall tolerability compared to adults, according to a new prospective comparative study.1

The findings address a critical evidence gap in neuromodulation for depression, as most existing data are derived from adult populations despite important developmental, neurobiological, and safety considerations in younger patients.

MST has emerged as a potential alternative to modified electroconvulsive therapy, offering antidepressant efficacy with reduced cognitive burden.2 However, age-related differences in response and tolerability have not been well characterized.

Investigators conducted a single-center, prospective study of 128 patients with treatment-resistant MDD, including 67 adolescents (ages 12–18) and 61 adults (ages 19–65), all treated with a standardized MST.1 Participants were assessed at baseline, 72 hours post-treatment, and 3 months post-treatment using validated clinical and safety measures: 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI), Columbia-Suicide Severity Rating Scale (C-SSRS), and the Montreal Cognitive Assessment (MoCA). Cognitive subdomains were analyzed to detect domain-specific effects.

Both age groups showed significant reductions in depressive, anxiety, and comorbid psychiatric symptoms following MST, with effects maintained at 3 months. However, adolescents demonstrated a more rapid early response, with significantly lower HAMD-17 and HAMA scores at 72 hours compared with adults (P <.001), while adults reached similar symptom severity by 3 months.

Cognitive outcomes differed by age: adults experienced greater short-term declines in delayed recall and executive function at 72 hours, whereas adolescents showed no significant cognitive change, with no between-group differences at 3 months. Adults also reported greater rates of headache, memory complaints, fatigue, and transient vital sign abnormalities, while adolescents experienced fewer somatic adverse events. The data suggest that MST is effective across age groups but may offer distinct clinical and safety advantages in adolescent MDD.

In a Q&A, investigator Lina Jia, MD, PhD, from Beth Israel Deaconess Medical Center, Harvard Medical School, and Xuanwu Hospital in China, discussed the implications of these findings.

HCPLive: How do your results support the use of MST as a treatment option for adolescent MDD compared to standard pharmacotherapy or cognitive behavioral therapy? What advantages does MST offer?

Jia: Our findings support MST as a promising neuromodulation option for adolescents with treatment-resistant depression, demonstrating clinically meaningful symptom reduction and a favorable tolerability profile. In our cohort, adolescents showed faster early symptom improvement (within 72 hours) and better cognitive preservation compared with adults, alongside fewer somatic side effects, suggesting that MST may be particularly suitable when rapid symptom relief and cognitive safety are prioritized.

While our study did not directly compare MST against medication or CBT, the results position MST as a potential alternative for adolescents who have [an] insufficient response to standard treatments or require faster improvement. Importantly, comparative data indicate MST may have cognitive safety advantages over ECT, including faster reorientation and fewer subjective cognitive or physical adverse effects in a randomized clinical trial. Clinically, this matters because concerns about cognitive adverse effects often constrain the use of seizure therapies in youth.

HCPLive: In your study, adolescents showed faster symptom improvement at 72 hours post-MST compared to adults. What neurobiological or developmental factors might explain this difference?

Jia: A plausible explanation is developmental neuroplasticity. Adolescence is characterized by ongoing maturation of prefrontal-limbic circuits, synaptic pruning, and dynamic changes in excitation-inhibition balance. Such developmental biology may confer greater responsiveness to stimulation-induced network modulation, resulting in earlier clinical change after MST. Our interpretation is consistent with the broader literature that seizure-based neuromodulation can alter large-scale functional connectivity patterns implicated in depressive symptomatology.

HCPLive: Despite faster early improvements in adolescents, adults showed continued symptom reduction over three months. How should clinicians interpret these different trajectories?

Jia: Clinicians can interpret these trajectories as age-dependent time courses of treatment response rather than differences in ultimate benefit. Adolescents may show a stronger “early response signal,” whereas adults may demonstrate a more gradual but sustained improvement over follow-up. This pattern is compatible with the idea that seizure-based therapies can trigger both acute state shifts and longer-term network-level adaptations that unfold over weeks to months.

Longitudinal neuroimaging studies of seizure therapies (such as ECT) support the concept that connectivity changes evolve over time and may relate to delayed clinical gains. For adolescents, early improvement may help engagement and adherence. For adults, lack of dramatic early change should not be misinterpreted as non-response; continued improvement may occur with time.

HCPLive: Suicidal ideation decreased in both groups, but adults had a greater reduction. How might psychosocial or developmental factors contribute to this age-related difference?

Jia: Developmental context may modulate how rapidly suicidal ideation resolves. In adolescents, suicidality can be more tightly linked to acute psychosocial stressors, family or environmental conflict, peer dynamics, and impulsivity, such that symptom relief may not immediately translate into proportional reductions in suicidal thinking. In adults, suicidal ideation may track more closely with core depressive severity and thus show larger reductions in tandem with symptomatic improvement.

For adolescents, MST or ECT should be delivered within a comprehensive care framework that includes structured psychotherapy and coordinated family and school support to reduce the risk of relapse and sustain clinical gains.

HCPLive: Adolescents required slightly more MST sessions on average than adults. What factors should guide the number of sessions in clinical practice?

Jia: Session number should be guided by a measurement-based care framework, balancing symptom trajectory, functional recovery, and tolerability. Key factors include baseline severity, pace of response, comorbidity (such as anxiety [or] trauma), and cognitive or somatic adverse effects. Because seizure therapies show inter-individual variability in response, session tailoring is standard practice.

HCPLive: What are the limitations of this study clinicians should be aware of when applying these findings in practice?

Jia: Clinicians should interpret these findings within several important contextual considerations. Our study was not randomized and did not include a direct comparator against pharmacotherapy, CBT, or ECT, which limits formal comparative effectiveness conclusions. In addition, the single-center design and modest sample size may affect generalizability, and heterogeneity in concomitant medications and comorbidities could introduce residual confounding. Cognitive outcomes were assessed using brief screening measures, which may not capture subtle domain-specific changes, and longer follow-up will be necessary to define [the] durability of response and cognitive trajectories.

As one of the first prospective real-world evaluations of MST in adolescents, our findings provide clinically informative evidence regarding feasibility, safety, and age-related response patterns, and support the need for larger controlled trials.

HCPLive: Based on your findings, what future research directions are most critical for optimizing age-specific MST protocols and understanding their underlying neurobiological mechanisms?

Jia: Future research should move beyond fixed, one-size-fits-all protocols toward a more individualized and precision-treatment framework. Large multi-center randomized controlled trials in adolescents are needed to compare MST with optimized standard care and…with ECT, in order to establish relative effectiveness and safety.

At the same time, incorporating neurobiological markers, such as resting-state functional connectivity, EEG measures, and detailed neurocognitive profiling, may help identify predictors of response and developmental moderators. These tools could enable more quantitative and personalized dosing strategies, with stimulation parameters (intensity, frequency, seizure threshold titration, and coil positioning) tailored to each patient’s clinical severity and tolerability.

References

1. Wang M, Wang W, Wan S, Zhang H, Lu Y, Jia L. Magnetic seizure therapy for major depressive disorder: age-related differences in efficacy and cognitive side effects. BMC Psychiatry. 2026;26(1):26. Published 2026 Jan 8. doi:10.1186/s12888-025-07573-x

2. Derman C. Magnetic Seizure Therapy Rivals ECT, Protects Cognition in Adolescent MDD. HCPLive. Published on October 16, 2025. Accessed on February 9, 2026. https://www.hcplive.com/view/magnetic-seizure-therapy-rivals-ect-protects-cognition-adolescent-mdd.