A recent study has identified that early improvements in specific depressive symptoms can predict the response to repetitive transcranial magnetic stimulation (rTMS) in patients with depression. The research, published in the Journal of Affective Disorders, highlights the importance of monitoring symptom trajectories during rTMS treatment to optimize patient outcomes.
The study, led by Winninge et al., recruited patients undergoing rTMS for unipolar or bipolar depressive episodes. The primary outcome was rTMS response, defined as a ≥50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS-S) total score and significant improvement on the Clinical Global Impression-Improvement Scale (CGI-I). Researchers also assessed rTMS remission, defined by CGI scale scores indicating normal or borderline mental health.
Study Design and Methods
The study included patients aged 18 years or older receiving left-sided intermittent θ-burst stimulation (iTBS) or right-sided 1-Hz short rTMS for the first time. The iTBS protocol involved 3 pulses at 50 Hz, repeated at 5 Hz for 2 seconds, followed by an 8-second break, repeated 20 times for a total of 600 pulses. The second-line rTMS protocol used 1-minute trains of 1-Hz stimulation followed by a 30-second break, repeated 6 times, resulting in 360 pulses. Treatment intensity was set at 120% of the resting motor threshold, administered daily on weekdays for 4 to 6 weeks, totaling 20 to 30 sessions, or until remission was achieved. Treatment was discontinued if there was <20% improvement in depressive symptoms at 4 weeks.
Key Findings
The study found that participants aged 40 years or older had significantly lower odds (OR, 0.25; 95% CI, 0.06-0.96) for rTMS response compared to younger age groups. Longer duration of depressive episodes (≥24 months; OR, 0.25; 95% CI, 0.07-0.93) and a history of previous ECT (OR, 0.14; 95% CI, 0.03-0.79) were also associated with lower odds of response. However, early improvement in initiative (OR, 3.1; 95% CI, 1.1-9.0), emotional involvement (OR, 3.0; 95% CI, 1.0-9.1), and pessimism (OR, 0.24; 95% CI, 0.07-0.80) were significant early predictors of response in multivariate analyses. Early improvement in the MADRS-S total score was a significant predictor of CGI-I response (OR, 3.6; 95% CI, 1.4-9.5).
Clinical Implications
These findings suggest that baseline clinical factors, such as age and duration of depressive episode, along with early improvements in specific depressive symptoms like initiative and emotional involvement, can predict response to rTMS. According to Dr. Miller, a professor in the Department of Psychiatry and Health Behavior at Augusta University, these results have direct clinical relevance to patient care, potentially allowing for more personalized and effective treatment strategies.
Limitations
The study acknowledges limitations, including a potential selection bias due to 24% of referred patients declining to participate and the lack of consideration for the effects of concurrent medications. Despite these limitations, the study's strengths include the recruitment of consecutive referrals for rTMS, providing valuable insights into predicting treatment response.
rTMS in MDD Treatment
rTMS is a non-invasive brain stimulation technique used to treat major depressive disorder (MDD). It involves using magnetic pulses to stimulate nerve cells in the brain, particularly in areas known to be involved in mood regulation. While rTMS has shown promise in clinical trials, predicting individual patient response remains a challenge. The pooled rTMS in MDD clinical trials is 40%,1 and 31% in natural clinical settings.
