Efficacy and Safety of Intensive Continuous Theta Burst Stimulation Over the Right Dorsolateral Prefrontal Cortex in Insomnia Disorder:A Randomized Sham-Controlled Trial

Prim Care Companion CNS Disord. 2026 Nov 12;28(6):26m04225. doi: 10.4088/PCC.26m04225.

ABSTRACT

Background: Insomnia disorder affects 10%-35% of the general population and is maintained by pathological cortical hyperarousal amenable to inhibitory neuromodulation. Continuous theta burst stimulation (cTBS) produces rapid inhibitory effects on cortical excitability, but its efficacy in insomnia disorder has not been evaluated in adequately powered randomized sham-controlled trials.

Methods: Thirty adults (n=15 per arm) meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for insomnia disorder (Sleep Condition Indicator [SCI] score <16) were randomized to active or sham cTBS targeting the right dorsolateral prefrontal cortex (F4 position, 80% of the resting motor threshold). The intervention comprised 21 sessions (600 pulses/session, ∼40 seconds) over 10 days.Data were collected from October 2024 to January 2026. Outcome measures were the SCI (primary), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), and World Health Organization Quality of Life-Brief (WHOQOL-BREF), assessed at baseline (day 0), posttreatment (day 10), and 2-week follow-up (day 25). The trial was conducted per Consolidated Standards of Reporting Trials 2010 guidelines and analyzed using intention-to-treat mixed-effects repeated-measures analysis of variance.

Results:Both groups improved significantly across all outcomes (all within-group P<.001; large effect sizes). Group×time interactions were nonsignificant for sleep-specific outcomes (PSQI: F=3.32, P=.060; SCI: F=2.14, P=.147; ISI: F=0.23, P=.720; FOSQ-10: F=0.88, P=.388). A significant and large interaction was observed for health-related quality of life (WHOQOL-BREF: F=8.92, P =.002, ηp²=0.242), favoring active cTBS. Three participants experienced transient mild headache; no serious adverse events occurred.

Conclusion: Right dorsolateral prefrontal cortex-targeted cTBS over 10 days is safe and well tolerated. Active cTBS conferred a significant and clinically meaningful advantage in health-related quality of life. Larger trials with objective sleep endpoints, medication-naive populations, and extended follow-up are warranted.

Trial Registration: Clinical Trials Registry-India (CTRI) identifier: CTRI/2024/10/075898.

Prim Care Companion CNS Disord 2026;28(6):26m04225.

Author affiliations are listed at the end of this article.

PMID:43024398 | DOI:10.4088/PCC.26m04225