Dual-site accelerated intermittent theta burst stimulation targeting the left dorsolateral prefrontal cortex and cerebellum could reduce suicidal ideation compared with prefrontal stimulation alone in adolescents with major depressive disorder, according to a randomized clinical trial.
In the double-blind, sham-controlled trial, researchers enrolled 59 patients aged 12 to 18 years with major depressive disorder diagnosed by two psychiatrists, a 24-item Hamilton Depression Rating Scale score higher than 20, a Beck Scale for Suicide Ideation score of 12 or higher, and a Young Mania Rating Scale score lower than 7.
The patients were randomly assigned to undergo dual-site accelerated intermittent theta burst stimulation (aiTBS) or single-site aiTBS. Both groups received active stimulation to the left dorsolateral prefrontal cortex, but the dual-site group received active left cerebellar stimulation while the single-site group received sham cerebellar stimulation.
Five daily sessions over 4 days were included in the protocol, totaling 20 sessions and 12,000 pulses at 1-hour intervals. The researchers delivered stimulation at 80% of each participant’s resting motor threshold. The primary endpoint was change in the Beck Scale for Suicide Ideation score from baseline to day 4.
The researchers found greater reductions in suicidal ideation scores in the dual-site group. Mean Beck Scale for Suicide Ideation scores decreased from 22.6 to 8.2 in the dual-site group and from 23.3 to 13.9 in the single-site group. The between-group difference in score reduction was about 4.9 points.
Lower suicidal ideation scores in the dual-site group were observed throughout the 4-day intervention period. Sensitivity analysis using the Columbia-Suicide Severity Rating Scale showed similar findings.
However, categorical suicidal ideation outcomes did not differ statistically between the groups. Response rates were 59% in the dual-site group vs. 37% in the single-site group, while remission rates were 48% vs. 30%, respectively.
Researchers also observed greater reductions in some depression measures with dual-site stimulation. Depression response rates were 72% in the dual-site group vs. 43% in the single-site group, and remission rates were 45% vs. 20%, respectively. Montgomery-Åsberg Depression Rating Scale scores were lower in the dual-site group on days 2 and 4.
At 1 month, the between-group differences in suicidal ideation and depression scores were no longer statistically significant. Beck Hopelessness Scale reductions remained greater in the dual-site group at follow-up.
The most common adverse events were pain at stimulation sites and dizziness. The researchers reported that these symptoms resolved within approximately 30 minutes following treatment cessation. No serious adverse events were reported in either group.
The researchers noted several limitations, including the single-center design, small sample size, lack of a dual-site sham group, and concomitant pharmacotherapy use. The study protocol treated changes in concomitant medication type or dose during the intervention as protocol violations, although the researchers stated the observed outcomes may reflect interactions between aiTBS and pharmacotherapy rather than stand-alone treatment effects.
“By achieving rapid antisuicidal effects with minimal pulses and treatment time, this protocol represents a promising strategy for clinical translation for adolescents with [major depressive disorder],” wrote lead study author Dong Huang, PhD, of the Department of Psychiatry at the First Affiliated Hospital of Jinan University in China, and colleagues.
Funding was provided by the National Key R&D Program of China, the National Natural Science Foundation of China, the Science and Technology Projects of Guangzhou, the Fundamental Research Funds for the Central Universities, and the Guangdong Basic and Applied Basic Research Foundation. The study authors reported no conflicts of interest.
Source: JAMA Network Open
