ECT sessions may shape depression treatment outcomes, reveals research

In a comprehensive peer-reviewed Genomic Press Thought Leaders Invited Review, researchers have unveiled critical insights into how the number of electroconvulsive therapy (ECT) sessions influences treatment outcomes for depression, potentially transforming clinical decision-making for one of psychiatry's most effective yet controversial treatments.

The review, published in Brain Medicine, synthesizes decades of research to address a fundamental question that has long puzzled clinicians: How many ECT sessions are optimal for treating severe depression while minimizing cognitive side effects?

"ECT is like a powerful medication where dosing matters tremendously," explains Professor Yanghua Tian from Anhui Medical University, the study's corresponding author. "Our analysis reveals that the relationship between session number and outcomes is far more nuanced than previously understood."

Early Gains, Diminishing Returns

The research team's analysis uncovered a striking pattern in treatment response. Patients typically experience substantial improvement within the first three ECT sessions, with depression scores dropping by approximately 26% after the first session and nearly 50% by the third. However, this rapid early response gives way to a plateau effect, raising questions about the optimal treatment duration.

"We found that some patients achieve remission after just four sessions, while others may receive 12 or more with minimal additional benefit," notes Dr. Yang Ji, the study's first author. "This variability suggests we need a more personalized approach."

The review identified distinct response trajectories, with approximately 25% of patients showing rapid improvement, 30% demonstrating moderate gains, and troublingly, about 13% experiencing minimal benefit despite continued treatment. Could genetic markers or brain imaging help predict which patients will respond quickly versus those who might need alternative approaches?

The Cognitive Cost of Treatment

Perhaps most significantly, the review highlights the accumulating cognitive burden associated with extended ECT courses. While early sessions produce dramatic symptom relief, each additional session increases the risk of memory impairment – a trade-off that has long troubled both patients and physicians.

The researchers found that cognitive deficits emerge as early as the second session and tend to accumulate throughout treatment. "It's a delicate balance," Professor Tian explains. "We must weigh the benefits of continued sessions against the mounting cognitive costs."

Intriguingly, seizure duration – long considered a marker of treatment adequacy – shows a progressive decline across sessions. This phenomenon raises fundamental questions about the mechanisms underlying ECT's effectiveness. Are shorter seizures in later sessions a sign of treatment resistance, or do they reflect the brain's adaptive response?

Biomarkers Paint a Dynamic Picture

The review's examination of neurobiological changes during ECT reveals a complex cascade of effects. Brain imaging studies show progressive increases in hippocampal volume – a region critical for memory formation – alongside changes in neurotransmitter systems and inflammatory markers.

"We're seeing the brain essentially rewiring itself session by session," Dr. Ji notes. "Understanding these dynamics could help us identify the sweet spot where therapeutic benefits are maximized before cognitive effects become problematic."

Blood-based biomarkers, including brain-derived neurotrophic factor (BDNF) and cortisol, show transient spikes after individual sessions but return to baseline over the treatment course. These patterns suggest that the brain's response to ECT is highly dynamic, adapting with each successive session. Could monitoring these biomarkers in real-time help clinicians make more informed decisions about when to stop or modify treatment?

A Revolutionary Sequential Strategy

Based on their comprehensive analysis, the researchers propose a paradigm-shifting approach: a response-guided sequential treatment strategy. Rather than adhering to fixed session numbers, this framework advocates for transitioning to alternative treatments once optimal ECT benefits are achieved.

"Think of it as an relay race where ECT runs the first leg," Professor Tian explains. "Once it's delivered its maximum benefit – often within 3-6 sessions for responders – we pass the baton to safer maintenance therapies."

The strategy categorizes patients into three groups based on their response patterns:

• Rapid responders who achieve remission quickly may transition to non-invasive brain stimulation or psychotherapy

• Slow responders might benefit from augmentation strategies like ketamine

• Non-responders could be switched to alternative treatments entirely

This approach addresses a critical gap in current practice, where session numbers often reflect institutional protocols rather than individual patient needs. How might implementing such personalized protocols change treatment outcomes on a population level?

Implications for Clinical Practice

The review's findings challenge the traditional "more is better" approach to ECT administration. Current guidelines recommending 6-12 sessions may need revision in light of evidence showing early response patterns and accumulating cognitive burden.

"We're not suggesting ECT is any less valuable," Dr. Ji emphasizes. "Rather, we're proposing smarter utilization that maximizes benefits while minimizing risks."

The researchers note that implementing response-guided protocols would require closer monitoring of both symptoms and cognitive function throughout treatment. This could involve regular assessments using validated scales and potentially incorporating novel biomarkers as they become clinically available.

Several questions emerge from this new framework: How would early ECT termination affect long-term relapse rates? Could combination therapies initiated after fewer ECT sessions prove more effective than extended ECT courses alone? What role might emerging technologies like transcranial magnetic stimulation play in these sequential protocols?

Future Directions

The review highlights numerous avenues for future research. Developing predictive algorithms that integrate clinical features, biomarkers, and early response patterns could help identify optimal session numbers for individual patients. Additionally, comparative studies of sequential treatment strategies versus traditional extended ECT courses are urgently needed.

"We're at a pivotal moment in ECT's evolution," Professor Tian concludes. "By embracing precision medicine principles, we can preserve ECT's remarkable efficacy while dramatically reducing its cognitive burden."

The implications extend beyond individual patient care. Healthcare systems struggling with ECT capacity could potentially treat more patients if average session numbers decrease without compromising outcomes. Moreover, patients hesitant about ECT due to cognitive concerns might be more willing to consider treatment if they knew it could be limited to just a few sessions.

As mental health systems worldwide grapple with rising depression rates, optimizing our most effective treatments becomes increasingly critical. This comprehensive review provides a roadmap for transforming ECT from a one-size-fits-all intervention to a precision tool in the psychiatric arsenal. Will this response-guided approach become the new standard of care, finally resolving ECT's efficacy-cognition dilemma?

Reference:

Yang Ji, Rethinking the impact and management of electroconvulsive therapy session number in depression, Brain Medicine, DOI: 10.61373/bm025i.0053